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We report on the 2019 XMM-Newton+NuSTAR monitoring campaign of the Seyfert galaxy NGC 2992, observed at one of its highest flux levels in the X-rays. The time-averaged spectra of the two XMM-Newton orbits show Ultra Fast Outflows (UFOs) absorbing structures above 9 keV with $> 3 \sigma$ significance. A detailed investigation of the temporal evolution on a $\sim$5 ks time scale reveals UFO absorption lines at a confidence level $>$95% (2$\sigma$) in 8 out of 50 XMM-Newton segments, estimated via Monte Carlo simulations. We observe a wind variability corresponding to a length scale of 5 Schwarzschild radii $r_S$. Adopting the novel Wind in the Ionised Nuclear Environment (WINE) model, we estimate the outflowing gas velocity ($v=0.21-0.45 c$), column density ($N_H=4-8\cdot 10^{24} cm^{-2}$) and ionisation state ($\log(\xi_0/erg\ cm\ s^{-1})=3.7-4.7$), taking into account geometrical and special relativity corrections. These parameters lead to instantaneous mass outflow rates $\dot{M}_{out}\simeq0.3-0.8 M_{\odot} yr^{-1}$, with associated outflow momentum rates $\dot{p}_{out}\simeq 20-90 L_{Bol}/c$ and kinetic energy rates $\dot{E}_K \simeq 2-25 L_{Bol}$. We estimate a wind duty cycle $\approx$ 12% and a total mechanical power $\approx$ 2 times the AGN bolometric luminosity, suggesting the wind may drive significant feedback effects between the AGN and the host galaxy. Notably, we also provide an estimate for the wind launching radius and density $\approx 5 r_S, 10^{11} {cm}^{-3}$, respectively., Comment: Accepted for publication in the Astrophysical Journal. 21 pages, 11 figures

Aim: The purpose of this study is to assess the benefit of laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) given recurrence and future need for liver transplantation (LT). Methods: Data on liver resections were gathered from the Istituto di Ricovero e Cura a Carattere Scientifico-Istituto Mediterraneo per i Trapianti e Terapie ad alta specializzazione (IRCCS-ISMETT) from 2003-2021. A retrospective analysis of 1408 consecutive adult patients who had a liver resection was performed with categorization based on the underlying disease process. A sub-analysis studied the 291 patients who had an LLR with an intention to transplant approach after LLR. Results: From 2012 to 2020, ISMETT’s mean annual LLR rate was 45%. Data suggests that a laparoscopic approach to iterative surgical treatment for HCC has demonstrated protective benefits. Compared to open surgery or LT, LLR is protective against the risk of de-listing, post-transplant patient death, tumor recurrence, adhesions, and bleeding in a cirrhotic patient. Kaplan Meier’s analysis showed no difference between post-LT survival curves for those with prior open abdominal surgery or LLR (P = 0.658). Conclusion: Laparoscopic surgery has important protective advantages over laparotomy surgery for the surgical treatment of HCC, particularly since treatment is not always curative. LLR can be considered a bridge therapy for transplantation, ensuring less crowding of waiting lists, a desirable condition in areas of donor storage.

Simple Summary Intrahepatic cholangiocarcinoma is a rare disease with increasing incidence and mortality still characterized by an insufficient clinical outcome. Growing attention has recently surrounded this disease, and liver transplantation has emerged as a novel curative treatment for cholangiocarcinoma, along with a better understanding of genetic alterations potentially capable of driving tumorigenesis. The aim of this paper is to present a clinical description of our case series of patients affected by intrahepatic cholangiocarcinoma and by mixed forms of hepatocellular and cholangiocellular carcinoma, together with a genomic profiling of mutations occurring in a panel of genes relevant to solid tumor cancer investigations. Mutations were observed in genes activating signaling pathways known to be involved in intrahepatic cholangiocarcinoma tumorigenesis; a strong association was observed between mutation in genes involving the Notch signaling pathway and tumor size (point-biserial rhopb = 0.93). Abstract Intrahepatic cholangiocarcinoma (iCCA) is a rare and aggressive primary liver tumor, characterized by a range of different clinical manifestations and by increasing incidence and mortality rates even after curative treatment with radical resection. In recent years, growing attention has been devoted to this disease and some evidence supports liver transplantation (LT) as an appropriate treatment for intrahepatic cholangiocarcinoma; evolving work has also provided a framework for better understanding the genetic basis of this cancer. The aim of this study was to provide a clinical description of our series of patients complemented with Next-Generation Sequencing genomic profiling. From 1999 to 2021, 12 patients who underwent LT with either iCCA or a combined hepatocellular and cholangiocellular carcinoma (HCC-iCCA) were included in this study. Mutations were observed in gene activating signaling pathways known to be involved with iCCA tumorigenesis (KRAS/MAPK, P53, PI3K-Akt/mTOR, cAMP, WNT, epigenetic regulation and chromatin remodeling). Among several others, a strong association was observed between the Notch pathway and tumor size (point-biserial rhopb = 0.93). Our results are suggestive of the benefit potentially derived from molecular analysis to improve our diagnostic capabilities and to devise new treatment protocols, and eventually ameliorate long-term survival of patients affected by iCCA or HCC-iCCA.

