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Background: MRI is the most reliable imaging modality that allows to assess liver metastases. Our purpose is to compare the per-lesion and per-patient detection rate of gadoxetic acid-(Gd-EOB) enhanced liver MRI and fast MR protocol including Diffusion Weighted Imaging (DWI) and T2-W Fat Suppression sequence in the detection of liver metastasis in pre surgical setting., Methods: One hundred and eight patients with pathologically proven liver metastases (756 liver metastases) underwent Gd-EOBMRI were enrolled in this study. Three radiologist independently graded the presence of liver lesions on a five-point confidence scale assessed only abbreviated protocol (DWI and sampling perfection with application-optimized contrasts using different flip angle evolution (SPACE) fat suppressed sequence) and after an interval of more than 2 weeks the conventional study (all acquired sequences). Per-lesion and per-patient detection rate of metastases were calculated. Weighted к values were used to evaluate inter-reader agreement of the confidence scale regarding the presence of the lesion., Results: MRI detected 732 liver metastases. All lesions were identified both by conventional study as by abbreviated protocol. In terms of per-lesion detection rate of liver metastasis, all three readers had higher detection rate both with abbreviated protocol and with standard protocol with Gd-EOB (96.8% [732 of 756] vs. 96.5% [730 of 756] for reader 1; 95.8% [725 of 756] vs. 95.2% [720 of 756] for reader 2; 96.5% [730 of 756] vs. 96.5% [730 of 756] for reader 3). Inter-reader agreement of lesions detection rate between the three radiologists was excellent (k range, 0.86-0.98) both for Gd-EOB MRI and for Fast protocol (k range, 0.89-0.99)., Conclusion: Abbreviated protocol showed the same detection rate than conventional study in detection of liver metastases.

Cardiomyopathies are a heterogeneous entity. The progress in the field of genetics has allowed over the years to determine its origin more and more often. The classification of these pathologies has changed over the years; it has been updated with new knowledge. Imaging allows to define the phenotypic characteristics of the different forms of cardiomyopathy. Cardiac magnetic resonance (CMR) allows a morphological evaluation of the associated (and sometimes pathognomonic) cardiac findings of any form of cardiomyopathy. The tissue characterization sequences also make magnetic resonance imaging unique in its ability to detect changes in myocardial tissue. This review aims to define the features that can be highlighted by CMR in hypertrophic and dilated forms and the possible differential diagnoses. In hypertrophic forms, CMR provides: precise evaluation of wall thickness in all segments, ventricular function and size and evaluation of possible presence of areas of fibrosis as well as changes in myocardial tissue (measurement of T1 mapping and extracellular volume values). In dilated forms, cardiac resonance is the gold standard in the assessment of ventricular volumes. CMR highlights also the potential alterations of the myocardial tissue.

On computed tomography (CT) and magnetic resonance imaging (MRI), hepatocellular tumors are characterized based on typical imaging findings. However, hepatocellular adenoma, focal nodular hyperplasia, and hepatocellular carcinoma can show uncommon appearances at CT and MRI, which may lead to diagnostic challenges. When assessing focal hepatic lesions, radiologists need to be aware of these atypical imaging findings to avoid misdiagnoses that can alter the management plan. The purpose of this review is to illustrate a variety of pitfalls and atypical features of hepatocellular tumors that can lead to misinterpretations providing specific clues to the correct diagnoses.

The management of patients undergoing surgical resection for liver malignancies requires a multidisciplinary team, including a dedicated radiologist. In the preoperative workup, the radiologist has to provide precise, relevant information to the surgeon. This requires the radiologist to know the basics of surgical techniques as well as liver surgical anatomy in order to help to avoid unexpected surgical scenarios and complications. Moreover, virtual resections and volumetries on radiological images will be discussed, and basic concepts of postoperative liver failure, regeneration, and methods for hypertrophy induction will be provided.

Primary heart tumors are rare, benign tumors represent the majority of these. If a cardiac mass is found, the probability that it is a metastasis or a so-called "pseudo-mass" is extremely higher than a primary tumor. The detection of a heart mass during a transthoracic echocardiography (TE) is often unexpected. The TE assessment can be difficult, particularly if the mass is located at the level of the right chambers. Cardiac Computed Tomography (CCT) can be useful in anatomical evaluation and Cardiac Magnetic Resonance (CMR) for masses characterization as well. We provide an overview of right cardiac masses and their imaging futures.

Objective: To estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer-CRC-or advanced adenoma)., Design: Prospective cohort of subjects aged 50-69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy., Methods: All programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces). We assessed the AN risk at subsequent exams, the cumulative AN detection rate (DR) over the 4-year period following the second FIT and the interval CRC (IC) risk following two negative FITs by cumulative amount of f-Hb concentration over two consecutive negative FITs, using multivariable logistic regression models and the Kaplan-Meier method., Results: The cumulative probability of a positive FIT result over the subsequent two rounds ranged between 7.8% (95% CI 7.5 to 8.2) for subjects with undetectable f-Hb at the initial two tests (50% of the screenees) and 48.4% (95% CI 44.0 to 53.0) among those (0.7% of the screenees) with a cumulative f-Hb concentration ≥20 µg/g faeces. The corresponding figures for cumulative DR were: 1.4% (95% CI 1.3 to 1.6) and 25.5% (95% CI 21.4 to 30.2) for AN; 0.17% (95% CI 0.12 to 0.23) and 4.5% (95% CI 2.8 to 7.1) for CRC. IC risk was also associated with cumulative f-Hb levels., Conclusion: The association of cumulative f-Hb concentration with subsequent AN and IC risk may allow to design tailored strategies to optimise the utilisation of endoscopy resources: subjects with cumulative f-Hb concentration ≥20 µg/g faeces over two negative tests could be referred immediately for total colonoscopy (TC), while screening interval might be extended for those with undetectable f-Hb., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In Italy, the use of nucleic acid testing for hepatitis B virus (HBV) in donor screening has allowed the detection of infections in the window phase, as well as the presence of occult infections which could potentially be transmitted. The aim of this study was to analyse the trends of epidemiological data focused on HBV infection in blood donors and to estimate the residual risk of transmitting HBV from both the window phase and occult infection over a 10-year period in Italy., Materials and Methods: Data were obtained from the Italian Haemovigilance System which includes the results of screening tests for transfusion transmissible infections. During the period of this survey (2009-2018), the molecular methods used for HBV screening were transcription-mediated amplification and polymerase chain reaction tests. Prevalence and incidence were calculated. The residual risk was estimated by applying the incidence-window period model for acute cases and a more recently reported model for estimating the risk due to occult infections., Results: A total of 17,424,535 blood donors and 30,842,794 donations were tested for HBV. Altogether, 6,250 donors tested positive for HBV markers: 4,782 (175.6×10 5 ) were first time donors and 1,468 (10.0×10 5 ) were repeat donors. The prevalence of HBV markers in first time donors was 275.9×10 5 in 2009, declining to 143.6×10 5 in 2018. The incidence of new infections was 3.37×10 5 in 2009 and 2.17×10 5 in 2018. The overall residual risk for HBV amounted to 1 in 2,566,854 donations calculated as the sum of risks of both acute infections in the window period (1 in 5,835,306 donations) and occult infections (1 in 4,582,270 blood units)., Discussion: In Italy, the residual risk of transfusing a blood unit infected with HBV, both from window phase and occult infections, is currently very low, amounting to levels that can be considered tolerable.

