Molecular Analysis With 16S rRNA PCR/Sanger Sequencing and Molecular Antibiogram Performed on DNA Extracted From Valve Improve Diagnosis and Targeted Therapy of Infective Endocarditis: A Prospective Study.

BACKGROUND: Molecular analysis (MA) on heart valve (HV) improves the microbiologic diagnosis of infectious endocarditis (IE). The main drawback of MA is the lack of antimicrobial susceptibility information. METHODS: We conducted a prospective cohort observational study of consecutive adult patients from April 2012 to May 2021 who underwent valve surgery at our hospital. The performance of MA, blood cultures (BC) and valve cultures (VC), and the diagnostic and therapeutic impact of MA were evaluated. Molecular antibiogram results were compared to culture-based antimicrobial susceptibility testing (AST). RESULTS: A total of 137 patients with definite IE and 52 patients with no IE were enrolled in the study. Among IE cases BC, VC, and MA were positive in 75 (55%), 30 (22%), and 120 (88%) of IE cases, respectively. Among 62 cases of BC-negative IE (BCNE), 57 achieved diagnosis with MA. MA led to a change of antimicrobial therapy in 92% of BCNE. MA was negative in 100% of patients with no IE. Molecular antibiogram performed on 17 valve specimens that resulted positive for pathogens potential carrier of genes encoding for multidrug resistant mechanisms showed 100% concordance with AST. CONCLUSIONS: MA showed a high specificity and sensitivity in etiological diagnosis of IE. Molecular antibiogram could overcome the major limitation of MA that is the lack of susceptibility testing. We advocate for the inclusion of MA among diagnostic criteria for IE and for a more extensive use of molecular antibiogram when the culture result is negative, and MA is the only positive test.

Right vs left portal branch puncture in TIPS creation with controlled expansion covered stent: comparison of hemodynamic and clinical outcomes.

PURPOSE: To retrospectively compare outcomes of TIPS performed by puncturing left portal vein (LPV) vs right portal vein (RPV) to access the portal system. MATERIALS AND METHODS: One hundred ninety-three consecutive patients underwent TIPS with controlled expansion covered stent by using the LPV (37 patients) or the RPV (156 patients). Patients were followed until the last clinical evaluation, liver transplantation, or death. RESULTS: Demographics and clinical characteristics of the two groups were comparable. The median follow-up was 9.6 months (range 0.1-50.6). Portosystemic pressure gradient (PSG) before TIPS 15.7 mmHg ± 4.7 in RPV group (RPVG) vs 15.4 mmHg ± 4.5 in LPV group (LPVG) (p = 0.725). After TIPS, PSG 6.3 mmHg ± 2.8 in RPVG vs 6.2 mmHg ± 2.2 (p = 0.839). In LPVG, the stent was dilated to 8-mm in 95% of patients vs 77% of RPVG (p = 0.015). Two (5.4%) and 22 (14%) patients underwent TIPS revision in LPVG and RPVG (p = 0.15). The incidence of overt HE was 13% in LPVG and 24% in RPVG (p = 0.177). Rebleeding occurred in 3 of 49 patients (6%) with variceal bleeding as an indication: 2/41 patients (4.9%) in RPVG vs 1/8 patients (12.5%) in LPVG (p = 0.417). Among 126 patients with refractory ascites 20 patients (15.9%) needed paracentesis 3 months after the procedure: 18/101 patients (17.8%) in RPVG vs 2/25 patients (8%) in LPVG (p = 0.231). Thirty-seven patients (19%) died: 32 (21%) in RPVG and 5 (14%) in LPVG (p = 0.337). CONCLUSION: Compared with RPV puncture, in TIPS created through the LPV, the targeted PSG was reached with a smaller stent diameter. However, no significant difference in clinical outcomes was observed. KEY POINTS: • A LPV approach for TIPS creation does not lead to better control of complications of portal hypertension as compared to a RPV approach.

Clinical outcomes of transjugular intrahepatic portosystemic shunt with PTFE-covered stents after liver transplantation and technical results in split and whole liver graft recipients.

