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Liver replacement therapy

Jou-Ku Chung, Eilish Brown, Bob Crooker, Kathleen J Palmieri, Thomas G McCauley
Enzyme replacement therapy with intravenous idursulfase (recombinant iduronate-2-sulfatase) is approved for the treatment of Hunter syndrome. Intravenous administration does not, however, treat the neurological manifestations, due to its low central nervous system bioavailability. Using intrathecal-lumbar administration, iduronate-2-sulfatase is delivered directly to the central nervous system. This study investigates the central nervous system biodistribution of intrathecal-lumbar administered iduronate-2-sulfatase in cynomolgus monkeys...
2016: PloS One
Thomas Gilliland, Sylvie Dufour, Gerald I Shulman, Kitt Falk Petersen, Sukru H Emre
NAFLD is a common condition linked to obesity, type 2 diabetes, and metabolic syndrome. Simple hepatic steatosis is a risk factor for inflammatory reactions in the liver (NASH), which may lead to cirrhosis. While the mechanism is unclear, NAFLD and NASH are associated with panhypopituitarism, which in the pediatric population often results from craniopharyngioma or pituitary adenoma and the sequelae of treatment, causing hypothyroidism, adrenal insufficiency, hypogonadotropic hypogonadism, and GH deficiency...
October 20, 2016: Pediatric Transplantation
Paolo Angeli, Dimitri Bezinover, Gianni Biancofiore, Anja Bienholz, James Findlay, Catherine Paugam Burtz, Koen Reyntjens, Tetsuro Sakai, Fuat H Saner, Dana Tomescu, Gebhard Wagener, Emmanuel Weiss
Acute kidney injury (AKI) is associated with high perioperative mortality. A series of AKI research breakthroughs are worth mentioning. First, in 2003, serum and urine biomarkers specific to AKI were identified. These biomarkers have contributed to early detection, prevention, and treatment of AKI. In 2004, AKI severity was defined with the Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) criteria, which was developed by the International Consensus Conference Workgroup of the Acute Dialysis Quality Initiative...
October 19, 2016: Minerva Anestesiologica
Takashi Kodama, Takahiro Tsukimura, Ikuo Kawashima, Atsuko Sato, Hitoshi Sakuraba, Tadayasu Togawa
In Fabry disease, large amounts of globotriaosylceramide (Gb3) and related glycosphingolipids accumulate in organs due to a deficiency of α-galactosidase A (GLA) activity. Enzyme replacement therapy (ERT) with recombinant GLA is now available, and it has been reported that ERT is beneficial for patients with Fabry disease, especially those who start treatment at an early stage of the disease. However, it seems that the efficacy of ERT differs with each organ, and Gb3 accumulated in the kidneys shows resistance to ERT when it is started at a late stage...
October 12, 2016: Molecular Genetics and Metabolism
Stacey S Huppert, Kathleen M Campbell
PURPOSE OF REVIEW: Although the liver possesses a unique, innate ability to regenerate through mass compensation, transplantation remains the only therapy when damage outpaces regeneration, or liver metabolic capacity is irreversibly impacted. Recent insight from developmental biology has greatly influenced the advancement of alternative options to transplantation in these settings. RECENT FINDINGS: Factors known to direct liver cell specification, expansion, and differentiation have been used to generate hepatocyte-like cells from stem and somatic cells for developing cell therapies...
October 15, 2016: Current Opinion in Organ Transplantation
L Benítez-Gutiérrez, C de Mendoza, I Baños, A Duca, A Arias, A Treviño, S Requena, M J Citores, V Cuervas-Mons
New direct-acting antivirals (DAAs) have dramatically improved sustained virologic response (SVR) rates in patients treated for chronic hepatitis C. Although the safety of these agents has been very good in registration trials, unexpected side effects have been reported after much broader use of DAAs on marketing. We retrospectively examined all liver transplant recipients with chronic hepatitis C that received sofosbuvir-based regimens at our clinic. A total of 24 liver transplant recipients with recurrent chronic hepatitis C had received sofosbuvir up to April 2015...
September 2016: Transplantation Proceedings
Gianluca Villa, Mauro Neri, Rinaldo Bellomo, Jorge Cerda, A Raffaele De Gaudio, Silvia De Rosa, Francesco Garzotto, Patrick M Honore, John Kellum, Anna Lorenzin, Didier Payen, Zaccaria Ricci, Sara Samoni, Jean-Louis Vincent, Julia Wendon, Marta Zaccaria, Claudio Ronco
This article reports the conclusions of the second part of a consensus expert conference on the nomenclature of renal replacement therapy (RRT) techniques currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients. A multidisciplinary approach was taken to achieve harmonization of definitions, components, techniques, and operations of the extracorporeal therapies. The article describes the RRT techniques in detail with the relevant technology, procedures, and phases of treatment and key aspects of volume management/fluid balance in critically ill patients...
