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hyperbilirubinemia adult

Masaharu Nagae, Moritoki Egi, Kenta Kubota, Shohei Makino, Satoshi Mizobuchi
Background: Hyperbilirubinemia is a common postoperative complication. Elevated direct bilirubin (D-Bil) and indirect bilirubin (I-Bil) levels are related to different pathophysiologies; therefore, their associations with outcomes also differ. However, there have been few comparative studies of such associations in postoperative patients. Methods: This retrospective study compared the associations of postoperative D-Bil and I-Bil with outcomes. We included adult patients requiring postoperative intensive care for more than 48 hours between 2008 and 2013, except those undergoing liver operations...
February 2018: Korean Journal of Anesthesiology
Rachael R Schulte, Manasi V Madiwale, Allyson Flower, Jessica Hochberg, Michael J Burke, Jennifer L McNeer, Adam DuVall, Archie Bleyer
Asparaginase, an important treatment component for acute lymphoblastic leukemia (ALL), causes severe hepatotoxicity in some patients. Levocarnitine is a mitochondrial co-factor that can potentially ameliorate the mitochondrial toxicity of asparaginase. In this retrospective case series, we describe the clinical presentation and management of six pediatric and young adult patients (mean age 12.7, range 9-24 years) with ALL who developed Grade 3-4 hyperbilirubinemia following administration of asparaginase as part of induction/re-induction therapy...
February 12, 2018: Leukemia & Lymphoma
Yoshiaki Takahashi, Toshiharu Matsuura, Koichiro Yoshimaru, Yusuke Yanagi, Makoto Hayashida, Tomoaki Taguchi
A graft volume/standard liver volume ratio (GV/SLV) > 35% or graft/recipient weight ratio (GRWR) > 0.8% has been considered as a standard criteria of graft selection. Even if the graft size meets these selection criteria, small-for-size syndrome can still occur depending on the portal venous flow (PVF). The aim of this study was to identify other factors contributing to portal hyperperfusion and the post-transplant course, focusing on the graft volume-to-spleen volume ratio (GV/SV). Thirty-seven BA patients who underwent living donor liver transplantation were reviewed retrospectively...
February 9, 2018: Transplant International: Official Journal of the European Society for Organ Transplantation
Patrick W Burke, Ibrahim Aldoss, Matthew A Lunning, Sean M Devlin, Martin S Tallman, Vinod Pullarkat, Ann M Mohrbacher, Dan Douer
Pediatric acute lymphoblastic leukemia (ALL) regimens, including higher cumulative asparaginase doses, have been investigated in adult ALL to improve outcomes. Preliminary results are promising, but hepatotoxicity rates with long-acting pegaspargase are greater in adults than children. However, adult pegaspargase-related hepatotoxicity is not as clearly defined despite being the commonest adult toxicity. We studied the frequency and characteristics of high-grade pegaspargase-related hepatotoxicity in newly diagnosed adults on a pediatric-inspired regimen that included six planned pegaspargase doses, 2000 IU/m2/dose intravenously, with doses given at least four weeks apart and not discontinued or dose-reduced for previous hepatotoxicity...
January 3, 2018: Leukemia Research
Ryoichi Fujiwara, Ryo Mitsugi, Asuka Uemura, Tomoo Itoh, Robert H Tukey
Neurotoxic bilirubin is solely conjugated by UDP-glucuronosyltransferase (UGT) 1A1. Due to an inadequate function of UGT1A1, human neonates develop mild to severe physiological hyperbilirubinemia. Accumulation of bilirubin in the brain leads to the onset of irreversible brain damage called kernicterus. Breastfeeding is one of the most significant factors that increase the risk of developing kernicterus in infants. Why does the most natural way of feeding increase the risk of brain damage or even death? This question leads to the hypothesis that breast milk-induced neonatal hyperbilirubinemia might bring certain benefits to the body...
