How to Improve Patients' Perceived Quality of Sleep During Hospitalization Through a Multicomponent "Good Sleep Bundle": A Prospective Before and After Controlled Study.

Introduction: Despite sound evidence on the importance of sleep for human beings and its role in healing, hospitalized patients still experience sleep disruption with deleterious effects. Many factors affecting patients' sleep can be removed or minimized. We evaluated the efficacy of a multicomponent Good Sleep Bundle (GSB) developed to improve patients' perceived quality of sleep, through which we modified environmental factors, timing of nighttime clinical interventions, and actively involved patients in order to positively influence their experience during hospitalization. Methods: In a prospective, before and after controlled study, two different groups of 65 patients each were admitted to a cardiothoracic unit in two different periods, receiving the usual care (control group) and the GSB (GSB group), respectively. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI) at the admission, discharge, and 30 days after discharge in all patients enrolled. Comparisons between the two groups evaluated changes in PSQI score from admission to discharge (primary endpoint), and from admission to 30 days after discharge (secondary endpoint). Results: The mean PSQI score difference between admission and discharge was 4.54 (SD 4.11) in the control group, and 2.05 (SD 4.25) in the GSB group. The mean difference in PSQI score change between the two groups, which was the primary endpoint, was 2.49 (SD 4.19). This difference was highly significant (p = 0.0009). Conclusion: The GSB was associated with a highly significant reduction of the negative effects that hospitalization produces on patients' perceived quality of sleep compared with the usual care group.

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.

Direct-acting antivirals ability to clear intestinal HCV-RNA in liver transplant patients.

The hepatitis C virus mainly infects the liver but is also able to infect and replicate in other body compartments by creating an extra-hepatic reservoir that may influence the persistence of the infection after transplantation. It is unknown whether antiviral drugs affect the viral extra-hepatic sites. We evaluated the ability of pegylated/interferon + ribavirin and sofosbuvir + ribavirin to clear the virus from the gastrointestinal mucosa of liver-transplanted patients with HCV recurrence after transplantation. A total of 51 liver-transplanted patients, 30 treated with pegylated/interferon + ribavirin (ERA1) and 21 treated with sofosbuvir + ribavirin (ERA2), were enrolled, and blood serum and gastrointestinal tissues analyzed for the presence of HCV-RNA. In the ERA1 group, the 46.6% of patients had a sustained viral response to antiviral treatment, and gastrointestinal biopsies were positive for HCV in 73.3% of cases, 54.5% of responders, and 45.5% of non-responders. In the ERA2 group, the 66.6% had a sustained viral response, and gastrointestinal HCV-RNA was present in the 14.3% of patients, all relapsers. Sofosbuvir + ribavirin cleared the intestinal HCV in 85.7% of patients with recurrent HCV infection, while pegylated/interferon + ribavirin cleared it in 26.6% of treated patients, demonstrating the better effectiveness of new direct antiviral agents in clearing HCV intestinal reservoir.

Design, development and validation of a system for automatic help to medical text understanding.

OBJECTIVE: The paper presents a web-based application, SIMPLE, that facilitates medical text comprehension by identifying the health-related terms of a medical text and providing the corresponding consumer terms and explanations. BACKGROUND: The comprehension of a medical text is often a difficult task for laypeople because it requires semantic abilities that can differ from a person to another, depending on his/her health-literacy level. Some systems have been developed for facilitating the comprehension of medical texts through text simplification, either syntactical or lexical. The ones dealing with lexical simplification usually replace the original text and do not provide additional information. We have developed a system that provides the consumer terms alongside the original medical terms and also adds consumer explanations. Moreover, differently from other solutions, our system works with multiple languages. METHODS: We have developed the SIMPLE application that is able to automatically: 1) identify medical terms in a medical text by using medical vocabularies; 2) translate the medical terms into consumer terms through medical-consumer thesauri; 3) provide term explanations by using health-consumer dictionaries. SIMPLE can be used as a standalone web application or can it be embedded into common health platforms for real time identification and explanation of medical terms. At present, it works with English and Italian texts but it can be easily extended to other languages. We have run subjective tests with both medical experts and non-experts as well as objective tests to verify the effectiveness of SIMPLE and its simplicity of use. RESULTS: Non-experts found SIMPLE easy to use and responsive. The big majority of respondents confirmed they were helped by SIMPLE in understanding medical texts and declared their willingness to continue using SIMPLE and to recommend it to other people. The subjective tests, conducted with medical experts on a set of Italian radiology reports, showed an agreement between SIMPLE and the experts, on the highlighted medical terms, that ranges between 74.05 % and 81.16 % as well as an agreement of around 60 % on the consumer term translation. The objective tests showed that the consumer terms, provided by SIMPLE, are, on average, eighteen times more familiar than the relative medical terms so proving, once more, the effectiveness of SIMPLE in simplifying the medical terms. CONCLUSIONS: The performed tests demonstrate the effectiveness of SIMPLE, its simplicity of use and the willingness of people in continuing with its use. SIMPLE provides, with a good agreement level, the same information that medical experts would provide. Finally, the consumer terms are 'objectively' more familiar than the related technical terms and as a consequence, much easier to understand.

