0000000000133276
AUTHOR
Massimo Rossi
The Intention-to-Treat Effect of Bridging Treatments in the Setting of Milan Criteria–In Patients Waiting for Liver Transplantation
In patients with hepatocellular carcinoma (HCC) meeting the Milan criteria (MC), the benefit of locoregional therapies (LRTs) in the context of liver transplantation (LT) is still debated. Initial biases in the selection between treated and untreated patients have yielded conflicting reported results. The study aimed to identify, using a competing risk analysis, risk factors for HCC-dependent LT failure, defined as pretransplant tumor-related delisting or posttransplant recurrence. The study was registered at www.clinicaltrials.gov (identification number NCT03723304). In order to offset the initial limitations of the investigated population, an inverse probability of treatment weighting (IP…
Human OX40 tunes the function of regulatory T cells in tumor and nontumor areas of hepatitis C virus-infected liver tissue.
International audience; Regulatory T cells (Tregs) can be considered as a mixed population of distinct subsets, endowed with a diverse extent and quality of adaptation to microenvironmental signals. Here, we uncovered an opposite distribution of Treg expansion, phenotype, and plasticity in different microenvironments in the same organ (liver) derived from patients with chronic hepatitis C: On the one side, cirrhotic and tumor fragments were moderately and highly infiltrated by Tregs, respectively, expressing OX40 and a T-bet high IFN-c – " T-helper (Th)1-suppressing " phenotype; on the other side, noncirrhotic liver specimens contained low frequencies of Tregs that expressed low levels of O…
An integrated geodetic and InSAR technique for the monitoring and detection of active faulting in southwestern Sicily
We present the results of the analysis of GNSS (Global Navigation Satellite System) and InSAR (Interferometric synthetic-aperture radar) data collected in the frame of a project financed by the “Struttura Terremoti” of INGV (Istituto Nazionale di Geofisica e Vulcanologia). Combined investigations pointed out for potential seismogenic sources for destructive earthquakes recorded in southwestern Sicily, including the 1968 Belice earthquake sequence and that supposed to have destroyed the Greek city of Selinunte which, according to geoarcheological data experienced two earthquakes in historical times. Our approach is aimed to evaluate the current deformation rate in SW Sicily and to improve th…
Renal Function at Two Years in Liver Transplant Patients Receiving Everolimus: Results of a Randomized, Multicenter Study
In a 24-month prospective, randomized, multicenter, open-label study, de novo liver transplant patients were randomized at 30 days to everolimus (EVR) + Reduced tacrolimus (TAC; n = 245), TAC Control (n = 243) or TAC Elimination (n = 231). Randomization to TAC Elimination was stopped prematurely due to a significantly higher rate of treated biopsy-proven acute rejection (tBPAR). The incidence of the primary efficacy endpoint, composite efficacy failure rate of tBPAR, graft loss or death postrandomization was similar with EVR + Reduced TAC (10.3%) or TAC Control (12.5%) at month 24 (difference -2.2%, 97.5% confidence interval [CI] -8.8%, 4.4%). BPAR was less frequent in the EVR + Reduced TAC…
Improved Survival in Liver Transplant Patients Receiving Prolonged-release Tacrolimus-based Immunosuppression in the European Liver Transplant Registry (ELTR): An Extension Study
BACKGROUND: We compared, through the European Liver Transplant Registry, long-term liver transplantation outcomes with prolonged-release tacrolimus (PR-T) versus immediate-release tacrolimus (IR-T)-based immunosuppression. This retrospective analysis comprises up to 8-year data collected between 2008 and 2016, in an extension of our previously published study. METHODS: Patients with <1 month follow-up were excluded; patients were propensity score matched for baseline characteristics. Efficacy measures included: univariate/multivariate analyses of risk factors influencing graft/patient survival up to 8 years posttransplantation, and graft/patient survival up to 4 years with PR-T versus IR-T.…
Reduction of hospitalizations for myocardial infarction in Italy in the COVID-19 era
Abstract Aims To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P &lt; 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P …
12-month follow-up analysis of a multicenter, randomized, prospective trial in de novo liver transplant recipients (LIS2T) comparing cyclosporine microemulsion (C2 monitoring) and tacrolimus.
The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C–positive pati…
Charting the Path Forward for Risk Prediction in Liver Transplant for Hepatocellular Carcinoma: International Validation of HALTHCC Among 4,089 Patients.
