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The daily patterns of feed intake and rumination influence rumen fermentation, rumen pH, and timing of absorbed nutrients in the dairy cow, but the effects of diet composition on these patterns are not well characterized. Data from 3 previously published experiments were examined to determine the influence of dietary starch, fiber, and fatty acids (FA) on daily patterns of intake, rumination, and rumen pH. Dietary neutral detergent fiber (NDF) and starch were investigated in 2 experiments, each with duplicated 4 × 4 Latin square designs with a 2 × 2 factorial arrangement of treatments in cows fed cows 1×/d at 1200 and 1400 h, respectively. To investigate fiber content and digestibility in the first experiment, brown midrib or isogenic conventional corn silage were fed in low- and high-NDF diets (29 and 38%, respectively). To investigate starch source and concentration in the second experiment, ground high-moisture corn or dry ground corn were fed in low- and high-starch diets (21 and 32%, respectively). Effect of fat concentration and saturation was investigated in the third experiment using a replicated 4 × 4 Latin square design that fed cows 1×/d at 0900 h; treatments included a control diet with no added fat and 2.5% added saturated FA, unsaturated FA, or a mixture of the saturated and unsaturated FA. In the first 2 experiments, intake followed a similar daily pattern regardless of starch and NDF concentration or digestibility. Rumination displayed a treatment by time interaction for both NDF and starch concentration, with high-fiber, low-starch diets causing greater rumination overnight but not midday. High-starch diets decreased total daily rumen pH equally across the day, but did not change the daily pattern. Type of corn silage did not affect the daily patterns of rumination or rumen pH, but pH was reduced throughout the day in brown midrib diets. In the third experiment, no interactions between fatty acid supplement and time of day were observed for intake, rumination, or rumen pH. Within all experiments, rumination fit or tended to fit a 24-h rhythm regardless of diet, with the amplitude of the rumination being reduced in low-starch diets and diets containing saturated FA or a mixture of saturated and unsaturated FA. Overall, intake, rumination, and rumen pH follow a daily pattern that was minimally modified by dietary fiber and starch type and level or fat level and fatty acid profile.

Objectives: The aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis. Methods: This was a case–control–control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission. Results: During the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (15 days (RRR 4.63 (95% CI 2.11–10.18), p

Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.

Coronavirus disease 2019 (COVID-19) may be associated with worse outcome in solid organ transplant (SOT) recipients. We performed a prospective cohort study of hospitalized patients with confirmed diagnosis of COVID-19, from March 15 to April 30, 2020, at two tertiary hospitals in Emilia-Romagna Region. SOT recipients were compared with non-SOT patients. Primary endpoint was all-cause 30-day mortality. Relationship between SOT status and mortality was investigated by univariable and multivariable Cox regression analysis. Patients were assessed from COVID-19 diagnosis to death or 30-day whichever occurred first. Study cohort consisted of 885 patients, of them 24 SOT recipients (n=22, kidney, n=2 liver). SOT recipients were younger, had lower BMI, but higher Charlson Index. At admission they presented less frequently with fever and respiratory failure. No difference in 30-day mortality between the two groups (19% vs 22.1%) was found; however, there was a trend toward higher rate of respiratory failure (50% vs 33.1%, P=.07) in SOT recipients. Superinfections were more represented in SOT recipients, (50% vs 15.5%, P&nbsp