October 2017: Hepatology Communications
Heather Sevinsky, Luna Zaru, Reena Wang, Xiaohui Xu, Cheryl Pikora, Todd A Correll, Timothy Eley
BACKGROUND: Two clinical studies (PRINCE-1 and -2) in HIV-1-infected children assessed the safety, efficacy, and pharmacokinetics of dual nucleos(t)ide reverse transcriptase inhibitor (NRTI) background therapy plus once-daily atazanavir powder formulation boosted with ritonavir (ATV+RTV). Here, we present a combined analysis of ATV pharmacokinetics and pharmacodynamics across these studies. METHODS: Intensive 24-hour pharmacokinetic profiles at steady state compared ATV exposures (area under the concentration-time curve in one dosing interval [AUCτ]) in 5 ATV+RTV baseline weight-band dosing categories with historic data in adults receiving ATV+RTV 300/100-mg capsules...
December 4, 2017: Pediatric Infectious Disease Journal
Yue Zhang, Youcai Zhang, Curtis D Klaassen, Xingguo Cheng
Perfluorochemicals produce hepatotoxic effects via activation of PPARα and CAR nuclear receptors in animals. Bile formation is one major liver function. But it remains unknown whether perfluorochemicals alter metabolism of bile acids (BAs) in liver. The present study was designed to determine the impact of perfluorononanoic acid (PFNA) on BA and cholesterol homeostasis in mice. A single dose of PFNA (0.1 mmol/kg) was intraperitoneally administered to adult male wild-type (WT), PPARα-null, and CAR-null mice...
November 3, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Somia Iqtadar, Nabeel Akbar, Naima Huma, Fawad Ahmad Randhawa
OBJECTIVES: To estimate the range of hepatic involvement in dengue infections by assessing clinical and biochemical profile of adult dengue infected patients. METHODS: Serologically confirmed 220 adult cases of dengue infections admitted to Mayo hospital from June 2013 to November 2013 were classified as having dengue fever, dengue haemorragic fever and dengue shock syndrome. The frequency and range of bilirubin, liver enzymes derangement and presence of liver enlargement in each group was calculated and further stratified according to age and gender...
July 2017: Pakistan Journal of Medical Sciences Quarterly
Ryoichi Fujiwara, Mathias Haag, Elke Schaeffeler, Anne T Nies, Ulrich M Zanger, Matthias Schwab
Neurotoxic bilirubin is the end product of heme catabolism in mammals. Bilirubin is solely conjugated by UDP-glucuronosyltransferase (UGT) 1A1, which is a membrane-bound enzyme that catalyzes a transfer of glucuronic acid. Due to low function of hepatic and intestinal UGT1A1 during the neonatal period, human neonates develop mild to severe physiological hyperbilirubinemia. The accumulation of bilirubin in the brain leads to the onset of irreversible brain damage, kernicterus. Breastfeeding is one of the most significant factors that increase the risk of developing kernicterus in infants...
October 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Van Thu Huynh, Sharon Bergeron
BACKGROUND: Acute lymphoblastic leukemia (ALL) is a common cancer in children, and outcomes have greatly improved because of the refinement of multiagent chemotherapy regimens that include intensified asparaginase therapy. Asparaginase, a cornerstone of modern pediatric chemotherapy regimens for ALL and asparaginase-containing protocols, is increasingly used in adolescent and adult patients historically treated with asparaginase-free regimens. 
. OBJECTIVES: This article is an overview of commonly encountered asparaginase-
associated toxicities and offers recommendations for treatment management...
October 1, 2017: Clinical Journal of Oncology Nursing
Prabhat Kumar, Gargi Sasmal, Shreya Gupta, Renu Saxena, Sudha Kohli
Crigler Najjar Syndrome (CNS) Type 2 is an uncommon genetic disorder characterised by non-haemolytic unconjugated hyperbilirubinemia. It is caused by mutations in the UGT1A1 gene which codes for the enzyme uridine diphosphate glucoronosyl transferase- 1, required for the conjugation and further excretion of bilirubin from the body. Affected individuals are usually asymptomatic apart from the jaundice and investigations reveal isolated indirect hyperbilirubinemia. It can be conveniently diagnosed by evaluating the response to phenobarbitone in terms of fall in bilirubin levels...