Since the inception of industrial plasma fractionation during the Second World War, a succession of protein therapies isolated from plasma have determined the volume of plasma requiring collection, and have also shaped the economics of the industry. These so-called plasma drivers have successively included albumin, coagulation Factor VIII (FVIII) and, for the past thirty years, intravenously (IV) and subcutaneously (SC) administered immunoglobulin (IG) solutions. The sale of IG underpins the profitability of the industry and has experienced continuous growth over the past decades, as the result of growing clinical demand. Modelling this demand using decision analysis indicates that supplying the evidence-based indications for IG therapies will generate a need for IG which exceeds the current plasma collection capacity of most countries. A notable exception to this situation is the United States (US) of America, whose population of compensated plasma donors generates two thirds of the global supply of plasma for fractionation. The US is also the leading consumer of IG, and its health care providers pay the highest price for the product globally. Shortages of IG occur whenever the demand for the product outstrips the supply. Current shortages, following other historical periods of shortage, threaten the well-being of patients dependant on these products and incur heavy costs on health systems. In Italy, the national blood system, which is based on voluntary unpaid donors, reflects a policy of national self-sufficiency in blood-derived therapies (a strategic objective of the national blood system itself), based on solidarity as an ethical principle. This system has increased the collection of plasma for fractionation by 3.8% per annum over 2008-2017, in accordance to a plan for plasma procurement targeting a collection rate of 14.1 L of plasma per thousand (10 3 ) population by 2020. Over the same period, IG usage has increased by 8.5/per annum, to 89.2 g IG/10 3 population. In this paper, we review the factors which, increasingly, are causing an imbalance between the global supply and demand for IG, and we assess Italy's capacity to ensure that increasing this level of independence is no longer simply an ethical, but also an economic imperative, with implications for the security of Italy's health system.

Objectives: To assess patients' experience of bowel preparation and procedure for screening CT colonography with reduced (r-CTC) and full cathartic preparation (f-CTC) that showed similar detection rate for advanced neoplasia in a randomised trial., Methods: Six hundred seventy-four subjects undergoing r-CTC and 612 undergoing f-CTC in the SAVE trial were asked to complete two pre-examination questionnaires-(1) Life Orientation Test - Revised (LOT-R) assessing optimism and (2) bowel preparation questionnaire-and a post-examination questionnaire evaluating overall experience of CTC screening test. Items were analysed with chi-square and t test separately and pooled., Results: LOT-R was completed by 529 (78%) of r-CTC and by 462 (75%) of f-CTC participants and bowel preparation questionnaire by 531 (79%) subjects in the r-CTC group and by 465 (76%) in the f-CTC group. Post-examination questionnaire was completed by 525 (78%) subjects in the r-CTC group and by 453 (74%) in the f-CTC group. LOT-R average score was not different between r-CTC (14.27 ± 3.66) and f-CTC (14.54 ± 3.35) (p = 0.22). In bowel preparation questionnaire, 88% of r-CTC subjects reported no preparation-related symptoms as compared to 70% of f-CTC subjects (p < 0.001). No interference of bowel preparation with daily activities was reported in 80% of subjects in the r-CTC group as compared to 53% of subjects in the f-CTC group (p < 0.001). In post-examination questionnaire, average scores for discomfort of the procedure were not significantly different between r-CTC (3.53 ± 0.04) and f-CTC (3.59 ± 0.04) groups (p = 0.84)., Conclusions: Reduced bowel preparation is better tolerated than full preparation for screening CT colonography., Key Points: • Reduced bowel preparation is better tolerated than full preparation for screening CT colonography. • Procedure-related discomfort of screening CT colonography is not influenced by bowel preparation. • Males tolerate bowel preparation and CT colonography screening procedure better than females.

Objectives: To evaluate the incidence of late-gadolinium-enhancement (LGE) in mitral valve prolapse (MVP) (in the absence of other heart/valvular diseases), and its association with the degree of mitral regurgitation (MR) and/or with complex ventricular arrhythmia (ComVA), and to analyse the role of T1 mapping in the evaluation of MVP patients., Methods: We included all consecutive patients with MVP who underwent during 2015-2016 a comprehensive cardiac magnetic resonance (CMR) examination at 1.5 T. We evaluated the association of LGE with the MR fraction and the presence of ComVA. We compared myocardial T1-native and post-contrast times and extracellular volume (ECV)-values between MVP patients, both with and without LGE, and the control group., Results: Thirty-four patients with MVP were selected (56 ± 14 years old, 59% male). All patients had MR; LGE and ComVA were present in 15 (44%) and 11 (34%) patients, respectively. Significant associations of LGE with both MR severity and ComVA were not found (p=0.72 and 0.79, respectively). T1 mapping confirmed the presence of LGE in all cases. In one patient a thin signal alteration resulted in more evident T1 mapping than LGE. Patients with MVP had higher native T1-values, lower post-contrast T1-values and increased ECV-values compared with controls (p=0.01, 0.01 and 0.00, respectively)., Conclusion: Focal fibrosis with LGE was found in about half the MVP patients and it was independent of the degree of the valve dysfunction and the presence of ComVA. T1 mapping allows diffuse myocardial wall alterations to be identified, but no significant associations between the MR severity and ComVA and T1/ECV values were found., Key Points: • MVP is a common valvulopathy affecting 2-3% of the general population. • MVP has been associated with an increased risk of arrhythmic complications and sudden cardiac death. • CMR is a non-invasive imaging method that provides a precise and more accurate assessment of patients with MVP.

