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Scientific Projects
2009 - 2013 Genetic and functional characterization of the natural killer cell immunity after liver transplantation for hepatitis C associated cirrhosis. [001: completed]
Project No.
001
Project Status
completed
Investigator
Villard J. et al.
Project Start
June 2009
Project End
June 2013
Abstract

C Bandelier, PY Bochuz, M De Maestral, C Gbame, S Rodel, JF Dufour, B Mulhaupt, G Menta, F Negro, E Giostra, J Villard
for the HCV and STCS study, University Hospital Geneva, University Hospital Zürich, University Hospital Lausanne

Goals Innate immunity plays a crucial role in the natural history of Hepatitis C infection. The Natural
Killer KIR receptor genes and SNPS IL28B polymorphism have been both associated with prediction
of HCV spontaneous clearance and treatment response. The role of KIR genes and IL28B SNPS in
the context of HCV hepatitis before and after liver transplantation has not been extensively studied.
We took the oportunity of the Swiss HCV Cohort Study and the Swiss Transplant Cohort Study to
analyze different parameters with regards to Hepatitis C infection.
Methods The following parameters were studied: spontaneous virus clearance in response to PEG
interferon therapy, relation between KIR genes and IL28B polymorphism in viremia, and finally the
relationship between KIR genes, IL28B polymorphism and hepatic fibrosis. 278 patients from the
Swiss HCV Cohort and 80 patients after liver transplantation for C-hepatitis- associated cirrhosis of the
Swiss Transplant Cohort Study were studied. All of them had liver biopsies, 23 of them had
spontaneous virus clearance. For HCV patient before transplantation, spontaneous clearance
stastically significant was associated with the presence of IL28 rsx9860 polymorphism (p=0.02). KIR
genes and HLA ligands didn't play a significant role in the spontaneous clearance in this cohort.
Similarly, the response to treatment was also mainly associated with the same IL28B polymorphism
(p=0.03). The level of viremia was associated with the presence of IL28B polymorphism, and also with
the absence of C1 ligand (p=0.05 and 0.02 respectively) in both cohort. The presence of high level of
hepatic fibrosis was exclusively associated with the C1 missing ligand (p=0.03) in both cohort. IL28B
SNPS do not play a significant role in the progression of fibrosis.
Status All the data have been generated. We wait for a minimum of year of follow up for the cohort of
transplanted patients. Manuscript is in preparation.
Relevance for clinical practice We believe that genetic polymorphism like IL28B and KIR genes
could help to predict patients who have a high risk of hepatitis C recurrence and more importantly the
severity of recurrence. Such prediction could change the clinical practice with regard to the timing of
introduction anti-viral therapy after liver transplantation for C-Hepatitis.

Publications
A significant effect of the killer cell immunoglobulin-like receptor ligand human leucocyte antigen-C on fibrosis progression in chronic C hepatitis with or without liver transplantation
2009 - 2020 The annual infectious diseases STCS report [002: completed]
Project No.
002
Project Status
completed
Investigator
van Delden C. et al.
Project Start
June 2009
Project End
January 2020
Abstract

Nicolas J. Mueller, Pascal Meylan, Oriol Manuel, Christian Garzoni, Hans H. Hirsch, Maja
Weisser, Katia Boggian, D. Nadal, R. Saccilotto, M. Koller, Christian van Delden, for the Swiss
Transplant Cohort Study

Goals Infectious diseases (ID) are a major cause of morbidity and mortality after SOT. Since May
2008, the STCS has registered 95% of all SOT recipients in Switzerland. The main goal is to describe
the epidemiology of post-transplant infectious diseases in a nationwide cohort across all transplant
types.
Methods The extensive data set includes pre- and post-transplant variables that are prospectively
collected at transplantation, 6 months post-transplant, and yearly thereafter. All ID events are recorded
using internationally validated definitions. We obtained data from 1101 patients (79 heart, 685 kidney,
29 kidney-pancreas, 212 liver, and 96 lung transplants)
Status So far the median observation times were 0.8 (IQR 0.3-1.4; heart); 1.1 (0.6-1.8, kidney); 1.1
(0.6-1.9, kidney-pancreas); 1.0 (0.5-1.7, liver); and 0.9 years (0.5-1.5, lung). The highest rates of
proven or probable ID events were seen in lung (76%), followed by liver (64%), heart (62%), kidney-
pancreas (62%), kidney (58%). During the observation period, ID was the cause of death in 19
patients (1.7 %). Rates of infections per person-years according to pathogen and type of
transplantation are shown in Figure 1.
Fig.1

Relevance for clinical practice The data indicate that virus infections are only second after bacteria
whereas fungi occur at relatively low rates. This prospective and standardized long-term collection of
all ID events will allow a comprehensive assessment of the burden of ID across all SOT types in
Switzerland. Regular analysis will identify new trends, serve as a quality control and help design anti-
infectious interventions aiming at increasing safety and improving overall transplantation outcome.

Publications
Burden and Timeline of Infectious Diseases in the First Year After Solid Organ Transplantation in the Swiss Transplant Cohort Study
The swiss transplant cohort study: lessons from the first 6 years
2009 - 2012 The Swiss Transplant Cohort Study: Design, rationale and methods. [004: completed]
Project No.
004
Project Status
completed
Investigator
Koller M.T. et al
Project Start
January 2009
Project End
January 2012
Abstract

Michael T. Koller, Christian van Delden, Nicolas J. Müller, Philippe Baumann, Christian Lovis,
Hans-Peter Marti, Thomas Fehr, Isabelle Binet, Sabina De Geest, Heiner C. Bucher, Pascal
Meylan, Manuel Pascual,Jürg Steiger

In Switzerland, organ procurement is well organized at the national-level but transplant outcomes have
not been systematically monitored so far. Therefore, a novel project, the Swiss Transplant Cohort
Study (STCS), was established. The STCS is a prospective multicenter study, designed as a dynamic
cohort, which enrolls all solid organ recipients at the national level. The features of the STCS are a
flexible patient-case system that allows capturing all transplant scenarios and collection of patient-
specific and allograft-specific data. Beyond comprehensive clinical data, specific focus is directed at
psychosocial and behavioral factors, infectious disease development, and bio-banking. Between May
2008 and end of 2011, the six Swiss transplant centers recruited 1,677 patients involving 1,721
transplantations, and a total of 1,800 organs implanted in 15 different transplantation scenarios. 10 %
of all patients underwent re-transplantation and 3% had a second transplantation, either in the past or
during follow-up. 34% of all kidney allografts originated from living donation. Until the end of 2011 we
observed 4,385 infection episodes in our patient population. The STCS showed operative capabilities
to collect high-quality data and to adequately reflect the complexity of the post-transplantation process.
The STCS represents a promising novel project for comparative effectiveness research in
transplantation medicine.

Status
Project completed. Published: Eur J Epidemiol. 2013 Apr 2. PubMed PMID: 23546766.

Relevance for clinical practice
The focus of this project was to describe the rational und study methodology of the STCS. It serves as
reference for all projects in the STCS and as reference for the STCS as role model in transplantation
medicine and complex interventions.

Publications
Design and methodology of the Swiss Transplant Cohort Study (STCS): a comprehensive prospective nationwide long-term follow-up cohort
2009 - 2020 Predictivity of sociodemographic, behavioural and psychosocial factors for short-term clinical TX outcomes. [005: completed]
Project No.
005
Project Status
completed
Investigator
De Geest Sabina et al.
Project Start
September 2009
Project End
September 2020
Abstract

Sabina De Geest, Lutz Goetzmann, Isabelle Binet, Hans-Peter Marti, Manuel Pascual, Christian
van Delden, Jürg Steiger for the STCS Psychosocial Interest Group - Consultants: Annette Boehler,
Michael Koller, Beat Müllhaupt and the Swiss Transplant Cohort Study

Background: Transplant (Tx) outcomes are influenced an interplay of biomedical,
sociodemographic, behavioral and psychosocial factors as well as the characteristics and practice
patterns in Tx centers. In contrast to biomedical factors, the evidence base of the predictive value of
preand post-Tx sociodemographic, behavioral and psychosocial factors is less well developed. We
hypothesize that part of the unexplained variability in Tx outcomes is associated with these
understudied factors.

Goals
1. To describe the baseline and evolution of sociodemographic, behavioral and psychosocial factors
from pre-Tx until post-Tx within and across organ Tx groups
2. To assess if the evolution of adherence to immunosuppressive regimen from pre- to post-Tx
predicts short term clinical outcomes (i.e. acute rejection (all), FEV1 (lung Tx), GFR and CAN
(renal Tx), and total bilirubin (liver Tx)) within organ Tx groups
3. To describe the prevalence of 1) poor sleep quality and 2) daytime sleepiness from pre- to post-Tx
and to explore if sleep quality or daytime sleepiness is associated with medication adherence

Methods: This study will build on the methodology of the STCS. This study will include adult Tx
patients with a 1st renal, liver, heart or lung Tx. In addition to selected biomedical factors, this study
focuses on socio-demographic (education level, marital status, employment status, socioeconomic
status), behavioral (medication adherence, smoking), and psychosocial (depression, sleep quality)
factors assessed by the STCS’ Psychosocial Questionnaire (PSQ) which derived its questions from
established instruments and other cohort studies. In addition to descriptive analyses, statistical
analyses will use Cox proportional hazards models to estimate the association between pre-Tx socio-
demographic, behavioral, psychosocial, and clinical covariates and acute rejection. In addition,
marginal structural Cox proportional hazards models will be used to estimate the causal effect of non-
adherence, for example, on acute rejection controlling for confounding factors. Center differences in
outcome will be explored and center may be included in the model as a fixed effect. Hazard ratios and
95% confidence intervals will be provided to describe the association between the covariates and
outcome.
Status: A conceptual framework to guide the program of research has been developed and published.
A validation paper concerning the measurement of sleep quality has been published. A paper
describing the prevalence and evolution of medication non-adherence has been submitted. The
project is ongoing with other aspects of the analysis in view of outcomes assessment being planned.

Relevance for clinical practice
Identification of sociodemographic, behavioral and psychosocial factors that show predictive validity
for clinical Tx outcome can support an evidence based Tx selection process. Modifiable
sociodemographic, behavioral and psychosocial predictors could be targeted for intervention with the
goal of enhancing long term outcomes after Tx.

Publications
Describing the evolution of medication nonadherence from pretransplant until 3 years post-transplant and determining pretransplant medication nonadherence as risk factor for post-transplant nonadherence to immunosuppressives: the Swiss Transplant Cohort S
2009 - 2020 Analysis and validation of deregulated metzincins and related genes in kidney transplant patients with interstitial fibrosis and tubular atrophy (IF/TA) as markers for disease classification and progression. [006: ongoing]
Project No.
006
Project Status
ongoing
Investigator
Marti H.P. et al.
Project Start
July 2009
Project End
September 2020
Abstract

Marti Hans-Peter and Mohacsi Paul

Goals First, we aim at investigating metzincins and related genes in formalin-fixed, paraffin-embedded
(FFPE) biopsies from IF/TA patients from Swiss transplant centers. Analyses in biopsies for cause and
in protocol biopsies are to be performed separately in microdissected glomeruli and tubulointerstitium.
Secondly, we propose to examine the same genes in urine, urinary cell pellets and sera samples of
these patients. From the Swiss Transplant Cohort Study (STCS), we only request respective clinical
patient data.
We hypothesize, that the results of previously detected deregulated metzincins and related genes in
IF/TA can be validated in this prospective multicenter study within the frame of the STCS. Deregulated
metzincins and related genes, located to the glomerular and/or tubulointerstitial space, can be used as
markers for IF/TA. In addition, selected target genes can be recovered non-invasively from urine and
from sera of IF/TA patients.
Methods The proposed investigation will be a cross-sectional comparison of consecutively recruited
patients belonging to one of three groups, normals (N), acute rejection (AR) and IF/TA, with a primary
comparison of groups N and IF/TA. We propose to include adult kidney transplant recipients
undergoing allograft biopsy for cause or protocol biopsy presenting with normal histology (N=controls;
n=20), acute rejection (AR; n=20) or IF/TA (n=60). We will only use material left over after completion
of routine diagnostic analyses. Thus, no extra biopsy material will be obtained for study purposes.
Experiments will be performed during a period of three years, as follows:
Part 1: Analyses using formalin-fixed, paraffin embedded (FFPE) renal allograft biopsies
• Microarrays of mRNA and miRNA from laser captured-microdissected glomeruli and
tubulointerstitium
• Immunohistochemistry of biopsy sections
Part 2: Analyses of selected genes in urine and serum samples
• QRT-PCR, ELISA and gelatin zymography of urine samples
• ELISA of serum samples

Status Focused on our genes of interest, bioinformatical analyses of Affymetrix  mic roarrays will be
performed in collaboration with Dr. Andreas Scherer from Spheromics, Kontiolahti, Finland.
Note, this study will be part of a larger biomarker investigation under the direction of Paul Mohacsi,
Inselspital Bern. These experiments are scheduled to start in fall of 2013 and have also been
approved by the STCS.
Relevance for clinical practice This proposal will define the use of metzincins and related genes as
(prognostic) markers and potential novel therapeutic targets of renal allografts with IF/TA.

Publications
No publications yet
2010 - 2020 Skin cancer development in organ transplant recipients. [007: ongoing]
Project No.
007
Project Status
ongoing
Investigator
Hofbauer G. et al.
Project Start
May 2010
Project End
September 2020
Abstract

Günther Hofbauer, Mark Anliker, Andreas Arnold, Thomas Fehr, Robert Hunger, Peter Itin,
Emmanuel Laffitte, Anne-Carine Lapointe, Carlo Mainetti, Laurent Parmentier, Francesco Pelloni,
Werner Kempf, Markus Streit for the Working Group “Organ transplantation” of the Swiss Society of
Dermatology; Michael Koller, Heiner C. Bucher, and the Swiss Transplant Cohort Study

Goals
1. To investigate the relationship between individual immunosuppressive drugs and SCC formation in
OTRs. 2. To study the interaction of photosensitization and immunosuppression of different drugs and
the associated risk for SCC formation in OTRs.
Methods
Baseline data routinely collected within the STCS. We will additionally collect skin type according to
Fitzpatrick I to IV, Occupation outdoor/indoor, Leisure sun exposure (nautic, alpine, cycling, golf,
tennis), History of skin cancer in the past, History of skin cancer within 1st degree family members
Status

A total of 757 OTR were followed up for 943 person years (py) with a median follow up of 435 days.
Median age at transplantation was 53.2 years (2.0-80.7 years). We found 66 SCC in 25 affected OTR
(3.3% of OTR). While most OTR showed one tumor, one OTR suffered from 18 SCCs within 778 days.
There were 32 BCC in 23 affected OTR (3.0% of OTR) and 33 other conditions, mostly intraepithelial
SCC in 17 affected patients (2.2% of OTR). No melanoma was found. The incidence of SCC in all
OTR was 26.5, of BCC 24.4, and of other conditions 18.0 per 1000 py. Median age of OTR affected by
skin cancer was significantly higher than for the rest of the cohort (SCC 58.6 vs. 53 years, P=0.002;
BCC 65.2 vs. 53 years, P=0.01, other 60.5 vs. 53 years, p=0.004). Males developed significantly more
BCC than females (p=0.033). OTR with a history of previous organ transplantation developed
significantly more SCC (p=0.043) or other conditions (p=0.012).
Relevance for clinical practice
Our data will allow, in particular with continued collection and analysis over the planned study period of
ten years, to identify risk factors and their respective weight for skin cancer risk. This information will
be clinically useful to recognize individual organ transplant recipients at particularly high risk for skin
cancer and to focus intensive screening and treatment on these patients in particular need of
attention.
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
OTR with skin cancer [%]

Publications
No publications yet
2010 - 2020 Role of Mannose Binding Lectin polymorphisms on the Incidence and Course of Cytomegalovirus and other Infections. [010: ongoing]
Project No.
010
Project Status
ongoing
Investigator
Meylan P. et al.
Project Start
May 2010
Project End
September 2020
Abstract

Nitisha Pyndiah, Georg Kralidis, Agnieszka Wójtowicz, Stephanie Bibert, Oriol Manuel, Nicolas J. Mueller, Hans H. Hirsch, Christian Garzoni, Christian van Delden, Christoph Berger, Katia Boggian, Alexia Cusini, Michael T. Koller, Maja Weisser, Manuel Pascual, Pierre-Yves Bochud, Pascal R. Meylan, and the Swiss Transplant Cohort Study

University Hospital Bern
Goals: MBL is the initial component of the third complement activation pathway. Genetically-determined deficiency which is very prevalent has been implicated in the host defenses against bacteria and fungi among immunodeficient patients. Conflicting results have been published regarding its role in CMV susceptibility. We aimed to assess the relationship between MBL genotype and phenotype and any relationship with the occurrence of CMV disease in a nationwide prospective cohort of SOT recipients in Switzerland.
Methods Patients participating in the Swiss Transplant Cohort Study (STCS) and transplanted from May 2008 until March 2011 were included. MBL genotypes were determined using a custom-made Illumina Golden Gate Genotyping assay on Beadxpress® and SNP specific PCR respectively for 6 polymorphisms rs11003125, rs1800450, rs1800451, rs5030737, rs7096206 and rs709589. MBL plasma level was measured using BioPorto’s MBL Oligomer Kit 029 based on Mab HYB 131-0. The effect of affinity-purified hMBL was also tested on the infection of human embryonic lung fibroblasts and ARPE-19 cells by CMV.
Status: The study is completed. 1139 patients were included, had a MBL blood level determined and were genotyped. Genotype tightly predicted MBL blood level. Across the different serostatus risk pattern, patients with and without CMV disease did not differ in MBL blood level. When MBL blood level was used as a diagnostic test to predict CMV disease, a receiver operating curve analysis did not reveal any cut off value associated with occurrence of CMV disease either in the whole population or CMV high risk recipients. In vitro, hMBL did not inhibit CMV replication. Poster presentation at ATC 2013, Manuscript in preparation.

Relevance for clinical practice: The present investigation did not confirm our preliminary data (Manuel et al, Transplantation, 2007;83:359); MBL deficiency was not associated with CMV disease in SOT recipients, nor did MBL inhibit CMV infection in vitro. This large scale study settles the controversy regarding whether MBL plays any role in the susceptibility of transplant patients to CMV disease.