July 2017: Journal of Clinical and Diagnostic Research: JCDR
Lin Lyu, Jingxin Yao, Guodong Gao, Cun Long, Feilong Hei, Bingyang Ji, Jinping Liu, Kun Yu, Qiang Hu, Jinxiao Hu
The aims of this study were to evaluate the incidence, risk factors, and outcomes of hyperbilirubinemia in cardiac patients with veno-arterial (VA) ECMO. Data on 89 adult patients with cardiac diseases who received VA ECMO implantation in our hospital were retrospectively reviewed. All patients were divided into the following three groups: 24 in normal group (N, total bilirubin [TBIL] ≤3 mg/dL), 30 in high bilirubin group (HB, 6 mg/dL ≥ TBIL > 3 mg/dL), and 35 in severe high bilirubin group (SHB, TBIL > 6 mg/dL)...
September 6, 2017: Artificial Organs
Kai-Wang Ma, Da-Hu Yao, Yang Li, Guang-da Li, Hemanth Cherukury, Ai-Hua Jing, Gao-Feng Liang
Neonatal hyperbilirubinemia (jaundice) is a common disease with high incidence. Currently, the clinical inefficiency of adult bilirubin hemoperfusion medical adsorbent is a major technical barrier for the application of hemoperfusion treatment to rescue the severe neonatal jaundice. Based on the well-known principle of synergistic effects, a series of customized bilirubin polymeric compounds, comprised of one or more of the following components (glycidyl methacrylate, sodium acrylate, methacrylic acid isooctyl, hexamethylene diamine, albumin), were designed and fabricated based on molecular design...
September 6, 2017: Journal of Biomaterials Science. Polymer Edition
Elias Jabbour, Farhad Ravandi, Partow Kebriaei, Xuelin Huang, Nicholas J Short, Deborah Thomas, Koji Sasaki, Michael Rytting, Nitin Jain, Marina Konopleva, Guillermo Garcia-Manero, Richard Champlin, David Marin, Tapan Kadia, Jorge Cortes, Zeev Estrov, Koichi Takahashi, Yogin Patel, Maria R Khouri, Jovitta Jacob, Rebecca Garris, Susan O'Brien, Hagop Kantarjian
Importance: The outcome of patients with relapsed or refractory (R/R) acute lymphoblastic leukemia (ALL) is poor. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has single-agent activity in R/R ALL. Objective: To evaluate the efficacy and safety of inotuzumab ozogamicin plus low-intensity chemotherapy in patients with R/R ALL. Design, Setting, and Participants: A single-arm, phase 2 study of adults with R/R B-cell ALL conducted at The University of Texas MD Anderson Cancer Center, Houston...
August 31, 2017: JAMA Oncology
Ronald J Wong, Vinod K Bhutani, David K Stevenson
Background: Hyperbilirubinemia is a benign transitional phenomenon that occurs in 60% to 80% of all term infants. The degree of hyperbilirubinemia and hence risk for developing bilirubin-induced neurologic dysfunction or BIND is dependent upon two major processes: (i) bilirubin production and its elimination. Objective: The aim of this review is to address the importance of hemolysis and its clinical detection in neonates with hyperbilirubinemia. Results: In newborns, an increased bilirubin production rate due to hemolysis is often the primary cause of hyperbilirubinemia during the first week of life...
August 7, 2017: Current Pediatric Reviews
Enrico Vidal, Francesco Garzotto, Mattia Parolin, Chiara Manenti, Anna Zanin, Massimo Bellettato, Giuseppe Remuzzi, Stuart L Goldstein, Luisa Murer, Claudio Ronco
Therapeutic plasma exchange (TPE) in neonates and small infants is a treatment method at the forefront that may become a potentially life-saving procedure in a wide array of severe conditions. Indications for TPE in the pediatric population have been mainly derived from adult literature, with neonatal hyperbilirubinemia being the most notable exception. The only alternative to TPE in small pediatric patients is manual blood exchange transfusion, which, however, bears an unacceptably high risk of severe complications...
