Publications by authors named "Leonard Seghers"

Complications like acute cellular rejection (ACR) and infection are known risk factors for the development of chronic lung allograft dysfunction, impacting long-term patient and graft survival after lung transplantation (LTx). Differentiating between complications remains challenging and time-sensitive, highlighting the need for accurate and rapid diagnostic modalities. We assessed the ability of exhaled breath analysis using an electronic nose (eNose) to distinguish between ACR, infection, and mechanical complications in LTx recipients (LTR) presenting with suspected complications.

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Background: Lung transplantation (LTX) is the last life-extending option for patients with progressive fibrosing interstitial lung diseases (fILD). Between 12% and 71% of patients with fILD are patients with underlying telomere-dysfunction (trILD) related to pathogenic telomere-related gene (TRG) variants and/or short telomere length. TrILD patients tend to have earlier disease onset, faster progression, and worse prognosis causing them to be referred for LTX more often.

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Background: Bacterial colonization (BC) of the lower airways is common in lung transplant recipients (LTRs) and increases the risk of chronic lung allograft dysfunction. Diagnosis often requires bronchoscopy. Exhaled breath analysis using electronic nose (eNose) technology may noninvasively detect BC in LTRs.

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Article Synopsis
  • Close monitoring of immunosuppressant levels after lung transplantation is crucial to avoid long-term complications, and therapeutic drug monitoring (TDM) is currently the method used for this.
  • The study explored the use of a novel electronic nose (eNose) technology to assess Tacrolimus levels in lung transplant recipients through non-invasive breathprints, measuring correlations and diagnostic ability.
  • Results showed a weak correlation between eNose measurements and Tacrolimus levels, with categorization accuracy ranging from 45%-69%, indicating that eNose technology is currently not reliable enough for TDM in this context.
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Background: There is a need for reliable biomarkers for the diagnosis of chronic lung allograft dysfunction (CLAD). In this light, we investigated the diagnostic value of exhaled breath analysis using an electronic nose (eNose) for CLAD, CLAD phenotype, and CLAD stage in lung transplant recipients (LTR).

Methods: We performed eNose measurements in LTR with and without CLAD, visiting the outpatient clinic.

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The use of extended criteria donor grafts is a promising strategy to increase the number of organ transplantations and reduce waitlist mortality. However, these organs are often compromised and/or damaged, are more susceptible to preservation injury, and are at risk for developing post-transplant complications. Ex vivo organ perfusion is a novel technology to preserve donor organs while providing oxygen and nutrients at distinct perfusion temperatures.

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Background: Evaluating and bridging patients to lung transplantation (LTx) on the intensive care unit (ICU) remains controversial, especially without a previous waitlist status. Long term outcome data after LTx from ICU remains scarce. We compared long-term survival and development of chronic lung allograft dysfunction (CLAD) in elective and LTx from ICU, with or without previous waitlist status.

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Several reports have been published on findings in COVID-19 patients leading to a proposition of new disease entity COVID-19-associated pulmonary aspergillosis. This scoping review is designed at clarifying the concepts on how the findings of spp. in COVID-19 patients were interpreted.

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Background: Acute respiratory distress syndrome (ARDS) often requires controlled ventilation, yielding high mechanical power and possibly further injury. Veno-venous extracorporeal membrane oxygenation (VV-ECMO) can be used as a bridge to recovery, however, if this fails the end result is destroyed lung parenchyma. This condition is fatal and the only remaining alternative is lung transplantation.

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Home spirometry after lung transplantation is common practice, to monitor graft function. However, there is little experience with online home monitoring applications with direct data transfer to the hospital. We evaluated the feasibility and patient experiences with a new online home monitoring application, integrated with a Bluetooth-enabled spirometer and real-time data transfer.

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Solid organ transplant (SOT) recipients may be at risk for severe COVID-19. Data on the clinical course of COVID-19 in immunosuppressed patients are limited, and the effective treatment strategy for these patients is unknown. We describe our institutional experience with COVID-19 in SOT.

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The aim of this study was to investigate whether there is an impact of donation rates on the quality of lungs used for transplantation and whether donor lung quality affects post-transplant outcome in the current Lung Allocation Score era. All consecutive adult LTx performed in Eurotransplant (ET) between January 2012 and December 2016 were included (N = 3053). Donors used for LTx in countries with high donation rate were younger (42% vs.

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Transforming growth factor-beta (TGF-β) stimulates both ischaemia induced angiogenesis and shear stress induced arteriogenesis by signalling through different receptors. How these receptors are involved in both these processes of blood flow recovery is not entirely clear. In this study the role of TGF-β receptors 1 and endoglin is assessed in neovascularization in mice.

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Aims: MicroRNA-126 (miR-126), which is enriched in endothelial cells, plays a role in angiogenesis. Based on the seed sequence, miR-126 can also be predicted to regulate vasculogenesis by modulating the endothelial expression of stromal cell-derived factor-1 (SDF-1).

Methods And Results: Using miR-reporter constructs, we first validated that miR-126 inhibits SDF-1 expression in endothelial cells in vitro.

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Aims: Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was designed to inhibit both protease systems simultaneously. MMP and plasmin activity were inhibited at the cell surface by this hybrid protein, consisting of the receptor-binding amino-terminal fragment (ATF) of urokinase-type PA, linked to both the tissue inhibitor of metalloproteinases (TIMP-1) and bovine pancreas trypsin inhibitor (BPTI), a potent protease inhibitor.

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Article Synopsis
  • A study was conducted to explore how different genetic backgrounds affect the development of hypertension and vascular remodeling in mice treated with an inhibitor of nitric oxide synthesis (l-NAME).
  • C57BL/6 mice experienced a significant increase in blood pressure and vascular changes after 4 weeks, while BALB/C mice did not show the same level of response despite similarities in their inflammatory response.
  • The findings suggest that the natural killer (NK) gene complex in C57BL/6 mice plays a crucial role in the sensitivity to hypertension, as mice with this genetic trait displayed a more pronounced reaction compared to others.
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MicroRNAs are negative regulators of gene expression that play a key role in cell-type specific differentiation and modulation of cell function and have been proposed to be involved in neovascularization. Previously, using an extensive cloning and sequencing approach, we identified miR-126 to be specifically and highly expressed in human endothelial cells (EC). Here, we demonstrate EC-specific expression of miR-126 in capillaries and the larger vessels in vivo.

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Objective: Vascular endothelial growth factor (VEGF)-induced stromal cell-derived factor-1 (SDF-1) has been implicated in angiogenesis in ischemic tissues by recruitment of CXCR4-positive bone marrow-derived circulating cells with paracrine functions in preclinical models. Here, evidence for this is provided in patients with peripheral artery disease.

Methods And Results: Expression patterns of VEGF, SDF-1, and CXCR4 were studied in amputated limbs of 16 patients.

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