Transplantation

Clostridium difficile: a frequent infection in children after intestinal transplantation Background: Organ transplantation is a risk factor for Clostridium difficile infection (CDI). After intestinal transplantation (ITx), few data are available on the impact of this graft infection and the possible induction of rejection. Methods: We included retrospectively all children after ITx in our unit, with at least one year of graft survival. All samples positive for Clostridium difficile and its toxin were considered. Results: Among the 57 ITx recipients (60 transplantations), 22 children (39%) developed culture-proven CDI, 12 after isolated small bowel Tx, 9 after liver-small bowel Tx, one after multivisceral Tx. Twenty patients had diarrhea, 8 bloody stools, 4 fever, one hypothermia. Nine were hospitalized for an average of 6.5 days (2-20), four with severe dehydration. Nine (40%) had received antibiotics for an average of 19 days (7-60) before CDI. Two patients were asymptomatic. CDI was treated with metronidazole in 12 children, vancomycin in 6 and both of them in 3. Three children presented mild to severe rejections. Two patients presented concomitantly CDI and rejection. The third patient presented a rejection with severe complications 4 years after CDI. Recurrence of toxinogenic CD was observed in 9 children, in 7 associated with clinical symptoms. During the last follow-up, the stool number was the same as before CDI except for one patient with ongoing infection. Conclusion: CDI is more prevalent in children after ITx compared with other organ Tx; it is most often symptomatic but mildly or moderately severe. Standard antibiotics efficiently control the symptoms. Induction of rejection is a rare event. RDL, FL, JB and LN participated, in the writing of the paper and in data analysis, AF, CC and OG participated in research design and in the writing of the paper. Disclosure: "The authors declare no conflict of interest." Financial disclosure:"The authors declare no financial disclosure." Corresponding Author: Dr Rémi Duclaux-Loras, Hôpital Femme Mère Enfant, 59 boulevard Pinel 69677 BRON, remi.duclaux-loras@chu-lyon.fr Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Role of preimplantation biopsies in kidney donors with acute kidney injury. No abstract available

The Forgotten Member of Patient Selection Committees: The U.S. Constitution No abstract available

The outcomes of portal vein reconstruction with vein graft interposition in pediatric liver transplantation for small children with biliary atresia Background: Several technical modifications in portal vein (PV) reconstruction have shown excellent outcomes in pediatric liver transplantation (LT); however, which procedure is the best for PV reconstruction of the hypoplastic PV in pediatric LT remains unclear. Methods: One hundred sixteen pediatric patients aged 1 or younger with BA undergoing living donor liver transplantation (LDLT) at our center were enrolled in the present study to investigate the outcomes of the different types of PV reconstruction. We compared the results between patients with and without VG interposition (VG group, n = 33; non-VG group, n = 83) to analyze the risk factors for PV complications (PVCs). The median follow-up period was 4.7 years. Results: PVCs occurred in 10 cases (7.2%), including 5 cases in the non-VG group and 5 in the VG group. Stenosis and thrombosis occurred in 10 and 3 cases, respectively, and 3 cases suffered from both. Three patients were surgically treated for PVCs and two underwent stent insertion to treat short-term recurrence after the initial treatment. The incidence of PVCs in the two groups did not differ to a statistically significant extent. Although retrograde PV flow was one of significant risk factors in a univariate analysis, a multivariate analysis revealed that early transplant era was the only independent risk factor for PVCs. Conclusions: VG interposition for PV reconstruction in LDLT appears to be a feasible alternative option with acceptable outcomes for patients with BA. Achieving sufficient PV flow is essential to preventing PVCs after LDLT. Authorship: S. Sakamoto, H. Uchida and T. Kitajima participated in study design, data analysis, and the writing of the paper, S. Shimizu critically reviewed the statistical analysis. S. Yoshimura, M. Takeda, Y. Hirata and A. Fukuda collected the clinical data, M. Kasahara critically reviewed the article. Conflict of interest: None Corresponding Author:Seisuke Sakamoto MD, PhD, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan. E-mail: sakamoto-si@ncchd.go.jp, Phone: +81-3-3416-0181. Fax: +81-3-3416-222 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Long-term