2017: Blood Purification
Elias Jabbour, Nicholas J Short, Farhad Ravandi, Xuelin Huang, Lianchun Xiao, Guillermo Garcia-Manero, William Plunkett, Varsha Gandhi, Koji Sasaki, Naveen Pemmaraju, Naval G Daver, Gautam Borthakur, Nitin Jain, Marina Konopleva, Zeev Estrov, Tapan M Kadia, William G Wierda, Courtney D DiNardo, Mark Brandt, Susan M O'Brien, Jorge E Cortes, Hagop Kantarjian
BACKGROUND: Fludarabine and clofarabine are purine nucleoside analogues with established clinical activity in patients with acute myeloid leukemia (AML). METHODS: Herein, the authors evaluated the efficacy and safety of idarubicin and cytarabine with either clofarabine (CIA) or fludarabine (FIA) in adults with newly diagnosed AML. Adults with newly diagnosed AML who were deemed suitable for intensive chemotherapy were randomized using a Bayesian adaptive design to receive CIA (106 patients) or FIA (76 patients)...
November 15, 2017: Cancer
Hongbiao Huang, Mingxing Guo, Ningning Liu, Chong Zhao, Haoyu Chen, Xiaoli Wang, Siyan Liao, Ping Zhou, Yuning Liao, Xin Chen, Xiaoying Lan, Jinghong Chen, Dacai Xu, Xiaofen Li, Xianping Shi, Li Yu, Yuqiang Nie, Xuejun Wang, Chang-E Zhang, Jinbao Liu
The molecular mechanism underlying bilirubin neurotoxicity remains obscure. Ubiquitin-proteasome system-mediated proteolysis is pivotal to virtually all cellular processes and cell survival. Here we report for the first time that bilirubin at a clinically relevant elevated level impairs proteasomal function via inhibiting both the 19S proteasome-associated deubiquitinases (USP14 and UCHL5) and the chymotrypsin-like (CT-like) peptidase activity of 20S proteasomes, thereby contributing to bilirubin neurotoxicity...
June 15, 2017: Cell Death & Disease
Roberto Lorusso, Sandro Gelsomino, Orlando Parise, Michele Di Mauro, Fabio Barili, Gijs Geskes, Enrico Vizzardi, Peter T Rycus, Raf Muellenbach, Thomas Mueller, Antonio Pesenti, Alain Combes, Giles Peek, Bjorn Frenckner, Matteo Di Nardo, Justyna Swol, Jos Maessen, Ravi R Thiagarajan
OBJECTIVES: To assess in-hospital neurologic (CNS) complications in adult patients undergoing veno-venous extracorporeal membrane oxygenation for respiratory failure. DESIGN: Retrospective analysis of the Extracorporeal Life Support Organization's data registry. SETTING: Data reported to Extracorporeal Life Support Organization from 350 international extracorporeal membrane oxygenation centers during 1992-2015. PATIENTS: Adults (≥ 18 yr old) supported with veno-venous extracorporeal membrane oxygenation for respiratory failure...
August 2017: Critical Care Medicine
Frank P Tverdek, Sang Taek Heo, Samuel L Aitken, Bruno Granwehr, Dimitrios P Kontoyiannis
Posaconazole is the preferred mold-active azole for prophylaxis against invasive fungal infections (IFIs) in patients with hematological malignancy. Delayed-release tablet and intravenous formulations of posaconazole have recently become available, but clinical data are limited. We sought to examine the real-world pharmacokinetics and prophylactic effectiveness of the new formulations of posaconazole given as prophylaxis for patients with hematological malignancy. A retrospective cohort of all consecutive adult inpatients with hematological malignancy who received ≥3 days of tablet or intravenous posaconazole therapy for primary IFI prophylaxis at the M...
August 2017: Antimicrobial Agents and Chemotherapy
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