October 10, 2016: Critical Care: the Official Journal of the Critical Care Forum
Francesco Barchiesi, Roberto Montalti, Pamela Castelli, Daniele Nicolini, Silvia Staffolani, Federico Mocchegiani, Alessandro Fiorentini, Esther Manso, Marco Vivarelli
BACKGROUND: Infections remain a leading cause of morbidity and mortality among liver transplant (LT) recipients. The aim of our study was to define the factors associated with outcome of early bacterial and fungal infections in a cohort of patients who underwent LT at the University Hospital of Ancona over a nine year period. METHODS: All consecutive patients who underwent LT in our center were considered. An early infection was defined as occurring in the first month post-transplantation...
October 4, 2016: BMC Infectious Diseases
Gaël Piton, Claire Chaignat, Mikhael Giabicani, Jean-Paul Cervoni, Fabienne Tamion, Emmanuel Weiss, Catherine Paugam-Burtz, Gilles Capellier, Vincent Di Martino
BACKGROUND: The prognosis of cirrhotic patients admitted to the ICU is considered to be poor but has been mainly reported in liver ICU. We aimed to describe the prognosis of cirrhotic patients admitted to a general ICU, to assess the predictors of mortality in this population, and, finally, to identify a subgroup of patients in whom intensive care escalation might be discussed. RESULTS: We performed a retrospective monocentric study of all cirrhotic patients consecutively admitted between 2002 and 2014 in a general ICU in a regional university hospital...
December 2016: Annals of Intensive Care
Carlo Castellani, Baroukh M Assael
Cystic fibrosis (CF), a monogenic disease caused by mutations in the CFTR gene on chromosome 7, is complex and greatly variable in clinical expression. Airways, pancreas, male genital system, intestine, liver, bone, and kidney are involved. The lack of CFTR or its impaired function causes fat malabsorption and chronic pulmonary infections leading to bronchiectasis and progressive lung damage. Previously considered lethal in infancy and childhood, CF has now attained median survivals of 50 years of age, mainly thanks to the early diagnosis through neonatal screening, recognition of mild forms, and an aggressive therapeutic attitude...
October 5, 2016: Cellular and Molecular Life Sciences: CMLS
Sandra Motas, Virginia Haurigot, Miguel Garcia, Sara Marcó, Albert Ribera, Carles Roca, Xavier Sánchez, Víctor Sánchez, Maria Molas, Joan Bertolin, Luca Maggioni, Xavier León, Jesús Ruberte, Fatima Bosch
Mucopolysaccharidosis type II (MPSII) is an X-linked lysosomal storage disease characterized by severe neurologic and somatic disease caused by deficiency of iduronate-2-sulfatase (IDS), an enzyme that catabolizes the glycosaminoglycans heparan and dermatan sulphate. Intravenous enzyme replacement therapy (ERT) currently constitutes the only approved therapeutic option for MPSII. However, the inability of recombinant IDS to efficiently cross the blood-brain barrier (BBB) limits ERT efficacy in treating neurological symptoms...
June 16, 2016: JCI Insight
Takashi Yazawa, Yoshitaka Imamichi, Kaoru Miyamoto, Md Rafiqul Islam Khan, Junsuke Uwada, Akihiro Umezawa, Takanobu Taniguchi
Steroid hormones are mainly produced in adrenal glands and gonads. Because steroid hormones play vital roles in various physiological processes, replacement of deficient steroid hormones by hormone replacement therapy (HRT) is necessary for patients with adrenal and gonadal failure. In addition to HRT, tissue regeneration using stem cells is predicted to provide novel therapy. Among various stem cell types, mesenchymal stem cells can be differentiated into steroidogenic cells following ectopic expression of nuclear receptor (NR) 5A subfamily proteins, steroidogenic factor-1 (also known as adrenal 4 binding protein) and liver receptor homolog-1, with the aid of cAMP signaling...
September 29, 2016: Endocrine Journal
Su Mi Lee, Young Ki Son, Seong Eun Kim, Won Suk An
♦ Background: Clinical results of long-term peritoneal dialysis (PD) therapy in patients with liver cirrhosis (LC) and end-stage renal disease (ESRD) are controversial. This study evaluated the clinical outcomes of LC patients undergoing PD. ♦ Methods: Clinical records were retrospectively collected from a single center between January 2007 and December 2014. An analysis of PD patients with LC and without liver disease was performed using propensity score matching. We further restricted matching by age, gender, and the presence of diabetes mellitus...