High mass X-ray binaries accrete via the stellar wind of their supermassive companion. The stellar wind does not appear as a smooth flow, but it shows strongly dense and highly perturbed regions or clumps. As these clumps cross our line of sight, part of the X-ray emission is absorbed, leading to dipping events in the light curves. We performed an analysis of the long XMM Newton monitoring of the black hole binary Cyg X-1/HDE 226868 during its hard state. This monitoring is part of the CHOCBOX (Cyg X-1 Hard state Observations of a Complete Binary Orbit in X-rays) campaign. In this talk, I will present the latest results on the effects of the stellar wind on the spectral-timing properties of Cyg X-1 for more than one and a half orbital periods. In particular, I will show how its properties change significantly as a function of the orbital phase, due to the orbital variability of wind absorption.

The use of expanded criteria donors is one of the strategies used to overcome the gap between the demand for organs and the number of donors. Physicians debate the extent to which marginal grafts can be used. In recent years, normothermic machine perfusion (NMP) has been used to test liver viability before transplantation. Grafts underwent NMP whenever histological steatosis was > 40% or there were at least three Eurotransplant criteria for expanded criteria donor (ECD). We used NMP to test 19 grafts, 3 from donation after type 3 controlled cardiac death (DCD), and 16 from donation after brain death (DBD). Only two grafts from DBD were not transplanted, because perfusion proved they were not suitable (total of 17 transplanted grafts of 19 tested grafts). Kaplan–Meier survival estimates at 30, 90, 180, and 1year after transplant were all 94% (95% CI 84–100%); estimated 3-years survival was 82% (95% CI 62–100%). Overall survival rates did not differ from those of patients transplanted with non-perfused grafts from an ECD. In our experience, the use of very marginal grafts preventively tested by NMP does not negatively influence the patient’s outcome, and increases the number of transplants in low donation areas.

We report the first detection of a Fe K$_{\alpha}$ line and soft X-ray lag in the ultraluminous X-ray source (ULX) NGC 7456 ULX-1. The XMM-Newton spectra show the presence of the 6.4 keV Fe line at 2.6$\sigma$ confidence and an upper limit on the FWHM of 32900 km s$^{-1}$. Assuming that the line arises by reflection from a Keplerian disk, it must originate beyond $85 r_{\rm g}$ from the compact object. As a result of Fourier timing analysis we found that the soft X-ray photons lag behind the hard X-ray photons with a $\sim$1300 s delay. The covariance spectra indicate that the hard spectral component is responsible for the correlated variability and the soft X-ray lag. This is the second ULX in which a Fe K$_{\alpha}$ line is found, the fifth with a soft X-ray lag, and the first with both features detected., Comment: 5 pages, 8 figures, accepted for publication in MNRAS Letters

Background: Liver resection (LR) remains the best therapeutic option for patients with early-stage hepatocellular carcinoma (HCC) with preserved hepatic function and who are not eligible for liver transplantation. After its inception, the enhanced recovery after surgery (ERAS) protocol was widely used for treating patients with liver cancer, although there are still no clear indications for improving upon it in both open and laparoscopic surgery. Objective: This study aims to describe our institute's experience in the application of the ERAS protocol in a cohort of HCC patients, and to explore possible factors that could have an impact on postoperative outcomes. Materials and Methods: We retrospectively analyzed our experience with LR performed from September 2017 to January 2020 in patients treated with ERAS protocol, focusing on describing impact on postoperative nutrition, analgesic requirements, and length of hospitalization. Demographics, operative factors, and postoperative complications of patients were reviewed. Results: During the study period, 89 HCC patients were eligible for LR, and 75% of patients presented with liver cirrhosis. The most prevalent among etiologic factors was hepatitis C virus infection (53 patients out of 89, 60%), followed by nonalcoholic steatohepatitis (18 patients, 20%). The median age was 70 years. Liver cirrhosis did not have an impact on postoperative course of patients. Patients who underwent laparoscopic surgery and nonanatomic LR experienced low complication rates, shorter length of stay, and shorter time of intravenous analgesic requirements. Conclusions: Continual refinement with ERAS protocol for treating HCC patients based on perioperative counseling and surgical decision-making is crucial to guarantee low complication rates, and reduce patient morbidity and time for recovery.

In this paper we describe the potential of the enhanced X-ray Timing and Polarimetry (eXTP) mission for studies related to accretion flows in the strong field gravity regime around both stellar-mass and supermassive black-holes. eXTP has the unique capability of using advanced “spectral-timing-polarimetry” techniques to analyze the rapid variations with three orthogonal diagnostics of the flow and its geometry, yielding unprecedented insight into the inner accreting regions, the effects of strong field gravity on the material within them and the powerful outflows which are driven by the accretion process. X-spinmeasurements.

