Drop-out rate from the liver transplant waiting list due to HCC progression in HCV-infected patients treated with direct acting antivirals.

BACKGROUND & AIM: concerns about an increased hepatocellular carcinoma (HCC) recurrence rate following directly acting antiviral (DAA) therapy in cirrhotic patients with a prior complete oncological response have been raised. Data regarding the impact of HCV-treatment with DAAs on waiting list drop-out rates in patients with active HCC and HCV-related cirrhosis awaiting liver transplantation (LT) are lacking. MATERIALS AND METHODS: HCV-HCC patients listed for LT between January 2015 and May 2016 at Padua Liver Transplant Centre were considered eligible for the study. After enrollment patients were divided into 2 groups, depending on whether they underwent DAAs treatment while awaiting LT or not. For each patient clinical, serological and virological data were collected. HCC characteristics were radiologically evaluated at baseline and during follow-up (FU). For transplanted patients, pathological assessment of the explants was performed and recurrence-rates were calculated. RESULTS: twenty-three patients treated with DAAs and 23 controls were enrolled. HCC characteristics at time of LT-listing were comparable between the 2 groups. Median FU was 10 and 7 months, respectively, during which 2/23 (8.7%) and 1/23 (4.3%) drop-out events due to HCC-progression were registered (p = 0.9). No significant differences in terms of radiological progression were highlighted (p = 0.16). Nine out of 23 cases (39%) and 14/23 (61%) controls underwent LT, and histopathological analysis showed no differences in terms of median number and total tumor volume of HCC nodules, tumor differentiation or microvascular invasion. During post-LT FU, 1/8 DAAs treated patient (12,5%) and 1/12 control (8,3%) experienced HCC recurrence (p = 0.6). CONCLUSIONS: Viral eradication does not seem to be associated with an increased risk of drop-out due to neoplastic progression in HCV-HCC patients awaiting LT

Medical Radiology: Current Progress

Recently, medical radiology has undergone significant improvements in patient management due to advancements in image acquisition by the last generation of machines, data processing, and the integration of artificial intelligence. In this way, cardiovascular imaging is one of the fastest-growing radiological subspecialties. In this study, a compressive review was focused on addressing how and why CT and MR have gained a I class indication in most cardiovascular diseases, and the potential impact of tissue and functional characterization by CT photon counting, quantitative MR mapping, and 4-D flow. Regarding rectal imaging, advances in cancer imaging using diffusion-weighted MRI sequences for identifying residual disease after neoadjuvant chemoradiotherapy and [18F] FDG PET/MRI were provided for high-resolution anatomical and functional data in oncological patients. The results present a large overview of the approach to the imaging of diffuse and focal liver diseases by US elastography, contrast-enhanced US, quantitative MRI, and CT for patient risk stratification. Italy is currently riding the wave of these improvements. The development of large networks will be crucial to create high-quality databases for patient-centered precision medicine using artificial intelligence. Dedicated radiologists with specific training and a close relationship with the referring clinicians will be essential human factors

The dolphin proline-rich antimicrobial peptide Tur1A inhibits protein synthesis by targeting the bacterial ribosome

Proline-rich antimicrobial peptides (PrAMPs) internalize into susceptible bacteria using specific transporters and interfere with protein synthesis and folding. To date, mammalian PrAMPs have so far only been identified in artiodactyls. Since cetaceans are co-phyletic with artiodactyls, we mined the genome of the bottlenose dolphin Tursiops truncates, leading to the identification of two PrAMPs, Tur1A and Tur1B. Tur1A, which is orthologous to the bovine PrAMP Bac7, is internalized into E. coli without damaging the membranes using the inner membrane transporters SbmA and YjiL/MdM. Furthermore, like Bac7, Tur1A also inhibits bacterial protein synthesis by binding to the ribosome and blocking the transition from the initiation to the elongation phase. By contrast, Tur1B is a poor inhibitor of protein synthesis and may utilize another mechanism of action. An X-ray structure of Tur1A bound within the ribosomal exit tunnel provides a basis to develop these peptides as novel antimicrobial agents

Platelets and hepatocellular cancer: Bridging the bench to the clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells\u2019 extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet\u2013tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC

Platelets and Hepatocellular Cancer: Bridging the Bench to the Clinics

Growing interest is recently being focused on the role played by the platelets in favoring hepatocellular cancer (HCC) growth and dissemination. The present review reports in detail both the experimental and clinical evidence published on this topic. Several growth factors and angiogenic molecules specifically secreted by platelets are directly connected with tumor progression and neo-angiogenesis. Among them, we can list the platelet-derived growth factor, the vascular endothelial growth factor, the endothelial growth factor, and serotonin. Platelets are also involved in tumor spread, favoring endothelium permeabilization and tumor cells' extravasation and survival in the bloodstream. From the bench to the clinics, all of these aspects were also investigated in clinical series, showing an evident correlation between platelet count and size of HCC, tumor biological behavior, metastatic spread, and overall survival rates. Moreover, a better understanding of the mechanisms involved in the platelet-tumor axis represents a paramount aspect for optimizing both current tumor treatment and development of new therapeutic strategies against HCC