Publications
Polymorphisms in the lectin pathway of complement activation in uence the incidence of acute rejection and graft outcome after kidney transplantation
2010 - 2020 Psychosocial profiles of living-donor compared to deceased-donor kidney allograft recipients [011: ongoing]
Project No.
011
Project Status
ongoing
Investigator
Koller M.T. et al
Project Start
May 2010
Project End
September 2020
Abstract

Michael T. Koller, Isabelle Binet, Sabina De Geest, Jürg Steiger
and Alexander Kiss for the
Psychosocial Interest Group of STCS and the Swiss Transplant Cohort Study (STCS)

Backgorund
Evidence from large scale US observational studies indicate that living-donor renal transplant
recipients (LDRT) have better allograft survival compared to deceased-donor transplant recipients
(DDRT). It seems that overall LDRT and DDRT populations are very different regarding patient and
donor characteristics. It is therefore of interest to study these recipient populations in more detail,
particularly with regard to psychosocial profiles and to explore the living-related and living-unrelated
recipient subpopulations in more detail.
Goals
This study will focus on psychosocial differences in particular education, profession, workability,
income, Quality of live (QoL, EQ-5D) and depression. Moreover, the longitudinal outcome after one-
year post-transplant for depression and QoL will be of interest. This project is viewed as a hypothesis
generating study that will be of interest to explain health outcome and transplantation outcome
discrepancies between LDRT and DDRT recipients.
Methods
All kidney transplant recipients enrolled in STCS with available STCS Psychosocial Questionnaire
(PSQ) data will be eligible for this analysis. We will perform cross-sectional analyses of patient
baseline data and longitudinal analyses of the pre- post-transplant course for QoL and depression,
stratified for LDRT and DDRT. We will analyze baseline distributional differences of LDRT and DDRT
for the psychosocial determinates mentioned and changes from baseline to 6 month and 1-year follow-
up for depression and QoL. For the repeated measures setup, we will be using a mixed modeling
approach.
Status
By autumn2013, and expected number of round 1400 kidney transplant recipients (~800 DDRT and
600 LDRT) will be available for analysis and the majority of the patients will have the one-year follo-up
period complete. There will be largely sufficient power to run meaningful exploratory analysis for this
project. The project will start in autumn 2013 shall be completed by spring 2014.
Relevance for clinical practice
The focus of this proposal is to identify baseline demographic and psychosocial disparities between
the LDRT and DDRT populations enrolled into STCS. It will be of interest to develop hypothesis of
patient characteristics that could explain health and transplantation outcome differences in LDRT and
DDRT. The STCS and the STCS PSQ are ideally designed for this research purpose.

Publications
No publications yet
2010 - 2013 Pattern Recognition Receptors Polymorphisms and Infection after Organ Transplantation [012: completed]
Project No.
012
Project Status
completed
Investigator
Manuel O. et al.
Project Start
November 2010
Project End
June 2013
Abstract

Oriol Manuel MD, Stephanie Bibert PhD, Pascal R Meylan MD, Nicolas Müller MD, Christian Garzoni MD, Christian Van Delden MD, Jürg Steiger MD, Isabelle Binet MD, Manuel Pascual MD, Pierre-Yves Bochud MD

Background Recent studies have unequivocally revealed the importance of host immunogenetics in susceptibility to infectious diseases (reviewed in [1]). Pattern recognitions receptors (PRRs) are proteins expressed by innate immune cells that detect specific molecular patterns from invading microbes and initiate inflammatory and adaptive immune responses. Main PRRs include Toll-like receptors (TLRs), C-type lectins receptors (CLRs), Nod-like receptors (NLRs) and RIG-I like receptors (RLRs). An increasing amount of data suggest that polymorphisms in these PRRs influence the clinical presentation of infectious diseases [2-5].

Infections are a major cause of morbidity and death after solid-organ transplantation [6-8]. However, it remains unclear why certain patients develop serious infectious complications while others undergoing identical transplant treatments with similar posttransplant immunosuppression, do not. Most infection prophylaxis strategies are universal and non-specific, thereby exposing the majority of patients to potentially toxic and/or costly drugs. Specific data on the role of PRRs polymorphisms in the control of infection after solid-organ transplantation is scarce.

The Swiss Transplant Cohort Study (STCS) has set up a prospective database of clinical information and blood sample biobank regarding solid-organ transplant recipients. All 6 Swiss transplant centers actively participate in the enrollement of patients. Since May 2008, clinical data are introduced in the database following standard diagnostic criteria, with special interest in infectious complications.

Study Aims The aim of the study is to detect associations between polymorphisms in candidate innate immune genes and major post transplant infections (CMV infection, invasive fungal infection, BK virus infection and bacteremia) in the frame of the STCS. These infections have a high incidence and are associated with morbidity and mortality in the transplant population.

Study Design

Baseline blood cells are collected from all STCS patients and donors. DNA will be extracted, quantified and aliquoted using standardized procedures to allow genotyping using most recent technologies.

Four types of infection phenotypes will be investigated: CMV infection and disease, BK virus viremia and nephropathy, invasive fungal infection (candida and mold infection), and bacteremia (Gram positive and Gram negative bacteremia). The presence of these different infectious diseases will be assessed in every patient using standard definitions from the Infectious Diseases Study group of the STCS. This selection is based on the relevance of these infections in the clinical practice as well as their frequency, in order to reach a reasonable statistical power to detect some associations.

Haplotype tagging single nucleotide polymorphisms (SNPs) in candidate genes will be genotyped from patients and donors. Our group has established a list of candidate genes (innate immunity genotyping kit), based on literature review and innate immunity pathway analysis. The candidate genes will includes genes such as TLRs, CLRs, NLRs, and RLRs, their relevant signaling molecules, as well as cytokines and cytokine-receptor genes. The risk of each infection by the different polymorphisms will be assessed using cumulative incidences curves and Cox regression models, after adjustment for appropriate covariates.

Publications
PTX3 Polymorphisms and Invasive Mold Infections After Solid Organ Transplant
IL1B and DEFB1 Polymorphisms Increase Susceptibility to Invasive Mold Infection After Solid-Organ Transplantation
Influence of IFNL3/4 Polymorphisms on the Incidence of Cytomegalovirus Infection After Solid-Organ Transplantation
2010 - 2013 Determinants, Clinical Manifestations and Significance of Late Onset Cytomegalovirus Disease [015: completed]
Project No.
015
Project Status
completed
Investigator
Meylan P. et al.
Project Start
November 2010
Project End
June 2013
Abstract

Oriol Manuel, Georg Kralidis, Nicolas J. Mueller, Hans H. Hirsch, Christian Garzoni, Christian van
Delden, Christoph Berger, Katia Boggian, Alexia Cusini, Michael T. Koller, Maja Weisser, Manuel
Pascual, Pascal R. Meylan, and the Swiss Transplant Cohort Study

Goals
Cytomegalovirus (CMV) disease has been considered as the most important viral infection developing
after solid-organ transplantation (SOT). To assess the impact of antiviral prophylaxis and preemptive
therapy on the incidence and outcomes of cytomegalovirus (CMV) disease in a nationwide prospective
cohort of solid-organ transplant recipients.
Methods
Risk factors associated with CMV disease and graft failure-free survival were analyzed using Cox
regression models.
Status
Study completed. 1239 patients transplanted from May 2008 until March 2011 were included; 466
(38%) patients received CMV prophylaxis and 522 (42%) patients were managed preemptively.
Overall incidence of CMV disease was 6.05% and it was linked to CMV serostatus (D+/R- vs. R+,
hazard ratio [HR] 5.18 [95% CI 3.04-8.81], p<0.001). No difference in the incidence of CMV disease
was observed in patients receiving antiviral prophylaxis as compared to the preemptive approach (HR
1.20 [95% CI 0.65-2.23], p=0.56). CMV disease was not associated with a lower graft failure-free
survival (HR 1.32 [95% CI 0.66 - 2.63], p= 0.44). Nevertheless, patients followed by the preemptive
approach had an inferior graft failure-free survival after a median of 1.05 years of follow-up (HR 1.63
[95% CI 1.01-2.63], p=0.044.
Relevance for clinical practice
The incidence of CMV disease in this cohort was low and not influenced by the preventive strategy
used. However, patients on CMV prophylaxis were more likely to be free from graft failure. A
manuscript has been submitted to Am J Transpl and is currently being edited along reviewers
suggestions. Upon publication, the present results will be used to promote prophylactic management
of CMV infection in SOT recipients.

Publications
Impact of antiviral preventive strategies on the incidence and outcomes of cytomegalovirus disease in solid organ transplant recipients.
2010 - 2017 Return to Work:a long-term follow-up study after solid organ transplantation in Switzerland [016: completed]
Project No.
016
Project Status
completed
Investigator
Danuser B. et al.
Project Start
November 2010
Project End
April 2017
Abstract

Amira A.Simcox, Michael T. Koller, Pascal Wild and Regina Kunz & Brigitta Danuser

Goals
We aim to identify barriers and facilitators of return to work in the framework of Swiss Transplant
Cohort Study (STCS). The proposed aims relate to all transplanted solid organs, particularly to kidney,
liver, lung and heart. All analyses will be stratified by organ and gender. Three main study aims were
identified:
1. Pre-transplant working status analyses: Identify the determinants of the pre-transplant working
status stratified by organ and gender.
2. Longitudinal evolution of working status analysis from pre-transplant over the entire post-transplant
period: Identify the predictors – both positive and negative- of working status after transplantation and
in particular of a sustained work. Identify typical patterns of return to work and explore their predictors.
3. Analysing the influence of working status on health and health behavior, including the role of
working status on allograft and patient survival or the role of working status on immunosuppressive
drug adherence.

Methods
Cross-sectional and longitudinal follow-up analyses of working status from pre-transplant over the
entire post-transplant period will be looked into. The study will be conducted within the framework of
the STCS which includes all solid organs transplant recipients transplanted in Switzerland.
Status
Analysis of pre-transplant working status: logistic regression shows that being older (p<.01) and had
no professional education (p<.001) plus having a depression and patients’ perceived health (p<.001)
were significantly correlated with not working before transplantation. Severity of the disease was
statistically significant in explaining the pre-transplant working status in kidney patients only. The
longer the patient was on dialysis, the higher the risk of not working (p<0.001). Manuscript in
preparation.
As a next step, we are looking into the working status one year after transplantation in order to identify
its predictors which consist of variables measured at baseline (pre-transplant) and during repeated
follow-up assessments. Specifically, we shall investigate age, education, pre-transplant working
status, professional status, and the history of marital status/living situation, socio-economic status,
perceived health status and depression as predictors of post-transplant return to work success.
Relevance for clinical practice
Maintaining and regaining work status are important topics in Switzerland and internationally. We aim
to generate future hypothesis that help to identify risk factors of poor long-term work re-integration. We
hope that the gained knowledge will help to develop tailored interventions for re-integration support
and reduce long-term work disability. However the indicators which might be obtained should not be
considered as discriminative criteria to favour or limit access to transplantation for individual patients.

Publications
Employment 12 months after kidney transplantation: An in-depth bio-psycho-social analysis of the Swiss Transplant Cohort
Predictors of Return to Work 12 Months After Solid Organ Transplantation: Results from the Swiss Transplant Cohort Study
2011 - 2020 Epidemiology of fungal infection and colonization in solid organ transplant recipients in the Swiss Transplant Cohort Study. A 3 year follow up. [017: ongoing]
Project No.
017
Project Status
ongoing
Investigator
Garzoni C. et al
Project Start
July 2011
Project End
September 2020
Abstract

Garzoni C, Lecompte T, Kradilis G, Berger C, Cusini A, Boggian K, Khanna N, Oriol M, Zimmerli S,
Müller N, van Delden C, and the Swiss Transplant Cohort Study

Goals
Morbidity and mortality of invasive fungal infections (IFI) in Solid Organ Transplant (SOT) recipients are
unacceptably high. Preventive strategies are expensive and need to take into account local epidemiology
and resistance data. Such data are missing in Switzerland for SOT
recipients. Primary aim: to describe the epidemiology of fungal infections and
colonization in Swiss SOT recipients. Specific aims: (1) describe the annual occurrences of IFI stratified
by SOT type, (2) analyze risk factors for IFI, (3) describe potential differences in the clinical characteristics
of invasive fungal infection according to the type of transplant, (4) describe local resistance pattern of
Candida spp. in different Swiss centers, (5) analyze if different local policies regarding fungal prophylaxis
could affect mold infection, (6) describe the experience with new antifungal therapies in SOT patients.
Methods
Prospective observational study involving all patients included in the STCS since May 2008 with at least six
months of follow-up. IFI was defined as proven, probable or possible disease according to EORTC
definitions. Epidemiological data were retrieved from the STCS database, when required additional data
were collected with specific CRFs for fungal infections.

Status
The first analysis of these data was presented as a poster at the Interscience Conference on Antimicrobial
Agents and Chemotherapy (ICAAC), in San Francisco in September 2012. We identified 192 patients with
281 fungal events, including 119 patients with 148 IFI. So far 21 Pneumocystis Jirovecii, 29 invasive
Aspergillus and 15 invasive Candida infections have been analyzed. Multivariate analysis identified specific
risk factors for these infections. Association studies with prophylaxis, including anti-fungal resistance are
ongoing. Four manuscripts describing these data are in preparation.

Repartition of IFI and
fungal species among SOT

Relevance for clinical practice
8.7% of all SOT recipients of the Swiss Transplant Cohort Study (STCS) had an IFI. These fungal
infections represented 3.4% of all infectious events recorded in the STCS. Almost 50% of all IFI occurred in
kidney transplant recipients, however heart (17%) and pancreas (12.5%) recipients were at the highest risk
for IFI. The repartition of fungal species was relatively homogenous between the different transplanted
organs, with Candida species being most prevalent in all organs. Mortality was high (26%) in SOT
recipients with IFI. We identified an outbreak of Pneumocystis Jirovecii infections in one Swiss transplant
center (center B). Immediate action, including prophylaxis and increased hospital hygiene control
measures, allowed controlling this epidemic. These data should provide adequate evidence for national
prophylaxis and treatment guidelines.

Publications
Epidemiology, risk factors and outcomes of invasive aspergillosis in solid organ transplant recipients in the Swiss Transplant Cohort Study
Pneumocystis jirovecii pneumonia in solid organ transplant recipients: a descriptive analysis for the Swiss Transplant Cohort
Multinational case-control study of risk factors for the development of late invasive pulmonary aspergillosis following kidney transplantation
Clinical Presentation and Determinants of Mortality of Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: A Multinational Cohort Study.
Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case-Control Study.
2011 - 2012 Epidemiology and management of enterococcal infections in patients from the Swiss Transplant Cohort Study (STCS) [018: completed]
Project No.
018
Project Status
completed
Investigator
Weisser M et al.
Project Start
July 2011
Project End
December 2012
Abstract

Goals
We aimed at analyzing the epidemiology of enterococcal events in patients followed in the Swiss
Transplant Cohort Study between May 2008 and September 2011 and analyzed risk factors for
infection, aminopenicillin-resistance, treatment and outcome.

Methods
Cumulative incidence curves were calculated by organ group. Risk factors on enterococcal infections,
risk factors for resistance and risk factors for poor outcome were investigated by fitting multivariable
hierarchical Poisson regression models.

Status
Out of 1’234 patients 255 (20.7%) suffered from 392 enterococcal events (185 (47.2%) infections, 205
(52.3%) colonizations, 2 events with missing clinical information). Only 2 isolates were VRE. Highest
infection rates were found early after liver transplantation (0.24/person-year) consisting in 58.6% of E.
faecium. Highest colonization rates were documented in lung transplant recipients (0.33/person-year),
with 46.5% E. faecium. Age, prophylaxis with a betalactam antibiotic and liver transplantation were
significantly associated with infection. Previous antibiotic treatment, intensive care unit and lung
transplantation were associated with aminopenicillin resistance. Only 4/205 (2%) colonization events
lead to an infection. Adequate treatment did not affect microbiological clearance rates. Overall
mortality was 8%, no deaths were attributable to enterococcal events.
Accepted for publication in Transplant Infectious Diseases.

Relevance for clinical practice
Enterococcal colonizations and infections are frequent in transplant recipients. Progression from
colonization to infection is rare. Therefore, antibiotic treatment should be used restrictively in
colonization. No increased mortality due to enterococcal infection was noted.

Publications
Impact of enterococcal colonization and infection in solid organ transplantation recipients from the Swiss Transplant Cohort Study
Enterococcal infection in kidney transplant recipients in a setting of low prevalence of vancomycin resistance
2012 - 2020 Correlation of vitamin D levels and risk of infectious disease complications after solid organ transplantation [019: ongoing]
Project No.
019
Project Status
ongoing
Investigator
Mueller et al.
Project Start
March 2012
Project End
September 2020
Abstract

Oriol Manuel, Christian van Delden, Maja Weisser, Hans H. Hirsch, Christian Garzoni, Katia Boggian, Lanja Saleh, Thomas Fehr, Heike A. Bischoff-Ferrari and the Swiss Transplant Cohort Study

Goals
1) To evaluate whether the number of infectious disease events are predicted by
25(OH)D levels at baseline, or 25(OH)D levels at 6 month follow-up while
controlling for season.
- Type of pathogen (virus, bacteria, fungi) will be analyzed separately
- Proven/probable infections will be analyzed only
2) To evaluate the relationship between baseline value of 25(OH)D and secondary
transplantation-related endpoints such as rejection and death.
3) To evaluate the relationship between baseline value of 25(OH)D and bone health
associated secondary endpoints: DEXA scans, PTH levels, marker for bone metabolism.
4) To analyze predictors of 25(OH)D status, including the following parameters: age,
gender, ethnicity, body mass index, season of measurements (fall versus spring),
calculated golmerular filtration rate (cGFR).

Methods 25(OH)D levels will be measured at start and six months later. These findings will be
correlated to the rate of incident infections during the first year after organ transplant. A bone
metabolism panel will be assessed in each sample: Vitamin D 1,25-(OH)2; Vitamin D 25 (OH); P1NP
(N-terminal propeptide of type 1 procollagen); CTX (C-terminal telopeptide); Creatinine; Calcium tot.;
Phosphate; Parathormone. Secondary endpoints analyses inlcude: Correlation with rejection, death,
bone health. Uni- and multivariable regression models for analyzing predictors of 25(OH)D status,
including the following parameters: age, gender, ethnicity, body mass index, season of measurements
(fall versus spring), calculated golmerular filtration rate (cGFR).
Status Samples are being retrieved, analyses is pending.
Relevance for clinical practice The STCS is the ideal tool to correlate vitamin D levels with a number
of outcome variables, across different transplanted organs.
The finding of an association between vitamin D levels and infectious disease events may well have
implications for clinical and basic research questions:
- will an adequate substitution have a protective effect?
- do we need to regularly screen patients for their vitamin D status?
- what are potential mechanisms for such an association?