outcomes following kidney transplantation from donors with acute kidney injury Background: Kidneys from deceased donors with acute kidney injury (AKI) are more likely to be discarded because of concerns for poor outcomes after transplantation. The aim of this study was to determine the long-term outcomes of a large cohort of patients transplanted utilizing kidneys from deceased donors with acute kidney injury. Methods: All patients receiving a deceased donor kidney transplant during a recent 10-year period were included. Acute Kidney Injury Network (AKIN) criteria were used to classify the donors. Donor kidneys with more than 10% cortical necrosis or more than mild chronic changes were discarded. The primary outcome is the combined endpoint of death or graft loss. Results: The cohort included 1,313 kidneys from 974 donors, AKIN stage 0 (no AKI) in 319 (24.3%), stage 1 in 370 (28.2%), stage 2 in 177 (13.5) and stage 3 in 447 (34.0%). Estimated 5-year graft survival (95% CI) was 78.5% (72.5-84.5), 77.8% (72.8-82.1), 83.8% (76.8-88.9) and 84.6% (79.5-88.7) for AKIN donor stage 0 to 3, respectively (log-rank p=0.10). After adjusting for baseline differences, the HR (95% CI) for the combined endpoint for the AKIN stage 3 group (relative to AKIN 0 group) was 0.70 (0.45-1.10). DGF occurred in 44.6% and 75.4% of AKIN 2 and 3 groups, as compared to 33.9% and 33.5% in AKIN 0 and 1 (p<.001). Conclusion We conclude that transplanting selected kidneys from deceased donors with AKI with preimplantation biopsy showing less than 10% cortical necrosis and no more than mild chronic changes have excellent long-term graft survival. Disclosures: The authors declare no conflicts of interest. Conclusion: We conclude that transplanting selected kidneys from deceased donors with AKI with pre-implantation biopsy showing less than 10% cortical necrosis and no more than mild chronic changes have excellent long-term graft survival. Corresponding Author: Raymond L. Heilman, MD, 5777 East Mayo Boulevard, Phoenix, AZ 85054, Email Heilman.raymond@mayo.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Performance of creatinine clearance and estimated GFR in assessing kidney function in living donor candidates Background: Glomerular filtration rate (GFR) assessment is a key aspect in the evaluation of living kidney donor candidates; however, data on performance of commonly used methods are limited. Methods: We examined 769 living kidney donor candidates with 24-hour urine collections assessed as accurate by comparing measured creatinine excretion rate (CER) to CER estimated using a four-variable equation previously developed and validated using robust methodology. Results: Of all collections, 42.6% would have been deemed inaccurate, mostly under-collections, using the conventional weight- and gender-based CER estimation. Creatinine clearance (CrCl) overestimated 125I-iothalamate GFR (iGFR), estimated GFR (eGFR) underestimated iGFR, and their average [Avg (CrCl and eGFR)] essentially eliminated the GFR bias (median bias = +2.2, -5.4 and -1.0 ml/min/1.73m2, respectively; p<0.001). This held true for all subgroups except blacks, where all three measures overestimated iGFR. Avg (CrCl and eGFR) also offered modestly improved accuracy compared with CrCl alone, as measured by the proportion of values falling within 10% (50.7% vs. 45.3%; p=0.009) and 30% of iGFR (94.5% vs. 89.3%; p<0.001). Conclusions: When measured GFR is unavailable, the Avg (CrCl and eGFR) provides a better estimate of kidney function in kidney donor candidates than either measure alone, although in blacks the estimates are neither better nor worse. The authors declare no conflicts of interest. Disclosures: The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation. * Authors contributed equally to the study Corresponding author: Emilio D. Poggio, M.D. Department of Nephrology and Hypertension, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio 44195, E-mail: poggioe@ccf.org, Tel: 216-659-2734, Fax: 216-444-9378 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Cytotoxic Effects of Rabbit Anti-Thymocyte Globulin preparations on Primary Human Thymic Epithelial Cells Background: Graft-versus-host disease (GvHD) presents a major cause for morbidity and mortality after allogeneic hematopoietic stem cell transplantation (alloHSCT). Rabbit anti-thymocyte globulin (rATG) treatment reduces the incidence of GvHD after alloHSCT. However, delayed immune reconstitution following rATG treatment, partly due to hampered thymic function, is being discussed. The present study aimed at elucidating possible cytotoxic effects of two commonly used rATG preparations on cultured human thymic stroma, especially thymic