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Summary Background Mortality in patients with COVID-19 pneumonia and systemic hyperinflammation is high. We aimed to examine whether mavrilimumab, an anti-granulocyte–macrophage colony-stimulating factor receptor-α monoclonal antibody, added to standard management, improves clinical outcomes in patients with COVID-19 pneumonia and systemic hyperinflammation. Methods This single-centre prospective cohort study included patients aged 18 years or older who were admitted to San Raffaele Hospital (Milan, Italy) with severe COVID-19 pneumonia, hypoxia, and systemic hyperinflammation. Patients received a single intravenous dose (6 mg/kg) of mavrilimumab added to standard care given by the hospital at the time. The control group consisted of contemporaneous patients with similar baseline characteristics who received standard care at the same hospital. The main outcome was time to clinical improvement (defined as improvement of two or more points on the seven-point ordinal scale of clinical status). Other outcomes included proportion of patients achieving clinical improvement, survival, mechanical ventilation-free survival, and time to fever resolution. Adverse events were monitored daily. Findings Between March 17 and April 15, 2020, 13 non-mechanically ventilated patients (median age 57 years [IQR 52–58], 12 [92%] men) received mavrilimumab and 26 patients (median age 60 [IQR 53–67], 17 [65%] men) in the control group received standard care. During the 28-day follow-up, no patients in the mavrilimumab group died, and seven (27%) patients in the control group died (p=0·086). At day 28, all patients in the mavrilimumab group and 17 (65%) patients in the control group showed clinical improvement (p=0·030), with earlier improvement in the mavrilimumab than in the control group (mean time to improvement 8 days [IQR 5 to 11] vs 19 days [11 to >28], p=0·0001). By day 28, one (8%) patient in the mavrilimumab group progressed to mechanical ventilation compared with nine (35%) patients in the control group who progressed to mechanical ventilation or died (p=0·14). By day 14, fever resolved in ten (91%) of 11 febrile patients in the mavrilimumab group, compared with 11 (61%) of 18 febrile patients in the control group (p=0·18); fever resolution was faster in mavrilimumab recipients versus controls (median time to resolution 1 day [IQR 1 to 2] vs 7 days [3 to >14], p=0·0093). Mavrilimumab was well tolerated, with no infusion reactions. Three (12%) patients in the control group developed infectious complications. Interpretation Mavrilimumab treatment was associated with improved clinical outcomes compared with standard care in non-mechanically ventilated patients with severe COVID-19 pneumonia and systemic hyperinflammation. Treatment was well tolerated. Confirmation of efficacy requires controlled testing. Funding IRCCS San Raffaele Scientific Institute.

Background Coronavirus disease 2019 acute respiratory distress syndrome (COVID‐19 ARDS) is a disease that often requires invasive ventilation. Little is known about COVID‐19 ARDS sequelae. We assessed the mid‐term lung status of COVID‐19 survivors and investigated factors associated with pulmonary sequelae. Methods All adult COVID‐19 patients admitted to the intensive care unit from 25th February to 27th April 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations. Results Forty‐nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89–105) days, whilst PFT after 142 (133–160) days. The median age was 58 (52–65) years and most patients were male (90%). The median duration of mechanical ventilation was 11 (6–16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71–7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. The diffusion capacity of carbon monoxide (DLCO) was reduced by 59%, with a median per cent of predicted DLCO of 72.1 (57.9–93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, whilst the duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs. Conclusions Both the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID‐19.

Highlight • This is the first study comparing tocilizumab to standard of care in severe COVID-19 • Tocilizumab in severe COVID-19 patients did influence 28-day clinical outcomes • Tocilizumab safety was safisfactory except for ICU-admitted patients, Background : Tocilizumab (TCZ), a humanized monoclonal antibody targeting the interleukin-6 (IL-6) receptor, has been proposed for the treatment of COVID-19 patients; however, limited data are available on the safety and efficacy. Methods : We performed a retrospective study on severe COVID-19 patients with hyper-inflammatory features admitted outside intensive care units (ICUs). Patients treated with intravenous TCZ in addition to standard of care were compared to patients treated with standard of care alone. Safety and efficacy were assessed over a 28-day follow-up. Results : 65 patients were included, 32 were of whose treated with TCZ. At baseline, all patients were on high-flow supplemental oxygen and most (78% of TCZ patients and 61% of standard treatment patients) were on non-invasive ventilation. During the 28-day follow-up, 69% of TCZ patients experienced a clinical improvement compared to 61% of standard treatment patients (p = 0.61). Mortality was 15% in the tocilizumab group and 33% in standard treatment group (p = 0.15). In TCZ group, at multivariate analysis, older age was a predictor of death, whereas higher baseline PaO2:FiO2 was a predictor of clinical improvement at day 28. The rate of infection and pulmonary thrombosis was similar between the two groups. Conclusions : At day 28, clinical improvement and mortality were not statistically significant different between tocilizumab and standard treatment patients in our cohort. Bacterial or fungal infections were recorded in 13% of tocilizumab patients and in 12% of standard treatment patients. Confirmation of efficacy and safety will require ongoing controlled trials.

To explore the potential role of two- (2D) and three-dimensional (3D) cardiac magnetic resonance (CMR) feature tracking (FT) myocardial strain analysis in identifying sub-clinical myocardial systolic and diastolic dysfunction in acute myocarditis patients with preserved ejection fraction (EF). Prospective two centre study-control study. Thirty patients (9 female, 37.2 ± 11.8years.) with a CMR diagnosis of acute myocarditis according to the Lake Louise Criteria and preserved EF (≥ 55%) were included in the analysis. CMR data from 24 healthy volunteers (11 female, 36.2 ± 12.5years.) served as control. 2D and 3D LV tissue tracking analysis were performed in a random fashion by two double-blinded operators. Variables were checked for normality and analysed with parametric test. The baseline characteristics of myocarditis patients with preserved EF and the healthy volunteers were perfectly comparable, except for the LV mass index and T1 and T2 mapping values (p < 0.001). The results of the interobserver variability in the 2D and 3D LV CMR FT myocardial strain analysis were p > 0.42, ICC > 0.80 and η 2 > 0.98. There was no statistical difference in 2D and 3D global radial, circumferential and longitudinal strain peak (%) and both systolic and diastolic strain rate (1/s) between acute myocarditis with preserved EF and healthy volunteers (all p = ns). There were no difference in 2D and 3D global radial, circumferential and longitudinal strain peak and both systolic and diastolic strain rate of the LV between acute myocarditis patients with preserved ejection fraction and healthy volunteers.

Aim: To evaluate whether perfusion heterogeneity of rectal cancer prior to chemoradiotherapy (CRT) using histogram analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) quantitative parameters can predict response to treatment. Materials and methods: Twenty-one patients with histologically proven rectal adenocarcinoma were enrolled prospectively. All patients underwent 1.5 T DCE-MRI before CRT. Tumour volumes were drawn on Ktrans and Ve maps, using T2-weighted (W) images as reference, and the following first-order texture parameters of Ve and Ktrans values were extracted: 25th, 50th, 75th percentile, mean, standard deviation, skewness, and kurtosis. After CRT, patients underwent surgery and according with Rödel's tumour regression grade (TRG), they were classified as poor responders “non-GR” (TRG 0–2) and good responders “GR” (TRG 3–4). Differences between GR and non-GR in DCE-MRI first-order texture parameters were evaluated using the Mann–Whitney test, and their role in the prediction of response was investigated using receiver operating characteristic (ROC) curve analysis. Results: Sixteen (76%) patients were classified as GR and five (24%) were non-GR. Skewness and kurtosis of Ve was significantly higher in non-GR (4.886±1.320 and 36.402±24.486, respectively) than in GR patients (1.809±1.280, p=0.003 and 6.268±8.130, p= 0.011). Ve skewness

Aim: To investigate the potential role of an additional magnetic resonance imaging (MRI) examination performed during neoadjuvant chemoradiation therapy (CRT) in the prediction of pathological response in locally advanced rectal cancer (LARC). Material and methods: Forty-eight consecutive patients with LARC underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2-weighted sequences that were acquired parallel and perpendicular to the main axis of the tumour were performed before (preMRI), during (midMRI), and 6-8 weeks after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn manually and the reduction rate calculated (ΔVmid, ΔVpost). According to Rödel's pathological tumour regression grade (TRG), patients were considered non-responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders (CR; TRG4). Multivariate regression analysis was performed to identify the best MRI predictors of NR, PR, and CR. Results: Twenty-five patients were considered PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly after CRT (ΔVmid: CR: 80±10% versus PR: 56±19% versus NR: 28±22%, p=2.2×10-16). Vmid, Vpost, ΔVmid, and ΔVpostcorrelated with TRG (p