Prognosticating outcomes in liver transplant (LT) for hepatocellular carcinoma (HCC) continues to challenge the field. Although Milan Criteria (MC) generalized the practice of LT for HCC and improved outcomes, its predictive character has degraded with increasing candidate and oncological heterogeneity. We sought to validate and recalibrate a previously developed, preoperatively calculated, continuous risk score, the Hazard Associated with Liver Transplantation for Hepatocellular Carcinoma (HALTHCC), in an international cohort. From 2002 to 2014, 4,089 patients (both MC in and out [25.2%]) across 16 centers in North America, Europe, and Asia were included. A continuous risk score using pre-…
An Intention-to-Treat Competing-Risk Model for Candidates with Hepatocellular Cancer Awaiting Liver Transplantation
Background: Since the introduction of the Milan Criteria (MC), all systems, which describe post-transplant prognosis of patients with hepatocellular cancer (HCC), are exclusively based on characteristics available at surgery, and neglect the intention-to-treat principles. This study, based on a large international HCC patient cohort, aimed to develop comprehensive intention-to-treat models through a competing-risk analysis. We used data available at first referral to predict the risk of delisting and HCC-related death after liver transplantation (LT). Methods: Twelve centres in the United States, Europe and Asia created a Derivation Set (n=2,318) and an external Validation Set (n=773) of …
Use of CORS Time Series for Geodynamics Applications in Western Sicily (Italy)
In the last few decades, the use of GNSS Continuously Operating Reference Station (CORS) networks allowed improving the accuracy of real-time positioning and post-processing positioning. In this way, several applications have been performed including remote sensing, agriculture, cultural heritage and geodynamics studies. The latter have been developed analysing CORS time-series and consistent data over long periods were needed to validate the results. In Italy, specifically in Sicily, two CORS networks were be used to monitor the geodynamics motions: the Istituto Nazionale di Geofisica e Vulcanologia (INGV) GNSS CORS network in the eastern part and the University of Palermo (UNIPA) GNSS COR…
Alpha-fetoprotein and modified response evaluation criteria in Solid Tumors progression after locoregional therapy as predictors of hepatocellular cancer recurrence and death after transplantation
Locoregional therapy (LRT) is being increasingly used for the management of hepatocellular cancer (HCC) in patients listed for liver transplantation (LT). Although several selection criteria have been developed, stratifications of survival according to the pathology of explanted livers and pre-LT LRT are lacking. Radiological progression according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST) and alpha-fetoprotein (AFP) behavior was reviewed for 306 patients within the Milan criteria (MC-IN) and 116 patients outside the Milan criteria (MC-OUT) who underwent LRT and LT between January 1999 and March 2010. A prospectively collected database originating from 6 collabor…
Dynamic α-Fetoprotein Response and Outcomes After Liver Transplant for Hepatocellular Carcinoma.
IMPORTANCE: Accurate preoperative prediction of hepatocellular carcinoma (HCC) recurrence after liver transplant is the mainstay of selection tools used by transplant-governing bodies to discern candidacy for patients with HCC. Although progress has been made, few tools incorporate objective measures of tumor biological characteristics, resulting in inclusion of patients with high recurrence rates and exclusion of others who could otherwise be cured. OBJECTIVE: To externally validate the New York/California (NYCA) score, a recently published multi-institutional US HCC selection tool that was the first model incorporating a dynamic α-fetoprotein response (AFP-R) and compare the validated sco…
Efficiency of transgenesis using sperm-mediated gene transfer: generation of hDAF transgenic pigs.
SINCE the beginning of this century, replacement of failing human organs with their animal counterparts has been an interesting topic of debate for writers and scientists. In the 1960s, prolonged survival after kidney transplantation from chimpanzee to human was obtained in the United States and Europe. Nevertheless, both the progressive improvement in surgical technique and in immunosuppressant therapy and the availability of cadaveric organs and living donation have reduced the interest in xenotransplantation. Because of the increasing requests for organs and the lack of donors to meet that need, xenotransplantation has become a reliable option again for temporary organ replacement (eg, o…
Recurrence of hepatocellular carcinoma after direct acting antiviral treatment for hepatitis C virus infection: Literature review and risk analysis
Although studies suggest decreased incident hepatocellular carcinoma (HCC) after treatment with direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection, data are conflicting regarding risk and aggressiveness of recurrence in patients who have a history of treated HCC. This review analyses data available in literature in order to elucidate the impact of DAAs on the risk of HCC recurrence after successful treatment of the tumor. Overall 24 papers were identified. The available data cannot be considered definitive, but the initial alarmist data indicating an increased risk of recurrence have not been confirmed by most subsequent studies. The suggested aggressive pattern (rapid gr…
Liver transplantation for severe alcoholic hepatitis: A multicenter Italian study
There is increasing evidence that early liver transplantation (eLT), performed within standardized protocols can improve survival in severe alcoholic hepatitis (sAH). The aim of the study was to assess outcomes after eLT for sAH in four Italian LT centers and to compare them with non-responders to medical therapy excluded from eLT. Patients admitted for sAH (2013–2019), according to NIAAA criteria, were included. Patients not responding to medical therapy were placed on the waiting list for eLT after a strict selection. Histological features of explanted livers were evaluated. Posttransplant survival and alcohol relapse were evaluated. Ninety-three patients with severe AH were evaluated (65…
Machine Perfusions in Liver Transplantation: The Evidence‐Based Position Paper of the Italian Society of Organ and Tissue Transplantation
The use of machine perfusion (MP) in liver transplantation (LT) is spreading worldwide. However, its efficacy has not been demonstrated, and its proper clinical use has far to go to be widely implemented. The Società Italiana Trapianti d’Organo (SITO) promoted the development of an evidence-based position paper. A 3-step approach has been adopted to develop this position paper. First, SITO appointed a chair and a cochair who then assembled a working group with specific experience of MP in LT. The Guideline Development Group framed the clinical questions into a patient, intervention, control, and outcome (PICO) format, extracted and analyzed the available literature, ranked the quality of th…
hDAF expression in hearts of transgenic pigs obtained by sperm-mediated gene transfer.
TRANSPLANTATON has been the choice option to treat successfully an increasing number of acute and chronic human pathologies with declining morbidity and mortality. However, availability of organs from human donors is limited and dramatically inadequate with respect to patient requests. Xenotransplantation from large-sized mammals has thus been reconsidered as a tool to overcome the present unbalance between organ offers and requests. Pigs have been chosen because they can be easily and cheaply bred; they do not raise ethical questions—their use as alimentary resources is generally admitted; and they possess organs largely human compatible for size, anatomical organization, and physiology. N…