Publications
Vitamin D status and risk of infections after liver transplantation in the Swiss Transplant Cohort Study
Bone metabolism dynamics in the early post-transplant period following kidney and liver transplantation
Vitamin D deficiency is common in kidney transplant recipients, but is not associated with infections after transplantation
2011 - 2013 Association of KIR genotype and CMV replication after solid organ transplantation [020: completed]
Project No.
020
Project Status
completed
Investigator
Stern et al.
Project Start
July 2011
Project End
June 2013
Abstract

Martin Stern, Jean Villard, Oriol Manuel, Pascal Meylan, Christoph Hess

Goals
Previous studies associated activating KIR genes with protection from cytomegalovirus (CMV)
replication after organ transplantation. We correlated KIR genotype with rates of CMV replication in
649 recipients of heart (n=74), kidney (n=291), liver (n=188), or lung (n=96) allografts reported to the
Swiss Transplant Cohort Study.
Methods
HLA-A and -B typing was performed using serological or molecular typing methods at each transplant
center. Typing of a polymorphism in HLA-C –allowing assignment of KIR2D inhibitory ligand status–
was retrospectively performed on stored DNA samples according to standard protocols. KIR
genotyping was performed using a reverse sequence-specific oligonucleotide method (OneLambda,
Canoga Park, CA).
Status
We found B haplotypes –which in contrast to A haplotypes may contain multiple activating KIR genes–
to associate with significantly reduced rates of CMV replication after transplantation of heart (29
versus 57%, p=0.02) and lung (24 versus 44%, p=0.03), but not kidney (36 versus 38%, p=0.79), or
liver allografts (38 versus 35%, p=0.46). The protective effect of B haplotypes was restricted to
patients receiving intensive immunosuppression (anti-thymocyte globulin induction and/or
triple/quadruple maintenance immunosuppression). In these high-risk patients, protection from CMV
replication conferred by B haplotypes was maintained after adjustment for covariates (hazard ratio
0.47, 95% confidence interval 0.31-0.70, p<0.001), and constant during early and late follow-up. A
significant protection was detected in patients CMV seropositive at the time of transplant (HR 0.41,
95% CI 0.24-0.70, p=0.001), but not in CMV seronegative patients (HR 0.84, 95% CI 0.31-2.29,
p=0.73) (Fig. 1).

Relevance for clinical practice
This analysis confirms recipient KIR genotype as a predictor of CMV replication after solid organ
transplantation. The data indicate a prominent role for KIR and presumably NK cells in anti-CMV
immunity in case of compromised adaptive immunity, which operates selectively in patients with
previous exposure to CMV. In all the study defines risk populations requiring a high index of suspicion
with regard to CMV-related disease post transplantation.

Publications
KIR-associated protection from CMV replication requires pre-existing immunity: a prospective study in solid organ transplant recipients
2012 - 2020 Evaluation of genomic and proteomic blood biomarkers for diagnosis of heart/kidney allograft rejection [021: ongoing]
Project No.
021
Project Status
ongoing
Investigator
Mohasci et al.
Project Start
May 2012
Project End
September 2020
Abstract

Background

Transplantation remains the main therapy for patients with end-stage organ failure. Despite recent advances, acute rejection is still a significant barrier to long-term allograft function and survival 1-6. Current methods for diagnosis of acute rejection have insufficient specificity, and can be invasive, costly, and inconclusive 1, 7-17. While other groups have explored blood-based biomarkers of acute rejection, in most cases there are still insufficient data with respect to their true clinical value. Thus, there is a major unmet clinical need for an accurate blood test that would diminish the risks, pain, and fear associated with current practices, while improving patient care options through proactive, timely interventions. Such a test would also greatly reduce the current socio-economic burden associated with technical and expensive diagnostic procedures, over-prescription costs and drug toxicities, thereby contributing significantly to a sustainable healthcare system.

The NCE CECR Centre of Excellence for Prevention of Organ Failure (PROOF Centre) is a not-for-profit organization with a mission to discover, develop, commercialize, and implement molecular blood-based biomarker solutions. During the discovery phase of its lead Biomarkers in Transplantation (BiT) program (BiT1), the PROOF Centre identified eight potential blood tests for diagnosing or predicting heart and kidney rejection. Six of these blood tests are being validated using patients enrolled in Canada, USA, Australia, and India in the ongoing validation phase (BiT2). Two-to-four of these validated blood tests will be migrated to an assay suitable for the clinical laboratory and tested in British Columbia. The PROOF team has a partnership with Luminex and OriGene in order to generate economically viable assays run in any clinical laboratory using the Luminex instrument. Through the current proposal, we wish to establish assays to monitor patients who have had a heart or kidney transplant in a clinical laboratory in Switzerland, in order to test their utility alongside standard clinical care in Switzerland.

Study Aims

The aim of the current proposal is to evaluate the clinical utility of the PROOF Centre’s genomic and proteomic biomarker panels for monitoring heart and kidney allograft recipients in Switzerland. This objective dovetails with the ongoing, Genome BC-funded “BiT3” program at the PROOF Centre, through which validated biomarker panels are being transferred to the Luminex platform and undergoing technical and clinical performance testing in Vancouver.

Publications
No publications yet
2011 - 2020 Bacterial Population Dynamics in Lung Transplant Patients [022: ongoing]
Project No.
022
Project Status
ongoing
Investigator
van Delden C. et al.
Project Start
November 2011
Project End
September 2020
Abstract

Gasche-Soccal P, Aubert JD, Schuurmans Macé , Benden C, Boehler A, Manuel O, Müller N, van Delden C and the Swiss Transplant Cohort Study

Goals
Early and late outcome after lung transplantation (LT) is worse than after other organ transplants. This is
due to allograft infections and development of chronic rejection (bronchiolitis obliterans syndrome; BOS).
Pseudomonas aeruginosa is a particularly threatening microorganism since it is responsible for both post-
transplant pneumonia and associated with BOS. Preventing allograft colonization by P. aeruginosa might
reduce both complications, and therefore significantly impact post-LT survival. We hypothesize that
composition and timing (dynamics) of colonization by the recipient host flora influences the establishment
of pathogenic species. The aim of this study is therefore to investigate the dynamics of bacterial
colonization of lung allografts, as well as intra- and inter-species bacterial competition involving especially
P. aeruginosa.
Methods
Clinical samples will be obtained during routine visits of LT recipients of three transplant centres (Geneva,
Lausanne and Zurich). From sequential bronchoalveolar lavage samples obtained before and after LT, P.
aeruginosa and other species will be recovered. Adaptation of P. aeruginosa isolates to the novel non-
cystic-fibrosis (CF) microenvironment will be tested by characterizing phenotypes important for colonization
including motility, nutrient utilisation, biofilm formation, hypermutators, and quorum-sensing. We will further
investigate the mechanisms involved in bacterial intra and inter-species competition. The dynamics of total
microbial communities during the allograft colonization will be studied using sequential metagenomic
analysis. Relevant clinical data will be obtained from the STCS database and correlated with
microbiological studies.
Status
This study is financially supported by the FNRS (grant 32473B_140929) and the Roche Organ Transplant
Research Foundation (ROTRF). So far 242 samples from 28 patients (6 CF and 22 non-CF) have been
collected. Five of the six CF-patients were colonized by P. aeruginosa before LT, while only 4 out of 22
non-CF patients had at least one positive sample for P. aeruginosa. Four of the 5 CF patients had the
same genotype before and after LT, and one patient was colonized by a different genotype. We are
currently investigating the phenotypes of isolates from 3 LT patients. The phenotypic results from the
patient colonized by two different genotypes before and after LT is shown in Fig. 1. The pre-LT clone was
mucoid and wild type for the Quorum-sensing regulator LasR, while the post-LT clone, was non-mucoid
and mutated in LasR. Characterization of additional phenotypes including motility, biofilm formation and
pyocin susceptibility, as well as metagenomic analysis on these sequential isolates are in progress.
Relevance for clinical practice
We expect to gain insight into the adaptive responses of bacteria during colonization. The sequential
collection of samples will allow us to follow the dynamic evolution of microbial communities and establish a
possible correlation with clinical outcome. This should allow to better anticipating the risk of colonization by
pathogenic species. The results of intra- and interspecies competition mechanisms could identify targets for
novel interventions possibly preventing colonization by pathogenic bacteria. Altogether the results should
improve the care of lung transplant recipients, increasing their comfort and life expectancy.

Publications
Rapid adaptation drives invasion of airway donor microbiota by Pseudomonas after lung transplantation.
Microbial Communities of Conducting and Respiratory Zones of Lung-Transplanted Patients
2012 - 2020 Innate and adaptive immune biomarkers and cytomegalovirus posttransplant [023: ongoing]
Project No.
023
Project Status
ongoing
Investigator
Egli A. et al.
Project Start
March 2012
Project End
September 2020
Abstract

Authors: Adrian Egli MD PhD, Volker Roth PhD, Pierre-Yves Bochud, Hans H. Hirsch, Maja Weisser, Christian Garzoni, Christian van Delden, Oriol Manuel, Pascal Meylan, Katia Boggian, Deepali Kumar, Nicolas Müller MD*, Atul Humar, MD MSc*; * shared last authors

Background

Posttransplant, Cytomegalovirus (CMV) is the most common opportunistic infection and has the potential to cause significant morbidity and graft lost. CMV replication is controlled by the innate and adaptive immune system. Due to immunosuppression, immune functions are impaired. In addition, CMV encodes proteins and miRNAs modulating the immune response and thereby influencing the control of viral replication. Prediction of CMV reactivation and progression to disease after transplantation using clinical risk stratification and viral load testing remains difficult. Especially CMV seropositive recipients (R+) without anti-viral prophylaxis might profit from more detailed risk stratifications. Our research project will primarly analyze CMV-specific T-cell responses (protein-, miRNA-, and cytokine-expression profiles) before transplantation in R+ patients. However, previous submitted projects on immune polymorphisms will be included into our analysis to match genotypic risk factors to functional outcomes (STCS No 12). Thereby, we will be able to include a functional and predictive network analysis of innate and adaptive immune functions as potential pre-transplant biomarkers to determine the post-transplant risk of CMV reactivation and disease.

The project has direct relevance to organ transplantation because 1) it is very novel, (i.e. has not been done before in this setting); 2) has potential to not only improve our understanding of the in vivo role of miRNAs/protein profiles as risk factor for CMV reactivation; 3) has potential for clinical importance, as the disease is common post-transplant and might increase the level of awareness in R+ patients; 4) uses easy available technology (PCR, ELISA, and western blot) to determine immune responses in pre-transplant samples, to determine the post-transplant risks for CMV reactivation.

The general aim is the adaptation and usage of basic science knowledge of host factors in clinical scenarios. The project focuses on pre-transplant immune system aspects influencing post-transplant virus reactivation in R+ patients. The focus is on discovery of novel innovative immune biomarkers. For the innate immune system we collaborate with Dr. Bochud and Dr. Manuel, who will provide polymorphism information. For the adaptive immune system, we focus on CMV-induced protein-, cytokine- and miRNA expression profiles of CMV-specific T-cells. The specific aim is the predication of CMV reactivation, replication and progression to disease using a network of biomarkers in R+ patients and interaction network analysis together with the computational science department of the mathematical faculty at the University of Basel. The STCS and our planned examinations allow increasing predication in a typical clinical scenario: About 20% of CMV sero-positive transplant recipients show CMV reactivation. Patients with particular immune risk patterns might benefit from targeted or prolonged prophylaxis. Thereby we might be able to reduce CMV reactivation and improve long-term graft survival, which is the ultimate goal of transplantation medicine.

Study Design

The study design is a prospective nested-cohort study. Immune factors will be determined in a single-blinded fashion in 700 CMV R+ patients and then compared between groups with and without CMV reactivation post-transplant. The primary outcome will be reactivation of CMV as determined by detection of CMV viremia within the first year of transplantation. Secondary outcomes will include development of symptomatic CMV disease, graft survival after 1 and 3 years, and mortality.

Publications
Human MicroRNA Responses Predict Cytomegalovirus Replication Following Solid Organ Transplantation
2012 - 2020 Epidemiology and therapy of orthopaedic implant and skin & soft tissue infections in transplant patients in the Swiss Transplant Cohort Study (STCS) [024: ongoing]
Project No.
024
Project Status
ongoing
Investigator
Uçkay I. et al.
Project Start
March 2012
Project End
September 2020
Abstract

Authors: I Uçkay (Geneva), C Garzoni (Bern), P Christofilopoulos (Geneva), M. Keel (Berne), C Van Delden (Geneva). Additional authors from all study centres in Switzerland may participate during the ongoing study and will figure on the authors’ list.

Background

Both the number of patients undergoing solid organ or bone marrow transplantation and those undergoing orthopaedic surgery with implantation of fracture devices or prosthetic joints is rising worldwide and in Switzerland [1]. In recent years, these two populations have further merged and it is not uncommon to see transplant patients with orthopaedic implants or with other osteo-articular or soft tissue infections treated in orthopaedic wards. However, the epidemiology and the risk factors for soft tissue and implant infections in the transplant patient, together with the associated pathogens, remain largely unknown.

The sparse literature almost exclusively reports unusual pathogens in transplanted patients with prosthetic joints, such as mycobacteria [2] or fungi [3], or non-infectious musculoskeletal complications [4]. Of note, to the best of our knowledge, no specific report concerning the epidemiology of risk factors for orthopaedic infections in transplanted patients has been published to date. Moreover, the few case reports available all concern experiences in single centres and no nationwide data have been published specifically on this topic.

The Swiss transplant cohort study with its large nationwide database compiled over three years has reached the point to be able to answer fundamental epidemiologic questions in this specific patient population.

Study aims

The primary aim of this study is to describe the clinical and microbiological epidemiology of skin & soft tissue and implant infections with all pathogens in the patient populations of the Swiss Transplant Cohort. Paediatric patients are included.

Specifically, the aims of the study will be:

  1. To describe the prevalence or incidence of different soft tissue and implant infections (fracture implant devices, or prosthetic joints).
  2. To analyze treatment options and treatment failures within the transplanted patient population by comparing similar data from non-transplanted patients from Switzerland (recurrences, surgical and medical treatment durations, choice of antimicrobial agents, associated organ rejections).
  3. To describe potential variables (risk factors) associated with these infections in the transplant population.

Study design

Prospective observational study involving all patients in the STCS with at least 6 months of follow-up. We expect to enrol approximately 1400 patients overall, and at least 25 with skin & soft tissue infections and at least 14 patients with implant-related infections. The study is divided in two parts:

1. Part A, Epidemiology: skin & soft tissue and implant-related infections have been added to the STCS dataset. The first part includes basic descriptive epidemiological features (prevalence, incidence, treatment failures, microbiology). Only information from the available dataset in the cohort study will be used. No additional variables or information will be required.

Publications
No publications yet
2012 - 2020 Impact of implantation of ventricular assist device on the incidence of post-transplant infection in heart transplant recipients [028: ongoing]
Project No.
028
Project Status
ongoing
Investigator
Manuel O. et al.
Project Start
March 2012
Project End
September 2020
Abstract

Delphine Zbinden, Georg Kralidis, Thierry Carrel, Alexia Cusini, Roger Hullin, Pascal Meylan,
Paul Mohacsi, Nicolas J. Mueller, Franz Ruschitzka, Piergiorgio Tozzi, Christian van Delden, Maja
Weisser, Markus Wilhelm, Manuel Pascual, Oriol Manuel and the Swiss Transplant Cohort Study (STCS)

Goals: Ventricular assist device (VAD) is a valuable option for patients with heart failure awaiting heart
transplantation. There are few data regarding the incidence of post-transplant infections in patients
with VAD pre-transplant as compared to those without VAD. The main goal of our study is to evaluate
the impact of the implantation of a VAD on post transplant outcomes
Methods: Cumulative incidence curves were used to calculate the incidence of infection and mortality
after transplant. Cox regression models treating death as competing risk were used to identify risk
factors for the development of infection after transplant.
Status: Study completed. 115 heart transplant recipients were included, 33 with a VAD and 82 without
VAD. Cumulative incidence of post transplant bacterial or candida infection was similar for patients
with and without VAD (p=0.73). In multivariate analysis, the absence of cotrimoxazole prophylaxis was
the only risk factor associated with bacterial/candida infection post transplant (HR 0.24, p<0.001), but
VAD was not (HR 0.90, p=0.77). An abstract has been accepted as a poster for the next American
Transplant Congress 2013 (May 18-22). The manuscript is in preparation and we expect to submit it in
June to the J Heart Lung Transplant.
Relevance for clinical practice: Our study will give important information on the epidemiology of
VAD infections in Switzerland and therefore may guide the standardization of preventive strategies for
decreasing the incidence of infections in these patients. The favorable outcomes post transplant
observed in patients with VAD will strength the use of these devices as a bridge to transplantation in
Switzerland.

Publications
Ventricular assist devices as bridge to heart transplantation: impact on post-transplant infections
2012 - 2020 Investigation of genetic markers potentially involved in the incidence of metabolic syndrome in the Swiss Transplant Cohort Study (STCS) [029: ongoing]
Project No.
029
Project Status
ongoing
Investigator
Qutaineh et al.
Project Start
September 2012
Project End
September 2020
Abstract

Lina Quteineh, Jean-Pierre Venetz, Pierre-Yves Bochud, Oriol Manuel, Roger Lehmann, Nicolas
Müller, Isabelle Binet, Christian Van Delden, Jürg Steiger, Ute Eisenberger, Paul Mohacsi, Jean-
francois Dufour, Paola Gasche-Soccal, Manuel Pascual, Chin B Eap

Goals:
The objective of the present study is to unravel the genetics of the metabolic syndrome (MetS, which
includes: obesity, diabetes, hypertension and hyperlipidemia) under immunosuppressive drug intake in
patients with organ transplantation and to provide some possible mechanisms of developing these
features. The project addresses the following key points:
- Investigate genetic polymorphisms that could influence body weight post-transplantation,
- Investigate genetic polymorphisms that could influence post-transplantation diabetes mellitus,
- Investigate genetic polymorphisms that could influence blood pressure post-transplantation,
- Investigate genetic polymorphisms that could influence lipid profile post-transplantation.

Methods:
Single nucleotide polymorphisms (SNPs) located within and around potential candidate genes that
could be implicated in the development of different components of the MetS will be genotyped using
DNA samples from the STCS. Statistical analyses will be performed taking into account potential
confounding factors such as age at transplantation, sex, BMI, smoking status and donor data.

Status:
Genetic polymorphisms within potential candidate genes as related to the development of post-
transplantation diabetes mellitus are already genotyped and statistical analyses for genetic
associations are ongoing. Interesting positive results are obtained, but correction for multiple testing is
still needed. The next step will be genotyping polymorphisms as related to obesity, hypertension and
hyperlipidemia post-transplantation.

Relevance for clinical practice:
The ultimate goal of this study is to identify patients at risk of developing MetS, to screen and detect
these patients before or early after transplantation. It could also allow early intervention when
symptoms of the MetS show, hence reducing the cardiovascular risk factors related to the MetS and
improving both graft and patient survival. In the long-term, these patients could benefit from
individualized immunosuppressive regimens adapted to their genetics and environment.

