Impact of Donor Core Body Temperature on Graft Survival After Heart Transplantation

Background A previous donor intervention trial found that induction of mild therapeutic hypothermia in the brain-dead donor reduced the dialysis requirement after kidney transplantation. Consequences on the performance of cardiac allografts after transplantation were not explored to date. Methods Cohort study investigating 3-year heart allograft survival according to spontaneous core body temperature (CBT) assessed on the day of organ procurement. The study is nested in the database of the randomized trial of donor pretreatment with low-dose dopamine (ClinicalTrials.gov identifier: NCT000115115). Results 99 heart transplant recipients who had received a cardiac allograft from a multiorgan donor enrolled in the dopamine trial were grouped by tertiles of the donor's CBT assessed by a mere temperature reading 4-20 hours before procurement (lowest, 32.0-36.2°C; middle, 36.3-36.8°C; highest, 36.9-38.8°C). Baseline characteristics considering demographics of donors and recipients, concomitant donor treatments, donor hemodynamic and respiratory parameters as well as underlying cardiac diseases in recipients, pretransplant hemodynamic assessments, including pretransplant inotropic / mechanical support, urgency, and waiting-time were similar. A lower CBT was associated with inferior heart allograft survival, hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.31-0.93, per tertile; p=0.02, and HR 0.68, 95% CI 0.50-0.93, per degree Celsius; p=0.02, when CBT was included as continuous explanatory variable in the Cox regression analysis. Conclusions A lower CBT in the brain-dead donor before procurement may associate with an unfavorable clinical course after heart transplantation. More research is required, before therapeutic hypothermia can routinely be used in multiorgan donors when a cardiac transplantation is intended. Address correspondence to: Dr. Peter Schnuelle, Center for Renal Diseases Weinheim, c/o University Medical Center Mannheim, Roentgenstrasse 1, D 69469 Weinheim, Germany, Tel.: 0049 6201 947931, Fax: 0049 6201 947920, e-mail: p.schnuelle@nierenzentrum-weinheim.de Authorship P.S. and U.B. contributed equally. P.S. drafted the manuscript. P.S., U.B., B.K.K., B.A.Y. participated in the study concept and design, statistical analysis and interpretation of data. A.Z., F.W., G.S., M.B., M.K., J.G. participated in the performance of research, acquisition of data, and critical revision of the manuscript for important intellectual content. All authors approved the final version of the manuscript. Disclosure The authors declare no conflicts of interest. Funding The randomized dopamine study was an investigator-driven clinical trial conducted by the University Medical Center Mannheim, Germany. It was partially supported by a medical school grant from Novartis Pharmaceuticals released in November 2002, before the study started recruiting eligible donors. Trial registry ClinicalTrials.gov identifier: NCT000115115 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Recurrent or De Novo Allograft Steatosis and Long-Term Outcomes After Liver Transplantation

Background Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft but the impact on survival and long term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long term posttransplant outcomes. Methods A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time dependent) was used to evaluate differences in time to steatosis post-LT, patient survival and cardiovascular outcomes. Results Mean age 51.9±10.6 years, 64.6% males, underlying NASH (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female gender (hazard ratio [HR] 1.47, 95% confidence interval [CI] 1.09-2.00, p=0.014), HCV diagnosis (HR 2.49, 95% CI 1.77-3.94, p

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Cold-storage injury to rat small-bowel transplants – beneficial effect of a modified HTK solution