OBJECTIVES: To assess the outcomes of transjugular intrahepatic portosystemic shunt (TIPS) creation using PTFE-covered stents in liver transplant (LT) recipients and to analyze the technical result of TIPS creation in split grafts (SG) compared with whole liver grafts (WG). METHODS AND MATERIALS: Single-center, retrospective study, analyzing LT patients who underwent TIPS using PTFE-covered stents. Clinical and technical variables were analyzed. RESULTS: Between 2005 and 2021, TIPS was created using PTFE-covered stents in 48 LT patients at a median of 43 months (range, 0.5-192) after LT. TIPS indications were refractory ascites (RA) in 33 patients (69%), variceal bleeding (VB) in 9 patients (19%), others in 6 (12%). Ten patients (21%) received a SG. Technical success rate was 100% in both groups: in two WG recipients, (5%) a second attempt was required. An unconventional approach (combined transhepatic or transplenic access) was needed in 2 WG (5%) and 2 SG recipients (20%). Two procedure-related death occurred in the WG group. After a median follow-up of 22 months (range, 0,1-144), 16 patients (48%) in the RA group did not require post-TIPS paracentesis, in the VB group rebleeding occurred in 3 patients (33%). Fifteen patients (31%) underwent TIPS revision. Overt hepatic encephalopathy occurred in 14 patients (29%). Patient survival at 6 months, 1 year, and 3 years was 77%, 66%, and 43%, respectively. CONCLUSIONS: The feasibility and safety of TIPS creation in SG are comparable to that of WG. TIPS creation using PTFE-covered stents represents a viable option to treat portal hypertensive complications in LT recipients. KEY POINTS: • TIPS creation using PTFE-covered stents represents a viable option to treat complications of PH in LT recipients. • TIPS creation in LT SG recipients appears to be safe and feasible as in WG. • Results from this study may help to refine the management of LT patients with recurrent portal hypertensive complications encouraging physicians to consider TIPS creation as a treatment option in both SG and WG recipients.

Infective Endocarditis After Percutaneous Device Closure of Atrial Septal Defects: Incidence, Diagnosis, and Treatment. Case Report and Literature Review.

Infective endocarditis (IE) on atrial septal defect (ASD) closure devices, while extremely rare, has been reported to be more frequent early after the procedure. We describe a case of late IE after percutaneous closure of patent foramen ovale (PFO). We also performed a literature review on this subject. We reviewed a total of 42,365 patients who were treated with percutaneous devices: 13,916 for ostium secundum (OS) (32%), 24,726 for PFO (58%) and 3,723 for OS+PFO (8%). Among these patients, we identified 50 cases of IE after atrial septal defect device closure (0.001%). In contrast to previous reports, nearly 66% of IE in this setting occurred late, after at least 6 months from the procedure (33/50 patients). A statistical analysis clearly showed that the mean time from the procedure to IE increased in the last five years, probably associated with a change in antiplatelet therapy after ASD closure. Management of IE on an ASD occluder should always be discussed in the setting of a multidisciplinary heart team that includes a cardiologist, cardiac surgeon, and anesthetist. While surgical strategies gave excellent results, conservative management might be considered in cases of small IE vegetations and for patients in good general condition. However, in these cases, the patient must be closely observed with repeated blood and instrumental tests.

Reducing Carbapenem-Resistant Enterobacteriaceae Using the Targeted Solution Tool: A Quality Improvement Project.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) is a worldwide urgent health problem. Hand hygiene (HH) is an effective intervention to reduce the spread of CRE. LOCAL PROBLEM: In 2017, an increase in the rate of health care-associated (HA) CRE colonization was observed in a large multiorgan transplant center in Italy. This study aimed to reduce the HA-CRE colonization rates by improving HH compliance. METHODS: A pre-/post-intervention project was conducted from November 2017 through December 2020. INTERVENTIONS: The DMAIC (Define, Measure, Analyze, Improve, and Control) framework was used to implement the HH Targeted Solution Tool (TST). RESULTS: Hand hygiene compliance increased from 49% to 76.9% after the Improve phase ( P = .0001), and to 81.9% after the second Control phase ( P = .0001). The rate of HA-CRE decreased from 24.9% to 5.6% ( P = .0001). CONCLUSIONS: Using the DMAIC framework to implement the TST can result in significant improvements in HH compliance and HA-CRE colonization rates.

Brain magnetic resonance imaging radiomics features associated with hepatic encephalopathy in adult cirrhotic patients.