Objective To investigate the impact of colonization with carbapenemase-producing Enterobacteriaceae (CPE) on the CPE infection risk after liver transplantation (LT). Methods Prospective cohort study of all adult patients undergoing LT at our centre over an 8-year period (2010–2017). Individuals were screened for CPE colonization by rectal swabs at inclusion onto the waiting list, immediately before LT and weekly after LT until hospital discharge. Asymptomatic carriers did not receive decolonization, anti-CPE prophylaxis or pre-emptive antibiotic therapy. Participants were followed up for 1 year after LT. Results We analysed 553 individuals who underwent a first LT, 38 were colonized with CPE at LT and 104 acquired colonization after LT. CPE colonization rates at LT and acquired after LT increased significantly over the study period: incidence rate ratios (IRR) 1.21 (95% CI 1.05–1.39) and 1.17 (95% CI 1.07–1.27), respectively. Overall, 57 patients developed CPE infection within a median of 31 (interquartile range 11–115) days after LT, with an incidence of 3.05 cases per 10 000 LT-recipient-days and a non-significant increase over the study period (IRR 1.11, 95% CI 0.98–1.26). In multivariable analysis, CPE colonization at LT (hazard ratio (HR) 18.50, 95% CI 6.76–50.54) and CPE colonization acquired after LT (HR 16.89, 95% CI 6.95–41.00) were the strongest risk factors for CPE infection, along with combined transplant (HR 2.60, 95% CI 1.20–5.59), higher Model for End-Stage Liver Disease at the time of LT (HR 1.03, 95% CI 1.00–1.07), prolonged mechanical ventilation (HR 2.63, 95% CI 1.48–4.67), re-intervention (HR 2.16, 95% CI 1.21–3.84) and rejection (HR 2.81, 95% CI 1.52–5.21). Conclusions CPE colonization at LT or acquired after LT were the strongest predictors of CPE infection. Prevention strategies focused on LT candidates and recipients colonized with CPE should be investigated.

Background: Despite the dominance of respiratory disease, acute-on-chronic liver failure (ACLF) and acute decompensation (AD) have been reported in patients with COVID-19 and preexisting liver disease, in particular cirrhosis. Moreover, COVID-19 has been associated with increased mortality in patients with end-stage liver disease (ESLD). Aim our study is to evaluate the impact of SARS-CoV-2 infection in patients with ESLD listed for liver transplant (LT). Methods: Data from adults listed for LT with laboratory-confirmed SARS-CoV-2 infection were collected from 7 LT centers across Italy. Results: From March 1st to October 31st 2020, 29 patients listed for LT were tested positive for SARS-CoV-2 infection. Twenty-one patients (72%) were male, median age was 59 years (20-71). The most common indication (70%) for LT was ESLD. The mean MELD score was 18 (8-32). At diagnosis, twenty patients (69%) presented at least one symptom: 38% fever, 28% dry cough, and 31% respiratory distress. Notably, 25% of patients presented hepatic encephalopathy as first presenting symptom. The remaining 9 patients (31%) were completely asymptomatic: nasopharyngeal swab was performed according to surveillance protocols. Twenty-one patients (70%) required hospitalization for the management of COVID-19. Respiratory support was necessary in 13 patients (45%): 5 (17%) required O2-supply, 4 (14%) non-invasive ventilation and 4 (14%) mechanical ventilation. Only five patients (17%) received at least one drug for infection treatment (see table). Heparin was administrated in 7 patients (28%). No bleeding episodes were reported. Eight (%) patients died after a median time of 6 days (2-29) from Covid-19 diagnosis, with a 30-day-mortality rate of 30%. Three patients died of liver failure, while the remaining of multiple organ failures. In the univariate analysis, factors associated with 30-days mortality were respectively presence of comorbidities (0.07), severity of liver disease according to MELD score (0.05) and severity of respiratory failure (0.011). In the cox-regression analysis, only the severity of respiratory failure was significantly associated with the mortality (HR 3.13, IC 1.53-6.3). Conclusions: COVID-19 is associated with elevated mortality in LT candidates, listed for ESLD.

