Publications by authors named "Thomas Barba"

The molecular profiling of gliomas for isocitrate dehydrogenase (IDH) mutations currently relies on resected tumor samples, highlighting the need for non-invasive, preoperative biomarkers. We investigated the integration of glioma polygenic risk scores (PRS) and radiographic features for prediction of IDH mutation status. We used 256 radiomic features, a glioma PRS and demographic information in 158 glioma cases within elastic net and neural network models.

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The notion of medical digital twins is gaining popularity both within the scientific community and among the general public; however, much of the recent enthusiasm has occurred in the absence of a consensus on their fundamental make-up. Digital twins originate in the field of engineering, in which a constantly updating virtual copy enables analysis, simulation, and prediction of a real-world object or process. In this Health Policy paper, we evaluate this concept in the context of medicine and outline five key components of the medical digital twin: the patient, data connection, patient-in-silico, interface, and twin synchronisation.

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Graft endothelial cells (ECs) express donor alloantigens and encounter cytotoxic T lymphocytes (CTLs) but are generally spared during T cell-mediated rejection (TCMR), which predominantly affects epithelial structures. The mechanisms underlying this vascular immune privilege are unclear. Transcriptomics analyses and endothelial-mesenchymal transition assessments confirmed that the graft endothelium was preserved during TCMR.

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Objectives: Current recommendations suggest treating eosinophilic granulomatosis with polyangiitis (EGPA) without severe manifestations with glucocorticoids (GCs) and EGPA with severe manifestations with GCs plus cyclophosphamide (CYC) regardless of poor-prognostic factors. However, GCs plus CYC and GCs alone have never been compared in EGPA without poor-prognosis factors assessed by the 1996 Five Factor Score (FFS). We aimed to compare the efficacy of GCs plus CYC vs GCs alone for the treatment of EGPA without poor-prognosis, including among patients with severe manifestations.

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Introduction: The role of internal medicine departments in the management of chronic diseases in older patients with more comorbidities is a topical issue.

Methods: For each internal medicine department of the Lyon University Hospital (North, Centre and South Hospices Civils de Lyon Hospital Group), Programme de médicalisation des systèmes d'information (PMSI) activity report data were used, with the number of medical unit summary (RUM) and standardised discharge summary (RSS) stays for 4 consecutive years from 2018 to 2022.

Results: Activity increased in the three internal medicine departments in outpatient day hospital activity, the rest of the activity remained stable.

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Artificial intelligence (AI) is experiencing considerable growth in medicine, driven by the explosion of available biomedical data and the emergence of new algorithmic architectures. Applications are rapidly multiplying, from diagnostic assistance to disease progression prediction, paving the way for more personalized medicine. The recent advent of large language models, such as ChatGPT, has particularly interested the medical community, thanks to their ease of use, but also raised questions about their reliability in medical contexts.

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The generation of donor-specific antibodies (DSA) requires that alloreactive B cells receive help from follicular helper T (T) cells. Recent works have suggested that γδ T cells could contribute to T cell-dependent humoral responses, leading us to investigate their role in DSA generation. Analysis of a cohort of 331 kidney transplant recipients found no relation between the number of circulating γδ T cells and the risk to develop DSA.

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Article Synopsis
  • The study aimed to assess the effectiveness of combining glucocorticoids (GCs) with cyclophosphamide (CYC) for treating patients with poor-prognosis eosinophilic granulomatosis with polyangiitis (EGPA) compared to using GCs alone.
  • Data from a European multicenter database were analyzed, involving 209 patients and focusing on relapse rates and other related outcomes over 12 to 24 months.
  • Results indicated that adding CYC significantly reduced the risk of relapse and related complications compared to GCs alone, suggesting a beneficial role for CYC in the treatment of poor-prognosis EGPA.
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Optimization of individual immunosuppression, which reduces the risks of both graft loss and patients' death, is considered the best approach to improve long-term outcomes of renal transplantation. Torque Teno Virus (TTV) DNAemia has emerged as a potential biomarker reflecting the depth of therapeutic immunosuppression during the initial year post-transplantation. However, its efficacy in long-term monitoring remains uncertain.

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Purpose: The study aims to determine the impact of initial management in Vogt-Koyanagi-Harada syndrome (VKHS).

Methods: Patients diagnosed with a VKHS between January 2001 and December 2020 in two French tertiary centers were included in a retrospective study.

Results: Fifty patients were included with a median duration of follow-up of 29.

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Objective: Dermatomyositis associated with anti-MDA5 autoantibodies (DM-MDA5+) is a rare autoimmune disease usually characterized by skin involvement, often-severe lung involvement, and general features. Several reports of infections have been described, sometimes early after the introduction of immunosuppressive therapy. We studied the infection risk in a DM-MDA5+ population.