PURPOSE: Hepatic encephalopathy (HE) is a potential complication of cirrhosis. Magnetic resonance imaging (MRI) may demonstrate hyperintense T1 signal in the globi pallidi. The purpose of this study was to evaluate the performance of MRI-based radiomic features for diagnosing and grading chronic HE in adult patients affected by cirrhosis. METHODS: Adult patients with and without cirrhosis underwent brain MRI with identical imaging protocol on a 3T scanner. Patients without history of chronic liver disease were the control population. HE grading was based on underlying liver disease, severity of clinical manifestation, and number of encephalopathic episodes. Texture analysis was performed on axial T1-weighted images on bilateral lentiform nuclei at the level of the foramina of Monro. Diagnostic performance of texture analysis for the diagnosis and grading of HE was assessed by calculating the area under the receiver operating characteristics (AUROC) with 95% confidence interval (CI). RESULTS: The final study population consisted of 124 patients, 70 cirrhotic patients, and 54 non-cirrhotic controls. Thirty-eight patients had history of HE with 22 having an HE grade > 1. The radiomic features predicted the presence of HE with an AUROC of 0.82 (95% CI: 0.73, 0.90; P < .0001; 82% sensitivity, 66% specificity). Radiomic features predicted grade 1 HE (AUROC 0.75; 95% CI: 0.61, 0.89; P < .0001; 94% sensitivity, 60% specificity) and grade ≥ 2 HE (AUROC 0.82; 95% CI: 0.71, 0.93; P < .0001, 95% sensitivity, 57% specificity). CONCLUSION: In cirrhotic patients, MR radiomic is effective in predicting the presence of chronic HE and in grading its severity.

Liver transplantation from active COVID-19 donors: A lifesaving opportunity worth grasping?

COVID-19 pandemic dramatically impacted transplantation landscape. Scientific societies recommend against the use of donors with active SARS-CoV-2 infection. Italian Transplant Authority recommended to test recipients/donors for SARS-CoV-2-RNA immediately before liver transplant (LT) and, starting from November 2020, grafts from deceased donors with active SARS-CoV-2 infection were allowed to be considered for urgent-need transplant candidates with active/resolved COVID-19. We present the results of the first 10 LTs with active COVID-19 donors within an Italian multicenter series. Only two recipients had a positive molecular test at LT and one of them remained positive up to 21 days post-LT. None of the other eight recipients was found to be SARS-CoV-2 positive during follow-up. IgG against SARS-CoV-2 at LT were positive in 80% (8/10) of recipients, and 71% (5/7) showed neutralizing antibodies, expression of protective immunity related to recent COVID-19. In addition, testing for SARS-CoV-2 RNA on donors' liver biopsy at transplantation was negative in 100% (9/9), suggesting a very low risk of transmission with LT. Immunosuppression regimen remained unchanged, according to standard protocol. Despite the small number of cases, these data suggest that transplanting livers from donors with active COVID-19 in informed candidates with SARS-CoV-2 immunity, might contribute to safely increase the donor pool.

Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology.

BACKGROUND & AIMS: Although the discriminative ability of the model for end-stage liver disease (MELD) score is generally considered acceptable, its calibration is still unclear. In a validation study, we assessed the discriminative performance and calibration of 3 versions of the model: original MELD-TIPS, used to predict survival after transjugular intrahepatic portosystemic shunt (TIPS); classic MELD-Mayo; and MELD-UNOS, used by the United Network for Organ Sharing (UNOS). We also explored recalibrating and updating the model. METHODS: In total, 776 patients who underwent elective TIPS (TIPS cohort) and 445 unselected patients (non-TIPS cohort) were included. Three, 6 and 12-month mortality predictions were calculated by the 3 MELD versions: discrimination was assessed by c-statistics and calibration by comparing deciles of predicted and observed risks. Cox and Fine and Grey models were used for recalibration and prognostic analyses. RESULTS: In the TIPS/non-TIPS cohorts, the etiology of liver disease was viral in 402/188, alcoholic in 185/130, and non-alcoholic steatohepatitis in 65/33; mean follow-up±SD was 25±9/19±21 months; and the number of deaths at 3-6-12 months was 57-102-142/31-47-99, respectively. C-statistics ranged from 0.66 to 0.72 in TIPS and 0.66 to 0.76 in non-TIPS cohorts across prediction times and scores. A post hoc analysis revealed worse c-statistics in non-viral cirrhosis with more pronounced and significant worsening in the non-TIPS cohort. Calibration was acceptable with MELD-TIPS but largely unsatisfactory with MELD-Mayo and -UNOS whose performance improved much after recalibration. A prognostic analysis showed that age, albumin, and TIPS indication might be used to update the MELD. CONCLUSIONS: In this validation study, the performance of the MELD score was largely unsatisfactory, particularly in non-viral cirrhosis. MELD recalibration and candidate variables for an update to the MELD score are proposed. LAY SUMMARY: While the discriminative performance of the model for end-stage liver disease (MELD) score is credited to be fair to good, its calibration, the correspondence of observed to predicted mortality, is still unsettled. We found that application of 3 different versions of the MELD in 2 independent cirrhosis cohorts yielded largely imprecise mortality predictions particularly in non-viral cirrhosis. Thus, we propose a recalibration and suggest candidate variables for an update to the model.

