Steven Bonneau

Primary graft dysfunction (PGD) is characterized by alveolar epithelial and vascular endothelial damage and inflammation, lung edema and hypoxemia. Up to one-third of recipients develop the most severe form of PGD (Grade 3; PGD3). Animal studies suggest that neutrophils contribute to the inflammatory process through neutrophil extracellular traps (NETs) release (NETosis). NETs are composed of DNA filaments decorated with granular proteins contributing to vascular occlusion associated with PGD. The main objective was to correlate NETosis in PGD3 (n = 9) versus non-PGD3 (n = 27) recipients in an exploratory study. Clinical data and blood samples were collected from donors and recipients pre-, intra- and postoperatively (up to 72 h). Inflammatory inducers of NETs’ release (IL-8, IL-6 and C-reactive protein [CRP]) and components (myeloperoxidase [MPO], MPO-DNA complexes and cell-free DNA [cfDNA]) were quantified by ELISA. When available, histology, immunohistochemistry and immunofluorescence techniques were performed on lung biopsies from donor grafts collected during the surgery to evaluate the presence of activated neutrophils and NETs. Lung biopsies from donor grafts collected during transplantation presented various degrees of vascular occlusion including neutrophils undergoing NETosis. Additionally, in recipients intra- and postoperatively, circulating inflammatory (IL-6, IL-8) and NETosis biomarkers (MPO-DNA, MPO, cfDNA) were up to 4-fold higher in PGD3 recipients compared to non-PGD3 (p = 0.041 to 0.001). In summary, perioperative elevation of NETosis biomarkers is associated with PGD3 following human lung transplantation and these biomarkers might serve to identify recipients at risk of PGD3 and initiate preventive therapies.

Penetrating keratoplasty (PKP) yields excellent results for restoring vision in end-stage corneal diseases. However, its success is limited to high-risk diseases such as aniridia, chemical burns, autoimmune corneal diseases, and herpetic eye disease. Boston type 1 keratoprosthesis (BKPro) offers another option to these patients. Since 1992, improvements in perioperative management and device construction have significantly increased the use of BKPro worldwide and challenged the therapeutic role of PKP in these patients. This review aims to evaluate BKPro’s place in the treatment algorithm of these high-risk patients to assist surgeons’ decision-making. PKP and BKPro are compared in three outcome categories: visual acuity, graft retention and failure, and complications profile. Special attention is given to comparing secondary BKPro versus repeated PKP as well as primary BKPro versus primary PKP. We conclude that secondary BKPro bears a better prognosis than repeated PKP in most high-risk patients. Similarly, primary BKPro likely confers improved outcomes over primary PKP in most high-risk recipients. However, current evidence is based on retrospective designs, and controlled prospective randomized trials are required to validate these conclusions.