Publications
Genetic and clinic predictors of new onset diabetes mellitus after transplantation
Genetic immune and inflammatory markers associated with diabetes in solid organ transplant recipients
CRTC2 polymorphism as a risk factor for the incidence of metabolic syndrome in patients with solid organ transplantation.
Weighted Genetic Risk Scores and Prediction of Weight Gain in Solid Organ Transplant Populations
2012 - 2020 Systems prediction of Chronic Lung Allograft Dysfunction SysCLAD [030: ongoing]
Project No.
030
Project Status
ongoing
Investigator
Aubert et al.
Project Start
November 2012
Project End
September 2020
Abstract

JD Aubert, P Soccal, B Marsland, LP Nicod, and the lung transplant centers.

Goals The objective of this project is to build the SysCLAD model to be used by clinicians and
researchers. The model will identify and validate a signature of chronic lung allograft dysfunction
(CLAD) integrating multilevel data in order to i) identify and mitigate the risk of chronic allograft
dysfunction and ii) allow for early intervention before irreversible damage. The SysCLAD model will
permit prediction within the first year post LT for recipients which are at risk to develop BOS or RAS by
3 years post LT. This prediction, will be derived from the complete integration of large experimental
bio-collection (clinicome, environmental data, omics, microbiome, and immunological assays)
collected from both donors and recipients
Methods 1. Recruitment of LT candidates and LT recipients will involve 14 european centres,
including the two swiss lung transplantation programme from Lausanne-Geneva and Zurich. A merged
clinical database from the French cohort (COLT) and the STCS will collect clinical and functional data
starting from June 2009. Of these, about 400 recipients will reach 3 years follow up by July 2014
(M18) and be used to build, calibrate and validate the SysCLAD prediction model.
2. Proteomics, transcriptomics and immunological assays of minimally invasive sampled fluids (blood
and bronchoalveolar lavage - BAL) will be carried out and used to achieve objective
3. Build a comprehensive clinical research information system (CRIS) centralising all the clinical and
experimental data (environment, phenotype, microbiome, biology, omics) collected from donors,
recipients in a longitudinal fashion.
4. CLAD signature profiling. The data generated from objective 3, together with additional data from
the literature will be integrated and modelled in order to build the first signature of CLAD.
5. Validation of SysCLAD. Refine and validate the SysCLAD model by iteration in consecutive sets

Status Although the SysCLAD study has officially started on Nov 1 2013, more than 700 transplanted
patients from either the Swiss STCS or the French COLT cohort have been included at Jan 1
st
2013.
Common clinical endpoints have been set for both clinical databases. In parallel the first modeling of
CLAD, based on the literature knowledge is being elaborated and is awaiting further adjustement after
incorporating data from the clinic ome and the other “-omics” collected.

Relevance for clinical practice, The strength of the SysCLAD consortium resides in its large
prospective cohort of LTR and established bio bank, the inclusion of multiple clinical centres and the
integration of the environmental dimension (e.g. exposure to pollution, viral infections, microbiome
characterisation, compliance to immunosuppressants and co-medications) in addition to the more
traditional clinical and immunological data sets. The widespread adoption and implementation of the
SysCLAD model has the potential to lead to a marked decrease in health care costs, specifically those
associated with hospitalisation, medication and the use of laboratory services. In addition to this, early
recognition and specific, adapted, intervention in patients at high risk of developing CLAD will limit the
risk of graft rejection in LTR, and ultimately lead to an improved quality of life and a prolonged life
expectancy for patients

Publications
Airway Microbiota Determines Innate Cell Inflammatory or Tissue Remodeling Profiles in Lung Transplantation
Prediction of chronic lung allograft dysfunction: a systems medicine challenge.
2013 - 2020 Post-Transplant Lymphoproliferative Disorders: The impact of advances in immunosuppressive drugs over the last three decades on the incidence, characteristics and outcome of lymphomas after solid organ transplantation in the Swiss Transplant Cohort Study [031: ongoing]
Project No.
031
Project Status
ongoing
Investigator
Steiner et al.
Project Start
March 2013
Project End
September 2020
Abstract

Authors: R. Steiner, R. Kridel, E. Giostra, TA. McKee, PY. Dietrich
STCS collaborators: N. Mueller, T. Fehr, O. Manuel, K. Hadaya, U. Huynh-Do, I. Binet, M.
Dickenmann, H. Hirsch
Other collaborators: M. Tinguely Kovarik, W Jochum, S. Dirnhofer, J-F. Dufour, A Perren, B. Mülhaupt,
J. Brockmann, M. Wilhem, M. Schuurmans

Goal
Major advances in immunosuppressive drugs have been achieved along the last decades, with significant
changes in clinical practice. To what extend this may change the incidence, characteristics and outcome of
PTLD after solid organ transplantation during the last 2 decades in Switzerland is the issue addressed in the
project.

Methods
Retrospective study of the records of all adult patients undergoing solid organ transplantation at the Hopitaux
Universitaires de Genève,CHUV, Inselspital Bern, Universitätsspital Basel, Kantonsspital St.Gallen and
Universitätsspital Zürich in the last 20 years, maximal duration for medical files conservation. This study will
include the patients in the Swisstransplant Cohort study, cohort containing all transplanted patients between
2008 and 2012. However, we intend to open the inclusion period to the last two decades to gather a
significant number of patients.

Status
The data are still being collected and it is too early to give preliminary results. Indeed, this study does not
only focus on the data from the STCS which started in 2008, but will include as well all the patients with a
PTLD disorder in the past 20 years in Switzerland.


Relevance for clinical practice
Lymphoproliferative disorders are among the most serious and potentially fatal complications of chronic
immunosuppression in organ transplant recipients. This study intends to better understand how advances in
immunosuppressive drugs change the incidence, characteristics and outcome these lymphomas, to finally
allow a decreasing of the risk of development and early diagnosis of PTLD.

Publications
Low 5-year cumulative incidence of post-transplant lymphoproliferative disorders after solid organ transplantation in Switzerland
2012 - 2020 Polymorphisms of pattern recognition receptors in correlation with skin cancer development in organ transplant recipients [032: ongoing]
Project No.
032
Project Status
ongoing
Investigator
Hofbauer G. et al.
Project Start
September 2012
Project End
September 2020
Abstract

Günther Hofbauer 1, Anaïs Schneider 1, Pierre-Yves Bochud 2, Dela Golshayan 2, Mark Anliker 3, Andreas Arnold 4, Andreas Serra 1, Patrick Oberholzer 5, Emmanuel Laffitte 6, Anne-Carine Lapointe 2, Carlo Mainetti 7, Francesco Pelloni 8, Werner Kempf 1, Markus Streit 9
1 University Hospital Zürich,
2 University Hospital Lausanne,
3 Kantonsspital St. Gallen,
4 University Hospital Basel,
5 University Hospital Bern,
6 University Hospital Geneva,
7 Ospedale San Giovanni Bellinzona,
8 Lugano,
9 Kantonsspital Aarau

Goals
1. To analyze the incidence and type of skin cancer after transplantation in patients enrolled in the
STCS.
2. To assess the correlation of SNP in innate immune genes, alone or in combination, with the
development of skin cancer.
3. To develop a predictive model for the development of skin cancer based on SNP in innate immune
genes, alone or in combination.
Methods
The primary endpoint of the study is the correlation of all skin cancer with different single nucleotide
polymorphisms in innate immune genes. The secondary endpoints of the study are the correlation of
squamous cell carcinoma of the skin, basal cell carcinoma, melanoma and other skin cancer with
different single nucleotide polymorphisms in innate immune genes.
This study does not require any new samples from the STCS. DNA extraction and genotyping are
currently being performed for all recipients from the STCS participating laboratories. We propose to
use the data available from two genetic studies currently performed on samples from the STCS
(FUP012: PRR Polymorphisms and Infection after Organ Transplantation, by Manuel O. et al. and
FUP010: Role of Complement Activating Lectins on the Incidence and Course of Infections in
Transplant Patients with a Focus on CMV, by Meylan P. et al.) to determine whether genetic
polymorphisms in innate immune genes are associated with development of skin cancer and skin
cancer type. In particular we will look for associations between single-nucleotide polymorphisms (SNP)
in PRR genes and the risk of developing skin cancer after Tx.
Statistical analysis. The risk of skin cancer by PRR SNP will be assessed using logistic regression,
cumulative incidences curves and Cox regression models, after adjustment for appropriate covariates.
Receiver operating characteristic (ROC) curves for individual or combined single nucleotide
polymorphisms will be calculated in a randomly selected data subset and validated in the remaining
data set. We will thus be able to first generate a model and subsequently validate this model in the
given set of patients. Statistical expertise will primarily come from PD Andreas Serra, while the
Nephrology Unit also has the capacity for biostatistical capacity to analyze SNP data. Results will be
accounted for multiple testing appropriately. First and foremost, we will analyze TLR4-related SNPs.
Should numbers permit, we will then enlarge the number of target SNPs.

Status
Currently, 1101 OTR have been analyzed for their single nucleotide polymorphisms in relationship to
innate immunity genes. Within this number of OTR, 108 cases of skin cancer are on record. A
selection of the SNP of highest interest was made to conduct the statistical analysis. While data clean-up is being performed, we have preliminary results indicating a correlation for skin cancer to age,
validating the cohort selection in line with published data. Out of the selected target SNPS, an
association of three SNPs was identified on multivariate regression analysis with squamous cell
carcinoma, for one SNP with basal cell carcinoma, and of one SNP with any other skin tumor. One
immunosuppressive drug appears correlated to the occurrence of any skin cancer in the post-
transplant period. To conclude this project, we are validating histological information on tumor cases
within the data bank.
Relevance for clinical practice
Our data will allow identifying genetic risk factors and their respective weight for skin cancer risk. This
information will be clinically useful to recognize individual organ transplant recipients at particularly
high risk for skin cancer before they start to develop the much-feared wave of multiple skin cancer
development. Knowledge about an inherently higher risk for skin cancer in some OTR should help to
selectively target this group at elevated risk within OTR at high-risk for skin cancer in general. Given
the limited resources in our health care system, such data should help us to individualize treatment
and follow-up to focus intensive screening and treatment on these patients in particular need of
attention.

Publications
rs34567942 a Novel Susceptibility Single Nucleotide Polymorphism for Cutaneous Squamous Cell Carcinoma in Organ Transplant Recipients
2012 - 2013 The reciprocal relationship between CMV and graft rejection after solid organ transplantation [033: completed]
Project No.
033
Project Status
completed
Investigator
Stern et al.
Project Start
November 2012
Project End
June 2013
Abstract

Martin Stern, Michael Dickenmann, all centers of the STCS

Goals
Infection with cytomegalovirus (CMV) has been associated with an increased risk for solid organ graft
rejection. We wondered whether this association still holds, when high-risk patients receive
prophylactic treatment for CMV; and whether differences exist between patients with symptomatic or
asymptomatic CMV infection.

Methods
We correlated CMV infection and biopsy proven graft rejection in 1414 patients receiving heart (n=97),
kidney (n=917), liver (n=237), or lung (n=163) allografts reported to the Swiss Transplant Cohort
Study. Episodes of CMV replication were coded as time-dependent covariates, differentiating between
asymptomatic and symptomatic infection, and in case of asymptomatic infection further between
episodes that did or did not require treatment. Further analyses compared the cumulative incidence of
graft rejection in CMV IgG D-/R- patients (where CMV infection is virtually absent), to transplants
involving a CMV seropositive donor or recipient.
Status
We found in all that types of transplant, patients were at increased risk for biopsy proven graft rejection
within four weeks after diagnosis of CMV infection. The relative risk was highest in lung, and lowest in
kidney transplant recipients (see Figure). Relative hazards were comparable between patients with asymptomatic or symptomatic CMV infection. The CMV donor/recipient
serological constellation also
predicted the incidence of graft
rejection after liver and lung
transplantation, with significantly
higher rates of rejection in transplants
in which either donor or recipient
were CMV seropositive, compared to
donor-negative/recipient-negative
transplants (hazard ratio 3.05,
p=0.002 for liver; and 2.42, p=0.01 for
lung transplants). In contrast, no
significant association of D/R CMV
serostatus with graft rejection was found in kidney and heart transplants.
Relevance for clinical practice
CMV infection and donor/recipient sero-constellation remain associated with graft rejection in the era
of prophylactic CMV treatment. More intensive or prolonged suppression of CMV replication might be
warranted to decrease the incidence of graft rejection, particularly among recipients of lung and liver
allografts.

Publications
Cytomegalovirus serology and replication remain associated with solid organ graft rejection and graft loss in the era of prophylactic treatment.
2014 - 2020 Trends in blood pressure control and treatment after solid organ transplant: a longitudinal prospective swiss transplant study [035: ongoing]
Project No.
035
Project Status
ongoing
Investigator
Wuerzner et al.
Project Start
September 2014
Project End
September 2020
Abstract

G. Wuerzner (Lausanne); M. Pascual (Lausanne); D. Golshayan (Lausanne); JP Venetz (Lausanne); O. Manuel (Lausanne); E. Catana (Lausanne); P. Marques-Vidal (Lausanne); J. Steiger (Basel); I. Binet (St-Gallen); R. Wüthrich (Zurich); K. Hadaya; E. Giostra (Geneva); N. Semmo (Berne); B. Vogt (Berne); M. Burnier (Lausanne)

Background

Solid organ transplantation (SOT) is the treatment of choice for end-stage organ failure such as the heart, the lung, the liver and the kidney. The introduction of the calcineurin inhibitors cyclosporine in the eighties was associated with an improvement in transplant and patient survival partly due to a lower incidence of acute rejection. However, the use of calcineurin inhibitors is associated with a higher incidence of hypertension and diabetes.

The prevalence of hypertension is high after solid organ transplantation ranging from 65 to 90% 5 years after lung, liver, heart or kidney transplantation. Hypertension after transplantation is associated with graft loss, congestive heart failure, ischemic heart disease, and death. For example, kidney transplant recipients with hypertension at one year post-transplantation have a 30% increase in graft loss as compared with patients without hypertension with each 10 mmHg increase in blood pressure. However, if this relationtionship is clear for systolic blood pressure, there may a threshold of diastolic blood pressure under which it may be harmful for the patient. Therefore, strategies are needed to detect, to prevent and to control hypertension in order to improve long term outcome after solid organ transplantation.

In Switzerland, as opposed to a detailed study that was conducted in the non-transplant setting, there is no cross-national study reporting the prevalence of hypertension after solid organ transplantation. The existence of a Swiss transplant cohort data base that includes office blood pressure measurements and other possibly related factor at specific time point after solid organ transplantation should enable 1) to analyse the overall prevalence of hypertension in SOT recipients at various time point after transplantation 2) to determine which factors are associated with the lack of blood pressure control and finally 3) to determine the influence of uncontrolled blood pressure and these factors on outcomes such as death and graft loss.

Hypotheses

  1. The prevalence of hypertension after solid organ transplantation is as high in Switzerland as in Europe or the United States.
  2. Factors associated with hypertension after solid organ transplantation in Switzerland are similar as those that have been published
  3. Uncontrolled hypertension is associated with unfavourable graft and patient survival

Study aims

  • To determine the prevalence of hypertension at 6, 12 and 24 months after solid organ transplant in Switzerland.
  • To determine the prevalence of uncontrolled hypertension at 6, 12 and 24 months after solid organ transplant in Switzerland.
  • To determine the factors associated with uncontrolled hypertension in Switzerland among transplanted patients.
  • To determine the effect of uncontrolled hypertension and hypertension treatment on graft and patient survival including cardiovascular events at 5 years.

Study design

Analysis of collected data from a prospective observational cohort study.

Patients: Only patients from the Swiss transplant cohort study will be included in the analysis.

Data will include baseline demographic characteristics, traditional cardiovascular risk factors and factors known to influence blood pressure (BP) in the usual population and in the transplant population (Appendix 1)..

No additional blood or other samples will be needed.

Hypertension will be defined as BP >140/90 mmHg or antihypertensive drug treatment (diuretics, blockers of the renin-angiotensin system, calcium channel inhibitors, beta-blockers,. alpha-blockers, centrally acting antihypertensive drug). Uncontrolled hypertension will be defined as BP ≥140/90 mm Hg despite antihypertensive drug treatment.

Publications
No publications yet
2013 - 2020 Does Sleep Quality Predict Health Related Quality of Life in Solid Organ Transplant Patients? A Prospective Cohort Study [036: completed]
Project No.
036
Project Status
completed
Investigator
Burkhalter et al.
Project Start
August 2013
Project End
September 2020
Abstract

Hanna Burkhalter1+2 MSc, RN, Kris Denhaerynck1 PhD, RN, Sabina De Geest1 PhD, RN for the Psychosocial Interest Group, Swiss Transplant Cohort Study

1 Institute of Nursing Science, University of Basel, Basel, Switzerland 2 Division of Transplant Immunology and Nephrology, University Hospital Basel, Switzerland

Background

Sleep is a critical determinant of health and poor sleep has been associated with a wide range of health consequences 8 such as daytime sleepiness 9, poorer performance in the medication adherence 10, impaired working memory 11, impaired quality of life 3,12 and a 16% higher relative risk of mortality 2 in chronically ill patient populations. Poor sleep quality (SQ) is a risk factor for poor clinical outcomes in solid organ transplant (Tx) recipients. In order to strengthen the evidence base in view of SQ in solid organ Tx there is a need to explore the prevalence and evolution of SQ from pre- to post-Tx and determining if SQ is a predictor of health related quality of life (HRQoL) in the different solid organ Tx populations.

The gap in the literature is that there are no studies assessing sleep longitudinally and in all solid organs populations simultaneously using the same methodology. The data of the Swiss Transplant Cohort Study provide a unique possibility to fill this gap in the literature.

Study aims

The aims of the study are therefore:

  • to describe the prevalence and evolution of SQ from pre-Tx until 24 months post-Tx in kidney, liver, lung and heart Tx recipients
  • to investigate differences in prevalence and evolution of SQ in kidney, liver, lung and heart Tx recipients groups within and across assessment times (pre-Tx, 6, 12 and 24 months post-Tx) controlling for age, gender, depressive symptomatology and the number of months between the pre-Tx measurement and the Tx date, and
  • to determine if poor SQ is predictive with regard to health-related quality of life across Tx groups and assessment times (pre-Tx, 6, 12 and 24 months post-Tx) controlling for age, gender, depressive symptomatology and the number of months between the pre-Tx measurement and the Tx date.

Study design

This study will use the data from the Swiss Transplant Cohort Study (STCS). The STCS is a prospective open cohort study including all patients transplanted in Switzerland in one of the 6 Tx centers (Lausanne, Geneva, Basel, Zürich, Bern, St. Gallen). Sleep quality will be assessed at pre-Tx, 6, 12 and 24 months post-Tx using a single question with answers ranging from 0 (very poor) to 10 (very good), where the cut-off for poor SQ will be <6. Modeling of SQ and health-related quality of life across time and organs will be performed using generalized linear mixed modeling. In both instances, ‘patient’ will be added as random variable. Simultaneously to entering transplanted organ and time into the equation, we will control for the following confounding variables: age, gender, depressive symptomatology and the number of months between the pre-Tx measurement and the Tx date. Analyses will be performed in SAS 9.1.3 (SAS Institute Inc., Cary, NC, USA). The alpha level will be set at 5%.