Self-expanding transcatheter aortic valve infolding: Current evidence, diagnosis, and management.

BACKGROUND: Prosthetic valve infolding is a rare but severe complication of transcatheter aortic valve implantation (TAVI) with self-expanding valves. However, currently available clinical data are limited and fragmented. OBJECTIVES: This report aims to provide a comprehensive overview of this complication focusing on predisposing factors, clinical presentation, diagnostic findings, treatment and clinical outcomes. METHODS: A systematic review of the literature was performed to identify cases of infolding occurring during TAVI with self-expanding valves published until August 2020. These data were pooled with all the retrospectively identified infolding cases occurred at San Raffaele Scientific Institute between December 2014 and August 2020. RESULTS: A total of 34 cases were included. Among patients with available data, 38% received a first-generation CoreValve, and 62% a second-generation Evolut R (82%) or Evolut PRO (18%). Infolding occurred mostly with ≥29-mm valves (94%). Predisposing factors included resheathing of a second-generation valve (82%), heavy calcification of the native valve (65%), lack of predilatation (16%), Sievers type-1 bicuspid aortic valve (11%), and improper valve loading (5%). Infolding resulted in severe PVL causing hemodynamic instability (29%) or cardiac arrest (12%). Postdilatation was the treatment strategy in 68%, while prosthesis replacement with a new device in 23% of cases. Device success rate was 82%. Death and stroke occurred in 3% and 12% of cases. CONCLUSIONS: Prosthetic valve infolding is typically observed after resheathing of a large-size self-expanding TAVI. When infolding is timely diagnosed, prosthesis removal and replacement should be pursued. Further studies are required to precisely define predisposing factors to prevent this complication.

Human amniotic stem cells improve hepatic microvascular dysfunction and portal hypertension in cirrhotic rats.

BACKGROUND AND AIMS: Portal hypertension is the main consequence of cirrhosis, responsible for the complications defining clinical decompensation. The only cure for decompensated cirrhosis is liver transplantation, but it is a limited resource and opens the possibility of regenerative therapy. We investigated the potential of primary human amniotic membrane-derived mesenchymal stromal (hAMSCs) and epithelial (hAECs) stem cells for the treatment of portal hypertension and decompensated cirrhosis. METHODS: In vitro: Primary liver sinusoidal endothelial cells (LSECs) and hepatic stellate cells (HSCs) from cirrhotic rats (chronic CCl4 inhalation) were co-cultured with hAMSCs, hAECs or vehicle for 24 hours, and their RNA profile was analysed. In vivo: CCl4-cirrhotic rats received 4x106 hAMSCs, 4x106 hAECs, or vehicle (NaCl 0.9%) (intraperitoneal). At 2-weeks we analysed: a) portal pressure (PP) and hepatic microvascular function; b) LSECs and HSCs phenotype; c) hepatic fibrosis and inflammation. RESULTS: In vitro experiments revealed sinusoidal cell phenotype amelioration when co-cultured with stem cells. Cirrhotic rats receiving stem cells, particularly hAMSCs, had significantly lower PP than vehicle-treated animals, together with improved liver microcirculatory function. This hemodynamic amelioration was associated with improvement in LSECs capillarization and HSCs de-activation, though hepatic collagen was not reduced. Rats that received amnion derived stem cells had markedly reduced hepatic inflammation and oxidative stress. Finally, liver function tests significantly improved in rats receiving hAMSCs. CONCLUSIONS: This preclinical study shows that infusion of human amniotic stem cells effectively decreases PP by ameliorating liver microcirculation, suggesting that it may represent a new treatment option for advanced cirrhosis with portal hypertension.

How can we optimise antifungal use in a solid organ transplant centre? Local epidemiology and antifungal stewardship implementation: A single-centre study.