"\"La tomografia computerizzata del cuore (CCT) è diventata uno strumento efficace in differenti contesti clinici. Lo sviluppo della tecnologia ha portato ad una progressiva espansione delle indicazioni con una concomitante riduzione della dose di radiazioni necessaria per l’esecuzione dell’indagine. Ancora oggi sono pochi i documenti delle maggiori società scientifiche internazionali che si esprimono sulle effettive modalità di utilizzo e sulle indicazioni cliniche della CCT; in particolare mancano delle linee guida complete. Questo documento rispecchia la visione del gruppo di lavoro della Sezione di Cardio-Radiologia della Società Italiana di Radiologia Medica in merito alle indicazioni correnti della CCT.\"" "\"Cardiac computed tomography (CCT) has grown as a useful means in different clinical contexts. Technological development has progressively extended the indications for CCT while reducing the required radiation dose. Even today there is little documentation from the main international scientific societies describing the proper use and clinical indications of CCT; in particular, there are no complete guidelines. This document reflects the position of the Working Group of the Cardiac Radiology Section of the Italian Society of Radiology concerning the indications for CCT.\""

Background Loco-regional treatments have improved the survival of patients with early hepatocellular carcinoma (HCC), but tumor relapse is a frequent event and survival rates remain low. Moreover, conflicting evidences address early HCC patients to surgery or radiofrequency ablation (RFA), with the clinical need to find predictive non-invasive biomarkers able to guide treatment choice and define patients survival. Methods Two independent case series of treatment-naive HCC patients treated with local RFA, and a cohort of 30 HCC patients treated with liver surgery were enrolled. On the basis of literature evidence, we customized a panel of 21 miRNAs correlated with relapse and prognosis after local curative treatment of HCC. Results Expression levels of let-7c predict tumor relapse after RFA; we also investigated the same panel in a small cohort of HCC patients undergoing surgery, finding no statistically significance in predicting tumor relapse or survival. Moreover, interaction test indicated that let-7c expression levels are predictive for identifying a subset of patients that should be addressed to surgery. Conclusion Results from this study could predict prognosis of early HCC patients, helping to address early HCC patients to surgery or RFA treatment.

We present the current clinical applications of radiomics in the context of prostate cancer (PCa) management. Several online databases for original articles using a combination of the following keywords: “(radiomic or radiomics) AND (prostate cancer or prostate tumour or prostate tumor or prostate neoplasia)” have been searched. The selected papers have been pooled as focus on (i) PCa detection, (ii) assessing the clinical significance of PCa, (iii) biochemical recurrence prediction, (iv) radiation-therapy outcome prediction and treatment efficacy monitoring, (v) metastases detection, (vi) metastases prediction, (vii) prediction of extra-prostatic extension. Seventy-six studies were included for qualitative analyses. Classifiers powered with radiomic features were able to discriminate between healthy tissue and PCa and between low- and high-risk PCa. However, before radiomics can be proposed for clinical use its methods have to be standardized, and these first encouraging results need to be robustly replicated in large and independent cohorts.

The aim of the present study is to investigate the synergic role of 68Ga-PSMA PET/MRI and 68Ga-DOTA-RM2 PET/MRI in prostate cancer (PCa) staging. We present pilot data on twenty-two patients with biopsy-proven PCa that underwent 68Ga-PSMA PET/MRI for staging purposes, with 19/22 also undergoing 68Gaa-DOTA-RM2 PET/MRI. TNM classification based on image findings was performed and quantitative imaging parameters were collected for each scan. Furthermore, twelve patients underwent radical prostatectomy with the availability of histological data that were used as the gold standard to validate intraprostatic findings. A DICE score between regions of interest manually segmented on the primary tumour on 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and on T2 MRI was computed. All imaging modalities detected the primary PCa in 18/19 patients, with 68Ga-DOTA-RM2 PET not detecting any lesion in 1/19 patients. In the remaining patients, 68Ga-PSMA and MRI were concordant. Seven patients presented seminal vesicles involvement on MRI, with two of these being also detected by 68Ga-PSMA, and 68Ga-DOTA-RM2 PET being negative. Regarding extraprostatic disease, 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI resulted positive in seven, four and five patients at lymph-nodal level, respectively, and at a bone level in three, zero and one patients, respectively. These preliminary results suggest the potential complementary role of 68Ga-PSMA PET, 68Ga-DOTA-RM2 PET and MRI in PCa characterization during the staging phase.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread worldwide determining dramatic impacts on healthcare systems. Early identification of high-risk parameters is required in order to provide the best therapeutic approach. Coronary, thoracic aorta and aortic valve calcium can be measured from a non-gated chest computer tomography (CT) and are validated predictors of cardiovascular events and all-cause mortality. However, their prognostic role in acute systemic inflammatory diseases, such as COVID-19, has not been investigated. OBJECTIVES: The aim was to evaluate the association of coronary artery calcium and total thoracic calcium on in-hospital mortality in COVID-19 patients. METHODS: 1093 consecutive patients from 16 Italian hospitals with a positive swab for COVID-19 and an admission chest CT for pneumonia severity assessment were included. At CT, coronary, aortic valve and thoracic aorta calcium were qualitatively and quantitatively evaluated separately and combined together (total thoracic calcium) by a central Core-lab blinded to patients' outcomes. RESULTS: Non-survivors compared to survivors had higher coronary artery [Agatston (467.76 ​± ​570.92 vs 206.80 ​± ​424.13 ​mm2, p ​

Purpose: In overwhelmed emergency departments (EDs) facing COVID-19 outbreak, a swift diagnosis is imperative. CT role was widely debated for its limited specificity. Here we report the diagnostic role of CT in two EDs in Lombardy, epicenter of Italian outbreak. Material and methods: Admitting chest CT from 142 consecutive patients with suspected COVID-19 were retrospectively analyzed. CT scans were classified in “highly likely,” “likely,” and “unlikely” COVID-19 pneumonia according to the presence of typical, indeterminate, and atypical findings, or “negative” in the absence of findings, or “alternative diagnosis” when a different diagnosis was found. Nasopharyngeal swab results, turnaround time, and time to positive results were collected. CT diagnostic performances were assessed considering RT-PCR as reference standard. Results: Most of cases (96/142, 68%) were classified as “highly likely” COVID-19 pneumonia. Ten (7%) and seven (5%) patients were classified as “likely” and “unlikely” COVID-19 pneumonia, respectively. In 21 (15%) patients a differential diagnosis was provided, including typical pneumonia, pulmonary edema, neoplasia, and pulmonary embolism. CT was negative in 8/142 (6%) patients. Mean turnaround time for the first COVID-19 RT-PCR was 30 ± 13h. CT diagnostic accuracy in respect of the first test swab was 79% and increased to 91.5% after repeated swabs and/or BAL, for 18 false-negative first swab. CT performance was good with 76% specificity, 99% sensitivity, 90% positive predictive value and 97% negative predictive value. Conclusion: Chest CT was useful to streamline patients’ triage while waiting for RT-PCR in the ED, supporting the clinical suspicion of COVID-19 or providing alternative diagnosis.

Visceral artery aneurysms (VAAs) are rare, usually asymptomatic and incidentally discovered during a routine radiological examination. Shared guidelines suggest their treatment in the following conditions: VAAs with diameter larger than 2 cm, or 3 times exceeding the target artery; VAAs with a progressive growth of at least 0.5 cm per year; symptomatic or ruptured VAAs. Endovascular treatment, less burdened by morbidity and mortality than surgery, is generally the preferred option. Selection of the best strategy depends on the visceral artery involved, aneurysm characteristics, the clinical scenario and the operator’s experience. Tortuosity of VAAs almost always makes embolization the only technically feasible option. The present narrative review reports state of the art and new perspectives on the main endovascular and other interventional options in the treatment of VAAs. Embolization techniques and materials, use of covered and flow-diverting stents and percutaneous approaches are accurately analyzed based on the current literature. Visceral artery-related considerations and targeted approaches are also provided and discussed.