Use of Hepatitis C-Positive Deceased Liver Donors in Response to the Organ Shortage in an Endemic Area.

The region of Sicily, Italy, is witnessing a chronic organ shortage. Thus, to face this critical issue, the use of marginal donors has increased over time. An example of marginal donor expansion is the use of liver donors who are positive for the hepatitis C antibody (HCV+) for HCV+ patients requiring liver transplantation (LT). In view of new advances in HCV therapy, including direct-acting agents (DAAs) to treat HCV in the post-transplant setting, our study focused on a monocentric experience in a series of consecutive LTs performed in adult patients receiving HCV+ liver donor allografts. From 2003 to 2016 at our institute we performed 10 LT using HCV+ deceased donors. In particular, the pre-LT histological examination in 1 case showed a framework of moderate steatosis (35% microvesicular and 10% macrovesicular) with micro/macrovesicular steatosis <10% in all the other cases. A fibrous framework of 1/6 according to the Ishak score in a single case, and 2/6 in 2 cases, were highlighted, while there was no fibrosis in the other 7 cases. A picture of periportal inflammation was still detected in 4 cases, with no evidence of inflammatory lesions in the remaining cases. The patient survival was 100% at 1 and 3 years, and 85.7% at 5 years post-LT. One-, three- and five-year graft survivals were 100.0%, 88.9%, and 71.4%, respectively. Only 1 patient underwent re-LT after 2 years, because of chronic rejection. Based on our experience using HCV+ deceased liver donors with a moderate degree of fibrosis, we believe that accepting marginal donors is a feasible therapeutic option when facing a liver donor shortage.

HCV replication in gastrointestinal mucosa: Potential extra-hepatic viral reservoir and possible role in HCV infection recurrence after liver transplantation.

PURPOSE: Hepatitis C virus (HCV) predominantly infects hepatocytes, although it is known that receptors for viral entry are distributed on a wide array of target cells. Chronic HCV infection is indeed characterized by multiple non-liver manifestations, suggesting a more complex HCV tropism extended to extrahepatic tissues and remains to be fully elucidated. In this study, we investigated the gastrointestinal mucosa (GIM) as a potential extrahepatic viral replication site and its contribution to HCV recurrence. METHODS: We analyzed GIM biopsies from a cohort of 76 patients, 11 of which were HCV-negative and 65 HCV-positive. Of these, 54 biopsies were from liver-transplanted patients. In 29 cases, we were able to investigate gastrointestinal biopsies from the same patient before and after transplant. To evaluate the presence of HCV, we looked for viral antigens and genome RNA, whilst to assess viral replicative activity, we searched for the replicative intermediate minus-strand RNA. We studied the genetic diversity and the phylogenetic relationship of HCV quasispecies from plasma, liver and gastrointestinal mucosa of HCV-liver-transplanted patients in order to assess HCV compartmentalization and possible contribution of gastrointestinal variants to liver re-infection after transplantation. RESULTS: Here we show that HCV infects and replicates in the cells of the GIM and that the favorite hosts were mostly enteroendocrine cells. Interestingly, we observed compartmentalization of the HCV quasispecies present in the gastrointestinal mucosa compared to other tissues of the same patient. Moreover, the phylogenetic analysis revealed a high similarity between HCV variants detected in gastrointestinal mucosa and those present in the re-infected graft. CONCLUSIONS: Our results demonstrated that the gastrointestinal mucosa might be considered as an extrahepatic reservoir of HCV and that could contribute to viral recurrence. Moreover, the finding that HCV infects and replicates in neuroendocrine cells opens new perspectives on the role of these cells in the natural history of HCV infection.

Determinants of influenza vaccination among solid organ transplant recipients attending Sicilian reference center.

