Oxygenated UW solution decreases ATP decay and improves survival after transplantation of DCD liver grafts

Background DCD liver grafts are known to be predisposed to primary nonfunction and ischemic cholangiopathy. Many DCD grafts are discarded because of older donor age or long warm ischemia times. Thus, it is critical to improve the quality of DCD liver grafts. Here, we have tested whether an enriched oxygen carrier added to the preservation solution can prolong graft survival and reduce biliary damage. Methods We assessed the ATP content decay of mouse liver grafts after cold ischemia, warm ischemia, and combined warm+cold ischemia. In addition, we used a rat model of liver transplantation to compare survival of DCD grafts preserved in high-oxygen solution (pre-oxygenated PFC+UW solution) vs. lower-oxygen solution (pre-oxygenated UW solution). Results ATP levels under UW preservation fall to less than 10% after 30 min of warm ischemia. Pre-oxygenated UW solution with PFC reached a significantly higher PaO2. After 45min of warm ischemia in oxygenated UW+PFC solution, grafts showed 63% higher levels of ATP (p=0.011). In addition, this was associated with better preservation of morphology when compared to grafts stored in standard UW solution. Animals that received DCD grafts preserved in higher oxygenation solution showed improved survival: 4 out of 6 animals survived long-term whereas all control group animals died within 24 hours. Conclusions The additional oxygen provided by PFC during static cold preservation of DCD livers can better sustain ATP levels, and thereby reduce the severity of ischemic tissue damage. PFC-based preservation solution extends the tolerance to warm ischemia, and may reduce the rate of ischemic cholangiopathy. Corresponding author: James F. Markmann MD, PhD, Transplant Center, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA, 02114, e-mail: jmarkmann@partners.org Authorship 1. Paulo N. Martins and James F. Markmann participated in research design, performance of the research and writing of the paper. 2. Timothy A. Berendsen, Heidi Yeh, Bote G. Bruinsma, Maria-Louisa Izamis, Sanna Op den Dries, Robert Porte, Martin L. Yarmush, and Korkut Uygun participated in performance of the research and writing of the paper. 3. Andrew R. Gillooly participated in writing of the paper. Disclosure The authors declare no conflicts of interest. Funding Departmental grant Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Asian Liver Transplant Network Clinical Guidelines on Immunosuppression in Liver Transplantation

Most management guidelines and much of the available clinical trial evidence for immunosuppressants in liver transplantation pertain to Western practice. While evidence from Western studies may not translate to Asian settings, there is a paucity of Asian randomized controlled trials of immunosuppression in liver recipients. Nonetheless, there are notable differences in the indications and procedures for liver transplantation between Western and Asian settings. The Asian Liver Transplant Network (ALTN) held its inaugural meeting in Singapore in November 2016 and aimed to provide an Asian perspective on aspects of immunosuppression following liver transplantation. Because of their importance to outcome following liver transplantation, the meeting focused on: (1) reducing the impact of renal toxicity, (2) hepatocellular carcinoma recurrence and (3) nonadherence with immunosuppressant therapy. Corresponding author: Poh Seng TAN, Division of Gastroenterology and Hepatology, National University Hospital, National University Health System, 1E Kent Ridge Road Tower Block, Level 10, Singapore 119228, DID (+65) 6772-4354; Fax (+65) 6775-1518, Email: poh_seng_tan@nuhs.edu.sg Authorship page Authorship P.S.T., M.D.M., and T.K. are co-first authors with equal contribution to writing the draft of the article. J.F., and K.L. are co-senior authors with equal contribution leading the project. All authors reviewed the draft, provided expertise for critical revisions, and approved the final version of the article. Disclosure P.S.T is a PI of a Novartis sponsored clinical trial (H2307). The other authors declare no conflict of interest. Funding The consensus meeting was supported by the educational grant provided by Novartis and Astellas. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Transplantation Society Consensus Statement on Immunosuppression in Liver Transplant Recipients: Erratum

No abstract available

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Analysis of Differentially Expressed Proteins in Hepatocellular Carcinoma: Erratum

No abstract available

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Oxygenated preservation solutions for organ preservation

No abstract available

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Association between hidradenitis suppurativa and hospitalization for psychiatric disorders: A cross‐sectional analysis of the National Inpatient Sample

Abstract

Background

Hidradenitis suppurativa (HS) is associated with pain, disfigurement, psychosocial distress and poor quality of life, all of which may lead to higher likelihood of mental health (MH) disorders. However, little is known about the MH comorbidities of HS.

Objectives

to determine the MH disorders and cost‐burden associated with HS.

Methods

Data were examined from the 2002‐2012 National Inpatient Sample, comprising a ~20% sample of all US pediatric and adult hospitalizations (n=87,053,155 admissions).

Results

MH disorders were much more common in inpatients with vs. without HS (34·27% vs. 20·05%). In multivariable logistic regression models controlling for gender, age, race/ethnicity, and insurance status, HS was associated with significantly higher odds of a MH disorder (adjusted odds ratio [95% confidence interval]: 2·53 [2·42‐2·63]), including 10 of 15 MH disorders examined. In contrast, HS was not associated with primary hospitalization for a MH disorder overall (0·95 [0·84‐1·07]), but was associated with primary hospitalization for 8 of 15 MH disorders examined. Among inpatients with HS, primary admission for a MH disorder was associated with female sex, public or no insurance, more chronic diseases, but inversely associated with older age, female sex, and non‐white race/ethnicity. HS was associated with >$38 million of excess mean annual costs of hospitalization for MH disorders.

Conclusions

Inpatients with HS had increased odds of comorbid mental health disorders, overall, and multiple primary mental health admissions, in particular, which were associated with considerable excess costs.

This article is protected by copyright. All rights reserved.

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Interaction of the mycotoxin metabolite dihydrocitrinone with serum albumin

Abstract

Citrinin (CIT) is a nephrotoxic mycotoxin produced by Penicillium, Monascus, and Aspergillus species. CIT appears as a contaminant in cereals, cereal-based products, fruits, nuts, and spices. During the biotransformation of CIT, its major urinary metabolite dihydrocitrinone (DHC) is formed. Albumin interacts with several compounds (including mycotoxins) affecting their tissue distribution and elimination. CIT-albumin interaction is known; however, the complex formation of DHC with albumin has not been reported previously. In this study, we aimed to investigate the interaction of DHC with albumin, employing fluorescence spectroscopy, circular dichroism, and molecular modeling studies. Furthermore, species differences and thermodynamics of the interaction as well as the effects of albumin on the acute in vitro toxicity of DHC and CIT were also tested. Our main observations/conclusions are as follows: (1) Fluorescence signal of DHC is strongly enhanced by albumin. (2) Formation of DHC-albumin complexes is supported by both fluorescence spectroscopic and circular dichroism studies. (3) DHC forms similarly stable complexes with human albumin (K~10⁵ L/mol) as CIT. (4) DHC-albumin interaction did not show significant species differences (tested with human, bovine, porcine, and rat albumins). (5) Based on modeling studies and investigations with site markers, DHC occupies the Heme binding site (subdomain IB) on human albumin. (6) The presence of albumin significantly decreased the acute in vitro cytotoxic effects of both DHC and CIT on MDCK cell line.

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