Background. Fatty liver is believed to be sustained by a higher than normal adipose-derived NEFA flux to the liver. Also, hepatic energy metabolism may be a rate-limiting step of intrahepatic fat (IHF) accumulation. Aims. To assess whole-body energy metabolism and hepatic high-energy phosphates (HEPs) in individuals with fatty liver. Methods. We studied 22 individuals with fatty liver and 22 control individuals matched for anthropometric features by means of (1) hepatic 1H-magnetic resonance spectroscopy (MRS) to measure the IHF content, (2) hepatic 31P-MRS to assess the relative content of HEPs (phosphomonoesters, phosphodiesters, inorganic phosphorus, and ATP), and (3) indirect calorimetry to assess whole-body resting energy expenditure and substrate oxidation. Results. Patients with newly diagnosed fatty liver and controls were not different for anthropometric parameters. Based on HOMA2%-S, individuals with fatty liver were more insulin resistant than controls. Resting energy expenditure and the pattern of substrate oxidation were not different between groups. Relative content of HEPs was not different between groups; in particular, the Pi/γ-ATP ratio, the most important signals in terms of monitoring energy homeostasis, was not different even if it was associated with indirect calorimetry-derived parameters of oxidative substrate disposal. Conclusions. These data demonstrate that fasting whole-body energy metabolism and the relative content of HEPs in nondiabetic patients with fatty liver are not different than those in controls when they are matched for anthropometric features.

Objective The impact of growth hormone (GH) deficiency of the adult on cardiovascular function remains only partially elucidated. Purpose of this study was to test cardiac function in adult GH deficient patients using cardiac magnetic resonance (CMR). Design Cardiac magnetic resonance (CMR) techniques, including cardiac 31P MR spectroscopy and evaluation of gadolinium late-enhancement, were applied to assess simultaneously, in a cross-sectional fashion, morphological, functional, metabolic, and structural parameters of the left (LV) and right ventricle (RV) in 15 patients with adult onset GH deficiency. Fifteen healthy individuals served as controls. Results In GH deficient patients LV systolic function (EF%: 61 ± 1.7 vs 62.1 ± 0.8; p = .44) was not different in spite of a lower LV mass (83.2 ± 5.3 vs 145.3 ± 11.9 g; p = .001), a subclinical impairment of diastolic function (E/A peak ratio: 1.6 ± 0.2 vs 2.1 ± 0.2 p = .05), and a trend for lower PCr/ATP ratio (2.1 ± 0.8 vs 2.3 ± 0.1 p = .07). The RV showed reduced chamber size (end diastolic volume 123.8 ± 9 vs 147.9 ± 7.6 mL; p = .021) with preserved mass. No structural alterations of the LV and RV at late-enhancement were detected in these patients. Conclusions GH deficient patients represent a unique model of reduced LV myocardial mass in which major structural and metabolic alterations are lacking. Mal-adaptive mechanisms developing in the long term in response to GH deficiency and more severely affecting the LV remain to be elucidated.

Aim: To establish the correlation between changes in body composition after neoadjuvant chemoradiotherapy (nCRT) and postoperative outcomes, in patients with advanced low rectal cancer. Methods: Patients with clinical stage T≥3 or N+ rectal cancer who underwent nCRT and surgical resection were studied. Skeletal muscle, visceral, and subcutaneous fat cross-sectional area were measured by computed tomography before and after nCRT. Postoperative morbidity, pathologic response to nCRT, overall and disease-free survival was assessed. Results: Fifty-two patients, median age 62 (range 32-79) were studied. A skeletal muscle loss >2% significantly correlated with a shorter disease-free survival both in the overall population (P = 0.048) and in the subgroup of N0 patients (P = 0.048). A subcutaneous fat loss >5% was also associated with a shorter disease-free survival (P = 0.012) in the whole population. Conclusions: Skeletal muscle loss, after neoadjuvant chemoradiotherapy, negatively impacts on disease-free survival in surgically treated rectal cancer patients.

Summary Background & aims Sarcopenia, a loss of muscle mass, quality and function, which is particularly evident in respiratory muscles, has been associated with many clinical adverse outcomes. In this study, we aimed at evaluating the role of reduced muscle mass and quality in predicting ventilation weaning, complications, length of intensive care unit (ICU) and of hospital stay and mortality in patients admitted to ICU for SARS-CoV-2-related pneumonia. Methods This was an observational study based on a review of medical records of all adult patients admitted to the ICU of a tertiary hospital in Milan and intubated for SARS-CoV-2-related pneumonia during the first wave of the COVID-19 pandemic. Muscle mass and quality measurement were retrieved from routine thoracic CT scans, when sections passing through the first, second or third lumbar vertebra were available. Results A total of 81 patients were enrolled. Muscle mass was associated with successful extubation (OR 1.02, 95% C.I. 1.00–1.03, p = 0.017), shorter ICU stay (OR 0.97, 95% C.I. 0.95–0.99, p = 0.03) and decreased hospital mortality (HR 0.98, 95% C.I. 0.96–0.99, p = 0.02). Muscle density was associated with successful extubation (OR 1.07, 95% C.I. 1.01–1.14; p = 0.02) and had an inverse association with the number of complications in ICU (Β −0.07, 95% C.I. −0.13 - −0.002, p = 0.03), length of hospitalization (Β −1.36, 95% C.I. −2.21 - −0.51, p = 0.002) and in-hospital mortality (HR 0.88, 95% C.I. 0.78–0.99, p = 0.046). Conclusions Leveraging routine CT imaging to measure muscle mass and quality might constitute a simple, inexpensive and powerful tool to predict survival and disease course in patients with COVID-19. Preserving muscle mass during hospitalisation might have an adjuvant role in facilitating remission from COVID-19.

Purpose: To determine whether Macklin effect (a linear collection of air contiguous to the bronchovascular sheath) on baseline CT imaging is an accurate predictor for subsequent pneumomediastinum (PMD)/pneumothorax (PNX) development in invasively ventilated patients with COVID-19-related acute respiratory distress syndrome (ARDS). Materials and methods: This is an observational, case-control study. From a prospectively acquired database, all consecutive invasively ventilated COVID-19 ARDS patients who underwent at least one baseline chest CT scan during the study time period (February 25th, 2020–December 31st, 2020) were identified; those who had tracheal lesion or already had PMD/PNX at the time of the first available chest imaging were excluded. Results: 37/173 (21.4%) patients enrolled had PMD/PNX; specifically, 20 (11.5%) had PMD, 10 (5.8%) PNX, 7 (4%) both. 33/37 patients with subsequent PMD/PNX had Macklin effect on baseline CT (89.2%, true positives) 8.5 days [range, 1–18] before the first actual radiological evidence of PMD/PNX. Conversely, 6/136 patients without PMD/PNX (4.4%, false positives) demonstrated Macklin effect (p < 0.001). Macklin effect yielded a sensitivity of 89.2% (95% confidence interval [CI]: 74.6–96.9), a specificity of 95.6% (95% CI: 90.6–98.4), a positive predictive value (PV) of 84.5% (95% CI: 71.3–92.3), a negative PV of 97.1% (95% CI: 74.6–96.9) and an accuracy of 94.2% (95% CI: 89.6–97.2) in predicting PMD/PNX (AUC:0.924). Conclusions: Macklin effect accurately predicts, 8.5 days in advance, PMD/PNX development in COVID-19 ARDS patients.

Objective: To assess the relationship between the volume of the index lesion (IL) measured at multiparametric magnetic resonance imaging (mpMRI; MRIvol) and at radical prostatectomy (RPvol), stratifying it according to Prostate Imaging-Reporting and Data System (PI-RADS) score. Patients and Methods: We identified 332 men with a positive mpMRI (single lesion with PI-RADS ≥3) who underwent systematic plus targeted biopsy and subsequent RP at two tertiary referral centres between 2013 and 2018. All mpMRIs were reviewed by experienced radiologists using PI-RADS scores. The study outcome was to assess the relationship between MRIvol (based on planimetry from MRI sequence best showing tumour) and RPvol (based on tumour involved area of each RP pathology slice). To achieve this endpoint, we performed a multivariable linear regression analysis (LRA) to predict RPvol using PI-RADS, prostate-specific antigen level, prostate volume, age, digital rectal examination, Gleason score at MRI-targeted biopsy, biopsy history and time from mpMRI to RP as covariates. Non-parametric locally estimated scatterplot smoothing (LOESS) function was used to graphically explore the relationship between MRIvol and RPvol, stratifying for PI-RADS score. Results: Overall, 24%, 49% and 27% of men had visible PI-RADS 3, 4 and 5 lesions at mpMRI. The median (interquartile range [IQR]) MRIvol and RPvol were 0.67(0.29–1.76)mL and 1.39(0.58–4.23)mL. At LRA, MRIvol was significantly correlated with a RPvol underestimation (slope: 2.4, 95% confidence interval [CI] 0.1–46.3). The non-parametric LOESS analysis showed a non-linear relationship between MRIvol and RPvol. Significant underestimation was reported across all volumes with the highest differences between MRIvol and RPvol in the low volume range (