Publications
Change of sleep quality from pre- to 3 years post-solid organ transplantation: The Swiss Transplant Cohort Study
Validation of a single item to assess daytime sleepiness
2013 - 2020 Blockade of the renin-Angiotensin System in vasoplegic syndrome early after heart transplantation [037: ongoing]
Project No.
037
Project Status
ongoing
Investigator
Hullin et al. 1
Project Start
July 2013
Project End
September 2020
Abstract

David Martin, Danielle Zaugg, +Frank Ruschitzka, ++Markus Wilhelm, ¶¶Piergiorgio Tozzi, ·Manuel Pascual, *Michele Martinelli, **Lars Englberger, ºPascal Meier, +Philippe Meyer, #Roger Hullin

Service de Cardiologie, ¶¶Service de Chirurgie cardiaque, Bâtiment hospitalier, CHUV, Rue du Bugnon 46, 1011 Lausanne; ·Centre de Transplantation d’Organes, Bâtiment hospitalier, CHUV, Rue du Bugnon 46, 1011 Lausanne, +Service de Cardiologie, Département de Médecine Interne, HUG, Rue Gabrielle-Perret-Gentil 4, 1205 Genève ; +Klinik für Kardiologe, ++Klinik für Herzchirurgie Universitätsklinik Zürich, Rämistrasse 100, 8091 Zürich; *Klinik für Kardiologie, **Klinik für Herz- und Gefässchirurgie, Inselspital, Universität Bern, Freiburger Strasse 4, CH-3010 Bern; ºThe Heart Hospital, University College London Hospitals, 16-18 Westmoreland Street, London W1G 8PH, United Kingdom; Yale University, 333 Cedar St, New Haven, CT 06520, USA.

Background

The vasoplegia syndrome after orthotopic heart transplantation (HTx) is characterized by therapy-refractory low systemic vascular resistance (<800 dynes x cm-5) despite of adequate fluid resuscitation and vasopressor treatment. Larger series report an incidence between 11 and 19%, and a mortality ranging from 17-25%. Various risk factors for vasoplegia after HTx have been reported such as preoperative treatment with aspirin or intravenous heparin, high body mass index, long cardiopulmonary bypass time, prior cardiothoracic surgery or mechanical support, and thyroid disease. However, the physiology remains unclear.

In mammalians, the renin-angiotensin system (RAS) is crucial for controlling blood pressure, cardiovascular and renal function. The angiotensin converting enzyme (ACE) plays a key role in the cascade of RAS by cleaving angiotensin I into angiotensin II which is a potent vasoconstrictor. A 287 base-pair insertion / deletion (I=insertion, D=deletion) polymorphism has been identified in the intron 16 of the ACE gene. This polymorphism is common in the population (II: 20%; ID: 43%; DD: 37%) and the D allele results in increased ACE-activity and angiotensin II levels. Furthermore, other proteins could also play a role in vasoplegic syndrome such as β1- and β2 adrenoreceptors, which regulate renin expression, and the angiotensin II receptors (type1 and type 2), which are activated by binding of angiotensin II. Polymorphisms of physiological relevance have been identified both for β-adrenoreceptors and the angiotensin II receptors suggesting that these variants may impact on activation and effector function of the RAS.

Chronic heart failure (CHF) is associated with pathological activation of the RAS, and inhibition of the ACE activity, β-receptor blockade as well as blockade of the angiotensin II receptor are nowadays cornerstone pharmacological treatment for CHF. However, because the half-life of some of these inhibitors may last up to 5 days, these long acting molecules may foster vasoplegia syndrome after HTx, especially when the recipient expresses polymorphisms which result in decreased activity of the respective proteins.

Study objectives

Characterization of the clinical relevance of polymorphisms of the β1- and β2 adrenoreceptors, of the ACE gene, and of the gene encoding the angiotensin II receptors for vasoplegia syndrome after orthotopic heart transplantation.

Method and Study design

This study is a correlational epidemiologic study with a genomic analysis of the β1- and β2-adrenoreceptor, of the ACE and of the AGTR1 and AGTR2 gene polymorphisms in HTx recipient blood cells. Results of genomic analysis will be correlated with results from arterial blood pressure, systemic vascular resistance, and cardiac index measurements.

Blockade of the renin-Angiotensin System in vasoplegic syndrome early after heart transplantation

Publications
No publications yet
2015 - 2020 Adrenergic receptor polymorphisms and maximal exercise capacity after orthotopic heart transplantation [038: ongoing]
Project No.
038
Project Status
ongoing
Investigator
Hullin et al. 2
Project Start
March 2015
Project End
September 2020
Abstract

David Martin, Danielle Zaugg, ·Frank Ruschitzka, ··Markus Wilhelm, Stephanie Perruchoud, +Sam Rotman, #Philippe Meyer, ºPascal Meier, ¶¶Piergiorgio Tozzi,+Roger Hullin

Service de Cardiologie, Département de Médecine Interne, ¶¶ Département de Chirurgie Cardiaque, CHUV, Rue du Bugnon 46, 1011 Lausanne; ·Klinik für Kardiologe, ··Klinik für Herzchirurgie, Universitätsklinik Zürich, Rämistrasse 100, 8091 Zürich; + Pathologie, UNIL, Rue du Bugnon 27, 1011 Lausanne; #Service de Cardiologie, Département de Médecine Interne, HUG, Rue Gabrielle-Perret-Gentil 4, 1205 Genève ; ºThe Heart Hospital, University College London Hospitals, 16-18 Westmoreland Street, London W1G 8PH, United Kingdom.

Background

Peak oxygen uptake (VO2max) is an established integrative measurement of maximal exercise capacity in cardiovascular disease. After heart transplantation (HTx), VO2max remains overall reduced to the 50-70% level of age-matched healthy controls. Our own studies showed that VO2max after HTx is dependent in declining order on recipient age, peak heart diastolic function, and BMI (Roten et al.).

Orthotopic HTx disrupts sympathetic and parasympathetic innervation in the cardiac allograft for the long-term, therefore, heart rate remains entirely dependent on β-adrenergic receptor stimulation by endogenous catecholamines. Polymorphism of the adrenoreceptor changes the physiological response to receptor agonist stimulation suggesting that β-adrenergic receptor polymorphism should be relevant for basal and peak heart rate after HTx. Preliminary proof of this concept is suggested from a small study of 20 HTx recipients showing that the β1-adrenergic receptor Ser49Gly polymorphism impacts on basal heart rate but miss significance for peak heart rate (Scharin et al.).

Polymorphisms of the α- and β-adrenergic receptors occur in up to 50% of the population, suggesting that HTx may result in different adrenoreceptor polymorphisms combinations in the donor heart and in the recipient. As a consequence, endogenous catecholamine production and secretion, which is adapted to the polymorphisms of the recipient α- and β-adrenoreceptors, may be inadequate for the adrenoreceptors expressed in the donor heart.

This study proposal aims at a comprehensive analysis of the β1-, β2-, α2a-, and α2c-adrenoreceptor gene polymorphisms in the cardiac allograft and in the recipient in order to characterize their functional relevance to maximal exercise capacity.

Study aim

Characterization of the effect of β1-, β2-, α2a-, and α2c-adrenergic receptor polymorphisms expressed in the recipient and in the donor on heart rate at rest and with exercise as well as maximal exercise capacity.

Study design

Correlational epidemiologic study with genomic analysis of the β1-, β2-, α2a-, and α2c-receptor polymorphisms in myocardial biopsies obtained from the cardiac allograft and in the recipient blood cells. Results of genomic analysis will be correlated with results from maximal exercise testing, in particular:

1. heart rate at rest

2. peak heart rate with maximal exercise

3. maximal exercise capacity as measured by the following parameters: VO2max, VE/VCO2, VO2-AT

4. arterial blood pressure at rest (before and after cardiopulmonary exercise testing) and with peak exercise


Publications
Adrenergic Receptor Polymorphism and Maximal Exercise Capacity after Orthotopic Heart Transplantation
2013 - 2020 Hepatitis C Virus evolution and virus-host interactions after orthotopic liver transplantation [039: completed]
Project No.
039
Project Status
completed
Investigator
Mueller et al.
Project Start
June 2013
Project End
September 2020
Abstract

1Nicolas Mueller, 2Andri Rauch, 3Nasser Semmo, 2Alexia Cusini, 4Hans H. Hirsch, 4Maja Weisser, 5Christian van Delden, 6Pascal Meylan, 6Oriol Manuel, 7Christoph Berger, 7David Nadal, 8Jean Villard, 9Juliane Gentzsch 9Thomas Kuntzen, 1Karin J. Metzner

1Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, 2Department of Infectious Diseases, Bern University Hospital and University of Bern, 3Hepatology, Bern University Hospital and University of Bern, 4Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, 5 Service of Transplantation, Department of Surgery, University Hospital Geneva, 6Transplantation Center, University Hospital (CHUV) and University of Lausanne, Infectious Diseases Service, University Hospital (CHUV) and University of Lausanne, 7Children’s Hospital, Zurich, 8Transplantation Immunology Unit, Geneva,9Department of Gastroenterology and Hepatology, University Hospital Zürich

Background

Liver transplantation replaces the main site of Hepatitis C virus (HCV) replication. When infection of the new allograft inevitably occurs after transplantation into a viremic patient, HLA antigens are rarely matched between donor and recipient, thus altering HCV antigen presentation and immune pressures on viral epitopes. In addition, immunosuppression inhibits innate, cellular and humoral immune responses, along with new host cell characteristics changing the environment for the preexisting HCV population substantially. In patients who received antiviral treatment with HCV protease inhibitors until the time point of transplantation drug selection pressures are removed, allowing reversion of the viral population from previously selected drug resistant strains back to wild type.

Study aims

We hypothesize that the altered post-transplant environment will result in changes that, on one hand, create new selection pressures on HCV that force the virus population to adapt to the new liver and, on the other hand, reduce certain selection pressures due to the immuno-suppressive treatment. On the virus side this likely includes HLA mediated cellular immune responses with escape mutations and their consequences on viral fitness, whereas on the host side removal of host HLA alleles that previously presented viral antigens may result in recovery of previously exhausted immune cell populations.

Our study aims are to characterize these virus host interactions before and after liver transplantation in several aspects:

  • Extent and rate of evolution in the HCV population
  • Extent and rate of de-novo selection, or reversion of previously selected immune escape mutations
  • Changes in drug-resistant HCV populations
  • Functional changes in cellular immune responses

Study design

Data on transplant history, infection status and history of antiviral treatment will be retrieved from the STCS. So far, 94 patients infected were transplanted for end stage liver disease due to hepatitis C in the STCS. Of these, 37 patients have samples at all three time points (0, 6 months and 12 months). HLA typing is available for all donors, and will be complemented for recipients by Jean Villard. Full-length Hepatitis C viral strains will be amplified by long range RT-PCR from STCS plasma samples (1.8 ml) before, and 6 and 12 months after liver transplantation (depending on sample availability). Next-generation sequencing (NGS) will be performed using the Illumina NGS technology. Viral evolution related to a change in the above listed selection pressures will be characterized by comparison to known escape mutations or HLA-associated viral footprints, or to newly identified mutations in adaptation to other host gene polymorphisms (ongoing research JG & TK). Cellular immune responses against epitopes selected based on HLA restriction and viral evolution with reversion or de novo immune escape will be characterized by FACS and/or Elispot.

Publications
No publications yet
2013 - 2020 Bloodstream infections with multiresistant pathogens in allogeneic Hematopoetic Stem Cell Recipients from the Swiss Transplant Cohort Study [040: ongoing]
Project No.
040
Project Status
ongoing
Investigator
Weisser M et al.
Project Start
June 2013
Project End
September 2020
Abstract

Maja Weisser (Basel), Veronika Bättig (Basel), S. Gerull (Hematology), M. Stern (Basel) K. Passweg (Basel), Nina Khanna (NK), Christian Garzoni (Lugano), Urs Schanz, (Zürich), Nicolas Mueller (Zürich), Christoph Berger (Zürich), Christian van Delden (Geneva)

Background

Bloodstream infection (BSI) is the most common infectious complication during aplasia after hematopoietic stem cell transplantation (HSCT) ranging from 28 to 56%, but can occur also later after recovery from aplasia. Causative bacteria are changing over time: During the 1960s and 1970s, gramnegative pathogens predominated, in the 1980s a shift towards grampositive bacteria occured, probably as a consequence of indwelling catheters and applied prophylaxis. Since a couple of years gramnegative bacteria are gaining importance and are associated in many countries with the emergence of multidrug resistance (MDR). Widely used quinolone prophylaxis during aplasia has been associated with breakthrough BSI caused by such MDR bacteria.

In 2012, the European Conference on Infections in Leukaemia (ECIL) released new recommendations for the empirical use of antibiotic treatment for patients with febrile neutropenia taking into account the emergence of MDR bacteria by introducing the concept of antibiotic de-escalation starting with a very broad antibiotic treatment in the empicial situation and streamlining or even stoping antibiotics in the abscence of a documented pathogen. These guidelines reflect the current dilemma of an increased need to cover for MDR bacteria in patients at high risk, and the necessity to reduce selection pressure.

Geographical and epidemiological factors greatly affect rates of antibiotic resistances and are key for the choice of empiric antibiotic treatment. We aim to analyze the frequency of MDR bacteria causing BSI in HSCT recipients included in the Swiss Transplant Cohort Study (STCS). Furthermore we will analyze risk factors to develop an MDR BSI, the impact of MDR BSI on outcome and the adequacy of empirical antibiotic treatment.

Study Aims

  • To determine the incidence of BSI and MDR BSI in patients after a allogeneic hematopoietic stem cell transplantation included in the STCS
  • To describe the antimicrobial susceptibility/resistance of MDR bacterial strains
  • To determine the risk factors for an MDR BSI during the first 30 days after HSCT
  • To determine the impact of an MDR BSI on patient outcome
  • To determine the adequacy of empiric antibiotic treatment

Study Design

We plan an observational study from prospectively enrolled patients with an allogeneic HSCT enrolled in both the Swiss Transplant Cohort Study (STCS) and in the European Group for Bone Marrow Transplantation (EBMT) since the start of the STCS in 2008.

After merging the two datasets, bacteremia episodes will be extracted and incidence rates of clinical relevant BSI will be calculated. By retrospective chart review, additional data on resistance of blood isolates and on empiric antibiotic treatment will be collected.

A risk factor analysis for the development of MDR BSI during the first 30 days posttransplant will be performed considering age, sex, epidemiological background, transplant type, underlying diseases, treatment modalities, center, duration of neutropenia, duration of hospital stay, type of immunosuppression, antibiotic prophylaxis and treatments as potential associated factors. Adequacy of treatment and outcome will be analysed.

Publications
No publications yet
2015 - 2020 The impact of Hyponatremia on allograft function and patient survival after renal transplantation. A prospective cohort study [041: ongoing]
Project No.
041
Project Status
ongoing
Investigator
Armpatzis et al.
Project Start
January 2015
Project End
September 2020
Abstract

Dr. med. Spyridon Arampatzis1 , Dr. med. Sophie de Seigneux2, Dr. med. K. Hadaya2, Vasileios Devetzis med. pract1, Prof. Dr. med. Pierre-Yves Martin2 , Prof. Dr. med Uyen Huynh-Do1

1Department of Nephrology, Hypertension and Clinical Pharmacology, Inselspital, Bern University Hospital

2Service de Néphrologie, Département de Médecine Interne, Hôpitaux Universitaires de Genève,

Background

After kidney transplantation, which is the most effective treatment modality for end-stage renal disease, renal electrolyte handling is impaired due to a number of deleterious factors, including ischemic tubular damage. Additional factors such as immunosuppressive drugs, rejection episodes and concomitant medication can influence electrolyte homeostasis. Hyponatremia is a common problem associated with high mortality in hospitalized patients; however the impact of hyponatremia in an ambulatory setting remains unclear. The impact of transplantation-associated hyponatremia on mortality and graft survival has never been prospectively investigated in an adequate large cohort of kidney transplanted patients.

Study aims

Here, we aim to determine the prevalence of hyponatremia (defined as serum sodium level of <136 mEq/l at 6 months of follow up) and test the hypothesis that hyponatremia is associated with mortality and graft-lost following kidney transplantation.

Study design

Prospective observational cohort study with additional retrospective data acquisition based on the STCS. Already available laboratory and clinical data (serum and urine electrolytes, relevant nutritional parameters, hormones, and medication) which are routinely collected during follow up visits, will be extracted from the STCS database and/or retrieved from the central laboratory units/patient records of each center by the investigators. Both primary involved centers (Bern and Geneva) have already collected relevant laboratory values proving evidence of the feasibility of this retrospective data collection method.

Future perspectives

The impact of hyponatremia on renal and overall survival will be calculated based on relevant endpoints and multiple regression analysis.

Publications
No publications yet
2013 - 2020 Incidence, Risk Factors and Outcomes of Clostridium difficile associated disease in Solid Organ Transplant Recipients in the Swiss Transplant Cohort Study [042: ongoing]
Project No.
042
Project Status
ongoing
Investigator
Cusini et al.
Project Start
June 2013
Project End
September 2020
Abstract

Authors: Alexia Cusini (Bern), Charles Béguelin (Bern), Susanne Stampf (Basel), Michael Koller (Basel), Katia Boggian (St. Gallen), Christian Garzoni (Lugano), Pascal Meylan (Lausanne), Manuel Oriol (Lausanne), Nicolas Müller (Zurich), Maja Weisser (Basel), Christian van Delden (Geneva)

Background

Clostridium difficile, a gram-positive anaerobic organism, is the leading cause of nosocomial diarrhea in the developed world and one of the most common bacterial etiologies of diarrhea in solid organ transplant (SOT) recipients. Among SOT recipients the reported rates of C. difficile associated disease (CDAD) range from 0.48 to 31% in the posttransplantation course. The degree of immunosuppression influences the risk of CDAD. SOT recipients frequently have a combination of different risk factors for developing CDAD: prolonged antibiotic treatment, medication suppressing gastric acid, age greater than 65 years, severe underlying diseases and prolonged hospital stay. The incidence of CDAD in SOT recipients is highest within the first three months after transplantation, probably because of intense immunosuppression and more frequent antimicrobial exposure. Knowledge about the clinical course including severity and recurrence of CDAD in SOT is scarce. These aspects of CDAD need further investigation as the recommended treatment regimens depend on the severity of the disease and it is likely that new antibiotics guidelines will give more emphasis to the reduction of recurrence of CDAD.