epithelial cells (TECs). Methods: A primary thymic epithelial cell culture was established and the binding and cytotoxicity of two rATG preparations to the aforementioned cells were assessed by flow cytometry and immunofluorescence analyses. The release of several cytokines by cultured TSCs in response to rATG was analyzed via multiplex ELISA. Results: Both preparations showed a comparable dose-dependent binding to TECs and exerted a similar complement-independent, dose-dependent cytotoxicity. rATG exposure further resulted in hampered secretion of IL-7, IL-15 and IL-6, cytokines being involved in thymic T cell development and proliferation. Pretreatment with keratinocyte growth factor (KGF) diminished rATG-induced cytotoxicity of TECs and restored their IL-7 and IL-15 secretion. Conclusions: Cytotoxic effects on TECs link a rATG-induced thymic damage to the delayed T cell reconstitution witnessed after rATG treatment. Our data support a combination treatment of rATG and thymus-protective strategies such as KGF in order to simultaneously offer sufficient GvHD prophylaxis and overcome delayed T cell reconstitution due to thymic damage. Funding and disclosure: The authors of this manuscript have conflicts of interest to disclose as described by Transplantation. The studies reported in this publication were supported by a grant from Neovii Biotech GmbH. Although a financial conflict of interest was identified for management based on the overall scope of the project and its potential benefit to Neovii Biotech GmbH, the research findings included in this publication may not be necessarily related to the interests of Neovii Biotech GmbH. The terms of this arrangement have been reviewed and approved by Charité Universitätsmedizin Berlin in accordance with its policy on objectivity in research. Corresponding author: Univ.-Prof. Dr. med. Il-Kang Na, Charité - Campus Virchow-Klinikum, Hematology, Oncology and Tumor Immunology, Augustenburger Platz 1, 13353 Berlin, Germany. Phone: +49 30 450-540155/ -653598, E-mail: il-kang.na@charite.de Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Long-Term Effects of Hypothermic Ex-Situ Perfusion on Skeletal Muscle Metabolism, Structure, and Force Generation After Transplantation Background: Hypothermic ex-situ perfusion (HESP) systems are used to prolong allograft survival in solid organ transplantations and have been shown to be superior to static cold storage (SCS) methods. However, the effect of this preservation method on limb allograft survival and long-term function has not yet been tested. In this study, we investigated the long-term effects of the HESP on skeletal muscle metabolism, structure, and force generation and compared it with the current standard of preservation . Methods: Forty male Lewis rats (250 ± 25 gr) were divided into 5 groups including naive control, sciatic nerve transection/repair, immediate transplantation, SCS, and HESP. For the SCS group, limbs were preserved at 4˚C for 6 hours. In the HESP group, limbs were continuously perfused with oxygenated Histidine-Tryptophan-Ketoglutarate (HTK) solution at 10-15˚C for 6 hours. Hemodynamic and biochemical parameters of perfusion were recorded throughout the experiment. At 12 weeks, electromyographyand muscle force measurements (maximum twitch and tetanic forces) were obtained along with muscle samples for histology and metabolomics analysis. Results: Histology demonstrated 48% myocyte injury in the HESP group compared to 49% in immediate transplantation (p=0.96), and 74% in the SCS groups (p<0.05). The maximum twitch force measurement revealed a significantly higher force in the HESP group compared to the SCS group (p=0.029). Essential amino acid levels of the gastrocnemius muscle did not reach significance, with the exception of higher proline levels in the HESP group. Conclusion: Hypothermic ex-situ perfusion using HTK protects viability of the limb but fails to restore muscle force in the long-term. Authorship: Study design: EG, and KO. Acquisition of data: EG, CK, EG, MP, and MJH. Analysis and interpretation: EG, CK, EG, and MJH. Manuscript drafted by EG. Revision: EG, AR, SK, RHB and KO. Disclosures The authors declare no conflicts of interest. Acknowledgment: This study was partially supported by the American Foundation for Surgery of Hand (Award Number 1429) and Michigan Regional Comprehensive Metabolomics Resource Core Grant U24 DK097153. * Corresponding Author: Kagan Ozer, MD, Clinical Professor, Surgical Director for Hand Transplantation Program, Hand and Upper Extremity, Department of Orthopedic Surgery, University of Michigan Hospitals, 2098 South Main St. , Ann Arbor, MI 48103 USA. Phone: +1 (734) 998-6541, E-mail: kozer@med.umich.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