Objectives: Clinically significant pancreatic fistula (POPF) has been established as a well-known risk factor for late and severe postpancreatectomy hemorrhage after pancreaticoduodenectomy (PD) (postpancreatectomy pancreatic fistula–associated hemorrhage [PPFH]). Our aim was to assess whether contrast-enhanced CT scan after PD is an effective tool for early prediction of PPFH. Methods: From a prospectively acquired database, all consecutive patients who underwent PD between January 2013 and May 2019 were identified; within this database, all patients who were evaluated, for clinical suspicion of POPF, with at least one contrast-enhanced CT scan examination, were enrolled in this retrospective study. The selected CT findings included perianastomotic fluid collections and air bubbles; pancreaticojejunostomy (PJ) was analyzed in terms of dehiscence and defect. Results: One hundred seventy-eight out of 953 PD patients (18.7%) suffered from clinically significant POPF; after exclusions, 166 patients were enrolled. Among this subset, 33 patients (19.9%) had at least one PPFH episode. In multivariable analysis, PPFH was associated with postoperative CT evidence of fluid collections (p = 0.046), air bubbles (p = 0.046), and posterior PJ defect (p < 0.001). Based on these findings, a practical 4-point prediction score was developed (AUC: 0.904, Se: 76%, Sp: 93.8%): patients with a score ≥ 3 demonstrated a significantly higher risk of PPFH development (OR = 45.6, 95% CI: 13.0–159.3). Conclusions: Postoperative CT scan permits early stratification of PPFH risk, thus providing an actual aid for patients’ management. Key Points: • Postpancreatectomy hemorrhage (PPH) is a dramatic, clinically unpredictable occurrence. • After pancreaticoduodenectomy (PD), early identification of posterior pancreaticojejunostomy defect, perianastomotic air bubbles, and retroperitoneal fluid collections enables effective PPH risk stratification by means of a practical CT-based 4-point scoring system. • CT scan after PD allows a paradigm shift in the management PPH, from a conventional “wait and see” approach, to a more proactive one that relies on early anticipation and timely prevention.

Objectives Enlarged main pulmonary artery diameter (MPAD) resulted to be associated with pulmonary hypertension and mortality in a non-COVID-19 setting. The aim was to investigate and validate the association between MPAD enlargement and overall survival in COVID-19 patients. Methods This is a cohort study on 1469 consecutive COVID-19 patients submitted to chest CT within 72 h from admission in seven tertiary level hospitals in Northern Italy, between March 1 and April 20, 2020. Derivation cohort (n = 761) included patients from the first three participating hospitals; validation cohort (n = 633) included patients from the remaining hospitals. CT images were centrally analyzed in a core-lab blinded to clinical data. The prognostic value of MPAD on overall survival was evaluated at adjusted and multivariable Cox’s regression analysis on the derivation cohort. The final multivariable model was tested on the validation cohort. Results In the derivation cohort, the median age was 69 (IQR, 58–77) years and 537 (70.6%) were males. In the validation cohort, the median age was 69 (IQR, 59–77) years with 421 (66.5%) males. Enlarged MPAD (≥ 31 mm) was a predictor of mortality at adjusted (hazard ratio, HR [95%CI]: 1.741 [1.253–2.418], p p = 0.005), together with male gender, old age, high creatinine, low well-aerated lung volume, and high pneumonia extension (c-index [95%CI] = 0.826 [0.796–0.851]). Model discrimination was confirmed on the validation cohort (c-index [95%CI] = 0.789 [0.758–0.823]), also using CT measurements from a second reader (c-index [95%CI] = 0.790 [0.753;0.825]). Conclusion Enlarged MPAD (≥ 31 mm) at admitting chest CT is an independent predictor of mortality in COVID-19. Key Points •Enlargement of main pulmonary artery diameter at chest CT performed within 72 h from the admission was associated with a higher rate of in-hospital mortality in COVID-19 patients. •Enlargement of main pulmonary artery diameter (≥ 31 mm) was an independent predictor of death in COVID-19 patients at adjusted and multivariable regression analysis. •The combined evaluation of clinical findings, lung CT features, and main pulmonary artery diameter may be useful for risk stratification in COVID-19 patients.

Cardiovascular diseases are still among the first causes of death worldwide with a huge impact on healthcare systems. Within these conditions, the correct diagnosis of coronary artery disease with the most appropriate imaging-based evaluations is of utmost importance. The sustainability of the healthcare systems, considering the high economic burden of modern cardiac imaging equipments, makes cost-effective analysis an important tool, currently used for weighing different costs and health outcomes, when policy makers have to allocate funds and to prioritize interventions, getting the most out of their financial resources. This review aims at evaluating cost-effective analysis in the more recent literature, focused on the role of Calcium Score, coronary computed tomography angiography and cardiac magnetic resonance.

ObjectivesTo assess the safety and efficacy of interleukin (IL)−6 blockade with sarilumab in patients with severe COVID-19 pneumonia and systemic hyperinflammation.MethodsWe conducted an open-label study of sarilumab in severe COVID-19 pneumonia (PaO2/FiO2 ResultsTwenty-eight patients were treated with sarilumab and 28 contemporary patients receiving standard of care alone were used as controls. At day 28 of follow-up, 61% of patients treated with sarilumab experienced clinical improvement and 7% died. These findings were not significantly different from the comparison group (clinical improvement 64%, mortality 18%; p=NS). Baseline PaO2/FiO2 ratio >100 mm Hg and lung consolidation ConclusionsAt day 28, overall clinical improvement and mortality in patients with severe COVID-19 were not significantly different between sarilumab and standard of care. Sarilumab was associated with faster recovery in a subset of patients showing minor lung consolidation at baseline.

Background: Preoperative evaluation of the number of lymph node metastasis (LNM) is the basis of individual treatment of locally advanced gastric cancer (LAGC). However, the routinely used preoperative determination method is not accurate enough. Patients and methods: We enrolled 730 LAGC patients from five centers in China and one center in Italy, and divided them into one primary cohort, three external validation cohorts, and one international validation cohort. A deep learning radiomic nomogram (DLRN) was built based on the images from multiphase computed tomography (CT) for preoperatively determining the number of LNM in LAGC. We comprehensively tested the DLRN and compared it with three state-of-the-art methods. Moreover, we investigated the value of the DLRN in survival analysis. Results: The DLRN showed good discrimination of the number of LNM on all cohorts [overall C-indexes (95% confidence interval): 0.821 (0.785–0.858) in the primary cohort, 0.797 (0.771–0.823) in the external validation cohorts, and 0.822 (0.756–0.887) in the international validation cohort]. The nomogram performed significantly better than the routinely used clinical N stages, tumor size, and clinical model (P < 0.05). Besides, DLRN was significantly associated with the overall survival of LAGC patients (n = 271). Conclusion: A deep learning-based radiomic nomogram had good predictive value for LNM in LAGC. In staging-oriented treatment of gastric cancer, this preoperative nomogram could provide baseline information for individual treatment of LAGC.

Purpose To report the safety and efficacy of the embolization of splenic artery aneurysms (SAAs) with coils plus ethylene vinyl alcohol copolymer (EVOH) agent. Materials and Methods A single-center retrospective study was conducted from 2016 to 2019 to collect SAAs. Twelve asymptomatic patients (mean age, 59 years) with 15 SAAs (mean size, 23.6 mm; size range, 15–40 mm) were treated with embolization. Embolization was performed with EVOH (Squid 8/34) and fibered detachable coils. Transfemoral embolization was performed with a microcatheter to achieve a splenic artery occlusion embolizing the SAA and its efferent and afferent branches. Follow-up was based on color Doppler ultrasound at 24 hours and on computed tomography (CT) angiography at 1 (n = 12) and 6 months (n = 12) after embolization. Mean number of coils and Squid vials used for each patient, major/minor complications, technical success, 30-day clinical success, cases of revascularization/reintervention, and mortality were assessed. Technical success was defined as complete exclusion of the aneurysmal segment and cessation of blood flow into the sac. Clinical success at 1 month was based on the absence of clinical symptoms and the exclusion of aneurysm revascularization on CT angiography. Results The mean number of coils and Squid vials was 5.75 (standard deviation [SD], 1.58; range, 3–9) and 1.41 (SD, 0.49; range, 1–2), respectively. Both technical and 30-day clinical success were 100%, with no cases of aneurysm revascularization (CT angiography performed in all patients at 1 month and 6 months and in 3 patients at 24 months). No major complications or fatal events were recorded. In terms of minor complications, 2 cases of mild pancreatitis (transient amylases increase) and 1 case of focal splenic ischemia without clinical sequelae were recorded. Conclusions Embolization in SAAs using coils plus EVOH was safe and effective without SAA revascularization