Background Targeted antifungal prophylaxis against Candida species or against Candida species and Aspergillus species, according to individual patient risk factors (RFs), is recommended by experts. However, recent studies have reported fluconazole is as effective as broader spectrum antifungals for preventing invasive fungal infection (IFI) after liver transplantation (LT). Methods We performed a retrospective cohort study of all adult patients who underwent LT at our 1420-bed tertiary teaching hospital, from June 2010 to December 2014, to assess the rate and etiology of IFI within 100 days after LT, to investigate the compliance with targeted prophylaxis, and to analyze risk factors for developing IFI. Results In total, 303 patients underwent LT. Patients were classified as having low (no RFs), intermediate (1 RF for invasive candidiasis [IC]), and high risk (1 RF for invasive aspergillosis [IA] or ≥2 RFs for IC) for IFI in 20%, 30%, and 50% of cases, respectively. A total of 139 patients received antifungal prophylaxis: 98 with a mold-active drug and 41 with fluconazole. Overall adherence to targeted prophylaxis was 53%. Nineteen patients (6.3%) developed IFI: 7 IC and 12 IA. Multivariate Cox regression analysis, adjusted for median model for end-stage liver disease score at LT, stratification risk group, and adherence to targeted prophylaxis, showed that graft dysfunction, renal replacement therapy, and prophylaxis with fluconazole were independent risk factors for IFI. Seven of the 9 patients who received fluconazole prophylaxis and developed IFI were classified as having high risk for IFI, and 6 developed IA. Conclusion Recommended stratification is accurate for predicting patients at very high risk for IFI, who should receive prophylaxis with a mold-active drug.

Improved understanding of risk factors associated with carbapenem-resistant-Klebsiella pneumoniae (CR-KP) infection after liver transplantation (LT) can aid development of effective preventive strategies. We performed a prospective cohort study of all adult patients undergoing LT at our hospital during 30-month period to define risk factors associated with CR-KP infection. All patients were screened for CR-KP carriage by rectal swabs before and after LT. No therapy was administered to decolonize or treat asymptomatic CR-KP carriers. All patients were monitored up to 180 days after LT. Of 237 transplant patients screened, 41 were identified as CR-KP carriers (11 at LT, 30 after LT), and 20 developed CR-KP infection (18 bloodstream-infection, 2 pneumonia) a median of 41.5 days after LT. CR-KP infection rates among patients non-colonized, colonized at LT, and colonized after LT were 2%, 18.2% and 46.7% (p 48 h; HCV recurrence, and colonization at any time with CR-KP. Based on these four variables, we developed a risk score that effectively discriminated patients at low versus higher risk for CR-KP infection (AUC 0.93, 95% CI 0.86-1.00, p < 0.001). Our results may help to design preventive strategies for LT recipients in CR-KP endemic areas.

Background To assess the safety and tolerability of high-dose weekly (10 mg/kg) liposomal amphotericin B (LamB) for antifungal prophylaxis in liver transplantation (LT) recipients with predefined risk factors for invasive fungal infection (IFI), a prospective phase II noncomparative trial was performed at our center over a 4-year period. Methods In the selected LT recipients, LamB was administered weekly until hospital discharge after LT for minimum 2 weeks. Criteria for early discontinuing prophylaxis were: (i) any adverse event (AE); (ii) suspicion of IFI. Safety and tolerability were assessed according to the incidence of grades 3 to 4 AEs based on Common Toxicity Criteria (CTC) classification. Post-LT follow-up was of 180 days. Results Overall, 76 patients were included. Liposomal amphotericin B was started within a median of 1 (interquartile range, 1-4) day after LT. Overall, 66 of 76 (86.8%) patients completed the prophylaxis, 10 discontinued the study protocol: 6 for infusion-related AE, 4 for suspected IFI. Adverse events consisted of five cases of lumbar pain and one case of thoracic pain which occurred after a median of 1.5 (interquartile range, 1-2) LamB infusions. None of the patients reported CTC grades 3 to 4 hypokalemia, three reported CTC grade 3 acute renal injury, none of which were deemed directly attributable to LamB. No drug-drug interactions with immunosuppressive drugs were reported, and no episode of rejection occurred during the prophylaxis. In only two of the four patients with suspected IFI was the diagnosis of invasive candidiasis confirmed. Conclusion Our results suggest high-dose weekly LamB may be a safe prophylactic strategy for high-risk LT recipients.