Aims: We aimed to present our series of gastrointestinal neuroendocrine tumours (GI-NETs) in order to illustrate and highlight the associated contrast-enhanced multi-detector computed tomography (MDCT) features. We also attempted to identify a relationship between MDCT imaging and the 2010 World Health Organization (WHO) classification system., Materials and Methods: We selected all patients with pathologically proven GI-NETs diagnosed between January 2010 and August 2017. Only patients undergone contrast-enhanced MDCT imaging in the immediate preoperative period were included in our study. Later, two expert radiologists retrospectively assessed MDCT intestinal and extra-intestinal signs. We also analysed the relationship between MDCT imaging and the 2010 WHO classification., Results: A total of 20 patients (13 males, 7 females, age range 37-89 years, mean age 69.9 years) were included in our study. The majority of GI-NETs (85%) occurred in the small bowel and mainly in the terminal ileum. Forty-five percentage of our GI-NETs were diagnosed after an access to emergency medical service for obstruction symptoms or gastrointestinal bleeding. Regarding intestinal signs, 15/20 patients showed an intraluminal nodular mass and 5/20 a wall thickening. Extra-intestinal signs were present in 75% of cases. Desmoplastic reaction and lymph nodes metastases were significantly correlated with higher grade of GI-NETs., Conclusions: The majority of GI-NETs appears as intraluminal mass often associated with extra-intestinal signs. We found a significantly correlation between higher grade of GI-NETs and extra-intestinal signs. MDCT imaging may be useful in predicting the pathological classification of GI-NETs.

Background: Chronic red blood cell transfusion is the first-line treatment for severe forms of thalassaemia. This therapy is, however, hampered by a number of adverse effects, including red blood cell alloimmunisation. The aim of this systematic review was to collect the current literature data on erythrocyte alloimmunisation., Materials and Methods: We performed a systematic search of the literature which identified 41 cohort studies involving 9,256 patients., Results: The prevalence of erythrocyte alloimmunisation was 11.4% (95% CI: 9.3-13.9%) with a higher rate of alloimmunisation against antigens of the Rh (52.4%) and Kell (25.6%) systems. Overall, alloantibodies against antigens belonging to the Rh and Kell systems accounted for 78% of the cases. A higher prevalence of red blood cell alloimmunisation was found in patients with thalassaemia intermedia compared to that among patients with thalassaemia major (15.5 vs 12.8%)., Discussion: Matching transfusion-dependent thalassaemia patients and red blood cell units for Rh and Kell antigens should be able to reduce the risk of red blood cell alloimmunisation by about 80%.

CLINICAL INTRODUCTION: A 71-year-old man, with a history of chronic aortic regurgitation and negative follow-up after bladder cancer resection 10 months before, had an aortic valve surgery. Two months after, a mass near the right side of the heart had been detected by transthoracic echocardiography performed for dyspnoea, without a cough or fever. The quality of ultrasound images did not allow for an appropriate evaluation due to the outcomes of the sternotomy and the presence of calcified pachypleurite. In order to evaluate this finding, coronary CT (CCT) (figure 1A,B) and positron-emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose (FDG-PET) (figure 1C) were performed. Finally, a cardiac magnetic resonance (CMR) was requested (figure 1D-F, see online supplementary videos).heartjnl;104/23/1936/F1F1F1Figure 1(A) Short axis image of early contrast enhancement phase coronary CT (CCT); (B) short axis of delayed phase of the same CCT; (C) lesion on positron-emission tomography with 2-[18F] fluoro-2-deoxy-D-glucose image (white arrow); CMR short axis (D) T2-weighted image with fat saturation; (E) T1-weighted image with fat-saturation; (F) T1-weighted image without fat-saturation. QUESTION: Which of the following is the most likely diagnosis of the pericardial mass?Primary pericardial tumour.Pericardial metastasis.Intrapericardial abscess.Intrapericardial haematoma., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To determine whether (1) computer-based self-training for CT colonography (CTC) improves interpretation performance of novice readers; (2) computer-aided detection (CAD) use during training affects learning., Methods: Institutional review board approval and patients' informed consent were obtained for all cases included in this study. Twenty readers (17 radiology residents, 3 radiologists) with no experience in CTC interpretation were recruited in three centres. After an introductory course, readers performed a baseline assessment test (37 cases) using CAD as second reader. Then they were randomized (1:1) to perform either a computer-based self-training (150 cases verified at colonoscopy) with CAD as second reader or the same training without CAD. The same assessment test was repeated after completion of the training programs. Main outcome was per lesion sensitivity (≥ 6 mm). A generalized estimating equation model was applied to evaluate readers' performance and the impact of CAD use during training., Results: After training, there was a significant improvement in average per lesion sensitivity in the unassisted phase, from 74% (356/480) to 83% (396/480) (p < 0.001), and in the CAD-assisted phase, from 83% (399/480) to 87% (417/480) (p = 0.021), but not in average per patient sensitivity, from 93% (390/420) to 94% (395/420) (p = 0.41), and specificity, from 81% (260/320) to 86% (276/320) (p = 0.15). No significant effect of CAD use during training was observed on per patient sensitivity and specificity, nor on per lesion sensitivity., Conclusions: A computer-based self-training program for CTC improves readers' per lesion sensitivity. CAD as second reader does not have a significant impact on learning if used during training., Key Points: • Computer-based self-training for CT colonography improves per lesion sensitivity of novice readers. • Self-training program does not increase per patient specificity of novice readers. • CAD used during training does not have significant impact on learning.