Purpose: Skeletal muscle mass (SMM) depletion and sarcopenia as predictors of postoperative complications and poorer overall survival (OS) have been validated in many surgical fields through cross-sectional imaging (CT, MRI), with potential limitations. We evaluated it in a stage III–IV head and neck squamous cell carcinoma (HNSCC) surgical cohort through ultrasound (US) of rectus femoris muscle (RF), a quick, cheap, repeatable alternative. Methods: Patients submitted to surgical treatment with curative purpose were recruited and prospectively evaluated through clinical, biometric, biochemical, surgical, pathological and functional prognosticators and with preoperative US of RF with regards to 30-day complications and OS. Results: Forty-seven patients completed the study. RF cross-sectional area (RF-CSA) was used to identify patients with low SMM (CSA ≤ 0.97cm2: 18/47, 38.3%). RF-CSA was lower in complicated cases (0.95 ± 0.48 vs 1.41 ± 0.49cm2; p = 0.003), remaining the only independent predictor of postoperative complications at multivariate analysis, with a model including ASA score and modified Frailty index (OR 9.84; p = 0.004). SMM depletion significantly impaired OS (13.6 ± 2.9 vs 26.3 ± 2.1months; p = 0.017), being its only independent prognosticator at multivariate Cox regression analysis (OR 4.42; p = 0.033). Conclusion: RF-CSA, evaluated with US, seems a reliable method for identification of patients with low SMM in a stage III–IV HNSCC cohort, defining a subset at high-risk of 30-day complications and poorer OS.

Background: In the PURE-01 study, pembrolizumab was given preoperatively before radical cystectomy in clinical T2-4aN0M0 patients. An accurate clinical response assessment may be useful for developing new perioperative strategies in these patients. Objective: To evaluate the association between bladder multiparametric magnetic resonance imaging (mpMRI) findings after pembrolizumab and the pathological complete response (CR; pT0). Design, setting, and participants: Patients were staged using bladder mpMRI whereby radiologists were asked to characterize the following parameters: residual disease at T1- and T2-weighted images (step 1: yes/no), presence of hyperintense spots within the bladder wall on diffusion-weighted imaging (step 2: yes/no), and presence of pathological contrast enhancement (step 3: yes/no), before and after three cycles of pembrolizumab. Examinations were internally assessed by two senior radiologists and externally evaluated by a third senior radiologist. Intervention: To evaluate bladder tumor response after neoadjuvant pembrolizumab, mpMRI was used. Outcome measurements and statistical analysis: The primary objective was to predict the pT0 after neoadjuvant pembrolizumab by relying on the mpMRI findings. Cohen's kappa statistics was used to assess interobserver variability. Univariable analyses for pT0 were performed including internal and external post-therapy mpMRI steps. Results and limitations: From February 2017 to October 2018, 82 patients (164 total mpMRI assessments) were analyzed. The agreement between the internal and external mpMRI assessments after therapy was acceptable (κ values ranging from 0.5 to 0.76). Each mpMRI step was significantly associated with pT0 in both internal and external assessments. In patients with CR/no evidence of residual disease (NED) in all internally evaluated mpMRI steps (N = 37), the pT0 was seen in 23 (62%), compared with 19 of 26 externally evaluated NED patients (73%). Conclusions: In post-pembrolizumab muscle-invasive bladder cancer, mpMRI sequence assessment had acceptable interobserver variability and represented the basis for the proposal of a radiological CR/NED status definition predicting the pT0 response to pembrolizumab. After validation of these findings with external datasets, we propose this tool for developing bladder-sparing immunotherapy maintenance therapies. Patient summary: Assessment of the extent of disease in patients with muscle-invasive bladder cancer using conventional imaging yields serious limitations. In the PURE-01 study, we evaluated the potential of bladder multiparametric magnetic resonance imaging (MRI) to predict the pathological complete response to neoadjuvant pembrolizumab. After validation with larger datasets, the proposed stepwise assessment incorporating multiparametric MRI sequences will be used at our center to develop bladder-sparing approaches in future studies. • In the PURE-01 study, multiparametric magnetic resonance imaging (mpMRI) of the bladder was used to stage and evaluate the response to pembrolizumab, before radical cystectomy. • Assessments of mpMRI sequence were externally reviewed, showing preliminary but promising reproducibility. • We proposed an mpMRI-based definition of complete response predicting the pathological complete response to pembrolizumab that was externally replicated.

Intraductal papillary mucinous neoplasms are common lesions with the potential of harbouring/developing a pancreatic cancer. An accurate evaluation of intraductal papillary mucinous neoplasms with high-resolution imaging techniques and endoscopic ultrasound is mandatory in order to identify patients worthy either of surgical treatment or surveillance. In this review, the diagnosis and management of patients with intraductal papillary mucinous neoplasms are discussed with a specific focus on current guidelines. Areas of uncertainty are also discussed, as there are controversies related to the optimal indications for surgery, surveillance protocols and surveillance discontinuation.

Background Based on patient and tumor characteristics, some authors favor laparoscopic microwave ablation (LMWA) over the percutaneous approach (PMWA) for treatment of hepatocellular carcinoma (HCC). We compared the two techniques in terms of technique efficacy, local tumor progression (LTP) and complication rates. Study design A retrospective comparative analysis was performed on 91 consecutive patients (102 HCC tumors) who underwent PMWA or LMWA between October 2014 and May 2019. Technique efficacy at one-month and LTP at follow-up were assessed by contrast-enhanced CT/MRI. Kaplan–Meier estimates and Cox regression were used to compare LTP-free survival (LTPFS). Results At baseline analysis, LMWA group showed higher frequency of multinodular disease (p

Objective Patients with COVID-19 frequently develop acute respiratory distress syndrome (ARDS) requiring intensive care unit (ICU) admission. Data on long-term survival of these patients are lacking. We investigated 1-year survival, quality of life and functional recovery of COVID-19 ARDS patients requiring invasive mechanical ventilation Design Prospective observational study Setting Tertiary-care university hospital Participants All COVID-19 ARDS patients receiving invasive mechanical ventilation and discharged alive from hospital Interventions Patients were contacted by phone after 1-year. Functional, cognitive, and psychological outcomes were explored through a questionnaire and assessed using validated scales. Patients were offered the possibility to undergo a follow-up chest CT scan. Measurements and Main Results The study included all adult (age ≥ 18 years) patients with COVID-19-related ARDS admitted to an ICU of our institution between February 25th, 2020 - April 27th, 2020), who received at least one day of invasive mechanical ventilation (IMV). Of 116 patients who received IMV, 61 (52.6%) survived to hospital discharge. These survivors were assessed one year after discharge and 56 completed a battery of tests of cognition, activities of daily living and interaction with family members. They had overall good functional recovery, with >80% reporting good recovery and no difficulties in usual activities. A total of 52 (93%) of patients had no dyspnea at rest. Severe anxiety/depression was reported by five (8.9%) of patients. Comparing 2-months and 1-year data, we observed the most significant improvements in the areas of working status and exertional dyspnea. One-year Chest CT scans were available for 36 patients: fibrotic-like changes were present in four patients. Conclusions All patients who survived the acute phase of the COVID-19 disease and were discharged from the hospital were alive at the 1-year follow up and the vast majority of them had good overall recovery and quality of life. Study Registration ClinicalTrials.gov NCT04318366

Purpose: To present the progresses of hybrid 18F-FDG PET/MR imagingin the staging/restaging setting of endometrial cancer (EC), with particular focus on performance evaluations and biomarker analyses. Methods: Original articles were searched on PubMed, EMBASE and Web of Science, until March 2021. Reports were screened to select studies using simultaneous PET/MR acquisition, discarding those using sequential protocols. Studies including heterogeneous and/or homogeneous cohorts of pelvic tumor patients were considered, while works for which the exact number of EC patients was not reported have been discarded. Evaluations of selected articles were focused on (i) performance evaluation, (ii) biomarker analysis. The quality of papers was assessed by QUADAS-2. Results: Eleven articles involving 18F-FDGPET/MRI EC-related objectives were selected. The quality of papers was generally high. Compared to other imaging techniques, PET/MRI seems to show a higher diagnostic accuracy in detecting soft tissue invasion and abdominopelvic metastases from primary EC. Among different PET- and MRI-derived biomarkers, SUV-to-ADC ratio seems to be the most informative index in differentiating EC aggressiveness. Moreover, PET/MRI provided the chance to differentiate post-therapeutic changes from local relapse, and to detect small, morphologically unsuspicious lymph node metastases in patients with recurrent EC, with better performances compared to other imaging modalities. Conclusions: Preliminary results demonstrated how 18F-FDG PET/MRI could be a valid imaging technique in patients with EC, both in staging and restaging, also considering the limited radiation exposure. From the limited availability of the existing literature, it is clear that further prospective trials on larger and homogeneous cohorts are needed.