Study aims

  • To determine the cumulative incidence of CDAD in SOT recipients in Switzerland.
  • To characterize risk factors for the development of CDAD in SOT.
  • To describe the severity of CDAD in SOT
  • To analyze the different antibiotic treatments used to treat CDAD and the frequency of colectomy for complicated colitis and to analyze the outcome defined as cure, failure, recurrence, graft loss and mortality.
    • Study Design

Study design

We plan an observational study involving all patients after liver, lung, heart, kidney and kidney-pancreas transplantation enrolled in the Swiss Transplant Cohort Study (STCS) since its start in 2008. A preliminary analysis of the STCS database on a total of 1963 patients transplanted from May 2008 till August 2012 identified 102 proven CDAD cases. We will extract all prospectively collected infections with C. difficile from the STCS database and calculate the cumulative incidence rates by organ.

In a further step we aim to evaluate the impact of possible risk factors contributing to the development of CDAD. Several possible risk factors leading to CDAD are prospectively registered within the STCS so that their occurrence can be compared between the CDAD-cases and the whole STCS population. However to analyze more specific risk factors like kind of antibiotic and antiviral treatment, intake of gastric acid suppressing agents, hospital stay and stay on the intensive care unit in the last 3 months prior to the current CDAD manifestation we will need to collect additional data by chart review.

In order to efficiently collect retrospective data by chart review, we propose to perform a case-control study nested within the STCS(a nested case-control study). Thus only a defined and limited number of SOT recipients will be selected as controls from the STCS. For this nested-case-control study, we propose to match two controls per CDAD case. Matching variables are type of organ, time after transplantation, age and sex. Additionally for the CDAD cases we will collect data about diagnostic methods, clinical presentation, treatment and outcome of CDAD.

Publications
Clostridium difficile infection is associated with graft loss in solid organ transplant recipients
2013 - 2020 KIR genotype and viral/fungal infections after solid organ transplantation [043: completed]
Project No.
043
Project Status
completed
Investigator
Stern et al.
Project Start
June 2013
Project End
September 2020
Abstract

KIR genotype and viral/fungal infections after solid organ transplantation

Publications
Protection From Varicella Zoster in Solid Organ Transplant Recipients Carrying Killer Cell Immunoglobulin-Like Receptor B Haplotypes.
2013 - 2020 Renal Transplantation, Employment and Disability: A Retrospective, observational before-and-after Feasibility Study by the Swiss Transplant Cohort. [044: ongoing]
Project No.
044
Project Status
ongoing
Investigator
Hug et al.
Project Start
December 2013
Project End
September 2020
Abstract

Renal Transplantation, Employment and Disability: A Retrospective, observational before-and-after Feasibility Study by the Swiss Transplant Cohort.

Publications
No publications yet
2014 - 2020 Impact of α-herpesviridae infections in solid organ transplant recipients [045: ongoing]
Project No.
045
Project Status
ongoing
Investigator
Manuel O. et al.
Project Start
March 2014
Project End
September 2020
Abstract
no abstract provided
Publications
Preventive Strategies Against Cytomegalovirus and Incidence of alpha-Herpesvirus Infections in Solid Organ Transplant Recipients: A Nationwide Cohort Study.
2013 - 2020 CMV-induced changes to NK cell repertoire and function [047: completed]
Project No.
047
Project Status
completed
Investigator
Stern et al.
Project Start
September 2013
Project End
September 2020
Abstract

CMV-induced changes to NK cell repertoire and function

Publications
Human Cytomegalovirus Infection Enhances NK Cell Activity In Vitro
2013 - 2020 Validation of scoring systems developed from the French DIVAT cohort for the prognosis of transplantation failures among kidney recipients [049: ongoing]
Project No.
049
Project Status
ongoing
Investigator
Foucher et al.
Project Start
September 2013
Project End
September 2020
Abstract

Validation of scoring systems developed from the French DIVAT cohort for the prognosis of transplantation failures among kidney recipients

Publications
No publications yet
2013 - 2018 Impact of Different Prophylactic or Treatment Strategies on the Epidemiology of Invasive Fungal Infections in Patients after Allogeneic Hematopoietic Stem Cell Transplantation [050: completed]
Project No.
050
Project Status
completed
Investigator
Khanna et al
Project Start
September 2013
Project End
August 2018
Abstract

Impact of Different Prophylactic or Treatment Strategies on the Epidemiology of Invasive Fungal Infections in Patients after Allogeneic Hematopoietic Stem Cell Transplantation

Publications
Incidence and outcome of invasive fungal diseases after allogeneic hematopoietic stem cell transplantation: A Swiss transplant cohort study
2014 - 2020 Validation of the “60-5 Criterion” Low Platelet Counts as an Early Predictor of Complications, Graft Survival and Death after Liver Transplantation. [051: completed]
Project No.
051
Project Status
completed
Investigator
Lesurtel et al.
Project Start
March 2014
Project End
September 2020
Abstract

Validation of the “60-5 Criterion” Low Platelet Counts as an Early Predictor of Complications, Graft Survival and Death after Liver Transplantation.

Publications
No publications yet
2015 - 2020 Monitoring of specific cytomegalovirus cell-mediated immunity (CMV-CMI) for optimisation of preventive strategies against CMV infection in high-risk solid-organ transplant recipients [052: ongoing]
Project No.
052
Project Status
ongoing
Investigator
Manuel et al
Project Start
April 2015
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2014 - 2017 Virological Monitoring of Teno Torque Virus (TTV) to evaluate Immunological Competence during Immunosuppression following Orthotopic Liver Transplantation [053: completed]
Project No.
053
Project Status
completed
Investigator
Simonetta et al
Project Start
March 2014
Project End
July 2017
Abstract
no abstract provided
Publications
Torque Teno Virus Load and Acute Rejection after Orthotopic Liver Transplantation.
2014 - 2020 Variation of CT-patterns of Pneumocystis jirovecii pneumonia (PCP) in HIV-infected individuals and recipients of solid organ transplants (SOT). [055: ongoing]
Project No.
055
Project Status
ongoing
Investigator
Christe et al
Project Start
September 2014
Project End
September 2020
Abstract
no abstract provided
Publications
Imaging patterns of Pneumocystis jirovecii pneumonia in HIV-positive and renal transplant patients - a multicentre study
2014 - 2020 Cellular immune responses to BK polyomavirus (BKPyV) predict clearance of BK viremia in kidney-transplant recipient [056: ongoing]
Project No.
056
Project Status
ongoing
Investigator
Hirsch et al
Project Start
March 2014
Project End
September 2020
Abstract
no abstract provided
Publications
Can HLA-B51 Protect Against BKPyV-DNAemia?
BK Polyomavirus-Specific 9mer CD8 T Cell Responses Correlate With Clearance of BK Viremia in Kidney Transplant Recipients: First Report From the Swiss Transplant Cohort Study.
2014 - 2017 Weight gain, overweight and obesity in solid organ transplantation – evolution from pre- to post transplant, risk factors and clinical outcomes [057: completed]
Project No.
057
Project Status
completed
Investigator
Beckmann et al
Project Start
March 2014
Project End
March 2017
Abstract
no abstract provided
Publications
Evolution of body weight parameters up to 3 years after solid organ transplantation: The prospective Swiss Transplant Cohort Study.
New-onset obesity after liver transplantationoutcomes and risk factors: the Swiss Transplant Cohort Study
2014 - 2020 Nocardia infection in solid organ transplant recipients: an international case-control study [058: ongoing]
Project No.
058
Project Status
ongoing
Investigator
van Delden C. et al
Project Start
March 2014
Project End
September 2020
Abstract
no abstract provided
Publications
Outcome and treatment of nocardiosis after solid organ transplantation: new insights from a European study
Nocardia Infection in Solid Organ Transplant Recipients: A Multicenter European Case-control Study.
2015 - 2020 Immunosuppressive drugs used to treat antibody-mediated rejection in kidney transplant recipients of the Swiss Transplant Cohort Study (STCS) [059: ongoing]
Project No.
059
Project Status
ongoing
Investigator
Perrottet et al
Project Start
May 2015
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2014 - 2020 Outcome following solid organ transplantation in Switzerland: the Swiss Transplant Cohort Study [060: ongoing]
Project No.
060
Project Status
ongoing
Investigator
Koller M.T. et al
Project Start
March 2014
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2014 - 2020 Impact of ageing on outcomes of solid organ transplantation in elderly transplant recipients [061: ongoing]
Project No.
061
Project Status
ongoing
Investigator
Mauthner et al.
Project Start
March 2014
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2015 - 2020 Cancer development in organ transplant recipients [062: completed]
Project No.
062
Project Status
completed
Investigator
Hofbauer G. et al.
Project Start
September 2015
Project End
September 2020
Abstract

Günther Hofbauer 1, Niklaus Schäfer 1, Emanuel Lengwiler 1, Alfred Zippelius 2, Julian Schardt 3, Emanuela Salati 4, Khalil Zaman 5, Marco Siano 6

1 UniversitätsSpital Zürich

2 Universitätsspital Basel

3 Inselspital Bern

4 HU Genève

5 CHUV Lausanne

6 Kantonsspital St. Gallen

Background

Cancer in solid organ transplant recipients (sOTR) belongs to the major complications after solid organ transplantation and counts as one of the most common causes of death 5 years after transplantation. Studies in the US have shown a 2- to 4-fold increased risk of cancer in sOTR compared to the general population. The incidence of cancer in sOTR has been accentuated over the last few years, as the life expectancy in sOTR has increased considerably. The excess risk of cancer is related to the exposure to immunosuppressive drugs over time, decreased control of oncogenic viral infections as well as underlying medical conditions in sOTR. Infection-related malignancies, such as Hodgkin’s lymphoma and Non-Hodgkin’s lymphoma (both due to EBV), Kaposi sarcoma (HHV 8), anogenital cancer (HPV) and liver cancer (HCV) have been reported to be especially increased in sOTR. Other malignancies such as cancer of the lung, kidney, skin and thyroid are also increased in sOTR. To this day, however, the cancer risk in sOTR, as well as its associated factors and other aspects of these malignancies have not yet been clearly delineated in the Swiss population. We will perform a pilot study to gather an initial impression of cancer incidence in the STCS preparing for a cancer audit and longer-term studies.

Study Aims

1. To descriptively report cancer incidence in the STCS 2008-2014.

2. To study the incidence of metastasis or death of solid cancers in sOTR, therapy and response to treatment 2008-2014.

Study Design

Prospective cohort study of kidney, heart, lung, pancreas and liver transplant recipients enrolled into the Swiss Transplant Cohort Study (STCS) until the end of 2014 using retrospective analysis of prospectively collected data.

Publications
Solid cancer development in solid organ transplant recipients within the Swiss Transplant Cohort Study
2015 - 2020 Association of viral reactivation and skin cancer in organ transplant recipients [063: ongoing]
Project No.
063
Project Status
ongoing
Investigator
Hofbauer G. et al.
Project Start
September 2015
Project End
September 2020
Abstract

Background:

Squamous Cell Carcinoma of the skin (SCC) affects people in high numbers worldwide. While a yearly increase of over 2 million patients, who develop cancer, is recorded (Einspahr et al., 2003), organ transplant recipients (OTR) have a 60- to 100-fold higher risk of developing skin cancer (Berg and Otley, 2002). In OTRs, skin cancer is the most frequent tumor that appears, whereas 95% are nonmelanoma skin cancer cells: squamous cells or basal cell carcinomas (Zwald and Brown, 2011). All OTRs need to be treated lifelong with immunosuppressants in order to prevent the rejection of the transplanted organ. However, this immunosuppressive treatment leads to a decrease of immunity, and therefore, cancer cells are able to proliferate easier (Fishman, 2013).

Several studies show that the incidence of skin cancer parallels the length and depth of immunosuppression (Bouwes Bavinck et al., 1996). The appearance of CD4 in OTRs with cutaneous carcinomas is significantly lower compared to those without skin lesions (Ducloux et al., 1998). Various findings have shown a positive correlation of the period of exposure to immunosuppressants and the risk of skin cancer. However, little is known about the dose or the type of drug is responsible for skin cancer (Euvrard et al., 2003). The uptake of three immunosuppressive medicaments compared to the uptake of two results in a 3-fold increased risk of developing cancer. The consequence of the immunosuppressive therapy is reversible; patients who stop immunosuppressive treatment often show a decrease in skin cancer (Moloney et al., 2004). The highest risk for organ rejection is during the first three months after transplantation. Therefore, an increased dose of immunosuppressants is used during this time (Zwald and Brown, 2011).

Herpesvirus infections due to the eight human herpesviruses (HHV) are more frequent by immunosuppression in OTRs. Once a patient is infected with one of the human herpesvirus types (Herpes simplex viruses 1 and 2, varicella-zoster virus, Epstein-Barr virus, human cytomegalovirus, human herpesvirus 6 and 7, or Kaposi’s sarcoma-associated herpesvirus), the virus is able to establish a latent, non-productive infection and maintains the capacity for a life-long reactivation. Due to the decrease of immunity, OTRs are highly susceptible to activate this latent herpesviral infection, which is a critical aspect of the immunosuppressive treatment. The risk of the reactivation of Cytomegalovirus and Epstein-Barr virus in OTRs is much higher compared to the general population (Fishman, 2013).

In addition to cancer, a high increase of viral infection and reactivation is seen in OTRs. Over 90% of the population carries herpesviruses (Einspahr et al., 2003). The risk of viral infection and reactivation is much higher in OTRs (Berg and Otley, 2002). While inducing a decrease in immunosurveillance, herpesvirus can spread easier.

Taking the above discussed findings together, we hypothesize that viral infection and reactivation correlate positively with skin cancer in OTRs. Furthermore, we think that viral infection and reactivation can be used as a marker for a later incidence of skin cancer. While virus infections and reactivations appear early, OTRs become affected by SCC in the early and in the late period after the transplantation. We thus aim to analyze existing data from the STCS and its nested studies to test these hypotheses: To assess the correlation of viral infection and replication and skin cancer in organ transplant recipients and to assess viral infection and replication as predictor for skin cancer. We are interested in all data available from other studies of the STCS and to divide all organ transplant recipients e.g. for CMV in four groups: no replication, a larger group who show asymptomatic viral replication, some of them with viral syndrome and the ones with proven disease.

Study aims:

To test the hypothesis that OTR with CMV, EBV, BKV seroconversion/primary infection, asymptomatic viral replication, viral syndrome, viral disease from the time of organ transplantation until 6 months after transplantation have a higher risk to develop SCC than OTR without CMV, EBV, BKV infection.

Study design:

Retrospective analysis of prospectively collected data of the STCS.