Background: Radiation-induced health risks are broadly questioned in the literature. As cone beam computed tomography (CBCT) is increasingly used in non-dental examinations, its effective dose needs to be known. This study aimed to review the published evidence on effective dose of non-dental CBCT for diagnostic use by focusing on dosimetry system used to estimate dose., Materials and Methods: A systematic review of the literature was performed on 12 November 2017. All the literature up to this date was included. The PubMed and web of science databases were searched. Studies were screened for inclusion based on defined inclusion and exclusion criteria according to the preferred reporting items for systematic reviews., Results: Fifteen studies met the inclusion criteria and were included in our review. Thirteen and two of them examined one and two anatomical areas, respectively. The anatomical areas were: ear (6), paranasal sinuses (4), ankle (3), wrist (2), knee (1), and cervical spine (1). Effective dose was estimated by different methods: (i) RANDO phantom associated with thermoluminescent dosimeters (6), metal oxide semiconductor field-effect transistor dosimeters (3), and optically stimulated luminescent dosimeters (1). (ii) Scanner outputs, namely computed tomography dose index (1) and dose area product (2). (iii) Monte Carlo simulations (2)., Conclusion: CBCT of extremities, cervical spine, ears and paranasal sinuses was found to be a low-dose volumetric imaging technique. Effective doses varied significantly because of different exposure settings of CBCT-units and different dosimetry systems used to estimate dose.

Introduction: This study aimed to evaluate the diagnostic accuracy of panoramic radiography (PAN) for the detection of clinically/surgically confirmed apical periodontitis (AP) in root canal-treated teeth using cone-beam computed tomographic (CBCT) imaging as the reference standard., Methods: Two hundred forty patients with endodontically treated AP (diseased group) were detected via CBCT imaging using the periapical index system. They were divided into groups of 20 each according to lesion size (2-4.5 mm and 4.6-7 mm) and anatomic area (incisor, canine/premolar, and molar) in both the upper and lower arches. Another 240 patients with root filling and a healthy periapex (healthy group) were selected. All diseased and healthy patients underwent PAN first and a CBCT scan within 40 days. The periapical index system was also used to assess AP using PAN. Sensitivity, specificity, diagnostic accuracy, positive predictive value, and negative predictive value for PAN images with respect to CBCT imaging were analyzed. The k value was calculated to assess both the interobserver reliability for PAN and the agreement between PAN and CBCT., Results: PAN showed low sensitivity (48.8), mediocre negative predictive value (64.7), good diagnostic accuracy (71.3), and high positive predictive value (88.6) and specificity (93.8). Both interobserver reliability for PAN and agreement between PAN and CBCT were moderate (k = 0.58 and 0.42, respectively). The best identified AP was located in the lower canine/premolar and molar areas, whereas the worst identified AP was located in the upper/lower incisor area and upper molar area., Conclusions: PAN showed good diagnostic accuracy, high specificity, and low sensitivity for the detection of endodontically treated AP., (Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Purpose: Our retrospective study sought to describe the spectrum of magnetic resonance imaging (MRI) features of primary hepatic lymphoma (PHL) by analyzing its morphological aspects, signal intensity before and after contrast agent (CA) administration, and diffusion-weighted imaging (DwI) with the apparent diffusion coefficient (ADC) values., Methods: A retrospective analysis was conducted on 25 patients with pathologically proven PHL who underwent MRI between January 2011 and December 2016. For the evaluation of the ADC, we used a control group of 87 patients (22 with hepatocellular carcinoma, 15 with cholangiocellular carcinoma, 23 with liver metastasis, 22 with focal nodular hyperplasia, and 5 with adenoma). Two radiologists evaluated the morphological features, the signal intensity before and after CA administration, and the DwI. The sensitivity and specificity of the ADC values in distinguishing the PHL lesions from other hepatic lesions were calculated by analyzing the receiver operating characteristic (ROC) curves., Results: Twenty-one patients had non-Hodgkin's lymphoma (18 had diffuse large B-cell lymphoma and three had mucosa-associated lymphoid tissue) and four had Hodgkin's lymphoma (nodular sclerosis). The PHL had a variable morphologic distribution (17 focal mass and eight multiple nodules) and mainly an insinuative growth (24/25). Usually, PHL was usually hypointense on the T1-weighted images (23/25) and hyperintense on the T2-weighted images (21/25); non-specific dynamic enhancement was found after CA administration, but in the hepatobiliary phase, PHL is mainly hypointense (92%). All PHLs showed a signal restriction in the DwI. The sensitivity and specificity in the differential diagnosis between PHL and the other malignant lesions were respectively 81.7% and 100%, with applying an ADC cut-off value of 0.918 × 10 -3  mm 2 /s., Conclusion: Although PHL is a rare disease and biopsy is still required, an MRI could be indicative. In our series, PHL showed an insinuative growth, hypointense signal in the hepatobiliary phase, signal restriction in the DwI, and an ADC value lower than that of the other hepatic lesions analyzed.

Background: In Italy nucleic acid testing (NAT) became mandatory for hepatitis C virus (HCV) in 2002 and for human immunodeficiency virus (HIV) and hepatitis B virus in 2008. The aim of this study was to monitor the incidence and prevalence of HIV and HCV infections in Italian blood donors and the current residual risk of these infections after the introduction of NAT., Materials and Methods: The Italian national blood surveillance system includes data from tests used to screen for transfusion-transmissible infections. During the period of this survey (2009-2015), the NAT methods used were the transcription-mediated amplification test, for individual donor testing, and polymerase chain reaction analysis, mainly for pools of six donors. Prevalence and incidence were calculated. Three published formulae were applied to estimate the residual risk (the window period ratio model and the formulae recommended by the European Medicines Agency and the World Health Organization)., Results: Overall, 12,258,587 blood donors and 21,808,352 donations were tested for HCV and HIV. The prevalence of HCV decreased from 110.3×10 5 to 58.9×10 5 in years 2009 and 2015, respectively, while that of HIV remained stable over time (15.5×10 5 vs 15.4×10 5 ). The incidence of HCV decreased from 3.19×10 5 in 2009 to 1.58×10 5 in 2015, while the incidence of HIV did not show any significant fluctuations (average incidence 4.39×10 5 ). The residual risk of a viraemic unit entering the blood supply was estimated to be 0.077×10 6 or 1 in 12,979,949 donations for HCV and 0.521×10 6 or 1 in 1,917,250 for HIV, according to the window period ratio model, and lower with the other two formulae., Discussion: HCV infection has declined over time in both first-time and repeat donors, while the data for HIV infection are stable. All three methods employed in this study showed that the residual risk of transmitting HCV or HIV through an infected blood unit is currently very low in Italy, but there are considerable differences in estimates between methods. Thus, harmonisation of these methods is advisable.