Background & Aims The risk of malignancy is uncertain for intraductal papillary mucinous neoplasms (IPMNs) with main pancreatic duct (MPD) of 5-9 mm. No study has correlated MPD size and malignancy considering the anatomic site of the gland (head versus body-tail). Our aim was to analyze the significance of MPD in pancreatic head/body-tail as a predictor of malignancy in main-duct/mixed IPMNs. Methods Retrospective analysis of resected patients between 2009-2018 was performed. Malignancy was defined as high-grade dysplasia and invasive carcinoma. MPD diameter was measured with magnetic resonance imaging. Receiver operating characteristic curve (ROC) analysis was utilized to identify optimal MPD cut-off for malignancy. Independent predictors of malignancy were searched. Results Malignancy was detected in 74% of 312 identified patients. 213 patients (68.3%) had IPMNs of the pancreatic head and 99 (31.7%) of the body-tail. ROC analysis identified 9 and 7 mm as the optimal MPD cut-offs for malignancy in IPMNs of head and body-tail of the pancreas, respectively. Multivariate analysis confirmed that MPD ≥9 mm (pancreatic head) and ≥7 mm (body-tail) were independent predictors of malignancy along with macroscopic solid components, positive cytology and elevated CA 19-9. The risk of malignancy was low for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) unless high-risk stigmata or multiple worrisome features were present. Conclusions Different thresholds of MPD dilation are associated with malignancy in IPMNs of the head and body-tail of the pancreas. The risk of malignancy for IPMNs with MPD ≤8 mm (pancreatic head) or ≤6 mm (pancreatic body-tail) lacking high-risk stigmata or multiple worrisome features is low.

Background: In clinical practice, the striking similarities observed at computed tomography (CT) between the diseases make it difficult to distinguish a COVID-19 pneumonia from a progression of interstitial lung disease (ILD) secondary to Systemic sclerosis (SSc). The aim of the present study was to identify the main CT features that may help distinguishing SSc-ILD from COVID-19 pneumonia. Methods: This multicentric study included 22 international readers divided in the radiologist group (RAD) and non-radiologist group (nRAD). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. Findings: Fibrosis inside focal ground glass opacities (GGO) in the upper lobes; fibrosis in the lower lobe GGO; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONS in the lower lobes (p

Severe Coronavirus disease 2019 (COVID-19) is characterized by acute respiratory distress syndrome (ARDS) which may lead to long-lasting pulmonary sequelae in the survivors. COVID-19 shares common molecular signatures with interstitial lung diseases (ILDs), including pro-angiogenic and tissue-remodeling mechanisms mediated by vascular endothelial growth factor receptor (VEGF-R), fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R). Nintedanib mainly targets these factors and is approved for ILDs. Therefore, we administered nintedanib through compassionate use to three patients with COVID-19 pneumonia requiring extra-corporeal membrane-oxygenation (ECMO). Here, we describe our experience in an attempt to explore the role of nintedanib in lung recovery in COVID-19. Three obese patients aged between 42 and 52 years were started on nintedanib due to difficulty in obtaining lung function restoration and weaning from ECMO support following the removal of orotracheal intubation (OTI). Soon after the start of the treatment, systemic inflammation and respiratory function rapidly improved and ECMO support was withdrawn. Serial chest CT scans confirmed the progressive lung amelioration, also reflected by functional tests during follow-up. Nintedanib was well-tolerated by all the three patients at the dosage used for ILDs and continued for 2–3 months based on drug availability. Although caution in interpreting events is required; it is tempting to speculate that nintedanib may have contributed to modulate lung inflammation and remodeling and to sustain lung repair. Altogether, nintedanib appears as a promising agent in patients with severe COVID-19 and delayed respiratory function recovery, for whom molecularly targeted therapies are still lacking. Clinical trials are necessary to confirm our observations.

The aim of the present study is to analyze the feasibility and the impact of a two-step approach in the treatment of giant hemangiomas (GH) i.e., exceeding 10 cm in maximum diameter, consisting of transarterial embolization (TAE) followed by laparoscopic liver resection (LLR). Ten patients with 11 GH were treated with TAE and subsequent LLR between 2017 and 2020 (Group A). A matched cohort of 10 patients with GH treated with upfront LLR between 2014 and 2017 was identified for comparison (Group B). Data were analyzed regarding intraoperative and postoperative outcomes, including successful completion of LLR, morbidity, and mortality. Successful microparticle embolization of the GH-feeding arteries was performed in all patients in group A. In three cases a liquid embolic agent (Squid-18) was also injected to obtain complete embolization. No complications were observed after TAE. Successful surgery was performed after a mean time interval of 2.2 days from TAE without any case of conversion to laparotomy. Statistically significant differences between group A and group B were found in intraoperative blood loss (250 ± 200 vs. 400 ± 300 mL, p = 0.039), operative time (245 ± 60 vs. 420 ± 60 min, p = 0.027), and length of stay (5 ± 1 vs. 8 ± 2 days, p = 0.046). Our data suggest that two-step TAE + LLR might be a safe and effective option for surgical treatment of GH &gt, 10 cm.

Simple Summary Recently, tumour local thermal ablation has been investigated in pancreatic ductal adenocarcinoma (PDAC), hypothesizing that it may add local efficacy to the chemotherapy systemic activity inducing changes of tumour microenvironment and increased intra-tumour drug efficacy. In this phase II randomized controlled trial we investigated the efficacy of thermal ablation with the HybridTherm probe under endoscopic ultrasound-guidance (EUS) as complement to chemotherapy (HTP-CT arm) versus standard chemotherapy alone (CT arm), in locally advanced and borderline resectable PDAC. A sample size of 33 patients per arm was calculated to verify a 20% improved 6-months progression-free survival (6-PFS) rate with HTP-CT. We randomized 17 and 20 patients to HTP-CT and CT arms, respectively. Although not significantly, we found an improved 6-PFS rate in the HTP-CT arm. However, the overall survival was similar between the two arms. Thus, as the study is underpowered, further investigation of EUS-guided thermal ablation in selected patients is suggested. Abstract Endoscopic ultrasound-ablation with HybridTherm-Probe (EUS-HTP) significantly reduces tumour volume (TV) in locally-advanced pancreatic ductal adenocarcinoma (LA-PDAC). We aimed at investigating the clinical efficacy of EUS-HTP plus chemotherapy versus chemotherapy (HTP-CT and CT arms) in LA- and borderline-resectable (BR) PDAC, with 6-months progression-free survival (6-PFS) rate as primary endpoint. In a phase-II randomized-controlled-trial, 33 LA/BR-PDAC patients per-arm were planned to verify 20% improved 6-PFS rate. Radiological response (Choi criteria), TV and serum CA19.9 were assessed up to 6-months. Seventeen and 20 LA/BR-PDAC patients were randomized to HTP-CT or CT. Baseline and CT-related features were balanced. At 6-months, 6-PFS rate was 41.2% and 30% in HTP-CT and CT arms (p = 0.48), respectively. A decrease ≥50% of serum CA19.9 was achieved in 75% and 64.3% of HTP-CT and CT patients (p = 0.53), respectively. TV reduced up to 6-months in 64.3% and 47.1% of HTP-CT and CT patients (p = 0.35), respectively. Resection rate, PFS-time and overall survival (OS-time) were similar. HTP-CT achieves a non-significant 11.2%, 10.7% and 17.2% improved 6-PFS, CA19.9 decrease ≥50% and TV reduction rates over CT, without any impact on resection rate, PFS-time and OS-time. As the study was underpowered, these results suggest further investigation of EUS-local ablation in selected patients with localized disease after induction CT.