Long-term functional outcomes of sofosbuvir-based antiviral treatment were evaluated in a cohort study involving 16 Italian centres within the international compassionate use programme for post-transplant hepatitis C virus (HCV) recurrence. Seventy-three patients with cirrhosis (n=52) or fibrosing cholestatic hepatitis (FCH, n=21) received 24-week sofosbuvir with ribavirin±pegylated interferon or interferon-free sofosbuvir-based regimen with daclatasvir/simeprevir+ribavirin. The patients were observed for a median time of 103 (82-112) weeks. Twelve of 73 (16.4%) died (10 non-FCH, 2 FCH) and two underwent re-LT. Sustained virological response was achieved in 46 of 66 (69.7%): 31 of 47 (66%) non-FCH and 15 of 19 (79%) FCH patients. All relapsers were successfully retreated. Comparing the data of baseline with last follow-up, MELD and Child-Turcotte-Pugh scores improved both in non-FCH (15.3±6.5 vs 10.5±3.8, P

Background Active tuberculosis (TB) is commonly considered a contraindication for liver transplantation (LT). However, in patients with TB who develop acute liver failure (ALF) due to toxicity induced by anti-tubercular treatment (ATT), LT could be the only opportunity for treatment. The aim of this study was to evaluate the feasibility of LT in this scenario. Methods We described 2 cases and comprehensively reviewed the literature finding 26 cases of LT performed in patients having a concomitant active TB and liver failure secondary to ATT toxicity. Results TB was classified as pulmonary in 18/26 (69%), nodal in 3/26 (11%) TB cases, while the remaining 5/26 cases included disseminated, pleural, renal, ovarian, and vertebral TB localization (1 case each). ATT following LT consisted mainly of isoniazid or rifampin (RIF)-sparing regimens and included primarily fluoroquinolones and ethambutol. Rejection episodes and liver toxicity were reported in 19% and 8% of patients respectively. Graft rejection was more frequent among patients treated with RIF-containing regimens (P

Introduction: The availability of interferon-sparing therapy with direct acting antivirals (DAAs) has expanded the pool of patients eligible for treatment. Despite this, data on the efficacy and safety of these treatments in elderly are lacking. Aim: To evaluate the efficacy and safety of the treatment with DAA-based regimens in HCV patients aged ≥65 years with advanced fibrosis/cirrhosis in a real life clinical setting. Methods: Retrospective data of elderly patients treated with DAAs from January to November 2015 in 7 tertiary referral center of Emilia-Romagna Region (Italy) were collected. Patients received: sofosbuvir (SOF) [n = 35], SOF + simeprevir (SMV) [n = 78], SOF + daclatasvir (DCV) [n = 21], SOF + ledipasvir [n = 17], SMV + DCV [n = 4], ombitasvir/paritaprevir/ritonavir only [n = 3] or with dasasbuvir [n = 42]. Ribavirin was added at the physician's discretion according weight. The primary efficacy endpoint was sustained virological response 12 weeks after the last dose of study drug (SVR12). Results: Overall, 200 consecutive elderly patients were treated. The median age was 74 years (range: 65-85) and 90 (45%) aged ≥75 years; 49% were male, 50.5% were treatment experienced and 85% had cirrhosis. The majority (76%) had genotype (GT) 1b. To date, 155 patients completed treatment. Two cirrhotics died during the therapy and were excluded from final analysis because the cause of death was unrelated to the treatment. Overall, 94 have reached week 12 of post-treatment and the SVR12 was 91.5% (86/94). According to GT, the SVR12 was achieved in 69/73 (94.5%) with GT1, in 16/18 (88.9%) with GT2 and in 1/3 (33.4%) with GT4 infection. Relapse occurred more commonly in cirrhotic patients. No serious adverse events have been reported until now. Complete safety data for the cohort and updated SVR data will be presented. Conclusions: This preliminary data indicate that DAA-based regimen have a similar efficacy compared to registrative studies and without significant side effects in HCV elderly patients in a real-world setting.