Objective: Unit costs of screening CT colonography (CTC) can be useful for cost-effectiveness analyses and for health care decision-making. We evaluated the unit costs of CTC as a primary screening test for colorectal cancer in the setting of a randomized trial in Italy., Methods: Data were collected within the randomized SAVE trial. Subjects were invited to screening CTC by mail and requested to have a pre-examination consultation. CTCs were performed with 64- and 128-slice CT scanners after reduced or full bowel preparation. Activity-based costing was used to determine unit costs per-process, per-participant to screening CTC, and per-subject with advanced neoplasia., Results: Among 5242 subjects invited to undergo screening CTC, 1312 had pre-examination consultation and 1286 ultimately underwent CTC. Among 129 subjects with a positive CTC, 126 underwent assessment colonoscopy and 67 were ultimately diagnosed with advanced neoplasia (i.e., cancer or advanced adenoma). Cost per-participant of the entire screening CTC pathway was €196.80. Average cost per-participant for the screening invitation process was €17.04 and €9.45 for the pre-examination consultation process. Average cost per-participant of the CTC execution and reading process was €146.08 and of the diagnostic assessment colonoscopy process was €24.23. Average cost per-subject with advanced neoplasia was €3777.30., Conclusions: Cost of screening CTC was €196.80 per-participant. Our data suggest that the more relevant cost of screening CTC, amenable of intervention, is related to CTC execution and reading process.

Background: Public cord blood banking is currently managed in Italy by a network of 19 regional cord blood banks coordinated by the National Blood Centre and the National Transplant Centre. A cost analysis was carried out within the Italian network to determine the relationship between cost of cord blood collection and banking and size of the bank inventory, which ranged from 106 to 9,341 units on December 31 st , 2012., Materials and Methods: The 19 banks were invited to report costs incurred in 2012 related to cord blood unit collection, transportation, biological validation, characterisation, manipulation, cryopreservation, storage, data management, and general costs. Missing information on selected items was replaced with standardised costs represented by average data obtained from the reporting banks. Eight banks (52%) participated in the study. Average costs were determined in the three banks with inventories of >3,000 units vs the three banks with inventories of <1,000 units., Results: Both cord blood collection and cord blood banking costs per unit were lower in the larger banks than in the smaller banks (average collection costs: € 119.25 and € 151.31, respectively; average banking costs: € 3,614.15 and € 8,158.37, respectively)., Discussion: The study outlined an inverse relationship between the costs of cord blood collection and banking and the size of the bank inventory, suggesting that scale economies could be obtained through centralisation of banking activities.

The aim of this study was to evaluate the participation and yield of the faecal immunochemical test (FIT) in nonattendees for computed tomography colonography (CTC) or optical colonoscopy (OC) screening, in the setting of a randomized trial. In the SAVE trial, 16087 individuals were randomly assigned and invited to one of four interventions for colorectal cancer screening: (i) biennial FIT for three rounds; (ii) reduced-preparation CTC; (iii) full-preparation CTC; and (iv) OC. Nonattendees of reduced-preparation CTC, full-preparation CTC and OC groups were invited to FIT. Here, we analysed the participation rate and the detection rate for cancer or advanced adenoma (advanced neoplasia) of FIT among nonattendees for reduced-preparation CTC, full-preparation CTC and OC. Nonattendees were 1721 of 2395 (71.9%) eligible invitees in the reduced-preparation CTC group, 1818 of 2430 (74.8%) in the full-preparation CTC group and 883 of 1036 (85.2%) in the OC group. Participation rates for FIT were 20.2% (347/1721) in nonattendees for reduced-preparation CTC, 21.4% (389/1818) in nonattendees for full-preparation CTC and 25.8% (228/883) in nonattendees for OC. Differences between both CTC groups and the OC group were statistically significant (P≤0.01), whereas the difference between reduced-preparation and full-preparation CTC groups was not statistically significant (P=0.38). The detection rate of FIT was not statistically significantly different among nonattendees for reduced-preparation CTC (0.9%; 3/347), nonattendees for full-preparation CTC (1.8%; 7/389) and nonattendees for OC (1.3%; 3/228) (P>0.05). Offering FIT to nonattendees for CTC or OC increases the overall participation in colorectal cancer screening and enables the detection of additional advanced neoplasia.

Computed tomographic colonography (CTC) is a minimally invasive imaging examination for the colon, and is safe, well tolerated and accurate for the detection of colorectal cancer (CRC) and advanced adenoma. While the role of CTC as a primary test for population screening of CRC is under investigation, the fecal occult blood test (FOBT) has been recommended for population screening of CRC in Europe. Subjects with positive FOBT are invited to undergo total colonoscopy, which has some critical issues, such as suboptimal compliance, contraindications and the possibility of an incomplete exploration of the colon. Based on available data, the integration of CTC in FOBT-based population screening programs for CRC may fall into three scenarios. First, CTC is recommended in FOBT-positive subjects when colonoscopy is refused, incomplete or contraindicated. For these indications CTC should replace double-contrast barium enema. Second, conversely, CTC is not currently recommended as a second-level examination prior to colonoscopy in all FOBT-positive subjects, as this strategy is most probably not cost-effective. Finally, CTC may be considered instead of colonoscopy for surveillance after adenoma removal, but specific studies are needed.

Haemoglobin (Hb) stability in faecal samples is an important issue in colorectal cancer screening by the faecal immunochemical test (FIT) for Hb. This study evaluated the performance of the FIT-Hb (OC-Sensor Eiken) used in the Florence screening programme by comparing two different formulations of the buffer, both in an analytical and in a clinical setting. In the laboratory simulation, six faecal pools (three in each buffer type) were stored at different temperatures and analysed eight times in 10 replicates over 21 days. In the clinical setting, 7695 screenees returned two samples, using both the old and the new specimen collection device (SCD). In the laboratory simulation, 5 days from sample preparation with the buffer of the old SCD, the Hb concentration decreased by 40% at room temperature (25°C, range 22-28°C) and up to 60% at outside temperature (29°C, range 16-39°C), whereas with the new one, Hb concentration decreased by 10%. In the clinical setting, a higher mean Hb concentration with the new SCD compared with the old one was found (6.3 vs. 5.0 µg Hb/g faeces, respectively, P<0.001); no statistically significant difference was found in the probability of having a positive result in the two SCDs. Better Hb stability was observed with the new buffer under laboratory conditions, but no difference was found in the clinical performance. In our study, only marginal advantages arise from the new buffer. Improvements in sample stability represent a significant target in the screening setting.

