Project description:Gut microbiome dynamics and Enterobacterales infection in liver transplant patients: a prospective observational study (metagenomics)
Project description:TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from liver transplant recipients and longitudinal data from renal and liver transplant recipients.
Project description:Rationale: We recently demonstrated that the triple combination CFTR modulator therapy elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) improves lung ventilation and airway mucus plugging determined by multiple-breath washout and magnetic resonance imaging in CF patients with at least one F508del allele. However, effects of ELX/TEZ/IVA on viscoelastic properties of airway mucus, chronic airway infection and inflammation have not been studied. Objectives: To examine the effects of ELX/TEZ/IVA on airway mucus rheology, microbiome and inflammation in CF patients with one or two F508del alleles aged 12 years and older. Methods: In this prospective observational study, we determined sputum rheology, microbiome, inflammation markers and proteome before and 1, 3 and 12 months after initiation of ELX/TEZ/IVA. Measurements and Main Results: CF patients with at least one F508del allele and healthy controls were enrolled in this study. ELX/TEZ/IVA improved the elastic and viscous modulus of CF sputum. Further, ELX/TEZ/IVA improved the microbiome α-diversity and decreased the relative abundance of Pseudomonas aeruginosa (P<0.05) in CF sputum. ELX/TEZ/IVA also reduced IL-8 and free NE activity, and shifted the CF sputum proteome towards healthy. Conclusions: Our data demonstrate that ELX/TEZ/IVA improves sputum viscoelastic properties, chronic airway infection and inflammation in CF patients with at least one F508del allele, however, without reaching levels close to healthy.
2023-06-22 | PXD041844 | Pride
Project description:Prospective study of multi-drug resistant organism colonization and infection in liver transplant recipients
Project description:In clinical organ transplantation complete cessation of immunosuppressive therapy can be successfully accomplished in selected recipients providing a proof-of-principle that allograft tolerance is attainable in humans. The intra-graft molecular pathways associated with human allograft tolerance, however, have not been comprehensively studied before. In this study we analyzed sequential liver tissue samples collected from liver recipients enrolled in a prospective multicenter immunosuppressive withdrawal clinical trial. Tolerant and non-tolerant recipients differed in the intra-graft expression of genes involved in the regulation of iron homeostasis.These results point to a critical role of iron homeostasis in the regulation of intra-graft alloimmune responses in humans and provide a set of novel biomarkers to conduct drug-weaning trials in liver transplantation. The complete database comprised the expression measurements of 48766 probes in liver biopsies. The liver biopsy specimens available for the study were obtained: a) before immunosuppressive drugs were discontinued from tolerant (TOL, n=24) and non-tolerant (Non-TOL, n=29) recipients; b) at the time of rejection from non-tolerant recipients (Non TOL REJ, n=18); In addition, liver tissue samples were also collected from the following control patient groups: a) liver transplant recipients with chronic hepatitis due to recurrent hepatitis C virus infection (HEPC, n=12); b) liver transplant recipients with typical acute cellular rejection taking place during the immediate post-transplant period (REJ, n=9); c) liver transplant recipients under maintenance immunosuppression with normal liver function and normal liver histology 1 year after transplantation (CONT-Tx, n=8); and d) non-transplanted patients undergoing surgery for colorectal liver metastases (CONT, n=10).
Project description:Background: Hepatitis E Virus (HEV) is a new causative agent of chronic hepatitis in solid organ transplant recipients in Europe. Factors associated with the occurrence and persistence of chronic HEV infection remain largely unknown but chronic evolution seems to be the consequence of hostM-bM-^@M-^Ys immunological factors rather than of viral factors. Method: In a prospective case-control study, we have determined in whole blood of chronically HEV-infected kidney-transplant recipients the host response using microarray technology. Results: Chronically HEV-infected kidney-transplant recipients exhibited a specific transcriptional program, in which interferon effectors were prominent. The intensity of expression of each signatureM-bM-^@M-^Ys gene was significantly lower in patients who were subsequently cleared of HEV than in patients who were not. Furthermore, in patients who were cleared of HEV, a higher expression of these genes was associated with a longer delay until HEV clearance. Conclusions: The specific transcriptional program determined in chronically HEV-infected kidney-transplant recipients suggests an activation of type I interferon response. Intensity of interferon-stimulated genes expression could be useful to forecast the outcome of infection. High expression of interferon-stimulated genes could signify a dysregulation in the interferon response that might favour the persistence of the HEV infection. TrialM-bM-^@M-^Ys registration number: NCT01090232; RegistryM-bM-^@M-^Ys URL: http://clinicaltrials.gov/ct2/show/study/NCT01090232?term=kidney+transplant+recipients&cntry1=EU%3AFR&rank=2 Total RNA was extracted from whole-blood sample or monocytes of kidney-transplant patients with or without chronic hepatitis E (CHE) infection. Control patients were matched up with CHE patients for age, sex, time since kidney transplant and immunosuppressive treatment.
Project description:Clinical study of critically ill patients with sepsis and sepsis-related ARDS with whole blood RNA collected within the first 24 hours of admission Goal of the study was to determine whether biologically relevant genes were identified to be differentially expressed genes in patients with sepsis alone and sepsis with ARDS Prospective observational study, case cohort design
Project description:Objective: Identify genes that are differentially expressed between critically ill trauma patients who go on to develop ventilator-associated pneumonia (VAP) compared to similar patients who do not develop VAP Using gene expression differences, develop a model that predicts which patients are at greater risk of developing VAP. Prospective observational study, analysis of gene expression in 20 patient samples, 10 that developed ventilator-associated pneumonia, 10 that did not
Project description:TransplantLines is designed as a single-center, prospective cohort study and biobank including all different types of solid organ transplant recipients as well as living organ donors. In the TransplantLines gut microbiome study the gut microbiome of solid organ transplant recipients is characterized and linked to clinical phenotypes. This batch contains the cross-sectional data from renal transplant recipients is.