Publications
No publications yet
2014 - 2020 Dialysis after renal graft loss (DAGL) in Switzerland [064: ongoing]
Project No.
064
Project Status
ongoing
Investigator
Segerer et al.
Project Start
September 2014
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2014 - 2020 LILRB1 polymorphisms and susceptibility to CMV infection and disease in the Swiss Transplant Cohort Study (STCS) [065: ongoing]
Project No.
065
Project Status
ongoing
Investigator
D. Burshtyn
Project Start
September 2014
Project End
September 2020
Abstract
no abstract provided
Publications
LILRB1 polymorphisms influence posttransplant HCMV susceptibility and ligand interactions
2017 - 2020 Prognostic capacities of the kidney transplant failure score (KTFS) and complementary biomarkers after living donation [066: ongoing]
Project No.
066
Project Status
ongoing
Investigator
S. Brouard
Project Start
December 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2014 - 2020 Echinococcus multilocularis infection in solid-organ transplant recipients [067: ongoing]
Project No.
067
Project Status
ongoing
Investigator
O. Manuel
Project Start
September 2014
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2015 - 2020 Epidemiology, microbiology and risk factor analysis of surgical site infections following solid organ transplantation in the STCS [068: ongoing]
Project No.
068
Project Status
ongoing
Investigator
P. Schreiber
Project Start
June 2015
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2014 - 2020 Host Immunogenetics of Clostridium difficile Infections in Patients from the Swiss Transplant Cohort Study (STCS) [069: ongoing]
Project No.
069
Project Status
ongoing
Investigator
A. Cusini
Project Start
December 2014
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2014 - 2020 Reviewing prevention measures and evaluating the burden of toxoplasmosis in transplant patients in European countries [070: ongoing]
Project No.
070
Project Status
ongoing
Investigator
O. Manuel
Project Start
December 2014
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2015 - 2020 Exploring a genomic basis for Medication Nonadherence in Transplantation: A subanalysis of the Swiss Transplant Cohort Study [071: ongoing]
Project No.
071
Project Status
ongoing
Investigator
S. de Geest
Project Start
September 2015
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2015 - 2017 Psychosocial questionnaire in hematopoietic stem cell transplant patients - association between relationship status and survival, relapse and graft-versus-host disease. [072: completed]
Project No.
072
Project Status
completed
Investigator
S.Gerull
Project Start
April 2015
Project End
October 2017
Abstract
no abstract provided
Publications
Lack of association between relationship status and clinical outcome in allogeneic stem cell transplantation-the Swiss Transplant Cohort Study
2015 - 2020 Exploring frailty and mild cognitive impairment in adult kidney tRansplant recipients to predict clinical, psychosocial and health economic outcomes: A repeated measures study design nested in a nationwide prospective cohort study (GERAS) [073: ongoing]
Project No.
073
Project Status
ongoing
Investigator
O. Mauthner
Project Start
June 2015
Project End
September 2020
Abstract
no abstract provided
Publications
ExplorinG frailty and mild cognitive impairmEnt in kidney tRansplantation to predict biomedicAl, psychosocial and health cost outcomeS (GERAS): protocol of a nationwide prospective cohort study.
2016 - 2020 Prevalence of, risk factors for, and outcome of infections caused by multidrug-resistant Enterobacteriaceae in solid organ transplant recipients [074: ongoing]
Project No.
074
Project Status
ongoing
Investigator
P. Kohler
Project Start
February 2016
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 Impact of donor and recipient PNPLA3 genotype on fibrosis progression in patients with recurrent hepatitis C after liver transplantation: analysis of the Swiss Hepatitis C Cohort Study and of the Swiss Transplant Cohort Study [075: revision]
Project No.
075
Project Status
revision
Investigator
P. Deltenre
Project Start
September 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 BIOKIT Study - Does Bariatric surgery Improve Outcome of KIdney Transplantation [076: revision]
Project No.
076
Project Status
revision
Investigator
C. Oberkofler
Project Start
September 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 Obstructive Sleep Apnea after orthotopic heart transplantation - a risk factor fortransplant vasculopathy ? [077: revision]
Project No.
077
Project Status
revision
Investigator
R. Hullin
Project Start
September 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2015 - 2019 How to cope successfully with an organ transplantation – the role of Antonowsky`s Sense of Coherence [078: completed]
Project No.
078
Project Status
completed
Investigator
Jenewein
Project Start
September 2015
Project End
February 2019
Abstract
no abstract provided
Publications
Health-related quality of life and stress-related post-transplant trajectories of lung transplant recipients: a three-year follow-up of the Swiss Transplant Cohort Study
2016 - 2020 Post-transplant trajectories of lung transplant recipients related to health-related quality of life and psychological distress within the first three years after transplantation. [079: ongoing]
Project No.
079
Project Status
ongoing
Investigator
Seiler
Project Start
March 2016
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2016 - 2020 Post-transplantation prognosis of patients transplanted for cirrhosis and refractory ascites [080: ongoing]
Project No.
080
Project Status
ongoing
Investigator
Elkrief
Project Start
December 2016
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2016 - 2020 Changes of mold-specific T cells and NK cells and impact of polymorphisms in T-helper 1 Cytokines and Natural Killer (NK) genes on the Development and Outcome of Invasive Mold Infections in Patients after Allogeneic Hematopoietic Stem Cell Transplantation. [081: ongoing]
Project No.
081
Project Status
ongoing
Investigator
Khanna et al
Project Start
February 2016
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2015 - 2020 Microbiologically confirmed infections in the first year following allogeneic HSCT adult transplantation in Switzerland: a cohort study of the STCS [082: completed]
Project No.
082
Project Status
completed
Investigator
Vu et al._1
Project Start
December 2015
Project End
April 2020
Abstract
no abstract provided
Publications
Microbiologically Documented Infections After Adult Allogeneic Hematopoietic Cell Transplantation
2015 - 2020 Infection in liver transplant recipients > 65 years: AST IDCOP study [084: ongoing]
Project No.
084
Project Status
ongoing
Investigator
Mueller et al.
Project Start
December 2015
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2015 - 2020 Current world expertise in thoracic transplantation in HIV-positive recipients: AST IDCOP study [085: ongoing]
Project No.
085
Project Status
ongoing
Investigator
Mueller et al.
Project Start
December 2015
Project End
September 2020
Abstract
no abstract provided
Publications
Heart or lung transplant outcomes in HIV-infected recipients
2016 - 2020 Posttransplant outcome and risk factors for recurrence in Swiss kidney transplant recipients with IgA nephropathy [086: ongoing]
Project No.
086
Project Status
ongoing
Investigator
Kim et al.
Project Start
September 2016
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Identification of peripheral blood mononuclear cells signatures associated with rejection and graft outcome after kidney transplantation, a longitudinal prospective study [087: ongoing]
Project No.
087
Project Status
ongoing
Investigator
Golshayan, D. et al.
Project Start
March 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 Retrospective analysis of the effect of rituximab on the incidence of EBV replication in kidney transplant recipients [088: ongoing]
Project No.
088
Project Status
ongoing
Investigator
Burkhalter et al.
Project Start
September 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 Impact of Renal Transplantation on Levels of Cardiovascular Biomarkers and their Prognostic Importance [089: revision]
Project No.
089
Project Status
revision
Investigator
Breidthardt et al.
Project Start
September 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Efficacy and safety of different antimicrobials in BSI due to ESBL or carbapenemase-producing Enterobacteriaceae in SOT [090: ongoing]
Project No.
090
Project Status
ongoing
Investigator
C. van Delden
Project Start
November 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2016 - 2020 Clinical spectrum of lethal infections after solid organ transplantation [091: ongoing]
Project No.
091
Project Status
ongoing
Investigator
B. Lüthi
Project Start
September 2016
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2016 - 2020 Novel Memory B Cell ELISPOT Assays to Predict Immune Responses in Renal Allograft Recipients Transplanted Across Donor-specific HLA Antibodies [092: ongoing]
Project No.
092
Project Status
ongoing
Investigator
C. Wehmeier
Project Start
October 2016
Project End
September 2020
Abstract
no abstract provided
Publications
Donor-specific B cell memory in alloimmunized kidney transplant recipients – first clinical application of a novel method
2017 - 2020 Impact of Respiratory Virus Infections in Solid-Organ Transplant Recipients [093: ongoing]
Project No.
093
Project Status
ongoing
Investigator
M. Mombelli
Project Start
January 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 UMOD gene variants and urinary tract infections after kidney transplantation [094: ongoing]
Project No.
094
Project Status
ongoing
Investigator
P. Cippà
Project Start
February 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Infections in AB0-Incompatible Kidney Transplant Recipients: An Observational Study by the Swiss Transplant Cohort. [095: ongoing]
Project No.
095
Project Status
ongoing
Investigator
C. Hirzel
Project Start
January 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2016 - 2019 Passive IgE transfer and allergy development after solid organ transplantation [096: completed]
Project No.
096
Project Status
completed
Investigator
Y. Muller
Project Start
December 2016
Project End
September 2019
Abstract
no abstract provided
Publications
Management of allergy transfer upon solid organ transplantation
2016 - 2020 Lymph vessel density in skin squamous-cell carcinoma patients and possible associations with parameters of immune responses [097: ongoing]
Project No.
097
Project Status
ongoing
Investigator
P. Marcos
Project Start
September 2016
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Atopy, a hallmark for Th2 responses in kidney transplantation? [098: ongoing]
Project No.
098
Project Status
ongoing
Investigator
Y. Muller
Project Start
May 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Preformed donor-specific antibodies and liver transplantation [099: ongoing]
Project No.
099
Project Status
ongoing
Investigator
J. Vionnet
Project Start
January 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Reconstitution of T cell immunity against cytomegalovirus (CMV) following allogeneic hematopoietic cell transplantation (HCT) [100: ongoing]
Project No.
100
Project Status
ongoing
Investigator
A. Müller
Project Start
June 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Variability in outcome of renal allograft pairs (twins) originating from the same deceased donor [101: ongoing]
Project No.
101
Project Status
ongoing
Investigator
M. Koller
Project Start
November 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Genome-wide association study (GWAS) of single nucleotide polymorphisms in patients with recurrent hepatocellular carcinoma (HCC) after liver transplantation [102: ongoing]
Project No.
102
Project Status
ongoing
Investigator
A. Lachenmayer
Project Start
June 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 A multicenter retropsective review of outcomes after VRE infections with daptomycin MIC >4 and 2-4 compared to daptomycin susceptible VRE infections in adult abdominal solid organ transplant recipients [103: ongoing]
Project No.
103
Project Status
ongoing
Investigator
Nicolas Mueller
Project Start
June 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 What matters to me: Patient involvement in clinical research within the STCS [104: ongoing]
Project No.
104
Project Status
ongoing
Investigator
S. De Geest
Project Start
June 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Influence of screening for tuberculosis on tuberculosis incidence after organ transplantation in regions of tuberculosis incidence of <40/100000 [105: ongoing]
Project No.
105
Project Status
ongoing
Investigator
Nicolas Müller
Project Start
June 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2017 Genetic Variants in TNF Superfamily Genes in the Susceptibility for Chronic Allograft Nephropathy after Transplantation [106: ongoing]
Project No.
106
Project Status
ongoing
Investigator
D. Sidler
Project Start
September 2020
Project End
September 2017
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Use and impact of induction therapy in pediatric heart transplantation [107: ongoing]
Project No.
107
Project Status
ongoing
Investigator
M. Schweiger
Project Start
December 2017
Project End
September 2020
Abstract

Authors

Martin Schweiger 1, Brian Stiasny 1, Stefano Di Bernardo 2, Michael Hübler 1, Paul Mohacsi 3

1 Children's Hospital Zurich

2 Lausanne University Hospital

3 University Hospital Bern

Background

The adverse events of immunosuppressive drugs observed in randomized clinical trials underscore the need for individualization of immunosuppression according to the characteristics and risks of transplant recipient especially in children. Number of pediatric patients undergoing heart transplantation is low and data on individualized immunosuppressive protocols is limited. It is of crucial importance for those who are involved in the care of this patient population to share data and experience to find the best way of treatment. The data on the use and impact of induction therapy especially with steroid-free or early steroid withdrawal strategies is very limited. There are no uniform recommendations or guidelines if and how to use induction therapy [1]. Even more, to the authors knowledge, up to date no evaluation of the use of induction therapy in Switzerland has been done so far.

Study Aim

The primary aim of this study is to describe use and outcome of induction therapy after heart transplantation in children (<19 years of age) within Switzerland. We would like to evaluate the use/dosage of induction therapy (either ATG or IL2 antagonists) and outcome data includes mortality, PRA/DSA, acute rejection rates, growth and development of PTLD, EBV match (donor versus recipient), diabetes mellitus and dyslipidemia.

Study Design

It should be a retrospective cohort study from the STCS database including all pediatric heart transplants (age <18ys of age). Statistical analysis will be done in the Epidemiology, Biostatistics and Prevention Institute of the University of Zurich (see also Budget).

Publications
No publications yet
2017 - 2020 The risk of urinary tract infection in different immunosuppressive regimen after renal transplantation in the Swiss Transplant Cohort Study [108: ongoing]
Project No.
108
Project Status
ongoing
Investigator
K. Hadaya
Project Start
October 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Posttransplant recurrence of membranous nephropathy in Swiss kidney transplant recipients and correlation with clinical and serological markers [109: ongoing]
Project No.
109
Project Status
ongoing
Investigator
Laila-Yasmin Mani
Project Start
February 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Reducing the Burden of Influenza after Solid-Organ Transplantation: the STOP-FLU trial [Swiss Trial in Solid Organ Transplantation on Prevention of InFLUenza] [110: ongoing]
Project No.
110
Project Status
ongoing
Investigator
Oriol Manuel
Project Start
September 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Baseline Cytomegalovirus-specific T-cell Mediated Immunity as an Independent Risk-stratification Tool Predicting CMV Infection after Kidney Transplantation [111: ongoing]
Project No.
111
Project Status
ongoing
Investigator
Oriol Manuel
Project Start
September 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Hepatitis E virus seroprevalence and incidence in solid organ and hematopoietic stem cell transplant recipients [112: ongoing]
Project No.
112
Project Status
ongoing
Investigator
C. Niederhauser
Project Start
July 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Epidemiology and Outcomes of Microbiologically Documented Bacterial Foodborne Infections in the Swiss Transplant Cohort Study [113: ongoing]
Project No.
113
Project Status
ongoing
Investigator
M. Mombelli
Project Start
December 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Influence of HLA-E genotype on the occurrence of herpesvirus infections and outcome in solid organ transplant recipients in the Swiss Transplant Cohort Study [114: ongoing]
Project No.
114
Project Status
ongoing
Investigator
C. Berger
Project Start
March 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2017 - 2020 Incidence and risk factors for infection in thoracic-organ transplant recipients on post-transplant extracorporeal membrane oxygenation (ECMO) [115: ongoing]
Project No.
115
Project Status
ongoing
Investigator
Oriol Manuel
Project Start
December 2017
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Comparison of Induction therapy with IL2RA in primary renal transplantations with standard immunological risk versus no induction [116: completed]
Project No.
116
Project Status
completed
Investigator
A. Krisl
Project Start
March 2018
Project End
August 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 The STCS - MATCH project: An inter-cohort collaboration between Switzerland and Denmark in transplant outcome research [117: ongoing]
Project No.
117
Project Status
ongoing
Investigator
Koller M. T. et al.
Project Start
January 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 The Relevance of Pretransplant Iron deficiency for All Cause Mortality and Maximal Exercise Capacity at 1–Year After Heart Transplantation [118: ongoing]
Project No.
118
Project Status
ongoing
Investigator
Hullin et al.
Project Start
August 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Validation of the diagnostic performance of an EBV DNAemia to predict PTLD among transplant recipients [119: ongoing]
Project No.
119
Project Status
ongoing
Investigator
Mueller et al.
Project Start
June 2018
Project End
September 2020
Abstract

Background:

EBV DNA screening is a widely recommended and used tool to detect early signs of Post-transplant lymphoprolipherative disorder (PTLD). However, the extent of clinical benefit from screening for EBV DNA is unclear. A study using data from the MATCH cohort showed that less than 1/5 of recipients with EBV DNAemia progressed to develop PTLD and the ability of an EBV DNAemia to predict PTLD had low sensitivity. Conversely, when EBV DNAemia was assessed together with other clinically relevant information, such as gender, age, transplant type, number of transplantations, and high-risk EBV serostatus, the prognostic value increased significantly with AUC of the ROC of above 80%, and we were better able to identify those with PTLD.

Aim:

To validate the results from the above mentioned study.

Methods:

Perform receiver operating characteristic (ROC) curves for assessing ability of models to predict PTLD among solid organ and hematopoietic stem cell transplant recipients.

Importance:

To our knowledge, our study is the first to propose a model where, if used in this context, information routinely available in addition to EBV DNA screening could be used to better predict those who would most likely develop PTLD and thus identify those who would benefit from early management or more intensive follow-up.

Publications
No publications yet
2018 - 2020 Characterization of differences in infectious disease events between first transplant and re-transplantation of identical organs in the STCS [120: ongoing]
Project No.
120
Project Status
ongoing
Investigator
Schreiber et al.
Project Start
November 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Evolution of cardiomyopathies after renal transplant [121: ongoing]
Project No.
121
Project Status
ongoing
Investigator
Dezelicourt et al.
Project Start
September 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Genome-wide association studies to determinate polymorphisms impacting Hepatic Cell Carcinoma [122: ongoing]
Project No.
122
Project Status
ongoing
Investigator
Keating et al.
Project Start
June 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Characteristics and risk factors for bacteraemia during the first year after solid organ transplantation [123: ongoing]
Project No.
123
Project Status
ongoing
Investigator
Van Delden
Project Start
June 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Genetic mechanisms of rejection and survival after heart transplantation [124: ongoing]
Project No.
124
Project Status
ongoing
Investigator
Van Setten
Project Start
September 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Evaluation of EBV-specific cell mediated immunity (EBV-CMI) for the prediction of posttransplant lymphoproliferative disorder (PTLD) in solid-organ transplant recipients [125: ongoing]
Project No.
125
Project Status
ongoing
Investigator
Mombelli et al.
Project Start
December 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 Role of Endogenous Hydrogen Sulfide in Kidney Transplantation [126: ongoing]
Project No.
126
Project Status
ongoing
Investigator
Longchamp
Project Start
January 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Central Nervous System infections in Solid Organ Transplant Recipients [127: ongoing]
Project No.
127
Project Status
ongoing
Investigator
Bogaart et al.
Project Start
March 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Association of Antiviral Prophylaxis and Post-Transplant Lymphoproliferative Disorders (PTLD) in the Swiss Transplant Cohort: An Observational Study. [128: ongoing]
Project No.
128
Project Status
ongoing
Investigator
Walti et al.
Project Start
December 2018
Project End
September 2020
Abstract

Laura N. Walti1, Daniel Sidler1, Andrew Atkinson1, Matteo Mombelli2, Oriol Manuel2, Hans H. Hirsch3, Nicolas Mueller4, Katia Boggian5, Christian Garzoni6, Dionysios Neofytos7 and Cédric Hirzel1

1) Inselspital Bern (Insel)

2) Centre Hospitalier Universitaire Vaudois (CHUV)

3) Universitätspital Basel (USB)

4) Universitätspital Zurich (USZ)

5) Kantonspital St. Gallen (KSSG)

6) Epatocentro Ticino

7) Hôpitaux Universitaire Génève (HUG)

Background:

Post-transplant lymphoproliferative disease (PTLD) is a serious and potentially fatal complication of transplantation. B cell proliferation induced by infection with Epstein-Barr virus (EBV) in the setting of chronic immunosuppression is associated with PTLD in most solid transplant recipients (SOT). Risk factors for PTLD are predominantly the degree of T cell immunosuppression and the EBV serostatus of the recipient. Prevention strategies in high-risk transplant recipients (D+/R-) to reduce EBV-associated PTLD include serial monitoring of EBV PCR during the first year post-transplantation, with lowering immunosuppression when EBV viral loads increase or preemptive Rituximab treatment, but no general recommendations exist.

The role of antiviral prophylaxis in the prevention of EBV-associated PTLD is controversial. There is currently no consensus about the use of antiviral agents in high-risk SOT recipients who are EBV-negative before transplant and who receive organs from seropositive donors. A recently published meta-analysis reported equal rates of EBV associated PTLD in SOT recipients who received EBV active antiviral prophylaxis (acyclovir, valacyclovir, ganciclovir, valganciclovir) compared to those who did not. However, in a recent monocentric study, late PTLD (<1 year after transplantation) was reduced in EBV negative kidney transplant recipients receiving antiviral prophylaxis.

Beside the antiviral prophylaxis strategy, also other factors such as the number of HLA mismatches were identified as a risk factor for PTLD. Further risk factors include types of transplanted organs, sex and age of the recipient, occurrence of cytomegalovirus (CMV) disease, induction therapy and rejection treatment.

Study aims:

The main objective of this study is to assess the incidence of EBV associated PTLD according to the CMV prophylaxis strategy (prophylaxis vs. preemptive approach). In addition we will compare incidence of EBV associated PTLD in patients who received EBV-active therapy against patients who did not.

Study design:

We plan an observational study of all patients enrolled in the STCS since 2008. A preliminary analysis of the STCS database identified 46 PTLD cases in an overall cohort of 4340 patients. No intervention is planned; it will be a nested STCS study with all data available from the database (no additional CRFs necessary, data from the CRFs of the STCS project “EBV cell mediated immunity in SOT” will be used in accordance with the principal investigators Matteo Mombelli and Oriol Manuel).

Variables of interest will include patients characteristics (such as transplanted organ, date of transplantation, immunosuppressive regimen and induction therapy, EBV serostatus of donor and recipient, HLA types of donor and recipient, CMV serostatus of donor and recipient, type of CMV prophylaxis, type and site of PTLD and outcomes (subsequent graft loss, PTLD associated mortality).

Definitions of infection (viral replication) will follow the STCS Infectious Diseases guidelines.

Descriptive statistics will be used to illustrate baseline characteristics of patients and the clinical features of PTLD cases and outcome. Cumulative incidence of PTLD will be calculated. We will use logistic regression and proportional hazard (PH) models (or alternative methods if PH is inappropriate) to evaluate the impact of CMV prophylaxis on EBV associated PTLD.