Background: Among these diseases, congenital bleeding disorders (CBD) represent a significant societal burden in terms of high morbidity costs and health outcomes. In Italy, the organization and provision of health care is a regional responsibility and regions must assure equity and quality to all their residents. This is also true for CBD care which is provided by 54 multidisciplinary Hemophilia Treatment Centers (HTCs) distributed among the regions. With the present study, we intend to stimulate a debate on the effect that the decentralization process have in the delivery of services to CBD patients across Italy., Methods: The available comparable measures of caseloads per center and interregional patient mobility, as proxies of quality and responsiveness of the regional network of HTCs, were first analyzed for the using data from the Italian Hemophilia Centers Association for the year 2012., Results: Nine thousand one hundred and thirty four Italian residents with CBD received care in at least one of the Italian HTC in 2012. Preliminary findings suggested room for improvement in health care delivery for CBD patients. In 2012, 16 HTCs out of 51 (31.4%) treated a number of patients under the minimum requirement for treatment center accreditation (10 severe patients). Moreover, data on interregional patient mobility highlighted differences in the ability of each region to retain its own residents or to attract residents from other regions., Conclusions: Preliminary study results showed significant disparities among regions in terms of volumes and mobility of residents with CBDs that cannot be completely explained by the different geographical characteristics. Therefore, the central government should consider taking concrete measures to bridge the gap between regions to assure access to quality care for all individuals with CBD independently from where they live and therefore to move toward a more integrated and homogeneous national network of care centers. Typology of disease, patients' needs, and cost for outcomes, should have high priority on the political agenda. For CBD patients, even in a federal healthcare system, the national government should have the global responsibility to guaranteeing uniform levels of quality care over the country and overcome local institutions when necessary.

Background: Two noninferiority, randomized, controlled trials were conducted in parallel comparing the safety and efficacy of platelets treated with Intercept or Mirasol pathogen-reduction technologies versus standard platelets., Study Design and Methods: The primary endpoint was the percentage of hematology patients who developed World Health Organization Grade 2 or greater bleeding. A noninferiority margin of 11% was chosen based on expected Grade 2 or greater bleeding in 20% of controls. The study was closed for financial restrictions before reaching the planned sample size of 828 patients, and an intention-to-treat analysis was conducted on 424 evaluable patients., Results: In the Intercept trial (113 treated vs. 115 control patients), the absolute risk difference in Grade 2 or greater bleeding was 6.1%, with an upper one-sided 97.5% confidence limit of 19.2%. The absolute risk difference in the Mirasol trial (99 treated vs. 97 control patients) was 4.1%, and the upper one-sided 97.5% confidence limit was 18.4%. Neither absolute risk difference was statistically significant. In both trials, posttransfusion platelet count increments were significantly lower in treated versus control patients. Mean blood component use in treated patients versus controls was 54% higher (95% confidence interval, 36%-74%; Intercept) and 34% higher (95% confidence interval, 16%-54%; Mirasol) for platelets and 23% higher (95% confidence interval, 8%-39%; Intercept) and 32% higher (95% confidence interval, 10%-57%; Mirasol) for red blood cells. Unexpected reactions and adverse events were not reported. Mortality did not differ significantly between treated and control patients., Conclusion: Although conclusions on noninferiority could not be drawn due to low statistical power, the study provides additional information on the safety and efficacy of pathogen-reduced platelets treated with two commercial pathogen-reduction technologies., (© 2017 AABB.)

Human pegivirus (HPgV, formerly called GB virus C/hepatitis G virus) is a poorly understood RNA virus of the Flaviviridae family. The HPgV infection is common worldwide and the virus is likely transmitted by blood products. At this time, no causal association between HPgV and human diseases has been identified. While waiting for new findings to better understand the Pegivirus genus, the aim of our narrative review is to discuss the currently available information on HPgV focusing on its prevalence in blood donors and its potential threat to transfusion safety.

Background: Techniques for banking cord blood units (CBUs) as source for hematopoietic stem cell transplantation have been developed over the past 20 years, aimed to improve laboratory efficiency without altering the biologic properties of the graft. A large-scale, registry-based assessment of the impact of the banking variables on the clinical outcome is currently missing., Study Design and Methods: A total of 677 single cord blood transplants (CBTs) carried out for acute leukemia in complete remission in centers affiliated with the European Society for Blood and Marrow Transplantation were selected. An extensive set of data concerning CBU banking were collected and correlations with clinical outcome were assessed. Clinical endpoints were transplant-related mortality, engraftment, and graft-versus-host disease (GVHD)., Results: The median time between collection and CBT was 4.1 years (range, 0.2-16.3 years). Volume reduction (VR) of CBUs before freezing was performed in 59.2% of available reports; in half of these the frozen volume was less than 30 mL. Cumulative incidences of neutrophil engraftment on Day 60, 100-day acute GVHD (II-IV), and 4-year chronic GVHD were 87, 29, and 21 ± 2%. The cumulative incidence of nonrelapse mortality (NRM) at 100 days and 4-year NRM were, respectively, 16 ± 2 and 30 ± 2%. Neither the variables related to banking procedures nor the interval between collection and CBT influenced the clinical outcome., Conclusion: These findings indicate a satisfactory validation of the techniques associated with CBU VR across the banks. Cell viability assessment varied among the banks, suggesting that efforts to improve the standardization of CBU quality controls are needed., (© 2016 The Authors Transfusion published by Wiley Periodicals, Inc. on behalf of AABB.)