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Article Synopsis
  • The study explores how recipient B cells produce donor-specific antibodies after organ transplantation, traditionally thought to require help from the recipient's own CD4 T cells.
  • Researchers found that even without these T cells, recipient mice after heart transplantation produced antibodies against donor MHC I molecules due to help from donor CD4 T cells present in the graft.
  • Similar mechanisms were observed in human kidney and lung transplants, suggesting that a new form of T cell interaction may explain early antibody responses and potentially worse transplant outcomes.
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Background: The standard-of-care protocol, based on plasma exchanges, high-dose intravenous immunoglobulin and optimization of maintenance immunosuppression, can slow down the evolution of antibody-mediated rejection (AMR), but with high interindividual variability. Identification of a reliable predictive tool of the response to AMR treatment is a mandatory step for personalization of the follow-up strategy and to guide second-line therapies.

Methods: Interrogation of the electronic databases of 2 French university hospitals (Lyon and Strasbourg) retrospectively identified 81 renal transplant recipients diagnosed with AMR without chronic lesions (cg score ≤1) at diagnosis and for whom a follow-up biopsy had been performed 3-6 months after initiation of therapy.

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Article Synopsis
  • VEXAS syndrome is an autoinflammatory condition linked to mutations, characterized by vacuoles in myeloid progenitors and somatic changes.
  • A study by Heiblig et al analyzed 30 patients with VEXAS syndrome who were treated with various Janus kinase (JAK) inhibitors.
  • The findings showed positive results for the JAK1/2 inhibitor ruxolitinib, leading to clinical remissions and less reliance on steroids for most patients.
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Despite the critical role of cytokines in allograft rejection, the relation of peripheral blood cytokine profiles to clinical kidney transplant rejection has not been fully elucidated. We assessed 28 cytokines through multiplex assay in 293 blood samples from kidney transplant recipients at time of graft dysfunction. Unsupervised hierarchical clustering identified a subset of patients with increased pro-inflammatory cytokine levels.

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Kidney transplant recipients (KTRs) have reduced ability to mount adequate antibody response after two doses of the COVID-19 mRNA vaccine. French health authorities have allowed a third booster dose (D3) for KTRs, but their response is heterogeneous and tools able to discriminate the responders are lacking. Anti-RBD IgG titers (chemiluminescence immunoassay), spike-specific cellular responses (IFN-γ-releasing assay, IGRA), and in vitro serum neutralization of the virus (the best available correlate of protection), were evaluated 7-14 days after the second dose (D2) of BNT162b2 vaccine in 93 KTRs.

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The level of protection achieved by the standard two doses of COVID-19 mRNA vaccines in patients receiving maintenance hemodialysis (MHD) remains unclear. To study this we used the French Renal Epidemiology and Information Network (REIN) Registry to compare the incidence and severity of 1474 cases of COVID-19 diagnosed in patients receiving MHD after none, one or two doses of vaccine. Vaccination significantly reduce COVID-19 incidence and severity, but 11% of patients infected after two doses still died.

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Patients on maintenance hemodialysis (MHD), which are at high risk of infection by SARS-CoV-2 virus and death due to COVID-19, have been prioritized for vaccination. However, because they were excluded from pivotal studies and have weakened immune responses, it is not known whether these patients are protected after the "standard" two doses of mRNA vaccines. To answer this, anti-spike receptor binding domain (RBD) IgG and interferon gamma-producing CD4 and CD8 specific-T cells were measured in the circulation 10-14 days after the second injection of BNT162b2 vaccine in 106 patients receiving MHD (14 with history of COVID-19) and compared to 30 healthy volunteers (four with history of COVID-19).

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The analysis of immune cell signaling is critical for the understanding of the biology and pathology of the immune system, and thus a mandatory step for the development of efficient biomarkers and targeted therapies. Phosflow, which has progressively replaced the traditional western blot approach, relies on flow cytometry to analyze various signaling pathways at a single-cell level. This technique however suffers a lack of sensitivity largely due to the low signal/noise ratio that characterizes cell signaling analysis.

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Background: Posttransplant lymphoproliferative disorders (PTLDs) encompass a spectrum of heterogeneous entities. Because the vast majority of cases PTLD arise from B cells, available data on PTLD of T or NK phenotype (T/NK-cell PTLD) are scarce, which limits the quality of the management of these patients.

Methods: All adult cases of PTLD diagnosed in France were prospectively recorded in the national registry between 1998 and 2007.

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