PURPOSE: We aimed to implement and to assess the impact of the antifungal stewardship programme (AFSp) on prescription appropriateness of antifungals, management and outcomes of candidaemia patients, and antifungal consumption and costs at our solid organ transplant (SOT) institute. METHODS: Local epidemiology of invasive fungal infections (IFIs) from 2009 to 2017 was analysed in order to prepare an effective AFSp, implemented in January 2018. It included suspension of empirical antifungal prescriptions after 72 hours (antifungal time-out), automated alert and infectious disease (ID) consult for empirical prescriptions and for every patient with IFI, and indication for step-down to oral fluconazole when possible. We used process measures and results measures to assess the effects of the implemented programme. RESULTS: The ASFp led to significant improvements in selection of the appropriate antifungal (40.5% in pre-AFS vs 78.6% in post-AFS), correct dosing (51.2% vs 79.8%), correct length of treatment (55.9% vs 75%) and better management of patients with candidaemia. Analysis of prescribed empirical antifungal revealed that defined daily doses (DDDs) per 100 patient days decreased by 36.7% in 2018 compared to the average of pre-AFSp period, with important savings in costs. CONCLUSION: This AFSp led to a better use of antifungal drugs in terms of appropriateness and consumption, with stable clinical and microbiological outcomes in patients with IFI.

Radiation exposure during transjugular intrahepatic portosystemic shunt creation in patients with complete portal vein thrombosis or portal cavernoma.

BACKGROUND: This study aims to evaluate radiation exposure in patients with complete portal vein thrombosis (CPVT) or portal cavernoma (PC) undergoing transjugular intrahepatic portosystemic shunt (TIPS) creation using real-time ultrasound guidance for portal vein targeting. MATERIALS AND METHODS: This is a single institution retrospective analysis. Between August 2009 and September 2018, TIPS was attempted in 49 patients with CPVT or PC. Radiation exposure (dose area product [DAP], air KERMA (AK) and fluoroscopy time [FT]), technical success, clinical success, complications and survival were analyzed. RESULTS: In total, 29 patients had CPVT and 20 patients had PC. 41/49 patients had cirrhosis. TIPS indications were refractory ascites (n = 25), variceal bleeding (n = 16) and other (n = 8). TIPS was successfully placed in 94% (46/49) of patients via a transjugular approach alone (n = 40), a transjugular/transhepatic approach (n = 5) and a transjugular/transsplenic approach (n = 1). Median DAP was 261 Gy * cm2 (range 29-950), median AK was 0.2 Gy (range 0.05-0.5), and median FT was 28.2 min (range 7.7-93.7). Mean portosystemic pressure gradient decreased from 16.8  ±  5.1 mmHg to 7.5  ±  3.3 mmHg (P <  0.01). There were no major procedural complications. Overall clinical success was achieved in 77% of patients (mean follow-up of 21.1 months). Encephalopathy was observed in 16 patients (34%), grade II-III encephalopathy in 7 patients (15%). TIPS revision was performed in 15 patients (32%). Overall survival rate was 75%. CONCLUSION: In our experience, the use of real-time ultrasound guidance allowed the majority of the TIPS to be performed via a transjugular approach alone with a reasonably low radiation exposure considering the high technical difficulties of the selected cohort of patients with CVPT or PC.

Epidemiology and successful containment of a carbapenem-resistant Enterobacteriaceae outbreak in a Southern Italian Transplant Institute.

INTRODUCTION: Carbapenem-resistant enterobacteriaceae (CRE) infections are difficult to treat and pose a serious threat to solid organ transplant (SOT) recipients. At our institute we observed an infection burden in 2012. METHODS: In order to contain the spread of CRE infections, we established a taskforce to implement guidelines suggested by the Centers for Disease Control and Prevention (CDC) for this type of outbreak. Here, we describe the epidemiology of the outbreak in our SOT population, and the effectiveness of such interventions, by comparing levels of CRE hospital-acquired infection (HAI) pre- and post-task force intervention (from January 2009 to December 2012, and from September 2013 to December 2016, respectively) through a linear regression model. RESULTS: In this study, we included 933 patients who underwent a total of 1017 SOT procedures, 286 of whom had a CRE-positive culture (28.8%), of which 65 (22.7% of CRE positive) developed infection. One-year mortality post-SOT was significantly higher in patients with CRE infection. After the taskforce intervention, the CRE HAI rate in SOT showed a significant inverse trend (event rate: -1.28, CI -1.70 to 0.86; P < 0.01). CONCLUSION: In the paucity of treatment options, the application of CDC measures in our SOT institute contributed significantly to containing CRE infections.

Under-dilated TIPS Associate With Efficacy and Reduced Encephalopathy in a Prospective, Non-randomized Study of Patients With Cirrhosis.