Introduction: Non-interferon-based therapy with direct acting antiviral agents (DAA) have become an integral component of treatment for HCV infection but little is known about their real-world effectiveness. Aim: To evaluate the efficacy and safety of the treatment with DAA-based regimen in HCV patients with advanced fibrosis/cirrhosis in a real life clinical setting. Methods: Retrospective data of patients treated with DAA from January to November 2015 in 7 tertiary referral centers in the Emilia-Romagna Region (Italy) were collected. Patients on the waiting list for orthotopic liver transplantation and with HIV co-infection were excluded. Patients received: sofosbuvir (SOF) [n = 74], SOF + simeprevir (SMV) [n = 149], SOF + daclatasvir (DCV) [n = 69], SOF + ledipasvir [n = 43], SMV + DCV [n = 4], ombitasvir/paritaprevir/ritonavir only [n = 11] or with dasasbuvir [n = 84]. Ribavirin was added at the physician's discretion according to weight. The primary efficacy endpoint was sustained virological response 12 weeks after the last dose of study drug (SVR12). Results: Overall, 435 consecutive patients were treated. The median age was 63 years (range: 29–85); 60% were male, 55.2% were treatment experienced and 81.1% had cirrhosis. The majority (56.6%) had genotype (GT) 1b, 12.4% GT1a, 11.3% GT2, 12.6% GT3 and 7.1% GT4. To date, 347 patients completed treatment and 179 the week 12 of post-treatment follow-up. Three cirrhotics died during treatment and were excluded from analysis. Overall, the SVR12 was 88.8% (159/179). According to GT, the SVR12 was achieved in 17/19 (89.5%) GT1a, in 100/111 (90.1%) GT1b, in 24/26 (92.3%) GT2, in 9/11 (81.8%) GT3 and in 9/12 (75%) GT4. Patients with cirrhosis had a lower response rate than those with advanced fibrosis (86.7% vs 97.2%; p = 0.082). Complete safety data for the entire cohort, updated SVR12 will be presented. Conclusions: The DAA-based regimen was efficacious with low relapse rates in HCV patients in a real-world setting. Patients with cirrhosis seems to respond less well to the different regimens used.

In the last US national conference on liver transplantation for hepatocellular carcinoma (HCC), a continuous priority score, that incorporates model for end-stage liver disease (MELD), alpha-fetoprotein and tumor size, was recommended to ensure a more equitable liver allocation. However, prioritizing highest alpha-fetoprotein levels or largest tumors may select lesions at a higher risk for recurrence; similarly, patients with higher degree of liver failure could have lower postoperative survival. Data from 300 adult HCC recipients were reviewed and the proposed HCC-MELD equation was applied to verify if it can predict post-transplantation survival. The 5-year survival and recurrence rates after transplantation were 72.8 and 13.5%, respectively. Cox regression analysis confirmed HCC-MELD as predictive of both postoperative survival and recurrence (p < 0.001). The 5-year predicted survival and recurrence rates were plotted against the HCC-MELD-based dropout probability: the higher the dropout probability while on waiting list, the lower the predicted survival after transplantation, that is worsened by hepatitis C positivity; similarly, the higher the predicted HCC recurrence rate after transplantation. The HCC priority score could predict the postoperative survival of HCC recipients and could be useful in selecting patients with greater possibilities of survival, resulting in higher post-transplantation survival rates of HCC populations.

In liver transplant, during anti-viral therapy for hepatitis C virus (HCV) recurrence, the immunosuppressant levels should be monitored to prevent both toxicity and rejection. Sofosbuvir (SOF) has been used within compassionate programs for HCV recurrence and, according to pharmacokinetic analyses, is not supposed to have significant pharmacological interactions with tacrolimus (Tac) or ciclosporin.1 This was reported in the review article by Koff recently published.2 We treated eight transplant recipients with SOF/ribavirin (RBV) for a severe HCV recurrence, and observed unexpected Tac/ciclosporin reduction during SOF.

Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm.

Background and aim: Sorafenib is a multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma (HCC). However, the predictive factors of outcome among treated patients have not been fully investigated. Aim of this study was to identify factors predictive for tumor control among patients with advanced HCC treated with sorafenib. Material and methods: All consecutive HCC patients treated with sorafenib at our Unit from October 2008 to October 2010 were evaluated. All patients received 800 mg/day of sorafenib until progression or unacceptable toxicities. Overall survival (OS) and time to progression (TTP) were estimated by using Kaplan-Meier curves. TTP was considered as a marker of tumor control. Univariate analysis included age, gender, etiology, AFP, Child-Pugh class, MELD, alanine aminotransferase (ALT), alkaline phosphatase, bilirubin, albumin, ascites, metastasis, portal vein thrombosis, oesophageal varices, effects related to VEGF inhibition: rash, arterial hypertension, bleeding, and hand-foot syndrome (HFS). To detect factors independently related to TTP, multivariate analysis by Cox’s model was done. Results: We treated 101 patients (median age 67 years; 81 males; 98 cirrhotics; Child A/B: 79/19; 55 macrovascular invasion; 39 extrahepatic spread). Median therapy duration was 4 (range 1-16) months. Median OS was 10 (95% CI 4.5-15.5) months. TTP was 9 (95%CI 3.7-14.3) months. Complete/partial response occurred in 21% of patients and stable disease in 19%. At univariate analysis, the variables significantly related to TTP were: female sex (14 months vs 6 months, p=.05), no portal thrombosis (13 months vs 6 months, p=.04), ALT =60UI (15 months vs 6 months, p=.02), no ascites (11 months vs 2 months, p=.003), and occurrence of HFS (16 months vs 5 months, p

511 LIVER MESENCHYMAL CELLS CONTRIBUTE TO IMPROVEMENT OF HUMAN CRYOPRESERVED HEPATOCYTES SURVIVAL AND FUNCTION A.-C. Dusabineza, D. Ngoc Khuu, L. Dolle, J. Abarca-Quinones, E. Sokal, L.A. van Grunsven, M. Najimi, I.A. Leclercq. Laboratory of Hepato-Gastroenterology, Institut de Recherche Experimentale et Clinique, IREC, Universite Catholique de Louvain, UCL, Laboratory of Pediatric Hepatology & Cell Therapy, Institut de Recherche Experimentale et Clinique, Universite Catholique de Louvain, UCL, Liver Cell Biology Lab, Department of Cell Biology, Vrije Universiteit Brussel, VUB, Brussels, Belgium E-mail: ange-clarisse.dusabineza@uclouvain.be

427 TREATMENT OF HEPATITIS C RECURRENCE AFTER LIVER TRANSPLANTATION: GENDER ISSUE ON THERAPY OUTCOME V. Giannelli, C. Lucidi, M. Giusto, F.R. Ponziani, M. Pompili, R. Vigano, R.M. Iemmolo, F.M. Donato, M. Rendina, P. Toniutto, L. Pasulo, S. Fagiuoli, M.C. Morelli, E. de Martin, L. Miglioresi, D. di Paolo, M. Merli, RECOLT-C. Sapienza University of Rome, Cattolica Sacro Cuore, Niguarda Ca’Granda Hospital, Rome, Modena University, Modena, Maggiore Hospital, Milan, Bari University, Bari, Udine University, Udine, Bergamo University, Bergamo, Sant’Orsola Malpighi Hospital, Bologna, Padua University Hospital, Padua, San Camillo-Spallanzani Hospital, Tor Vergata University Hospital, Rome, Italy E-mail: mr_valegiann84@hotmail.it