Objective: We aimed at optimizing the follow-up for patients with a positive multiparametric magnetic resonance of the prostate (mpMRI) and a subsequent negative targeted biopsy (TBx) plus systematic biopsy (SBx). Materials and methods: A total of 308 men with a clinical suspicion of PCa and a positive mpMRI (PI-RADS ≥ 3) with concomitant negative systematic and targeted Bx performed at a single tertiary referral center. All patients were then followed with serial PSA measurements, digital rectal examination and eventual follow-up mpMRI and/or repeat Bx. The primary outcome was to evaluate the overall clinically significant PCa (csPCa)-free survival. The secondary outcome was to assess the role of a repeat mpMRI (Fu-mpMRI) and PSA density as predictors of csPCa diagnosis (defined as Gleason score ≥ 3 + 4) during follow-up. Kaplan Meier analysis and univariable Cox regression were used for survival and predictive analyses. Results: Median follow-up was 31 months (IQR: 23–43). During the study period 116 (37.7%) and 68 (22.1%) of men received a Fu-mpMRI and a Fu-Bx, respectively. Overall, 51 (16.6%) and 15 (4.9%) patients had a positive mpMRI and clinically significant (csPCa) diagnosis during follow-up, respectively. Among 68 men who received a Fu-Bx, the 2- and 3-years csPCa diagnosis-free survival in men with negative vs. positive Fu-mpMRI was 97% vs. 65% and 92% vs. 65%, respectively. At univariate Cox-regression analysis the presence of a positive Fu-mpMRI resulted to be significantly associated with the presence of csPCa at Fu-Bx (HR: 5.8, 95% CI: 1.3–26.6, P = 0.008). The 2- and 3-years csPCa diagnosis-free survival in men with PSAd

Background: Cardiac CT with late iodine enhancement (LIE-CT) may characterize the scarred myocardium, but the role of readers’ experience and scar pattern on LIE-CT diagnostic performance is unknown. Aim was to assess the diagnostic performance of LIE-CT according to readers’ experience, scar pattern and contrast-to-noise ratio (CNR) using late gadolinium enhancement MRI (LGE-MRI) as reference. Methods: LIE-CT and LGE-MRI images of 40 consecutive patients were analyzed. Two readers with different experience (8 and 2years) independently analyzed LIE-CT images defining the presence/absence of scar and scar CNR, segmental involvement, transmural pattern and scar etiology. The same parameters were extracted from LGE-MRI by two expert readers in consensus, blinded to the LIE-CT results. Results: Scars were identified at LGE-MRI in 29/40 patients and 141/680 segments. Scar burden at LIE-CT versus LGE-MRI correlated better for the most experienced reader than for the least experienced one (ρ = 0.954 and ρ = 0.797, p < 0.001). The most experienced reader missed scars in 2 patients and in 21/141 segments; the least experienced in 5 patients and 53/141 segments. The most experienced reader showed higher accuracy and sensitivity compared to the least experienced in per-patient (accuracy: 95% vs. 88%; sensitivity: 93% vs. 83%) and per-segment analysis (accuracy: 96% vs. 92%; sensitivity: 85% vs. 62%). Specificity was excellent (100% per-patient, 99% per-segment,) regardless of readers’ experience. Missed scars had non-ischemic pattern, low scar burden (< 6%) and lower CNR compared to ischemic scars (2.33 vs. 3.54, p = 0.005). Conclusion: LIE-CT represents an alternative to LGE-MRI, although the impact of readers’ experience on sensitivity for small non-ischemic scars should be considered.

Percutaneous ablation is an increasingly applied technique for the treatment of localized renal tumors, especially for elderly or co-morbid patients, where co-morbidities increase the risk of traditional nephrectomy. Ablative techniques are technically suited for the treatment of tumors generally not exceeding 4 cm, which has been set as general consensus cutoff and is described as the upper threshold of T1a kidney tumors. This threshold cutoff is being challenged, but with still limited evidence. Percutaneous ablation techniques for the treatment of renal cell carcinoma (RCC) include radiofrequency ablation, cryoablation, laser or microwave ablation; the main advantage of all these techniques over surgery is less invasiveness, lower complication rates and better patient tolerability. Currently, international guidelines recommend percutaneous ablation either as intervention for frail patients or as a first line tool, provided that the tumor can be radically ablated. The purpose of this article is to describe the basic concepts of percutaneous ablation in the treatment of RCC. Controversies concerning techniques and products and the need for patient-centered tailored approaches during selection among the different techniques available will be discussed.

Purpose: PET with radiolabeled somatostatin receptors (SSTR) analogues, such as 68Ga-DOTATOC, is commonly used in all stages of gastroenteropancreatic neuroendocrine tumours (GEP-NETs). Magnetic resonance Imaging (MRI) has excellent soft-tissue contrast and it is mainly applied in this oncological setting for assessing liver disease. Simultaneous PET/MRI scanners allow the combined acquisition of PET and MRI data with improved patient comfort and reduced radiation dose. The aim of the present pictorial essay is to highlight the assets and limits of fully hybrid PET/MRI in the field of GEP-NETs, presenting significant clinical cases performed in our Centre. Technique and findings: PET/MRI protocol: simultaneous PET/MRI acquisition started approximately 60min after 68Ga-DOTATOC tracer injection; MR localizer was performed to define the number of table positions (PET-FOV) for PET/MRI whole-body acquisition. A dedicated MRI protocol was performed on the abdomen, following the whole-body PET/MRI scan. Conclusion: 68Ga-DOTATOC PET/MRI combines the high sensitivity and specificity of 68Ga-DOTATOC PET tracer and MR high-quality imaging, especially for the liver. The clinical setting of GEP-NETs represents an interesting setting of application of this imaging technique, although the pros and cons should be taken into account until further methodological improvements will occur, especially for the characterization of lung findings.

Purpose: To test the potential impact of pharmacokinetic parameters, derived from DCE-MRI analysis, on the diagnostic performance of PI-RADSv.2 classification in prostate lesions characterization. Method: Among patients who underwent multiparametric prostate MRI (mpMRI) (January 2016-March 2018) followed by histological evaluation (targeted biopsies/prostatectomy), 103 men were retrospectively selected. For each patient the index lesion was identified and pharmacokinetic parameters (Ktrans, Kep, Ve, Vp) were assessed. MRI diagnostic performance in the detection of significant tumors [Gleason Score (GS)≥7] was assessed, considering PI-RADS≥3 as positive. Results: GS ≥ 7 (n = 59) showed higher Ktrans (p < 0.01) and Kep (p = 0.01) compared to GS < 7. At ROC curve analysis, a Ktrans cut-off of 191 × 10−3/min was identified to predict the presence of GS ≥ 7 (AUC:0.75; sensitivity:95%; specificity:61%). Sensitivity and PPV of mpMRI using PI-RADSv.2 were 98% and 61%. Reclassifying PI-RADS≥3 lesions according to Ktrans cut-off, 22 false positives were shifted to true negatives with 3 false negative findings; PPV raised to 79%. Appling Ktrans cut-off to PI-RADS 3 lesions of peripheral zone (n = 18), 12 true negatives, 4 true positives, 2 false positives were identified. Conclusions: Despite its high sensitivity prostate mpMRI generates many false positive cases: Ktrans in addition to PIRADS v.2 seems to improve MRI-PPV and may help in avoiding redundant biopsies.

Objective To determine the incidence, predictors, and outcome of pneumothorax (PNX)/pneumomediastinum (PMD) in coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS). Design Observational study. Setting Tertiary-care university hospital. Participants One hundred sixteen consecutive critically ill, invasively ventilated patients with COVID-19 ARDS. Interventions The authors collected demographic, mechanical ventilation, imaging, laboratory, and outcome data. Primary outcome was the incidence of PNX/PMD. Multiple logistic regression analyses were performed to identify predictors of PNX/PMD. Measurements and Main Results PNX/PMD occurred in a total of 28 patients (24.1%), with 22 patients developing PNX (19.0%) and 13 developing PMD (11.2%). Mean time to development of PNX/PMD was 14 ± 11 days from intubation. The authors found no significant difference in mechanical ventilation parameters between patients who developed PNX/PMD and those who did not. Mechanical ventilation parameters were within recommended limits for protective ventilation in both groups. Ninety-five percent of patients with PNX/PMD had the Macklin effect (linear collections of air contiguous to the bronchovascular sheaths) on a baseline computed tomography scan, and tended to have a higher lung involvement at intensive care unit (ICU) admission (Radiographic Assessment of Lung Edema score 32.2 ± 13.4 v 18.7 ± 9.8 in patients without PNX/PMD, p = 0.08). Time from symptom onset to intubation and time from total bilirubin on day two after ICU admission were the only independent predictors of PNX/PMD. Mortality was 60.7% in patients who developed PNX/PMD versus 38.6% in those who did not (p = 0.04). Conclusion PNX/PMD occurs frequently in COVID-19 patients with ARDS requiring mechanical ventilation, and is associated with increased mortality. Development of PNX/PMD seems to occur despite use of protective mechanical ventilation and has a radiologic predictor sign.