Publications
No publications yet
2019 - 2020 Optimal duration of treatment of invasive Pseudomonas aeruginosa pneumonia in hematopoietic cell transplant (HCT) recipients [129: completed]
Project No.
129
Project Status
completed
Investigator
Olearo et al
Project Start
February 2019
Project End
September 2020
Abstract
no abstract provided
Publications
Optimal Treatment Duration of Pseudomonas aeruginosa Infections in Allogeneic Hematopoietic Cell Transplant Recipients
2019 - 2020 Cumulative deficit frailty index in cystic fibrosis lung transplant candidates: a retrospective validation study [130: ongoing]
Project No.
130
Project Status
ongoing
Investigator
Koutsokera et al.
Project Start
June 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2018 - 2020 Safety of intravenously administered cidofovir in hematopoietic cell transplant recipients [132: ongoing]
Project No.
132
Project Status
ongoing
Investigator
Neofytos et al.
Project Start
December 2018
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Clostridioides difficile infection in allogeneic HCT recipients from the STCS [133: ongoing]
Project No.
133
Project Status
ongoing
Investigator
Khanna et al.
Project Start
June 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Posaconazole dosing and association with therapeutic drug levels in allogeneic cell transplant recipients [134: ongoing]
Project No.
134
Project Status
ongoing
Investigator
Neofytos et al
Project Start
March 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Impact of trimethoprim-sulfamethoxazole on engraftment in hematopoietic stem cell transplant recipients [135: ongoing]
Project No.
135
Project Status
ongoing
Investigator
Neofytos et al
Project Start
September 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 mTX: The STCS transplant mHealth interaction, network and disease management platform [136: ongoing]
Project No.
136
Project Status
ongoing
Investigator
Michael T. Koller
Project Start
March 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Association between primary immunosuppression after KTx in children and adolescents and infectious episodes [137: ongoing]
Project No.
137
Project Status
ongoing
Investigator
M. Feldkötter
Project Start
July 2019
Project End
September 2020
Abstract

Authors: Markus Feldkötter (Zurich), Paolo Paioni (Zurich), Paloma Parvex (Geneva/Lausanne), Sibylle Tschumi (Bern), Christoph Berger (Zurich) and Guido Laube (Zurich)

Background

The calcineurin inhibitors (CNI) cyclosporin A (CsA) and tacrolimus (Tac) are commonly used in kidney transplantation (KTx) to prevent acute rejection (AR). CsA is in use since 1983 and Tac since 1997. In the early 2000s a shift in the primary immunosuppression therapy from CsA to Tac began, as the long-term allograft survival with Tac was shown to be superior compared to CsA. As in the adult population, the primary immunosuppression protocol for pediatric (KTx) recipients uses nowadays Tac instead of CsA.

Acute rejection (AR) is lower in pediatric KTx recipients on Tac compared with CsA. Data comparing infection outcomes for children treated with these agents are limited. Possibly, due to the more effective immunosuppression accompanied with Tac it seems that rates of infectious complications have been increased. Infections have now become the most common cause of mortality and hospitalization after KTx.

Study Aims

  • To assess the incidence, severity and etiology (bacterial, fungal, parasitic and viral) of infectious episodes after KTx in patients less than 18 years at time of KTx.
  • To compare the incidence and severity of infectious episodes after pediatric KTx depending on the immunosuppressive therapy in children treated with CsA vs. Tac.
  • To compare the incidence and severity of episodes with AR and loss of transplant/-function depending on the immunosuppressive therapy in children treated with CsA vs. Tac.

Study Design

Our study will address the question whether the more potent immunosuppression with Tac compared to CsA has an effect on incidence and severity of infectious diseases after KTx in children and adolescents. We plan a retrospective cohort analysis involving all KTx recipients younger than 18 years at the time of transplantation enrolled in the STCS from 2008 to 2018. As primary outcome we will quantify the cumulative incidences of bacterial, fungal, parasitic and viral (including EBV-, BKV- and CMV-associated) infectious episodes. The overall morbidity (including occurrence of AR, graft loss/survival, infection episodes, or other disease events) and mortality will be assessed as secondary outcomes. Furthermore, we will compare patient baseline characteristics including age at KTx, gender, underlying diseases and transplant setting (especially EBV and CMV serology mismatch between donor and recipient, induction therapy, immunosuppressive regimen, val-/ganciclovir prophylaxis).

Publications
No publications yet
2019 - 2020 Prediction of cardiovascular risk in the Swiss Transplant Cohort Study [138: ongoing]
Project No.
138
Project Status
ongoing
Investigator
Vionnet Julien
Project Start
September 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Liver transplantation and overall mortality rates in candidates with and without hepatocellular carcinoma in Switzerland [139: ongoing]
Project No.
139
Project Status
ongoing
Investigator
Project Start
May 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 Clinical impact of hypomagnesaemia and polymorphisms of genes related to Mgmetabolism in SOT patients from the STCS [140: approved]
Project No.
140
Project Status
approved
Investigator
Huynh-Do
Project Start
September 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Indications for liver transplantation in Switzerland: Is there a shift from hepatitis C to non-alcoholic fatty liver disease? [141: ongoing]
Project No.
141
Project Status
ongoing
Investigator
Montserrat Fraga et al.
Project Start
September 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Frequency and determinants of renal allograft loss and unsatisfactory allograft function in the first year post-transplant [142: ongoing]
Project No.
142
Project Status
ongoing
Investigator
Wehmeier
Project Start
December 2019
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2019 - 2020 Outcome of Kidney Transplantation from Very Marginal Donors in Switzerland [143: ongoing]
Project No.
143
Project Status
ongoing
Investigator
Sidler
Project Start
December 2019
Project End
September 2020
Abstract

Kidney transplantation (TPL) represents an effective therapy for end stage renal disease. Donor organs are scarce and therefore in the last decades the donor pool was successfully expanded (living donors, donors with circulatory death, donors with pre-existing chronic diseases). Large studies, mainly from US-consortia demonstrate that TPL from marginal donors (in general defined as aged above of 60 years) is superior compared to remaining on dialysis. Yet, studies investigating allograft outcomes for TPLs from donors aged 70 years and older are scarce and rather small.

In Switzerland and other parts of the world, the transplant community experiences a rapidly changing donor epidemiology. The indicence of septuagenarian and octogenarian donors is increasing and a relevant fraction of these donors has a chronic disease burden, including hypertension, diabetes and vascular disease. In consultation with the current demographic development, these trends will continue and the efficacy and safety of TPLs from such very marginal donors (VMD) needs to be evaluated.

Naturally, organ conversion rate (organs transplanted per donor) is lowest for VMD. Also, if organs are transplanted in such a setting, the outcome is highly variable with marginal allograft function and premature failure in some situations and unexpected good organ function and long-term survival in other situations. Cleary, a retrospective analysis of a large and prospectively collected data set such as the STCS will allow to identify donor-derived factors to predicte acceptable outcome for VMD kidney TPL and thereby path the way to a more sophisticated allocation process. Optimistically, such strategies could lead to an improved selection of VMD with discharge of suboptimal donor organs and successful TPL of acceaptable offers.

Abbrevations: TPL Transplantation, VMD very marginal donor, MD marginal donor, SD standad donor, QoL Quality of Life, STCS Swiss Transplant Cohort Study, KDPI Kidney Donor Profile Index.

Publications
No publications yet
2020 - 2020 Missing-self triggers NK cell-mediated rejection of kidney transplants [146: revision]
Project No.
146
Project Status
revision
Investigator
Villard Jean
Project Start
September 2020
Project End
September 2020
Abstract

The spectacular progresses in the control of T cell alloimmune response did not translate into better graft half-life, leading to the emergence of the "humoral theory" of chronic rejection. This theory was

substantiated by large-scale clinical trials showing that renal recipients with anti-HLA DSA had twice the graft failure rate as those without. Although MVI lesions epitomise ABMR, in almost half of the cases, graft MVI was not caused by host humoral response. NK cells seems to play a critical role to

explain MVI without DSA. NK cells are weakly inhibited by the current immunosuppressive drugs used to prevent rejection except mTOR inhibitor. MVI without DSA in NK-HLA pseudo-missing self-situation could lead to modify in the immunosuppression strategy.

Publications
No publications yet
2020 - 2020 Identifying Variability and Immune Escape of BK Polyomavirus in Kidney Transplant Patients by Next Generation Sequencing [148: revision]
Project No.
148
Project Status
revision
Investigator
Karoline Leuzinger
Project Start
September 2020
Project End
September 2020
Abstract

Virus infections with a propensity for persistent or chronic replication have been shown to employ diverse mechanisms of immune escape, some of which involve mutations in immunodominant epitopes of relevance to antiviral T-cells or neutralizing antibody responses. While these mechanisms have been well characterized for human immunodeficiency virus 1 (HIV-1) or hepatitis C virus (HCV), little is known for BK polyomavirus (BKPyV).

BKPyV is remarkable since significant human disease occurs almost selectively in the allogeneic transplant setting. Thus, BKPyV-associated nephropathy affects 1%-15% of kidney transplant patients, and BKPyV-associated hemorrhagic cystitis 5%-25% of allogeneic hematopoietic stem cell transplant patients. In both situations, compartmentalized BKPyV replication in the respective organ site causes significant damage and morbidity. According to several studies, HLA-mismatching has been reported as risk factor for either disease, which likely impairs the antiviral immune control and may require more intense immunosuppression to avoid cellular and humoral rejection episodes, or graft-versus-host disease, respectively. The resulting persistent BKPyV replication may permit the occurrence of mutations in immunodominant epitopes, which impair immune control despite adequately reduced immunosuppression.

In this proposal, we describe a first approach by next generation sequencing to identify and characterize the presence of BKPyV variants and their potential change in immunodominant epitopes regarding T-cell and neutralizing antibodies. The data will provide important insights predicting virological response following reduction of immunosuppression, impact on plasma BKPyV load measurement, and the potential role of adoptive neutralizing and T-cell therapies.

Publications
No publications yet
2020 - 2020 Characterization of the effects of statins in the setting of liver transplantation [149: ongoing]
Project No.
149
Project Status
ongoing
Investigator
Annalisa Berzigotti, Jaume Bosch
Project Start
May 2020
Project End
September 2020
Abstract

Statins are inhibitors of 3&dash;hydroxy&dash;3&dash;methyl&dash;glutaryl&dash;coenzyme A reductase routinely used in dyslipidemia [1]. Recently, there have been several studies addressing the beneficial effects of statins on the pathophysiology of liver disease [6]. Despite this available evidence, there is scarce information regarding the benefit of statins in patients with end stage liver disease, such as those awaiting liver transplantation. This is also true for the post-LT setting. Since the use of statins might be implicated in the amelioration of survival rate after-LT [5] and in improving of graft injury after cold storage [4, 7], the question that arises is whether statin treatment in the recipient, the donor or both could have a beneficial effect on graft function and patient survival after-LT.

Publications
No publications yet
2020 - 2020 CMV Resistance in solid organ patients in the STCS [150: ongoing]
Project No.
150
Project Status
ongoing
Investigator
Irene Abela
Project Start
March 2020
Project End
September 2020
Abstract

Cytomegalovirus is an important cause of severe disease after transplantation. Different antiviral drugs have been introduced in transplantation guidelines as prophylaxis to reduce the complications of CMV disease in transplant patients. As a consequence resistance to this antiviral drugs can emerge. We will investigate which patients are most at risk of developing an antiviral resistance. This knowledge will allow us to adapt treatment and monitoring strategies for transplant patients

Publications
No publications yet
2020 - 2020 Busulfan-Cyclophosphamide versus Cyclophosphamide-Busulfan as Conditioning Regimen before Allogeneic Hematopoietic Cell Transplantation: a Prospective Randomized Trial [151: revision]
Project No.
151
Project Status
revision
Investigator
Nathan Cantoni
Project Start
September 2020
Project End
September 2020
Abstract

As predictive biomarkers (polymorphisms, cytokines profiling, gene expression) exhibit differential expression pre and during conditioning in the context of an allo-HCT, they could function as early indicators for toxicity and response to these therapies. A biomarker could act as a surrogate marker of clinical outcome and would be useful for identifying patients most likely responding to therapy and thus prevent unnecessary side effects and toxicity. Dose adjusting of the conditioning regimen could help to find the optimal balance between efficacy and toxicity.

Publications
No publications yet
2020 - 2020 Characterization of the geographic influence on liver-disease associated mortality and liver transplantation. [152: revision]
Project No.
152
Project Status
revision
Investigator
Ansgar Deibel
Project Start
September 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 Trans-national comparison of CMV management of SOT recipients in the MATCH and STCS cohort [153: ongoing]
Project No.
153
Project Status
ongoing
Investigator
Nicolas Mueller
Project Start
May 2020
Project End
September 2020
Abstract

The MATCH and STCS cohorts both represent unique systems in their countries and are characterized by comprehensive and close post-transplant outcome monitoring with low follow-up attrition and high data quality standards in place (6-9). The following project aims to perform basic cross-national comparisons of patient characteristics, CMV management with particular focus on prevention strategies, and key CMV outcomes, and to describe how CMV events may influence allograft and patient outcomes.

Publications
No publications yet
2020 - 2020 Treatment outcome of cancer under checkpoint inhibitor administration in transplanted patients - case series [154: ongoing]
Project No.
154
Project Status
ongoing
Investigator
Rahel Looser
Project Start
March 2020
Project End
September 2020
Abstract

There is very limited data of cancer outcome under checkpoint inhibitor (CPI) administration in transplanted patients due to fear of graft rejection or failure. Parameters like patients’ demographics and characteristics (e.g. age, gender, disease history), prescribed medication and its dosage and so on may influence cancer control and side effects like graft rejection.

The study aims to investigate the effect of CPI prescription on different cancer types (for example skin cancer, hepatocellular carcinoma) in transplanted patients. With further analysis of specific case reports we also try to reveal possible, yet unknown influences on CPI treatment. The final goal is to conclude on therapy suggestions, ensure patients security and minimize their risks by precise data analysis.

Publications
No publications yet
2020 - 2020 Liquid biopsy-based genomic assay to enable non-invasive precision diagnostics and monitoring for post-transplant lymphoproliferative disorders (PTLD) [155: revision]
Project No.
155
Project Status
revision
Investigator
Lang et al.
Project Start
September 2020
Project End
September 2020
Abstract

Post-transplant lymphoproliferative disorder (PTLD) represents a frequent and serious complication of solid organ transplantation (SOT) with a high morbidity and mortality. 1,2

Actual management of PTLD is focusing on prevention to allow early detection of PTLD. For this purpose, preemptive EBV DNA levels monitoring is widely used, but due to a lack of standardized procedure fail to reliably diagnose PTLD. Moreover, this approach is useless for the early detection of EBV-negative PTLD whose relative incidence is increasing. Therefore, there is a clear need for novel sophisticated screening and monitoring tools that would allow early detection and treatment of both EBV-positive and EBV-negative PTLD. 4,6,7

Digital droplet PCR (dPCR) is a powerful molecular technique which allow to accurately identify and quantify mutations in markers in samples with very low tumor involvement such as plasma circulating DNA (ctDNA). 40,41

A recent report from Stanford University School of Medicine using Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq) technology showed that 5 PTLD patients have detectable ctDNA prior to clinical diagnosis and conclude that utilizing both ctDNA and EBV titers might facilitate early detection of PTLD in the transplant population.39 This study aims to confirm these preliminary results and assess the feasibility and relevance of liquid biopsy-based genomic assay by dPCR for early detection of PTLD. Ultimately, this project could lead to the implementation of ctDNA-based screening test that would allow to better delineate subjects who will develop PTLD and subsequently improving the diagnostic and follow-up workflow of these patients.

Publications
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2020 - 2020 Geographic Distribution of Kidney Transplantations in Switzerland and Impact on Socioeconomic Reintegration [156: revision]
Project No.
156
Project Status
revision
Investigator
Federico Storni
Project Start
September 2020
Project End
September 2020
Abstract

Kidney transplants represent a very efficient and safe therapy for patients with severe kidney diseases and are associated with a better prognosis regarding survival and quality of life. Kidney transplants are only offered at six centres in Switzerland and early postoperative checks are generally carried out at the transplant centre. The logistical burden for patients is considerable, not only for routine controls but especially in case of complications requiring regular consultations and outpatient or inpatient therapies. Here are undoubtedly patients with long journeys to the transplant center. It is possible that these long distances limit the patients' quality of life, make professional and social reintegration more difficult and influence the prognosis for the transplant and the patient. The present study investigates a relationship between the patient's origin on the one hand and access to kidney transplantation and transplantation outcome on the other.

For the first time, the study combines results from kidney transplant recipients with statistical and geographical data from the Swiss Federal Statistical Office.

Publications
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2020 - 2020 Changes in graft steatosis after liver transplantation: A Retrospective Single-Centre Pilot Study [157: ongoing]
Project No.
157
Project Status
ongoing
Investigator
Vanessa Banz
Project Start
May 2020
Project End
September 2020
Abstract

Coping with the effects of obesity is increasingly becoming an issue worldwide in many medical fields, including transplantation. More and more patients are requiring a liver transplantation due to the presence of non-alcoholic fatty liver disease (NAFLD) resulting in irreversible organ damage. In certain countries, such as America, NALFD and the consequence of NAFLD are becoming the leading indication for liver transplantation. However, the obesity pandemic equally affects potential donors, often resulting in transplant doctors having to accept organs which are already showing signs of damage due to large quantities of fatty deposits. This brings with it many other challenges, including increased risk of primary no- functioning of organ at the time point of transplantation (resulting more often than not in the need for a super urgent re-transplantation) as well as putting the recipient of the organ at risk for developing new onset NAFLD after transplantation. And with it, again all the consequence of having a fatty liver. To what extent fatty donor livers can “regenerate” and lose their fat or to what extent normal donor livers become fatty if transplanted in obese recipients still remains a matter of uncertainty and its assessment is the current aim of this study.

Publications
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2020 - 2020 SARS-CoV-2 infections in Solid Organ Transplant Recipients [158: ongoing]
Project No.
158
Project Status
ongoing
Investigator
Christian van Delden
Project Start
June 2020
Project End
September 2020
Abstract

The main objective of the study is to describe the clinical characteristics, management and outcomes of microbiologically or serologically proven SARS-CoV-2 infection in SOT recipients from the Swiss Transplant Cohort Study (STCS).

Publications
No publications yet
2020 - 2020 Epidemiology, Management and Outcomes of Non-Tuberculous Mycobacteria infections in Transplant Recipients in Europe and America (EMOTE study) [159: ongoing]
Project No.
159
Project Status
ongoing
Investigator
Nicolas Mueller
Project Start
September 2020
Project End
September 2020
Abstract
no abstract provided
Publications
No publications yet
2020 - 2020 Epidemiology and characteristics of Parvovirus B19 infections in the Swiss Transplant Cohort Study [161: ongoing]
Project No.
161
Project Status
ongoing
Investigator
Mombelli et al.
Project Start
July 2020
Project End
September 2020
Abstract

Infection with parvovirus B19 is among the most common infections of childhood and is also known under the name of “Fifth disease” or “Erythema infectiosum”. The infection is acquired by respiratory droplets and, although often asymptomatic, in children may result in a febrile illness accompanied by a skin eruption. In immunocompetent individuals, the infection is self-limiting because of adequate antiviral immune response. However, in immunocompromised patients the antibody production may be deficient, resulting in prolonged infection and profound anaemia. In transplant recipients, the infection may be acquired through the transplanted organ or may result from reactivation of a past infection, and the clinical presentation may be atypical rendering difficult a timely diagnosis. The treatment in transplant recipients generally consist in the injection of immunoglobulins. Despite treatment, multiple recurrences may be observed.

This study will assess the incidence of parvovirus B19 infection in the Swiss Transplant Cohort Study and describe the clinical presentation, treatment and consequences of the episodes of infection collected in this cohort. The results of this study will increase our knowledge on the epidemiology of this infection after organ transplantation.

Publications
No publications yet