Overview of prognostic systems for hepatocellular carcinoma and ITA.LI.CA external validation of MESH and CNLC classifications

Prognostic assessment in patients with HCC remains an extremely difficult clinical task due to the complexity of this cancer where tumour characteristics interact with degree of liver dysfunction, patient general health status, and a large span of available treatment options. Several prognostic systems have been proposed in the last three decades, both from the Asian and European/North American countries. Prognostic scores, such as the CLIP score and the recent MESH score, have been generated on a solid statistical basis from real life population data, while staging systems, such as the BCLC scheme and the recent CNLC classification, have been created by experts according to recent HCC prognostic evidences from the literature. A third category includes combined prognostic systems that can be used both as prognostic scores and staging systems. A recent example is the ITA.LI.CA prognostic system including either a prognostic score and a simplified staging system. This review focuses first on an overview of the main prognostic systems for HCC classified according to the above three categories, and, second, on a comprehensive description of the methodology required for a correct comparison between different systems in terms of prognostic performance. In this second section the main studies in the literature comparing different prognostic systems are described in detail. Lastly, a formal comparison between the last prognostic systems proposed for each of the above three categories is performed using a large Italian database including 6882 HCC patients in order to concretely apply the comparison rules previously described

Nash Up, Virus Down: How the Waiting List Is Changing for Liver Transplantation: A Single Center Experience from Italy

Background and Objectives: Non‐alcoholic steatohepatitis (NASH) has become the leading indication for liver transplantation in many countries, with a growing rate in the Western world. NASH patients are older and share a higher risk of comorbidities and cancer than patients with viral and/or alcoholic etiologies. The aims of this study were to evaluate waiting list (WL) registration and liver transplantation rates in patients with NASH‐related cirrhosis at Padua University Hospital in the last fifteen years (1.2006–6.2020) and to compare clinical characteristics and indications for liver transplantation between patients with and without NASH, as well as the WL survival and post‐transplant outcome. Materials and Methods: All adult patients with cirrhosis listed for liver transplantation at Padua University Hospital between 1.2006 and 6.2020 were retrospectively col-lected using a prospectively updated database; patients with NASH‐related cirrhosis were divided by indication for liver transplantation (Dec‐NASH vs. hepatocellular carcinoma (HCC)‐NASH) and compared with patients with other etiologies of liver disease. The outcomes in terms of waiting list survival and post‐transplant outcome were assessed. Results: One thousand four hundred and ninety‐one adult cirrhotic patients were waitlisted during the study period. NASH patients ac-counted for 12% of all WL registrations, showing an increasing trend over time (from 2.5% in 2006 to 23% in 2020). In the last five years, NASH was the third, but most rapidly growing, indication for liver transplantation at our center. This trend was confirmed both for patients with decompensated cirrhosis (from 1.8% to 18%) and HCC as leading indication for transplantation (from 4% to 30%). NASH patients were older than non‐NASH ones (mean ± SD age 59 ± 9 vs. 56 ± 9 years; p < 0.01), whereas no difference was found in gender or Child‐Pugh of the model for end‐stage liver disease score at WL registration. A majority (60.9%) of NASH patients underwent liver transplantation, showing 1‐, 5‐ and 10‐y post‐transplant survivals of 86%, 73% and 60%, respectively. Conclusion: NASH cirrhosis has become a rapidly growing indication for liver transplantation at our center, both for HCC and decompensated disease, with good post‐transplant survival

DeCO - Guidelines for the deconstruction of recent buildings

The project "DeCO - Guidelines for the Deconstruction of recent buildings" developed standardized procedures (guidelines) for the deconstruction of recent and contemporary buildings. DeCO associated a Deconstruction Worksheet with each reference construction package, covering contemporary construction techniques almost entirely. End-of-life worksheets of the most common insulating materials complete this documentation. The authors developed practical procedures that can be used directly on site and may represent a direct and rapid impact in increasing construction material recycling and reuse rates within the perspective of Circular Economy models in the Construction sector thus reducing waste disposal. The project highlighted that deconstruction practices are more labour intensive than conventional mechanical demolition activities thus can cause an increase in estimated demolition costs while on the other hand a systematic disassembly could decrease costs and volumes of landfilling mineral CDW and can be a first step in increasing construction material recycling and reuse rates, within the perspective of Circular Economy models in the Construction sector