BACKGROUND & AIMS: Portosystemic encephalopathy (PSE) is a major complication of trans-jugular intrahepatic porto-systemic shunt (TIPS) placement. Most devices are self-expandable polytetrafluoroethylene-covered stent grafts (PTFE-SGs) that are dilated to their nominal diameter (8 or 10 mm). We investigated whether PTFE-SGs dilated to a smaller caliber (under-dilated TIPS) reduce PSE yet maintain clinical and hemodynamic efficacy. We also studied whether under-dilated TIPS self-expand to nominal diameter over time. METHODS: We performed a prospective, non-randomized study of 42 unselected patients with cirrhosis who received under-dilated TIPS (7 and 6 mm) and 53 patients who received PTFE-SGs of 8 mm or more (controls) at referral centers in Italy. After completion of this study, dilation to 6 mm became the standard and 47 patients were included in a validation study. All patients were followed for 6 months; Doppler ultrasonography was performed 2 weeks and 3 months after TIPS placement and every 6 months thereafter. Stability of PTFE-SG diameter was evaluated by computed tomography analysis of 226 patients with cirrhosis whose stent grafts increased to 6, 7, 8, 9, or 10 mm. The primary outcomes were incidence of at least 1 episode of PSE grade 2 or higher during follow up, incidence of recurrent variceal hemorrhage or ascites, incidence of shunt dysfunction requiring TIPS recanalization, and reduction in porto-caval pressure gradient. RESULTS: PSE developed in a significantly lower proportion of patients with under-dilated TIPS (27%) than controls (54%) during the first year after the procedure (P = .015), but the proportions of patients with recurrent variceal hemorrhage or ascites did not differ significantly between groups. No TIPS occlusions were observed. These results were confirmed in the validation cohort. In an analysis of self-expansion of stent grafts, during a mean follow-up period of 252 days after placement, none of the PTFE-SGs self-expanded to the nominal diameter in hemodynamically relevant sites (such as portal and hepatic vein vascular walls). CONCLUSIONS: In prospective, non-randomized study of patients with cirrhosis, we found under-dilation of PTFE-SGs during TIPS placement to be feasible, associated with lower rates of PSE, and effective.

The addition of simvastatin administration to cold storage solution of explanted whole liver grafts for facing ischemia/reperfusion injury in an area with a low rate of deceased donation: a monocentric randomized controlled double-blinded phase 2 study.

BACKGROUND: Liver transplantation is the best treatment for end-stage liver disease. The interruption of the blood supply to the donor liver during cold storage damages the liver, affecting how well the liver will function after transplant. The drug Simvastatin may help to protect donor livers against this damage and improve outcomes for transplant recipients. The aim of this study is to evaluate the benefits of treating the donor liver with Simvastatin compared with the standard transplant procedure. PATIENT AND METHODS: We propose a prospective, double-blinded, randomized phase 2 study of 2 parallel groups of eligible adult patients. We will compare 3-month, 6-month, and 12-month graft survival after LT, in order to identify a significant relation between the two homogenous groups of LT patients. The two groups only differ by the Simvastatin or placebo administration regimen while following the same procedure, with identical surgical instruments, and medical and nursing skilled staff. To reach these goals, we determined that we needed to recruit 106 patients. This sample size achieves 90% power to detect a difference of 14.6% between the two groups survival using a one-sided binomial test. DISCUSSION: This trial is designed to confirm the effectiveness of Simvastatin to protect healthy and steatotic livers undergoing cold storage and warm reperfusion before transplantation and to evaluate if the addition of Simvastatin translates into improved graft outcomes. TRIAL REGISTRATION: ISRCTN27083228 .

Transjugular Intrahepatic Portosystemic Shunts in Patients with Cirrhosis with Refractory Ascites: Comparison of Clinical Outcomes by Using 8- and 10-mm PTFE-covered Stents.