Although existing clinical evidence shows that the transfusion of blood components is becoming increasingly safe, the risk of transmission of known and unknown pathogens, new pathogens or re-emerging pathogens still persists. Pathogen reduction technologies may offer a new approach to increase blood safety. The study is the output of collaboration between the Italian National Blood Centre and the Post-Graduate School of Health Economics and Management, Catholic University of the Sacred Heart, Rome, Italy. A large, multidisciplinary team was created and divided into six groups, each of which addressed one or more HTA domains.Plasma treated with amotosalen + UV light, riboflavin + UV light, methylene blue or a solvent/detergent process was compared to fresh-frozen plasma with regards to current use, technical features, effectiveness, safety, economic and organisational impact, and ethical, social and legal implications. The available evidence is not sufficient to state which of the techniques compared is superior in terms of efficacy, safety and cost-effectiveness. Evidence on efficacy is only available for the solvent/detergent method, which proved to be non-inferior to untreated fresh-frozen plasma in the treatment of a wide range of congenital and acquired bleeding disorders. With regards to safety, the solvent/detergent technique apparently has the most favourable risk-benefit profile. Further research is needed to provide a comprehensive overview of the cost-effectiveness profile of the different pathogen-reduction techniques. The wide heterogeneity of results and the lack of comparative evidence are reasons why more comparative studies need to be performed.

Over the past 30 years, it has been demonstrated that removal of white blood cells from blood components is effective in preventing some adverse reactions such as febrile non-haemolytic transfusion reactions, immunisation against human leucocyte antigens and human platelet antigens, and transmission of cytomegalovirus. In this review we discuss indications for leucoreduction and classify them into three categories: evidence-based indications for which the clinical efficacy is proven, indications based on the analysis of observational clinical studies with very consistent results and indications for which the clinical efficacy is partial or unproven.

Passive immunisation for the prevention and treatment of human infectious diseases can be traced back to the 20(th) century. The recent Ebola virus outbreak in West Africa has turned the spotlight onto the possible use of convalescent whole blood and convalescent plasma in the treatment of infectious diseases because they are the only therapeutic strategy available in some cases, given the unavailability of vaccines, drugs or other specific treatments. Convalescent blood products could be a valid option in the treatment/prophylaxis of several infectious diseases both in association with other drugs/preventive measures and as the only therapy when a specific treatment is not available. However, there are still some issues to consider in determining the advisability of implementing a large-scale convalescent plasma transfusion programme.

In the last few years, the transfusion medicine community has been paying special attention to emerging vector-borne diseases transmitted by arboviruses. Zika virus is the latest of these pathogens and is responsible for major outbreaks in Africa, Asia and, more recently, in previously infection-naïve territories of the Pacific area. Many issues regarding this emerging pathogen remain unclear and require further investigation. National health authorities have adopted different prevention strategies. The aim of this review article is to discuss the currently available, though limited, information and the potential impact of this virus on transfusion medicine.

Background: Transfusion-transmissible infections have made both blood bankers and health authorities overly cautious. The general public expects and hence reinforces this policy. To obtain a high level of blood product safety, blood and plasma donors have to meet increasingly stringent eligibility criteria; however, it is not known whether this policy translates into improved outcomes for patients. There is a risk that the management of donors does not match the ambition of greater safety for patients. European directives related to the collection process and donor selection will probably be reconsidered in the next few years., Material and Methods: The development of European directives on donor selection and their basis in the literature were reviewed with an emphasis on the background and considerations for eligibility criteria to be included in the directives., Results: The precautionary principle appears to be the predominant reason behind the set of eligibility criteria. However, the formal eligibility criteria, put into force in 2004, do not balance with the developments of the past decade in laboratory tests and measures that have substantially reduced actual infection risks. In no cases were the effects of eligibility criteria on the donor pool and donor well-being quantified. Regional differences in the epidemiology of transfusion-transmissible infections were not taken into consideration either., Discussion: First, the Authors promote the collection of epidemiological data on the incidence and prevalence of conditions in the general population and in blood and plasma donors which could pose a risk for transfused patients, in order to use these data as a basis for decision-making in donor-selection policies. Second, the Authors suggest including allowance for differential deferral criteria throughout Europe, based on factual risk levels. There should be an accepted balance between donor and patient welfare, and also between risk to transfusion safety and risk of compromising the blood supply.

Background and Objectives: Despite the procedures adopted for the selection of blood donors, in Italy the HIV prevalence per 100 000 repeat tested donors (RTD) and first-time tested donors (FTD) is high compared to most other Council of Europe member states. To evaluate the effectiveness of predonation procedures, we studied both the characteristics and the undisclosed risk behaviours of HIV-positive donors., Materials and Methods: We analysed the data from the Italian blood donor surveillance system in 2009, 2010 and 2011. Based on the postdonation interview, HIV-positive donors were classified by risk behaviour (heterosexual, MSM, 'non-sexual' and 'not determined') and by time elapsed from risk behaviour to donation. In Italy, the temporary deferral for exposure to behaviour at risk is 4 months., Results: In the postdonation interview, 113 HIV-positive donors (32·4%), who denied at-risk behaviours in the predonation selection, reported sexual risk behaviours <4 months prior to donation; they were predominantly males (84·1%) and RTD (63·7%). The main reason for not having reported the risk behaviour in the predonation selection was 'not realizing having engaged in at-risk behaviour' (66·4%)., Conclusion: These findings underline the need for more comprehensible educational material, a clearer predonation questionnaire, and effective information campaigns to improve the awareness of HIV sexual risk behaviours among blood donors., (© 2015 International Society of Blood Transfusion.)

Human T-cell leukemia viruses (HTLV-1 and HTLV-2) are associated with a variety of human diseases, including some severe ones. Transfusion transmission of HTLV through cellular blood components is undeniable. HTLV screening of blood donations became mandatory in different countries to improve the safety of blood supplies. In Japan and Europe, most HTLV-infected donors are HTLV-1 positive, whereas in the United States a higher prevalence of HTLV-2 is reported. Many industrialized countries have also introduced universal leukoreduction of blood components, and pathogen inactivation technologies might be another effective preventive strategy, especially if and when generalized to all blood cellular products. Considering all measures available to minimize HTLV blood transmission, the question is what would be the most suitable and cost-effective strategy to ensure a high level of blood safety regarding these viruses, considering that there is no solution that can be deemed optimal for all countries., (© 2015 AABB.)