Background The small bowel is prone to ischaemic injury during transport prior to transplantation, an injury that endangers the recipient patient. The small-bowel mucosal microcirculation in particular appears to be highly sensitive to injury. Current preservation solutions such as histidine-tryptophan-ketoglutarate (HTK) solution provide some protection to the graft. However, these were developed decades ago and do not address several critical processes, such as hypoxia-induced membrane pores and free radical-mediated hypothermic injury. Methods To protect the graft from cold ischaemic injury, we implemented a modified HTK solution here including glycine, alanine, and iron chelators in a heterotopic, syngeneic small-bowel transplantation model of the rat. The effects of the modified solution and its major components were compared against the conventional HTK solution using intravital microscopy in the early reperfusion period. Results The amino acid glycine, added to HTK solution, slightly improved mucosal perfusion. Both, the modified base solution (without iron chelators) and iron chelators increased functional capillary density of the mucosa during the early reperfusion period. The complete modified solution (with glycine, alanine, and iron chelators) significantly increased the perfusion index, functional capillary density of the mucosa and red blood cell velocity in the grafts following reperfusion in comparison with the grafts preserved with HTK. Conclusions The modified preservation solution improved the microcirculation of the transplants and needs detailed evaluation in further models of small-bowel transplantation. Received 15 December 2017. Revision received 31 May 2018. Accepted 3 June 2018. *deceased Address for correspondence: Dr Gesine Pless-Petig, Institut für Physiologische Chemie, Universitätsklinikum Essen, Hufelandstr. 55, 45122 Essen. gesine.pless@uni-duisburg-essen.de Authorship statement I. Lautenschläger participated in research design, writing the paper, research work and data analysis G. Pless-Petig participated in writing the paper and data analysis P. Middel participated in research work and data analysis H. de Groot participated in research design U. Rauen participated in research design, writing the paper and data analysis T. Stojanovic participated in research design, writing the paper, research work and data analysis Disclosure U. Rauen obtained consulting fees from Dr Franz Köhler Chemie GmbH, Bensheim, Germany. Dr F. Köhler Chemie holds a patent on a preservation solution covering the modified solution used in this study, and U. Rauen is one of the inventors of the solution. Funding The work was partially funded by Dr F. Köhler Chemie GmbH. However, the study design and data interpretation were nDrever influenced by the company at any point in time, which was also stipulated and agreed upon in the funding contract. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Gender differences in medication adherence among adolescent and young adult kidney transplant recipients

Background Among kidney transplant recipients, gender differences in medication adherence may contribute to the higher graft failure risks observed in girls and young women compared with boys and young men. Our aim was to determine whether adherence differs by gender, and whether gender differences vary by age in adolescent and young adult kidney transplant recipients. Methods We examined data from the 3-month run-in period (no intervention) of the randomized TAKE-IT trial. Adherence was monitored using electronic pillboxes in 136 patients (11-24 y) followed in 8 transplant centers in Canada and USA. We used ordinal logistic regression with generalized estimating equations to estimate the association between gender and each of daily taking (proportion of prescribed doses taken) and timing (proportion of prescribed doses taken on time) adherence, considering effect modification by age (11-16 vs. 17-24 years). Results No difference in taking adherence was observed by gender among participants 11-16 years (OR=0.92 (95%CI 0.55-1.54)), whereas among participants 17-24 years, women had significantly greater odds of higher taking adherence scores (OR=3.03 (95%CI 1.20-7.66)) than men. Results were similar for timing adherence, with no difference among participants 11-16 years (OR=1.03 (95%CI 0.65-1.63)) but a greater odds of higher timing adherence scores in women than in men among participants 17-24 years (OR=3.26 (95%CI 1.43-7.45)). There were no differences in adherence assessed by self-report or SD of tacrolimus trough levels. Conclusions Gender differences in adherence vary by age. Whereas younger adolescents show no adherence differences by gender, young women show much better adherence than young men. Correspondence to: Bethany J Foster, E-mail: bethany.foster@mcgill.ca. 1001 Decarie Blvd, Montreal, QC. H4A 3J1 TAKE-IT registration number: Clinicaltrials.gov registration: NCT01356277 (May 17, 2011) Authorship All authors participated in research design, in the writing of the paper and in data analysis. Disclosure The authors of this manuscript have no relevant conflicts of interest to disclose, except Dr. Foster, who is a co-investigator on 2 investigator-initiated studies funded by Astellas Canada. Funding The study was funded by the American National Institutes of Health, National Institutes of Diabetes, Digestive and Kidney diseases (NIDDK; R01DK092977). The funder had no role in study design, data collection, analysis, interpretation of data, writing the report, or and the decision to submit the report for publication. Dr. Boucquemont, who was a postdoctoral fellow at the Research Institute of the McGill University Health Centre when this study was done, was supported by an RI MUHC – Desjardins Studentship in Child Health Research. Dr. Foster, a member of the Research Institute of the McGill University Health Centre, was supported by a Fonds de recherche du Quebec Santé Chercheur-boursier clinicien award. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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EVOLUTIONARY DISTANCE PREDICTS RECURRENCE AFTER LIVER TRANSPLANTATION IN MULTIFOCAL HEPATOCELLULAR CARCINOMA

