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.

Diastolic dysfunction diagnosed by tissue Doppler imaging in cirrhotic patients: Prevalence and its possible relationship with clinical outcome.

BACKGROUND: Cirrhotic cardiomyopathy has been characterized by impaired contractile response to stress and/or altered diastolic relaxation, with electrophysiological abnormalities in the absence of known cardiac disease. However, the clinical significance of diastolic dysfunction (DDF) in cirrhotic patients has not been clarified. METHODS: We studied 84 cirrhotic patients with normal systolic function to evaluate the prevalence of DDF using tissue Doppler imaging, and to investigate the possible correlation of DDF with outcomes (hospitalization, death) and with the specific causes of death. RESULTS: The mean follow-up was 10±8months. DDF was diagnosed in 22 patients (26.2%). Patients with DDF more frequently had ascites (90.9% vs. 64.5 %; p=0.026), lower levels of albumin (OR: 5.39; p=0.004), higher NT-proBNP levels, and longer QTc interval (464±23ms vs. 452±30ms; p=0.039). At follow-up, patients with DDF did not have a higher incidence of adverse events in terms of hospitalization and death. CONCLUSIONS: The presence of diastolic dysfunction has not been found to be clearly associated with outcome, and prognosis has been determined primarily by the severity of liver disease.

Circulatory response to volume expansion and transjugular intrahepatic portosystemic shunt in refractory ascites: Relationship with diastolic dysfunction.

BACKGROUND: Cirrhotic cardiomyopathy may lead to heart failure in stressful circumstances, such as after transjugular intrahepatic portosystemic shunt (TIPS) placement. AIM: To examine whether acute volume expansion predicts haemodynamic changes after TIPS and elicits signs of impending heart failure. METHODS: We prospectively evaluated refractory ascites patients (group A) and compensated cirrhotics (group B), who underwent echocardiography, NT-proBNP measurement, and heart catheterization before and after volume load; group A repeated measurements after TIPS. RESULTS: 15 patients in group A (80% male; 54±12.4 years) and 8 in group B (100% male; 56±6.2 years) were enrolled. Echocardiography disclosed diastolic dysfunction in 30% and 12.5%, respectively. In group A, volume load and TIPS induced a significant increase in right atrial, mean pulmonary, capillary wedge pressure and cardiac index, and a decrease in systemic vascular resistance (respectively, 4.7±2.8 vs. 9.9±3.6 mmHg; 13.3±3.5 vs. 21.9±5.9 mmHg; 8.3±3.4 vs. 15.4±4.7 mmHg; 3.7±0.7 vs. 4.6±11 t/min/m2; 961±278 vs. 767±285 dynscm(-5); and 10.1±3.3 vs. 14.2±3.4 mmHg; 17.5±4 vs. 25.2±4.2 mmHg; 12.3±4 vs. 19.3±3.4 mmHg; 3.4±0.8 vs. 4.5±0.91l t/min/m2; 779±62 vs. 596±199 dynscm(-5), p<0.001 for all pairs). At 24h, cardiopulmonary pressures returned towards baseline. CONCLUSIONS: Acute volume expansion predicted haemodynamic changes immediately after TIPS. All patients had adequate haemodynamic adaptation to TIPS; none developed signs of heart failure.

Liver Volume Restoration and Hepatic Microarchitecture in Small-for-Size Syndrome.

BACKGROUND: We investigated preoperative parameters that could work as markers of liver regeneration (LR), and tried to create an algorithm for therapeutic decision-making, looking at the clinical setting of post-hepatectomy liver failure (PHLF) after major liver resection for malignancies (LRM) and of the small-for-size syndrome (SFSS) after adult-to-adult living related liver transplantation (LRLT), considering PHLF and SFSS a single clinical entity. MATERIAL AND METHODS: The clinical data of 2 series of 10 consecutive patients who experienced liver-specific complications after LRLT or LRM between 2008 and 2013 were analyzed. LR was evaluated by multidetector computed tomography (MDCT) and hepatic parenchymal findings with specific re-examinations of liver biopsies. The analysis was done according to demographics, tumor characteristics, and postoperative complications occurring within 90 days of surgery and codified within the Clavien classification. RESULTS: A total of 13 cases of SFSS occurred in 8 LRLT recipients (61.5%) and in 5 patients after LRM (38.5%). The incidence of SFSS was significantly associated with a greater spleen volume/future remnant liver volume ratio (1.08±0.5; P=0.02) and a reduced number of hepatic tumors (0.58±0.6; P=0.04). A greater degree of LR was not associated with a lesser likelihood of developing SFSS (P=0.31). SFSS incidence and re-examination of post-operative liver biopsies differed according to the evidence of focal endothelial denudation in the portal vein and centrilobular hepatocanalicular cholestasis. We found an association between SFSS incidence and the immunohistochemical overexpression of cytological proliferation marker Ki-67 (29.3±29.8%; P=0.007), which was a significant predictor of poor post-operative survival (OR=1.12, C.I.: 1.013; 1.242). CONCLUSIONS: SFSS is a rare but dangerous clinical entity characterized by anarchic hepatic regeneration. We suggest focusing on early diagnosis in order to establish non-surgical modulation of the portal inflow, in conjunction with optimization of medical management.