Among solid organ transplant recipients, influenza infection is commonly associated with higher morbidity and mortality than immunocompetent hosts. Therefore, in these subjects influenza vaccination is of paramount importance. The main objective of the study was to assess compliance to vaccination and analyze factors associated with influenza vaccination of solid organ transplant recipients admitted to the Sicilian solid organ transplant Reference Center IRCCS-ISMETT in Palermo during 2014-2015 influenza season. Thirty one (37.8%) out of 82 solid organ transplant recipients were vaccinated against influenza. The main reason for vaccination refusal was fear of adverse reaction (n = 16, 31.4%), impaired health status (n = 14, 27.4%) and low vaccine efficacy (n = 10, 19.6%). Vaccinated solid organ transplant recipients compare with unvaccinated had smaller hospital admissions for infectious respiratory diseases (9.7% Vs 23.5%) during surveillance period. On multivariate analysis the factors positively associated with influenza vaccination were the advice of Reference Center physicians (OR 53.4, p < 0.001) and to perform vaccine against pneumococcus (OR 7.0, p = 0.016). This study showed that Reference Center physicians play a key role on vaccine communication and recommendation for patients at risk and it underlines the effectiveness of influenza vaccination in solid organ transplant recipients. However, it remains that, although physician advice resulted a strong determinant for vaccination, influenza vaccination coverage in this subset of population remains still unsatisfactory.

Complications and Near-Miss Events After Hepatectomy for Living-Related Liver Donation: An Italian Single Center Report of One Hundred Cases.

BACKGROUND In healthy individuals, such as liver living donors, potential complications may occur during surgery. Reporting such complications and near-miss events is mandatory to improve living donor management and safety. MATERIAL AND METHODS This retrospective study was performed on a prospective database with the aim of providing a brief analysis of the perioperative, medium-term, and long-term complications, and the near-miss events in a single center series of 100 consecutive liver resections for adult-to-adult living-donor liver transplantation. RESULTS Only 23.3% of potential living donors underwent surgery. No living donor mortality was reported; 29 patients (29%) experienced at least one complication. Five patients developed mild long-term dysfunction; two aborted hepatectomies, and there were two near-miss events reported. CONCLUSIONS A strategy for an accurate assessment of living donor complications and strict selection criterion cannot be overemphasized, as well as the need to continuously update center patient outcome reports.

Laparoscopic Approach for Thermoablation Microwave in the Treatment of Hepatocellular Carcinoma: A Single Center Experience.

BACKGROUND: The surgical therapy of choice for hepatocellular carcinoma (HCC) is liver transplantation (LT) or hepatic resection, although only a small percentage of patients can undergo these procedures. Microwave thermal ablation (MWTA) can be an effective alternative treatment for HCC that complicates a cirrhotic liver disease, either as a final procedure or for downstaging patients on the waiting list for LT, or in combination with resective surgery to achieve oncological radicality. OBJECTIVE: The purpose of this retrospective study was to evaluate experience with the laparoscopic approach of MWTA at our center. MATERIALS AND METHODS: In a cohort of 35 consecutive patients undergoing MWTA with laparoscopic approach between January, 2013 and May, 2016, we reviewed the demographic data, the Barcelona clinic liver cancer stage, the severity of cirrhotic liver disease, the size of the ablated lesion, the duration of the procedure, and complications occurring within 90 days of surgery. RESULTS: MWTA was performed by applying one to three hepatic parenchymal insertions (mean 1.8) per patient. The mean duration of surgery was 163 ± 18 minutes. There was no blood loss in any of the procedures. Complete necrosis on CT scan was achieved in 26/35 patients (75%). The mean hospital stay was 4.6 (range 2-7) days; major complications were postablation syndrome in 2/35 (5.7%), peritoneal fluid in 4/35 (11.4%), and transient jaundice in 1/35 (2.8%) patients. There was no mortality. CONCLUSIONS: Laparoscopic MTWA is a safe and effective treatment for unresectable HCC and when a percutaneous procedure is not feasible.

Mini-Invasive Approach Contributes to Expand the Indication for Liver Resection for Hepatocellular Carcinoma Without Increasing the Incidence of Posthepatectomy Liver Failure and Other Perioperative Complications: A Single-Center Analysis.

BACKGROUND: Liver resection (LR) for hepatocellular carcinoma (HCC) is the best alternative option for increasing the survival of many patients with intermediate or advanced stages of the Barcelona Clinic Liver Cancer staging classification. Mini-invasive approach may play a positive role in treating a tumor rising almost exclusively in a diseased liver. METHODS: A prospectively collected database was retrospectively reviewed for 167 consecutive patients who underwent LR between 1999 and 2015. RESULTS: A total of 38 LRs were performed from 1999 to 2009 (Period I), and 129 between 2010 and 2015 (Period II). Laparoscopic procedures increased from 5.3% to 38.1%. Not undergoing laparoscopic LR increased length of stay, and Clavien Grade II or worse complications. Ninety-day mortality decreased from 5.2% to 0%, and morbidity did not differ significantly, despite the fact that the most complex patients were in Period II. CONCLUSIONS: Mini-invasive approaches allow to safely expand limits of LR for HCC; in particular, laparoscopic approach favors surgical option even in more complex patients without increase the risk of posthepatic liver failure or other postsurgical complications.