Publications by authors named "Olivier Aubert"

The XVI-th Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from 19th-23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30 anniversary of the first Banff Classification, pre-meeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis.

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Background: The heterogeneous clinical presentation of graft microvascular inflammation poses a major challenge to successful kidney transplantation. The effect of microvascular inflammation on allograft outcomes is unclear.

Methods: We conducted a cohort study that included kidney-transplant recipients from more than 30 transplantation centers in Europe and North America who had undergone allograft biopsy between 2004 and 2023.

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Background: In kidney transplantation, molecular diagnostics may be a valuable approach to improve the precision of the diagnosis. Using next-generation sequencing (NGS), we aimed to identify clinically relevant archetypes.

Methods: We conducted an Illumina bulk RNA sequencing on 770 kidney biopsies (540 kidney recipients) collected between 2006 and 2021 from 11 European centers.

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Article Synopsis
  • The study investigates how competing risks, like allograft failure and death with a functioning graft, affect the performance of prognostic models used for kidney transplant recipients.
  • The research involves 11,046 kidney transplant recipients across 10 countries, developing models using various regression techniques to predict long-term graft failure while carefully evaluating their accuracy and reliability.
  • Results indicate that both standard Cox models and competing risk models provide similar predictions for graft failure, with high concordance indices, confirming their usefulness in clinical settings.
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Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020.

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Article Synopsis
  • There is increasing interest in analyzing kidney biopsies through transcriptomic assessments to understand gene expression changes related to rejection.
  • This study used next-generation sequencing (NGS) on RNA from 770 kidney biopsies to identify differentially expressed genes (DEGs) associated with antibody-mediated rejection (AMR) and T cell-mediated rejection (TCMR), revealing 603 and 1,186 new specific genes, respectively.
  • Pathway analysis linked established panels to immunological processes in AMR and TCMR, while NGS uncovered novel transcripts that could inform future drug design and therapeutic strategies.
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Introduction: The position of the pelvis in the sagittal plane can vary considerably between different functional positions. Adapting the position of the acetabular cup in relation to the alignment between the spine and the hip of each individual, prior to prosthesis placement, can prevent the risk of prosthetic impingement. Taken individually, risk factors for unfavorable spinopelvic kinematics can be difficult to interpret when trying to precisely predict which patients are at risk.

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Article Synopsis
  • - The XVIth Banff meeting in September 2022 marked the 30th anniversary of the Banff classification and focused on improving the classification system for kidney transplantation, resulting in two new publications.
  • - A group of 16 experts reviewed the manuscripts, highlighting the addition of two new entities that enhance the classification and enable better understanding of kidney transplant biopsies and their clinical implications.
  • - Despite the improvements, the Banff classification's complexity may still limit its use, necessitating further evidence and clinical trials to support the incorporation of molecular diagnostics and to refine diagnostic approaches for various types of kidney rejection.
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  • Donor-derived cell-free DNA (dd-cfDNA) is an innovative noninvasive biomarker being studied for its ability to detect kidney allograft injuries, such as rejection.
  • In a study involving 2,882 kidney transplant recipients, high levels of dd-cfDNA were strongly linked to various types of allograft rejection, and it significantly improved prediction models beyond what's typically used in patient monitoring.
  • The study, which included diverse cohorts, reinforced that measuring dd-cfDNA could enhance the detection of even subtle rejection in stable patients, providing valuable insights for better transplant management.
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  • The KTD-Innov study aims to address the lack of reliable biomarkers for kidney allograft rejection by analyzing a diverse group of kidney transplant recipients over one year, involving 733 participants across seven French centers.
  • The study involved comprehensive data collection, including clinical, biological, immunological, and histological parameters, and developed a biobank with over 16,000 samples to facilitate future research.
  • The findings reveal that the cumulative incidence of allograft rejection was 9.7% at one year, and the study population reflects the broader demographic of kidney transplant recipients in France and beyond, supporting its clinical relevance.
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De novo thrombotic microangiopathy (dnTMA), after renal transplantation may significantly alter graft outcomes. However, its pathogenesis and the role of complement alternative pathway dysregulation remain elusive. We studied all consecutive adult patients with a kidney allograft biopsy performed between January 2004 and March 2016 displaying dnTMA.

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Background: Conversion to a belatacept-based immunosuppression is currently used as a calcineurin inhibitor (CNI) avoidance strategy when the CNI-based standard-of-care immunosuppression is not tolerated after kidney transplantation. However, there is a lack of evidence on the long-term benefit and safety after conversion to belatacept.