Purpose To compare the efficacy and complications of transjugular intrahepatic portosystemic shunt (TIPS) creation performed by using a 10-mm or an 8-mm-diameter polytetrafluoroethylene (PTFE)-covered stent in a consecutive series of patients with cirrhosis with refractory ascites (RA). Materials and Methods The institutional review board approved this retrospective study and informed consent was waived. One hundred seventy-one patients with RA (mean age, 58.7 years ± 10.3; 95% confidence interval [CI]: 57.2 years, 60.3 years) had undergone TIPS placement by using 10-mm (60 patients) or 8-mm (111 patients) covered stent between January 2004 and December 2012. Median follow-up time was 16.8 months (range, 3.4-84.8 months). Hemodynamic changes, incidence of hepatic encephalopathy, and long-term (>3 months) need for paracentesis after TIPS placement were evaluated and calculated by using the Kaplan-Meier method and were compared by using the log-rank test. Results Pre-TIPS demographics and clinical characteristics of the two groups were comparable. The portosystemic gradient before TIPS was 17.0 mm Hg ± 4.2 (95% CI: 15.9 mm Hg, 18.1 mm Hg) in the 10-mm group versus 16.1 mm Hg ± 3.7 (95% CI: 15.4 mm Hg, 16.8 mm Hg) in the 8-mm group (P = .164). After TIPS, the portosystemic gradient was 6.5 mm Hg ± 3.4 (95% CI: 5.7 mm Hg, 7.4 mm Hg) in the 10-mm group versus 7.5 mm Hg ± 2.6 (95% CI: 6.9 mm Hg, 7.9 mm Hg) in the 8-mm group (P = .039). The long-term need for paracentesis was greater in the 8-mm group (64 of 111 patients [58%] vs 18 of 60 patients [31%], P = .003). Overall, hepatic encephalopathy was similar in both groups (45 of 111 patients [41%] vs 26 of 60 patients [44%], P = .728). Conclusion A10-mm PTFE-covered stent leads to better control of RA secondary to portal hypertension in patients with cirrhosis, compared with an 8-mm stent, without increasing the incidence of hepatic encephalopathy. © RSNA, 2017.

Radiation doses to operators performing transjugular intrahepatic portosystemic shunt using a flat-panel detector-based system and ultrasound guidance for portal vein targeting.

OBJECTIVES: The aim of this study was to prospectively evaluate effective dose (E) of operators performing transjugular intrahepatic portosystemic shunts (TIPS) in a single centre. Patients' radiation exposure was also collected. METHODS: Between 8/2015 and 6/2016, 45 consecutive TIPS were performed in adult patients using a flat-panel detector-based system (FPDS) and real-time ultrasound guidance (USG) for portal vein targeting. Electronic personal dosimeters were used to measure radiation doses to the primary and assistant operators, anaesthesia nurse and radiographer. Patients' radiation exposure was measured with dose area product (DAP); fluoroscopy time (FT) was also collected. RESULTS: Mean E for the primary operator was 1.40 µSv (SD 2.68, median 0.42, range 0.12 - 12.18), for the assistant operator was 1.29 µSv (SD 1.79, median 0.40, range 0.10 - 4.89), for the anaesthesia nurse was 0.21 µSv (SD 0.67, median 0.10, range 0.03 - 3.99), for the radiographer was 0.42 µSv (SD 0.71, median 0.25, range 0.03 - 2.67). Mean patient DAP was 59.31 GyCm2 (SD 56.91, median 31.58, range 7.66 - 281.40); mean FT was 10.20 min (SD 7.40, median 10.40, range 3.8 - 31.8). CONCLUSION: The use of FPDS and USG for portal vein targeting allows a reasonably low E to operators performing TIPS. KEY POINTS: • The operators' E vary according to the complexity of the procedure. • FPDS and USG allow a reasonably low E to TIPS operators. • FPDS and USG have an important role in reducing the occupational exposure.

Three-dimensional parametric modeling of bicuspid aortopathy and comparison with computational flow predictions.

Bicuspid aortic valve (BAV)-associated ascending aneurysmal aortopathy (namely "bicuspid aortopathy") is a heterogeneous disease making surgeon predictions particularly challenging. Computational flow analysis can be used to evaluate the BAV-related hemodynamic disturbances, which likely lead to aneurysm enlargement and progression. However, the anatomic reconstruction process is time consuming so that predicting hemodynamic and structural evolution by computational modeling is unfeasible in routine clinical practice. The aim of the study was to design and develop a parametric program for three-dimensional (3D) representations of aneurysmal aorta and different BAV phenotypes starting from several measures derived by computed-tomography angiography (CTA). Assuming that wall shear stress (WSS) has an important implication on bicuspid aortopathy, computational flow analyses were then performed to estimate how different would such an important parameter be, if a parametric aortic geometry was used as compared to standard geometric reconstructions obtained by CTA scans. Morphologic parameters here documented can be used to rapidly model the aorta and any phenotypes of BAV. t-test and Bland-Altman plot demonstrated that WSS obtained by flow analysis of parametric aortic geometries was in good agreement with that obtained from the flow analysis of CTA-related geometries. The proposed program offers a rapid and automated tool for 3D anatomic representations of bicuspid aortopathy with promising application in routine clinical practice by reducing the amount of time for anatomic reconstructions.

