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.
Background: Medical students are increasingly choosing nonsurgical specialties; observership programs can address factors influencing them toward surgical careers by allowing preclerkship exposure and mentorship, and correcting misconceptions. The aims of this study were to assess the influence of a peer-led observership program at the Université de Montréal on the career choices of preclinical medical students and to determine the factors associated with a positive observership experience. Methods: We used a quasi-experimental convergent mixed-methods questionnaire design. From Nov. 19 to Dec. 31, 2018, and Mar. 1 to Apr. 4, 2019, all medical students participating in the observership program were eligible for the study; there were no ineligibility criteria. Using a prospective purposive sampling method, we recruited students via the email sent to confirm their observership. In the week after their observership, we invited the students by email to complete a postintervention survey. We used nonparametric tests to evaluate the impact of the observership on participants’ career choices and an inductive data-driven thematic analysis to analyze their responses. Results: Of the 204 students who participated, 157 provided consent, of whom 85 (54.1%) completed questionnaires both before and after the observership. The majority of participants were interested in a surgical specialty before (72 [85%]) and after (68 [84%]) the observership. There was no significant change in the students’ choices of surgical specialties after the observership. However, most (68 [81%]) reported being more interested in a surgical career as a result of the observership, which allowed them to see that the type of practice they considered was congruent with a surgical career. Their perceptions of the field of surgery became positive, particularly regarding its pace and atmosphere and the humanistic patient–doctor relationship it required. The experience was influenced by surgeons’ and teams’ attitudes toward students, knowledge-sharing and quality of exposure. Participants mentioned that their willingness to participate was in part responsible for the success of their experience. Conclusion: This observership program allowed an early, positive introduction of students to surgery while challenging stereotypes. It provided a better understanding of surgery, enabling participants to consider this field and potentially influencing their residency application.
Background Neutrophils induce the synthesis and release of angiopoietin 1 (Ang1), a cytosolic growth factor involved in angiogenesis and capable of inducing several pro-inflammatory activities in neutrophils. Neutrophils also synthesize and release neutrophil extracellular traps (NETs), comprised from decondensed nuclear DNA filaments carrying proteins such as neutrophil elastase (NE), myeloperoxidase (MPO), proteinase 3 (PR3) and calprotectin (S100A8/S100A9), which together, contribute to the innate immune response against pathogens (e.g., bacteria). NETs are involved in various pathological conditions through pro-inflammatory, pro-thrombotic and endothelial dysfunction effects and have recently been found in heart failure (HF) and type 2 diabetes (T2DM) patients. The aim of the present study was to investigate the role of NETs on the synthesis and release of Ang1 by the neutrophils in patients with T2DM and HF with preserved ejection fraction (HFpEF) (stable or acute decompensated; ADHFpEF) with or without T2DM. Results Our data show that at basal level (PBS) and upon treatment with LPS, levels of NETs are slightly increased in patients suffering from T2DM, HFpEF ± T2DM and ADHF without (w/o) T2DM, whereas this increase was significant in ADHFpEF + T2DM patients compared to healthy control (HC) volunteers and ADHFpEF w/o T2DM. We also observed that treatments with PMA or A23187 increase the synthesis of Ang1 (from 150 to 250%) in HC and this effect is amplified in T2DM and in all cohorts of HF patients. Ang1 is completely released (100%) by neutrophils of all groups and does not bind to NETs as opposed to calprotectin. Conclusions Our study suggests that severely ill patients with HFpEF and diabetes synthesize and release a greater abundance of NETs while Ang1 exocytosis is independent of NETs synthesis.
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