An outpatient hospital-based exercise training programme for patients with cirrhotic liver disease awaiting transplantation: a feasibility trial Background: Time spent on the waiting list prior to liver transplantation (LT) provides an opportunity to optimise recipient fitness through prehabilitation; potentially reducing the physiological impact of major surgery. We assessed the feasibility and effectiveness of a six-week exercise programme in patients with cirrhotic liver disease awaiting LT. Methods: This single centre, prospective cohort, feasibility study, enrolled patients awaiting LT to a six week period of thrice weekly, supervised exercise on a static bike. Cardiopulmonary exercise testing (CPET) was used to objectively assess cardiopulmonary fitness at baseline and after six weeks of exercise. A follow-up CPET was performed at 12 weeks. CPET-derived measures were used to guide prescription of the training programme. A non-randomised control cohort of LT patients were selected to match the exercise group based on specific demographic data. Allocation to study arms was primarily based on the distance participants lived from the hospital where training occurred. Both groups received structured nutritional advice. Results: The exercise programme was feasible, with 9/16 (56%) patients completing the full programme of six weeks. Peak oxygen consumption (VO2peak) in the exercise group rose from a mean (SD) of 16.2 (± 3.4) ml/kg/min at baseline to 18.5 (±4.6) ml/kg/min at week 6 (p=0.02). In the control group VO2peak decreased from a mean (SD) of 19.0 (± 6.1) ml/kg/min to 17.1 (±6.0) at week 6 (p=0.03). Conclusion: We have demonstrated that it is feasible to engage patients awaiting LT in an intensive aerobic exercise programme with a signal of improvement in fitness being detected. Grants and financial support: None Conflicts of interest: None declared Acknowledgments: We would like to thank all the patients that contributed to this study whilst awaiting their liver transplants. Corresponding author: Dr Clare Morkane MBBCh, MRCP, FRCA, FFICM, Royal Free Perioperative Research Group (RoFPoR), Department of Anaesthesia, Royal Free Hospital, Pond Street, London. c.morkane@nhs.net, 07725269398 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Differential impact of delayed graft function in deceased donor renal transplant recipients with and without donor-specific HLA-antibodies Background: Delayed graft function (DGF) and pre-transplant donor-specific HLA-antibodies (DSA) are both regarded as risk factors for rejection and lower graft survival. However, the combined impact of DGF and DSA has not been studied in detail. Methods: We investigated 375 deceased donor kidney transplantations, which had DSA assignment by single-antigen bead technology and which had surveillance biopsies at 3/6 months. Median follow-up time was 6.1 years. Results: DGF occurred in 137/375 patients (37%), and DSA were present in 85/375 patients (23%). The incidence of DGF was similar in DSApos-patients and DSAneg-patients (40% vs 36%; p=0.45). In DSAneg-patients, five-year graft survival was not different with/without DGF (81% vs 83%; p=0.48). By contrast, in DSApos-patients, five-year graft survival was significantly lower with DGF (64% vs 79%; p=0.01). Moreover, DSApos-patients with DGF had a higher one-year incidence of (sub)clinical rejection, which were mostly antibody-mediated or mixed rejection phenotypes. Graft loss due to rejection was significantly more frequent in DSApos-patients with DGF (5/34; 15%) compared to DSApos-patients without DGF (2/51; 4%), and DSAneg-patients with/without DGF (3/103; 3% and 4/187; 2%, respectively) (p=0.005). In a multivariate Cox model, DSA with DGF was an independent predictor for graft (HR=2.84 [95%-CI 1.54-5.06]; p=0.001) and death-censored graft loss (HR=4.65 [95%-CI 1.83-11.51]; p=0.002). Conclusions: DGF has a much more detrimental impact in DSApos-patients than in DSAneg-patients, which is likely related to a higher incidence of antibody-mediated rejection. If possible, the combined risks of DGF and DSA should be avoided. Disclosure: None Funding: SS is supported by the Swiss National Foundation (grant # 32003B_169310). Acknowledgments: We thank the nurses in the outpatient clinic for their outstanding help in the management of the patients. Corresponding Author: Stefan Schaub, MD MSc, Clinic for Transplantation Immunology and Nephrology, University Hospital Basel, Petersgraben 4, 4031 Basel, Switzerland. Tel: 0041 61 265 45 33, Fax: 0041 61 265 24 10, e-mail: stefan.schaub@usb.ch, ORCID: 0000-0002-9170-1341 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com