Background Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single nucleotide polymorphism (SNP) data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after liver transplantation for multifocal HCC. Methods In a retrospective multicenter study, clinical data and formalin fixed paraffin embedded (FFPE) specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from FFPE specimens followed by genome wide SNP genotyping. Results Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (p=0.04) and in the replication datasets (p=0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined p=0.0002). In a univariate analysis, evolutionary distance (p=7.4×10-6) and microvascular invasion (p=1.31×10-5) were significantly associated with survival in a Cox regression analysis. Conclusions Evolutionary distance allows for the determination of a high-risk group of recurrence, if preoperative liver biopsy is considered. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. *N.H., M.B. and A.H. contributed equally to the study and the manuscript §C.S., F.B. and J.H. contributed equally to the study and the manuscript and assume equal responsibility for senior authorship Corresponding author: #to whom correspondence should be addressed: Clemens Schafmayer, MD, Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, Kiel Campus, Christian-Albrechts-University Kiel, Arnold-Heller-Str. 3, 24105 Kiel / Germany, Tel.: +49 (0) 431 500-20411, Fax: +49 (0) 431 500-20404. Email: Clemens.Schafmayer@uksh.de AUTHORSHIP PAGE Authorship: a. Substantial contributions to the conception or design of the work. b. Acquisition, analysis, or interpretation of data for the work. c. Drafting the work or revising it critically for important intellectual content. d. Final approval of the version to be published. e. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Nils Heits a, b, c, d, e Mario Brosch a, b, c, d, e Alexander Herrmann a, b, c, d, e Robin Behrens b, d, e Christoph Röcken b, d, e Harald Schrem b, d, e Alexander Kaltenborn b, d, e Jürgen Klempnauer b, d, e Hans-Heinrich Kreipe b, d, e Benedikt Reichert b, d, e Christina Lenschow b, d, e Christian Wilms b, d, e Thomas Vogel b, d, e Heiner Wolters b, d, e Eva Wardelmann b, d, e Daniel Seehofer b, d, e Stephan Buch b, d, e Sebastian Zeissig b, d, e Sven Pannach b, d, e Nathanael Raschzok b, d, e Manfred Dietel b, d, e Witigo von Schoenfels b, d, e Sebastian Hinz b, d, e Andreas Teufel b, d, e Matthias Evert b, d, e Andre Franke b, d, e Thomas Becker b, d, e Felix Braun a, b, c, d, e Jochen Hampe a, b, c, d, e Clemens Schafmayer a, b, c, d, e Disclosure: The authors declare no conflicts of interest. Funding: This work was supported by institutional funds from the Medical Faculties of the Christian-Albrechts University Kiel and the Technical University Dresden. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Syndrome d’activation macrophagique secondaire à une fièvre boutonneuse méditerranéenne

Publication date: Available online 10 July 2018

Source: Annales de Dermatologie et de Vénéréologie

Author(s): A.-S. Bertrand, M. Fondain, P. Rullier, C. Fontaine, B. Guillot

Résumé

Introduction

Le syndrome d'activation macrophagique (SAM) est une pathologie rare de pronostic sévère définie par des critères cliniques, biologiques et cyto-histologiques. Les infections représentent une cause classique de SAM. Les SAM secondaires à une fièvre boutonneuse méditerranéenne sont rares ; seuls quelques cas sont rapportés dans la littérature.