Cardiovascular magnetic resonance (CMR) has emerged as an accurate diagnostic technique for the evaluation of patients with cardiac disease in the majority of clinical settings, thanks to an established additional diagnostic and prognostic value. This document has been developed by a joined group of experts of the Italian Society of Cardiology (SIC) and Italian Society of Radiology (SIRM) to provide a summary about the current state of technology and clinical applications of CMR, to improve the clinical diagnostic pathways and to promote its inclusion in clinical practice. The writing committee consisted of members and experts of both societies in order to develop a more integrated approach in the field of cardiac imaging. This section 2 will cover myocarditis, pericardial disease, cardiomyopathies and valvular heart disease.

Introduction Several studies have invariably shown that the risk of Grade Group (GG) upgrading between biopsy and radical prostatectomy (RP) is higher in elderly men. Whether this is due to a real biological effect or to a diagnostic bias is still unknown. We hypothesized that the introduction of multiparametric magnetic resonance imaging (MRI) has improved the diagnostic accuracy of PCa detection in older men thus reducing the risk of GG upgrading at RP reported in the pre-MRI era. Materials and Methods We selected 424 men who received a systematic plus targeted biopsy for a positive MRI and subsequent RP at two referral centers between 2013 and 2019. Upgrading was defined as an increase in GG at final pathology as compared to biopsy. Multivariable logistic regressions tested the risk of upgrading over increasing age according to any upgrading definition and after stratifying definitions according to GG group and biopsy type. Non-parametric functions explored the relationship between age and upgrading rate. Results Median rate of upgrading was 17%. In multivariable models, while age was not associated with increased risk of GG upgrading (p=0.4). At non-parametric analyses, probability of upgrading slightly decreased with age, without reaching statistical significance. In subgroup analyses according to different upgrading definition and to biopsy type, age did not predict higher risk of upgrading regardless of outcome definitions (GG 1 to 2 P = 0.1; GG 2 to 3 P = 0.2; GG 3 to 4-5 P = 0.2) and in GG detected at TBx (OR 0.998, P = 0.8). Conclusions We showed that use of MRI has obliterated the association between older age and increased risk of upgrading mainly due to improved diagnostic approaches in this group of men. Therefore, it is likely that the effect of age and GG upgrading reported in previous studies in elderly men was due to misdiagnosis and lead-time bias in the pre-MRI era.

Background: The aim of this study was to quantify COVID-19 pneumonia features using CT performed at time of admission to emergency department in order to predict patients' hypoxia during the hospitalization and outcome. Methods: Consecutive chest CT performed in the emergency department between March 1st and April 7th 2020 for COVID-19 pneumonia were analyzed. The three features of pneumonia (GGO, semi-consolidation and consolidation) and the percentage of well-aerated lung were quantified using a HU threshold based software. ROC curves identified the optimal cut-off values of CT parameters to predict hypoxia worsening and hospital discharge. Multiple Cox proportional hazards regression was used to analyze the capability of CT quantitative features, demographic and clinical variables to predict the time to hospital discharge. Results: Seventy-seven patients (median age 56-years-old, 51 men) with COVID-19 pneumonia at CT were enrolled. The quantitative features of COVID-19 pneumonia were not associated to age, sex and time-from-symptoms onset, whereas higher number of comorbidities was correlated to lower well-aerated parenchyma ratio (rho = −0.234, p = 0.04) and increased semi-consolidation ratio (rho = −0.303, p = 0.008). Well-aerated lung (≤57%), semi-consolidation (≥17%) and consolidation (≥9%) predicted worst hypoxemia during hospitalization, with moderate areas under curves (AUC 0.76, 0.75, 0.77, respectively). Multiple Cox regression identified younger age (p < 0.01), female sex (p < 0.001), longer time-from-symptoms onset (p = 0.049), semi-consolidation ≤17% (p < 0.01) and consolidation ≤13% (p = 0.03) as independent predictors of shorter time to hospital discharge. Conclusion: Quantification of pneumonia features on admitting chest CT predicted hypoxia worsening during hospitalization and time to hospital discharge in COVID-19 patients.

Purpose: To train and validate a predictive model of mortality for hospitalized COVID-19 patients based on lung densitometry. Methods: Two-hundred-fifty-one patients with respiratory symptoms underwent CT few days after hospitalization. “Aerated” (AV), “consolidated” (CV) and “intermediate” (IV) lung sub-volumes were quantified by an operator-independent method based on individual HU maximum gradient recognition. AV, CV, IV, CV/AV, IV/AV, and HU of the first peak position were extracted. Relevant clinical parameters were prospectively collected. The population was composed by training (n = 166) and validation (n = 85) consecutive cohorts, and backward multi-variate logistic regression was applied on the training group to build a CT_model. Similarly, models including only clinical parameters (CLIN_model) and both CT/clinical parameters (COMB_model) were developed. Model's performances were assessed by goodness-of-fit (H&L-test), calibration and discrimination. Model's performances were tested in the validation group. Results: Forty-three patients died (25/18 in training/validation). CT_model included AVmax (i.e. maximum AV between lungs), CV and CV/AE, while CLIN_model included random glycemia, C-reactive protein and biological drugs (protective). Goodness-of-fit and discrimination were similar (H&L:0.70 vs 0.80; AUC:0.80 vs 0.80). COMB_model including AVmax, CV, CV/AE, random glycemia, biological drugs and active cancer, outperformed both models (H&L:0.91; AUC:0.89, 95%CI:0.82–0.93). All models showed good calibration (R2:0.77–0.97). Despite several patient's characteristics were different between training and validation cohorts, performances in the validation cohort confirmed good calibration (R2:0–70-0.81) and discrimination for CT_model/COMB_model (AUC:0.72/0.76), while CLIN_model performed worse (AUC:0.64). Conclusions: Few automatically extracted densitometry parameters with clear functional meaning predicted mortality of COVID-19 patients. Combined with clinical features, the resulting predictive model showed higher discrimination/calibration.

Anatomical substrate and mechanical trigger co-act in arrhythmia’s onset in patients with bileaflet mitral valve prolapse (bMVP). Feature tracking (FT) may improve risk stratification provided by cardiac magnetic resonance (CMR). The aim was to investigate differences in CMR and FT parameters in bMVP patients with and without complex arrhythmias (cVA and no-cVA). In this retrospective study, 52 patients with bMVP underwent 1.5 T CMR and were classified either as no-cVA (n = 32; 12 males; 49.6 ± 17.4 years) or cVA (n = 20; 3 males; 44.7 ± 11.2 years), the latter group including 6 patients (1 male; 45.7 ± 12.7 years) with sustained ventricular tachycardia or ventricular fibrillation (SVT-FV). Twenty-four healthy volunteers (11 males, 36.2 ± 12.5 years) served as control. Curling, prolapse distance, mitral annulus disjunction (MAD), and late gadolinium enhancement (LGE) were recorded and CMR-FT analysis performed. Statistical analysis included non-parametric tests and binary logistic regression. LGE and MAD distance were associated with cVA with an odds ratio (OR) of 8.51 for LGE (95% CI 1.76, 41.28; p = 0.008) and of 1.25 for MAD (95% CI 1.02, 1.54; p = 0.03). GLS 2D (− 11.65 ± 6.58 vs − 16.55 ± 5.09 1/s; p = 0.04), PSSR longitudinal 2D (0.04 ± 1.62 1/s vs − 1.06 ± 0.35 1/s; p = 0.0001), and PSSR radial 3D (3.95 ± 1.97 1/s vs 2.64 ± 1.03 1/s; p = 0.0001) were different for SVT-VF versus the others. PDSR circumferential 2D (1.10 ± 0.54 vs. 0.84 ± 0.34 1/s; p = 0.04) and 3D (0.94 ± 0.42 vs. 0.69 ± 0.17 1/s; p = 0.04) differed between patients with and without papillary muscle LGE. CMR-FT allowed identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT-VF. LGE and MAD distance were associated with cVA. • CMR-FT allows identifying several subtle myocardial deformation abnormalities in bMVP patients, especially those involving the papillary muscle. • CMR-FT allows identifying subtle myocardial deformation abnormalities in bMVP patients at risk of SVT and VF. • In patients with bMVP, the stronger predictor of cVA is LGE (OR = 8.51; 95% CI 1.76, 41.28; p = 0.008), followed by MAD distance (OR = 1.25; 95% CI 1.02, 1.54; p = 0.03).