Methods: We prospectively enrolled 311 kidney transplant recipients from 2007 to 2020 from two referral centers, converted from CNI to belatacept after transplant according to a prespecified protocol.

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In kidney transplantation, day-zero biopsies are used to assess organ quality and discriminate between donor-inherited lesions and those acquired post-transplantation. However, many centers do not perform such biopsies since they are invasive, costly and may delay the transplant procedure. We aim to generate a non-invasive virtual biopsy system using routinely collected donor parameters.

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The intricate association between histologic lesions and circulating antihuman leucocyte antigen donor-specific antibodies (DSA) in liver transplantation (LT) requires further clarification. We conducted a probabilistic, unsupervised approach in a comprehensively well-annotated LT cohort to identify clinically relevant archetypes. We evaluated 490 pairs of LT biopsies with DSA testing from 325 recipients transplanted between 2010 and 2020 across 3 French centers and an external cohort of 202 biopsies from 128 recipients.

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Significance Statement: Why are there so few biomarkers accepted by health authorities and implemented in clinical practice, despite the high and growing number of biomaker studies in medical research ? In this meta-epidemiological study, including 804 studies that were critically appraised by expert reviewers, the authors have identified all prognostic kidney transplant biomarkers and showed overall suboptimal study designs, methods, results, interpretation, reproducible research standards, and transparency. The authors also demonstrated for the first time that the limited number of studies challenged the added value of their candidate biomarkers against standard-of-care routine patient monitoring parameters. Most biomarker studies tended to be single-center, retrospective studies with a small number of patients and clinical events.

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The XVI-th Banff Meeting for Allograft Pathology was held at Banff, Alberta, Canada, from 19th to 23rd September 2022, as a joint meeting with the Canadian Society of Transplantation. To mark the 30th anniversary of the first Banff Classification, premeeting discussions were held on the past, present, and future of the Banff Classification. This report is a summary of the meeting highlights that were most important in terms of their effect on the Classification, including discussions around microvascular inflammation and biopsy-based transcript analysis for diagnosis.

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The XVIth Banff Meeting for Allograft Pathology was held in Banff, Alberta, Canada, from September 19 to 23, 2022, as a joint meeting with the Canadian Society of Transplantation. In addition to a key focus on the impact of microvascular inflammation and biopsy-based transcript analysis on the Banff Classification, further sessions were devoted to other aspects of kidney transplant pathology, in particular T cell-mediated rejection, activity and chronicity indices, digital pathology, xenotransplantation, clinical trials, and surrogate endpoints. Although the output of these sessions has not led to any changes in the classification, the key role of Banff Working Groups in phrasing unanswered questions, and coordinating and disseminating results of investigations addressing these unanswered questions was emphasized.

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Introduction: Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.

Methods: We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants.

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Article Synopsis
  • New immunosuppressive therapies are needed to enhance long-term survival rates in kidney transplants.
  • The iBOX Scoring System has received qualification from the European Medicines Agency as a new method to measure treatment outcomes in kidney transplant clinical trials.
  • This system allows researchers to compare the effectiveness of new therapies against standard treatments over a 6 to 24-month period, aiming to show that new treatments are superior rather than just comparable.
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The molecular refinement of the diagnosis of heart allograft rejection based on whole-transcriptome analyses faces several hurdles that greatly limit its widespread clinical application. The targeted Banff Human Organ Transplant gene panel (B-HOT, including 770 genes of interest) has been developed to facilitate reproducible and cost-effective gene expression analysis of solid organ allografts. We aimed to determine the ability of this targeted panel to capture the antibody-mediated rejection (AMR) molecular profile using whole-transcriptome data from 137 heart allograft biopsies (71 biopsies reflecting the entire landscape of histologic AMR, 66 non-AMR control biopsies including cellular rejection and non-rejection cases).

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New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials.

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Predicting long-term kidney allograft failure is an unmet need for clinical care and clinical trial optimization in children. We aimed to validate a kidney allograft failure risk prediction system in a large international cohort of pediatric kidney transplant recipients. Patients from 20 centers in Europe and the United States, transplanted between 2004 and 2017, were included.

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Article Synopsis
  • More old people are getting kidney transplants, and we’re seeing more cases of a condition called MGUS, but we don't know much about how it affects them in the long run.
  • The study looked at 70 kidney transplant patients who had MGUS before their surgery and compared them to 114 patients who developed MGUS afterward.
  • Patients with MGUS before transplant didn't have higher chances of rejecting their new kidney or dying, but they were more likely to get certain cancers and infections, so doctors should keep an eye on them.
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