Rash and multiorgan dysfunction following lamotrigine: could genetic be involved?

CASE (DESCRIPTION): We report the case of a 38-year-old woman treated with lamotrigine who experienced multi-organ dysfunction. The patient received the drug at the dose of 100 mg per day. One week later, the treatment was suspended because of an extensive body rash. Twenty-four hours later, the patient appeared drowsy and stuporous and was hospitalized. On the fifth day, the patient was admitted with a clinical picture of acute multi-organ failure in our Institute, where, she, despite the support of vital functions with vasoactive drugs, continuous hemofiltration and ventilation with oxygen, died. Serum lamotrigine concentration was measured 110 h after its last dose and the drug resulted to be still present at 1 mg/L. The patient was homozygous for the UGT1A4-70C and UGT2B7-161C alleles and heterozygous for the UGT2B7-372A>G polymorphism. Regarding ABCB1 the patient showed the 3435CC, 2677GT and 1236CT genotypes. CONCLUSION: Our results may suggest a role of the UGT2B7-372A>G polymorphism in this reaction.

IL28B polymorphisms of both recipient and donor cooperate to influence IFN treatment response in HCV recurrence after liver transplantation, but IL28B SNPs of the recipient play a major role in IFN-induced blocking of HCV replication.

Single nucleotide polymorphisms (SNPs) of the IL28B locus are associated with a positive response to pegylated interferon-alpha and ribavirin (pegIFN-alpha/RBV) treatment of HCV-infected patients. This study evaluated the association between SNPs rs12980275, rs12979860 and rs8099917 and treatment outcome of HCV recurrent infection in HCV-positive patients who underwent liver transplant. We aimed to assess to what extent recipient and/or graft donor IL28B polymorphisms contribute to HCV clearance after transplantation influencing the response to the antiviral treatment. We found that the allele frequencies in donors were in agreement with the pattern expected in the European population. The frequency of favourable genotypes was significantly lower in recipients than in donors, reasonably because the recipients represented a group of patients affected by chronic Hepatitis C. Our study demonstrated that the positive outcome of the pegIFN-alpha/RBV treatment of HCV recurrence is associated with the co-presence of favourable genotypes of both donors and recipients. However, IL28B SNPs of the recipient seem to play a major role in this clinical setting. In particular, homozygosis of rs12979860 favourable genotype in recipients was associated with sustained virological response independently from the donor's genotype. Thus, identification of these SNPs may be useful to predict the response to IFN-based therapy of HCV recurrent infection in liver-transplanted patients.

Head and neck and esophageal cancers after liver transplant: results from a multicenter cohort study. Italy, 1997-2010.

This study quantified the risk of head and neck (HN) and esophageal cancers in 2770 Italian liver transplant (LT) recipients. A total of 186 post-transplant cancers were diagnosed-including 32 cases of HN cancers and nine cases of esophageal carcinoma. The 10-year cumulative risk for HN and esophageal carcinoma was 2.59%. Overall, HN cancers were nearly fivefold more frequent in LT recipients than expected (standardized incidence ratios - SIR=4.7, 95% CI: 3.2-6.6), while esophageal carcinoma was ninefold more frequent (SIR=9.1, 95% CI: 4.1-17.2). SIRs ranged from 11.8 in LT with alcoholic liver disease (ALD) to 1.8 for LT without ALD for HN cancers, and from 23.7 to 2.9, respectively, for esophageal carcinoma. Particularly elevated SIRs in LT with ALD were noted for carcinomas of tongue (23.0) or larynx (13.7). Our findings confirmed and quantified the large cancer excess risk in LT recipients with ALD. The risk magnitude and the prevalence of ALD herein documented stress the need of timely and specifically organized programs for the early diagnosis of cancer among LT recipients, particularly for high-risk recipients like those with ALD.

Liver Transplantation for Hemoperitoneum Secondary to Huge Multiple Hemangiomatosis: A Case Report of a Tele-intensive Care Unit in Deceased-Donor Management.