Background: In addition to a largely prevalent use for bleeding prophylaxis, platelet concentrates from adult blood have also been used for many years to prepare platelet gels for the repair of topical skin ulcers. Platelet gel can be obtained by activation of fresh, cryopreserved, autologous or allogeneic platelet concentrates with calcium gluconate, thrombin and/or batroxobin. The high content of tissue regenerative factors in cord blood platelets and the widespread availability of allogeneic cord blood units generously donated for haematopoietic transplant but unsuitable for this use solely because of low haematopoietic stem cell content prompted us to develop a national programme to standardise the production of allogeneic cryopreserved cord blood platelet concentrates (CBPC) suitable for later preparation of clinical-grade cord blood platelet gel., Materials and Methods: Cord blood units collected at public banks with total nucleated cell counts <1.5×10(9), platelet count >150×10(9)/L and volume >50 mL, underwent soft centrifugation within 48 hours of collection. Platelet-rich plasma was centrifuged at high speed to obtain a CBPC with target platelet concentration of 800-1,200×10(9)/L, which was cryopreserved, without cryoprotectant, below -40 °C., Results: During 14 months, 13 banks produced 1,080 CBPC with mean (± standard deviation) volume of 11.4±4.4 mL and platelet concentration of 1,003±229×10(9)/L. Total platelet count per CBPC was 11.3±4.9×10(9). Platelet recovery from cord blood was 47.7±17.8%. About one-third of cord blood units donated for haematopoietic transplant could meet the requirements for preparation of CBPC. The cost of preparation was € 160.92/CBPC. About 2 hours were needed for one technician to prepare four CBPC., Discussion: This study yielded valuable scientific and operational information regarding the development of clinical trials using allogeneic CBPC.

Background: Population screening for colorectal cancer (CRC) is widely adopted, but the preferred strategy is still under debate. We aimed to compare reduced (r-CTC) and full cathartic preparation CT colonography (f-CTC), fecal immunochemical test (FIT), and optical colonoscopy (OC) as primary screening tests for CRC., Methods: Citizens of a district of Florence, Italy, age 54 to 65 years, were allocated (8:2.5:2.5:1) with simple randomization to be invited by mail to one of four screening interventions: 1) biennial FIT for three rounds, 2) r-CTC, 3) f-CTC, 4) OC. Patients tested positive to FIT or CTC (at least one polyp ≥6mm) were referred to OC work-up. The primary outcomes were participation rate and detection rate (DR) for cancer or advanced adenoma (advanced neoplasia). All statistical tests were two-sided., Results: Sixteen thousand eighty-seven randomly assigned subjects were invited to the assigned screening test. Participation rates were 50.4% (4677/9288) for first-round FIT, 28.1% (674/2395) for r-CTC, 25.2% (612/2430) for f-CTC, and 14.8% (153/1036) for OC. All differences between groups were statistically significant (P = .047 for r-CTC vs f-CTC; P < .001 for all others). DRs for advanced neoplasia were 1.7% (79/4677) for first-round FIT, 5.5% (37/674) for r-CTC, 4.9% (30/612) for f-CTC, and 7.2% (11/153) for OC. Differences in DR between CTC groups and FIT were statistically significant (P < .001), but not between r-CTC and f-CTC (P = .65)., Conclusions: Reduced preparation increases participation in CTC. Lower attendance and higher DR of CTC as compared with FIT are key factors for the optimization of its role in population screening of CRC., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The overall use of allogeneic blood transfusions in clinical practice remains relatively high and still varies widely among centres and practitioners. Moreover, allogeneic blood transfusions have historically been linked with risks and complications: some of them (e.g. transfusion reactions and transmission of pathogens) have been largely mitigated through advancements in blood banking whereas some others (e.g. immunomodulation and transfusion-related acute lung injury) appear to have more subtle etiologies and are more difficult to tackle. Furthermore, blood transfusions are costly and the supply of blood is limited. Finally, evidence indicates that a great number of the critically ill patients who are being transfused today may not be having tangible benefits from the transfusion. Patient blood management is an evidence-based, multidisciplinary, multimodal, and patient-tailored approach aimed at reducing or eliminating the need for allogeneic transfusion by managing anaemia, perioperative blood conservation, surgical haemostasis, and blood as well as plasma-derivative drug use. From this point of view, the reduction of allogeneic blood usage is not an end in itself but a tool to achieve better patient clinical outcome. This article focuses on the three-pillar matrix of patient blood management where the understanding of basic physiology and pathophysiology is at the core of evidence-based approaches to optimizing erythropoiesis, minimising bleeding and tolerating anemia. Anesthesiologists and critical care physicians clearly have a key role in patient blood management programmes are and should incorporate its principles into clinical practice-based initiatives that improve patient safety and clinical outcomes.

The aim of this work was to evaluate differences in energy flows between normal and immortalized cells when these distinct biological systems are exposed to environmental stimulation. These differences were considered using a constructal thermodynamic approach, and were subsequently verified experimentally. The application of constructal law to cell analysis led to the conclusion that temperature differences between cells with distinct behaviour can be amplified by interaction between cells and external fields. Experimental validation of the principle was carried out on two cellular models exposed to electromagnetic fields. By infrared thermography we were able to assess small changes in heat dissipation measured as a variation in cell internal energy. The experimental data thus obtained are in agreement with the theoretical calculation, because they show a different thermal dispersion pattern when normal and immortalized cells are exposed to electromagnetic fields. By using two methods that support and validate each other, we have demonstrated that the cell/environment interaction can be exploited to enhance cell behavior differences, in particular heat dissipation. We propose infrared thermography as a technique effective in discriminating distinct patterns of thermal dispersion and therefore able to distinguish a normal phenotype from a transformed one.

Solvent/detergent-treated plasma was licensed >30 years ago. It has several specific characteristics, the most important being the standardized content of clotting factors, the lack of antibodies implicated in transfusion-related acute lung injury pathogenesis and the very high level of safety against transfusion-related viral infections. Since 1992, many clinical studies have confirmed its safety and efficacy in a wide range of congenital and acquired bleeding disorders. After a brief analysis of the pharmaceutical characteristics of solvent/detergent plasma, this review will focus on the clinical experience with this virus-inactivated plasma.