September 28, 2016: Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis
I Carmona, P Cordero, J Ampuero, A Rojas, M Romero-Gómez
Fibrosis progression is common in hepatitis C. Both host and viral factors influence its natural history. Liver fibrosis is a key predictive factor for advanced disease including endpoints such as liver failure, cirrhosis and hepatocellular carcinoma (HCC). METAVIR fibrosis stages F3-F4 have been considered as the threshold for antiviral therapy. However, this aspect is controversial after the advent of new direct-acting antivirals (DAAs) because they show an excellent efficacy and safety profile. Moreover, in the DAA era, fibrosis stage seems not to be a predictive factor of a sustained virological response (SVR)...
September 24, 2016: Clinical Microbiology and Infection
Andreas Weltin, Steffen Hammer, Fozia Noor, Yeda Kaminski, Jochen Kieninger, Gerald A Urban
3D hepatic microtissues, unlike 2D cell cultures, retain many of the in-vivo-like functionalities even after long-term cultivation. Such 3D cultures are increasingly applied to investigate liver damage due to drug exposure in toxicology. However, there is a need for thorough metabolic characterization of these microtissues for mechanistic understanding of effects on culture behaviour. We measured metabolic parameters from single human HepaRG hepatocyte spheroids online and continuously with electrochemical microsensors...
July 28, 2016: Biosensors & Bioelectronics
C Michael Gibson, Serge Korjian, Pierluigi Tricoci, Yazan Daaboul, John H Alexander, Philippe G Steg, A Michael Lincoff, John J P Kastelein, Roxana Mehran, Denise D'Andrea, Bela Merkely, Maciej Zarebinski, Ton Oude Ophius, Robert A Harrington
BACKGROUND: Despite aggressive pharmacotherapy and stenting, there is a residual risk of major adverse cardiovascular events among patients with acute coronary syndrome. High-density lipoprotein (HDL) has been a major target for secondary acute coronary syndrome prevention; however, a better understanding of the physiologic function of HDL has demonstrated that a high cholesterol efflux capacity, rather than high HDL concentrations alone, may be critical to improving outcomes. CSL112, a reconstituted, infusible human apolipoprotein A-I, has been demonstrated to increase cholesterol efflux capacity and to have a protective effect in experimental models of atherosclerotic cardiovascular disease...
October 2016: American Heart Journal
Maimoona Ahmed, Sunil T Pandya, Tarakeswari Supraneni
PURPOSE: To determine the risk factors and associated comorbidities with a relaparotomy after primary surgery in pregnant mothers and to identify preventable causes. METHODS: A retrospective observational study was done at a tertiary care centre from January 2009 till August 2014. All records of exploratory laparotomy following primary surgery in the obstetric population during this period were retrieved from the hospital database and analysed. RESULTS: The incidence of relaparotomy was 0...
October 2016: Journal of Obstetrics and Gynaecology of India
V Filingeri, S Francioso, D Sforza, F Santopaolo, F M Oddi, G Tisone
OBJECTIVE: In the last decades, liver biopsy was the reference procedure for the diagnosis and follow-up of liver disease. Aim of present retrospective analysis was to assess the prevalence of complications and risk factors after Percutaneous Liver Biopsy (PLB) performed for diagnosis and staging in patients with chronic liver disease and for monitoring the graft in liver transplanted patients PATIENTS AND METHODS: Data were collected from a total of 1.011 PLB performed with the Menghini technique between January 2004 and December 2014 at the Hepatology and Transplant Units of the University of Rome Tor Vergata...
September 2016: European Review for Medical and Pharmacological Sciences
Rohan M Modi, Nishi Patel, Sherif N Metwally, Khalid Mumtaz
Hepatorenal syndrome (HRS) plays an important role in patients with liver cirrhosis on the wait list for liver transplantation (LT). The 1 and 5-year probability of developing HRS in cirrhotic with ascites is 20% and 40%, respectively. In this article, we reviewed current concepts in HRS pathophysiology, guidelines for HRS diagnosis, effective treatment options presently available, and controversies surrounding liver alone vs simultaneous liver kidney transplant (SLKT) in transplant candidates. Many treatment options including albumin, vasoconstrictors, renal replacement therapy, and eventual LT have remained a mainstay in the treatment of HRS...
August 28, 2016: World Journal of Hepatology
P Cuny, M Houot, S Ginisty, S Horowicz, F Plassart, H Mentec, P Eftekhari
INTRODUCTION: The aim of this paper is to underline the need for systematic monitoring of patients treated with anticholinergic antipsychotic drugs. We present the clinical history of a 34-year-old adult, treated with quetiapine in combination with other drugs with anticholinergic effects. CASE REPORT: A 34-year-old male adult had been suffering from bipolar disorder since 2001. He was treated with risperidone, but he was not compliant due to adverse effects, including decreased libido and erectile dysfunction...
September 13, 2016: L'Encéphale
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