BACKGROUND: Patients with growing and nonresectable liver hemangiomas should be followed up by a transplant center with extensive experience in complex liver disease. They could be treated on an emergency basis with orthotopic liver transplantation, with an expectation of good long-term results. MATERIALS AND METHODS: We describe the case of a 37-year-old woman with liver hemangiomatosis followed up for 8 years, who presented with bleeding requiring transfusions and developed hemodynamic instability. We listed her for emergency transplant before her sister's living donor work-up could be completed. A liver from a cadaveric donor became available at a small local hospital with no experience in organ donation. Tele-intensive care unit (tele-ICU) technology was used for providing clinical data electronically to physicians, nurses, and other critical care specialists, creating medication orders, and communicating with on-site caregivers to implement changes in donor care. RESULTS: The recipient was transplanted on an emergency basis with a specific customization and application of the telemedicine system in the management of the organ procurement by the recipient team. Tele-ICU technology was used for providing an effective intensive care unit service, managing and stabilizing the deceased donor and allowing the procurement to be carried out uneventfully. CONCLUSIONS: Tele-ICU technology could be a promising resource for emergency transplantation, reducing the urgent need for a living donation and allowing prompt recipient team management of the deceased donor. Our first tele-ICU case offers early confirmation of the feasibility of the telemedicine system in deceased-donor management.

Thalassemia and heart surgery: aortic valve repair after endocarditis.

Outcome after heart valve surgery in patients affected by thalassemia is an unreported issue and to the best of our knowledge only 7 cases have been described in the literature. Heart valve disease is commonly encountered in thalassemia patients and heart valve replacement carries high risk of prosthesis complications including thrombosis and embolization despite optimal anticoagulation management. We report a successful long-term outcome after a case of aortic valve repair after mycotic valve endocarditis.

Phases I-II Matched Case-Control Study of Human Fetal Liver Cell Transplantation for Treatment of Chronic Liver Disease.

Fetal hepatocytes have a high regenerative capacity. The aim of the study was to assess treatment safety and clinical efficacy of human fetal liver cell transplantation through splenic artery infusion. Patients with end-stage chronic liver disease on the waiting list for liver transplantation were enrolled. A retrospectively selected contemporary matched-pair group served as control. Nonsorted raw fetal liver cell preparations were isolated from therapeutically aborted fetuses. The end points of the study were safety and improvement of the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores. Nine patients received a total of 13 intrasplenic infusions and were compared with 16 patients on standard therapy. There were no side effects related to the infusion procedure. At the end of follow-up, the MELD score (mean ± SD) in the treatment group remained stable from baseline (16.0 ± 2.9) to the last observation (15.7 ± 3.8), while it increased in the control group from 15.3 ± 2.5 to 19 ± 5.7 (p = 0.0437). The Child-Pugh score (mean ± SD) dropped from 10.1 ± 1.5 to 9.1 ± 1.4 in the treatment group and increased from 10.0 ± 1.2 to 11.1 ± 1.6 in the control group (p = 0.0076). All treated patients with history of recurrent portosystemic encephalopathy (PSE) had no further episodes during 1-year follow-up. No improvement was observed in the control group patients with PSE at study inclusion. Treatment was considered a failure in six of the nine patients (three deaths not liver related, one liver transplant, two MELD score increases) compared with 14 of the 16 patients in the control group (six deaths, five of which were caused by liver failure, four liver transplants, and four MELD score increases). Intrasplenic fetal liver cell infusion is a safe and well-tolerated procedure in patients with end-stage chronic liver disease. A positive effect on clinical scores and on encephalopathy emerged from this preliminary study.

Characterization of Liver-Specific Functions of Human Fetal Hepatocytes in Culture.

This study was designed to assess liver-specific functions of human fetal liver cells proposed as a potential source for hepatocyte transplantation. Fetal liver cells were isolated from livers of different gestational ages (16-22 weeks), and the functions of cell preparations were evaluated by establishing primary cultures. We observed that 20- to 22-week-gestation fetal liver cell cultures contained a predominance of cells with hepatocytic traits that did not divide in vitro but were functionally competent. Fetal hepatocytes performed liver-specific functions at levels comparable to those of their adult counterpart. Moreover, exposure to dexamethasone in combination with oncostatin M promptly induced further maturation of the cells through the acquisition of additional functions (i.e., ability to store glycogen and uptake of indocyanine green). In some cases, particularly in cultures obtained from fetuses of earlier gestational ages (16-18 weeks gestation), cells with mature hepatocytic traits proved to be sporadic, and the primary cultures were mainly populated by clusters of proliferating cells. Consequently, the values of liver-specific functions detected in these cultures were low. We observed that a low cell density culture system rapidly prompted loss of the mature hepatocytic phenotype with downregulations of all the liver-specific functions. We found that human fetal liver cells can be cryopreserved without significant loss of viability and function and evaluated up to 1 year in storage in liquid nitrogen. They might, therefore, be suitable for cell banking and allow for the transplantation of large numbers of cells, thus improving clinical outcomes. Overall, our results indicate that fetal hepatocytes could be used as a cell source for hepatocyte transplantation. Fetal liver cells have been used so far to treat end-stage liver disease. Additional studies are needed to include these cells in cell-based therapies aimed to treat liver failure and inborn errors of metabolism.