Observations

Nous rapportons les cas de deux hommes de 77 et 63 ans qui avaient une éruption maculo-purpurique fébrile avec escarre d'inoculation associée à des anomalies biologiques comprenant cytopénie, hyperferritinémie et hypertriglycéridémie. Une hémophagocytose était présente dans les deux cas. La sérologie et la PCR Rickettsia conorii étaient positives en faveur d'une infection récente, confirmant le diagnostic de fièvre boutonneuse méditerranéenne (FBM). Ces éléments permettaient dans les deux cas de poser le diagnostic de SAM secondaire à une FBM.

Discussion

Le premier cas de SAM a été décrit en 1979. Seize cas de SAM secondaires à une FBM sont décrits dans la littérature. La présence d'une cytopénie associée à une hyperferritinémie et une hypertriglycéridémie au cours d'une FBM est fortement évocatrice du diagnostic de SAM. Le pronostic dépend du délai diagnostique et des facteurs propres à l'hôte. L'association d'immunosuppresseurs à l'antibiothérapie peut être nécessaire pour obtenir la guérison.

Conclusion

Les rickettsioses peuvent induire un syndrome d'hémophagocytose ; la survenue possible de cette complication de mauvais pronostic mérite d'être connue.

Summary

Introduction

Haemophagocytic syndrome (HS) is a rare disease with a severe prognosis that is defined by clinical, laboratory and histopathological criteria. Infections represent the classical cause of HS. HS secondary to Mediterranean spotted fever (MSF) is rare with only a few cases being reported in the literature.

Observations

We report two cases of HS secondary to MSF in 2 men aged 77 and 63 years presenting a febrile maculo-purpuric eruption with inoculation ulcer associated with laboratory abnormalities (cytopenia, elevated ferritin, hypertriglyceridaemia). Haemophagocytosis was present in 2 cases. Serology and PCR for Rickettsia conorii were positive and militated in favour of recent infection responsible for the diagnosis of MSF.

Discussion

The first case of HS was described in 1979. Sixteen cases of HS secondary to MSF are described in the literature. Cytopenia associated with hyperferritinaemia and hypertriglyceridaemia strongly suggests MSF complicated by HS. The prognosis depends on the time elapsed since diagnosis and host-specific factors. Immunosuppressants and antibiotics may be necessary to ensure healing.

Conclusion

Rickettsioses can induce HS, and this potential complication with a severe prognosis must be known.

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Ceramic soft tissue trimming bur: A new tool for gingival depigmentation

Publication date: Available online 10 July 2018

Source: Journal of Oral Biology and Craniofacial Research

Author(s): Rohini Negi, Rajan Gupta, Parveen Dahiya, Mukesh Kumar, Vrishti Bansal, Japnit Kaur Samlok

Abstract

Objective

Pigmentation of the gingiva plays a negative role in an otherwise acceptable "smile window". In the present world, people are more concerned about their aesthetics. Several techniques have been employed such as scalpel surgery, electrosurgery, cryosurgery, chemical agents, abrasion and LASER method for the removal of melanin hyper-pigmentation. The present study is aimed at comparing the efficacy of LASER and soft tissue trimmer for gingival depigmentation.

Methods

A randomized split-mouth study was conducted for twenty patients with gingival pigmentation. Dummet Oral Pigmentation Index (DOPI), Gingival Pigmentation Index (GPI) for pigmentation, bleeding factor, wound healing factor, gingival colour and visual analogue scale (VAS) score for pain were evaluated for both the groups at baseline, 7th day, 1st month and 6th month.

Results

Intra-group comparison between baseline and 6th month showed highly significant difference for both LASER and bur groups. There was no statistically significant difference found between both the groups at 6th month using gingival pigmentation index.

Conclusion

It can be concluded that LASER and soft tissue trimmer both are comparable in achieving aesthetic satisfaction. Hence, the soft tissue trimmer could also be used for depigmentation as it is very cost effective, readily available and acceptable by the patients.

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