Sorafenib or placebo plus TACE with doxorubicin-eluting beads for intermediate stage HCC: The SPACE trial.

BACKGROUND & AIMS: Transarterial chemoembolization with doxorubicin-eluting beads (DC Bead®; DEB-TACE) is effective in patients with Barcelona clinic liver cancer stage B hepatocellular carcinoma (HCC). The multikinase inhibitor sorafenib enhances overall survival (OS) and time-to-tumor progression (TTP) in patients with advanced HCC. This exploratory phase II trial tested the efficacy and safety of DEB-TACE plus sorafenib in patients with intermediate stage HCC. METHODS: Patients with intermediate stage multinodular HCC without macrovascular invasion (MVI) or extrahepatic spread (EHS) were randomized 1:1 to DEB-TACE (150 mg doxorubicin) plus sorafenib 400 mg twice daily or placebo. The primary endpoint was TTP by blinded central review. Secondary endpoints included time to MVI/EHS, OS, overall response rate (ORR) using modified response evaluation criteria in solid tumors, disease control rate (DCR), time to unTACEable progression (TTUP), and safety. RESULTS: Of 307 patients randomized, 154 received sorafenib and 153 received placebo. Median TTP for subjects receiving sorafenib plus DEB-TACE or placebo plus DEB-TACE was similar (169 vs. 166 days, respectively; hazard ratio (HR) 0.797, p=0.072). Median time to MVI/EHS (HR 0.621, p=0.076) and OS (HR 0.898, p=0.29) had not been reached. The ORRs for patients in the sorafenib and placebo groups with post-baseline scans were 55.9% and 41.3%, respectively, and the DCRs were 89.2% and 76.1%, respectively. TTUP was lower with sorafenib than with placebo (HR 1.586; 95% confidence intervals, 1.200-2.096; median 95 vs. 224 days). No unexpected adverse events related to sorafenib were observed. CONCLUSION: Sorafenib plus DEB-TACE was technically feasible, but the combination did not improve TTP in a clinically meaningful manner compared with DEB-TACE alone.

Early Liver Failure after Transjugular Intrahepatic Portosystemic Shunt in Patients with Cirrhosis with Model for End-Stage Liver Disease Score of 12 or Less: Incidence, Outcome, and Prognostic Factors.

Purpose To evaluate the incidence, outcomes, and prognostic factors of early liver failure (ELF) after transjugular intrahepatic portosystemic shunt (TIPS) creation in patients with cirrhosis with Model for End-Stage Liver Disease (MELD) score of 12 or less. Materials and Methods Institutional review board approved this retrospective study, with waiver of written informed consent. Two-hundred sixteen consecutive patients with cirrhosis (140 men, 76 women; mean age, 55.9 years; virus-related cirrhosis, 67.6% [146 of 216 patients]) with baseline MELD score of 12 or less who underwent TIPS placement between September 1999 and July 2012 were followed until last clinical evaluation, liver transplantation, or death. The Kaplan-Meier method, log-rank test, area under the receiver operating characteristic curve, and univariate and multivariate analyses were used, as appropriate. Results Twenty of 216 patients (9.2%) developed ELF within 3 months of TIPS (10 patients died, one required liver transplantation, and nine increased the MELD score to >18). ELF was associated with lower survival, 37% versus 95% at 6 months, and 24% versus 86% at 12 months (P < .001) compared with patients without ELF. ELF occurred in 16 of 95 (16.8%) patients with refractory ascites and in four of 121 (3.3%) patients with other indications for TIPS. Multivariate analysis confirmed MELD scores of 11 or 12 (odds ratio, 3.96 [95% confidence interval: 1.07, 14.67]; P = .040), decreased hemoglobin level (odds ratio, 0.68 [95% confidence interval: 0.49, 0.95]; P = .022), and decreased platelet count (odds ratio, 0.99 [95% confidence interval: 0.99, 0.99]; P = .024) as predictors for ELF in patients with refractory ascites. Conclusion ELF is not uncommon in cirrhotic patients with a MELD score of 12 or less who undergo TIPS placement for refractory ascites (especially in patients with MELD of 11 or 12) and decreased hemoglobin level and platelet count. (©) RSNA, 2016.