Background The ability to predict which recipients will successfully complete their posttransplant clinical course, which is crucial for liver transplant (LT) programs. The assessment of natural killer (NK) cell subset determined by flow cytometry from a monocentric series of consecutive liver perfusates could help identify risk factors portending adverse LT outcomes. Methods Liver perfusates were collected during the back-table surgical time after the procurement procedures for donors after brain death. Lymphocytic concentrations and phenotypes were matched with donors after brain death characteristics and indications, timing, surgical techniques, outcomes, and biopsy-proven acute cellular rejections (ACRs) in 46 adult recipients who underwent LT between 2010 and 2014 at our institute. Cox regression models were used to study relevant risk factors in order to estimate hazard ratios for episodes of rejection after LT. Results Percentage of NK cells was significantly associated with donor age (P = 0.05) and the percentage of NK T cellular subset (P = 0.001). The length of follow-up after LT was 41.0 ± 20.9 months, and 11 (23.9%) recipients experienced biopsy-proven ACR. At time-to-rejection proportional regression analysis, a cutoff value of 33.7% was optimal, with a sensitivity of 1, specificity of 0.57, and positive and negative predictive values of 0.42 and 1, respectively. The liver perfusate NK cell subset was strongly associated with biopsy-proven ACR (hazard ratio, 10.7; P = 0.02). Conclusions Liver perfusate cytofluorimetric phenotyping may contribute as a targeted preoperative tool to predict the risk of ACR, and as clinical test in translational studies that aim to improve donor allograft procurement and transplant outcomes.

Background: Liver transplantation (LT) is the only definitive and curative treatment for patients with end-stage liver disease and hepatocellular carcinoma. We aimed to evaluate the impact of the Italian score for organ allocation (ISO) in terms of the waiting-list mortality, probability of LT, and patient survival after LT. Patient and methods: All of the adult patients on the waiting list for LT at our institute from January 2014 to December 2017 were included in the study. The probabilities of death while on the waiting list, dropout from the list, and LT were compared by means of cumulative incidence functions, in a competing risk time-to-event analysis setting. Uni- and multivariable logistic regression models were used to estimate and compare the probability of death and to find potential risk factors for waiting-list death. Results: There were 286 patients on the waiting list for LT during the study period, 122 of whom entered the waiting list prior to the implementation of ISO (Group A) and 164 afterward (Group B). Group A had 62 transplants, and Group B had 116 transplants. Group B showed a lesser probability of death (P = .005) and a greater probability of transplant (P < .001) compared to Group A. In the 2 groups, post-transplant survival was similar. Conclusion: Based on preliminary clinical experience from a single transplant center, the ISO allocation system demonstrated an overall reduced probability of patient death while on the waiting list without impairing post-LT survival, suggesting that the ISO system might represent an improved method of organ allocation, with a more beneficial distribution of livers.

Background & Aims: Studies have produced conflicting results of the incidence of hepatocellular carcinoma (HCC) in patients with hepatitis C virus–associated cirrhosis treated with direct-acting antivirals (DAAs). Data from clinics are needed to accurately assess the occurrence rate of HCC in patients with cirrhosis in the real world. Methods: We collected data from a large prospective study of 2,249 consecutive patients (mean age = 65.4 years, 56.9% male) with hepatitis C virus–associated cirrhosis (90.5% with Child-Pugh class A and 9.5% with Child-Pugh class B) treated with DAAs from March 2015 through July 2016 at 22 academic and community liver centers in Sicily, Italy. HCC occurrence was evaluated by Kaplan-Meier curves. Cox regression analysis was used to identify variables associated with HCC development. Results: A sustained virologic response (SVR) was achieved by 2,140 patients (total = 95.2%; 95.9% with Child Pugh class A and 88.3% with Child Pugh class B; P

Background: Liver pathology in cats represents a frequent clinical condition occurring in animals of any age. Dietary supplementation with hepatoprotective and antioxidant products could represent a beneficial strategy to prevent and treat these disorders. We evaluated the tolerability and efficacy of long-term treatment with a multi-component, dietary supplement containing functional natural ingredients with recognized hepatoprotective properties in cats suffering from liver diseases Methods: 20 European domestic cats of either gender, 10 with hepatic lipidosis and 10 with cholangitis received for 180 consecutive days a multi-component formulation based on the silibinin-phosphatidylcholine complex as paste or tablet. Clinical assessment and blood and urine parameters were evaluated at T0 (inclusion time) and after 7, 28, 60, 90 and 180 days from the initiation of the study. Results: The oral supplementation with the silibinin-phosphatidylcholine complex significantly reduced the activity of liver enzymes in serum (alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, γ -glutamyl transferase) and the content of total bilirubin, albumin, pre- and post- bile acids, in cats with hepatic lipidosis or cholangitis, normalizing their liver function parameters. Moreover, following the supplementation, the appetite was restored in all cats and the frequent episodes of diarrhea and vomit reported at inclusion almost disappeared. Discussion: Dietary supplementation with the silibinin-phosphatidylcholine complex containing functional natural ingredients with recognized hepatoprotective and antioxidant actions might represent an effective strategy to improve the conditions of liver dysfunction, such as hepatitis lipidosis and cholangitis, in cats.