Exploring the impact of Choroideremia on women with phenotypic and/or genotypic evidence of disease: insights from a global survey.

INTRODUCTION: Choroideremia (CHM) is an X-linked inherited retinal disease mostly affecting males. However, women with phenotypic and/or genotypic evidence of CHM may develop degenerative visual disability with advancing age. Our objective was to determine the visual impacts of phenotypic and/or genotypic evidence of CHM in women and its associated psychosocial burden and influence on activities of daily living (ADLs). METHODS: We conducted an international cross-sectional survey from April to December 2022 using an e-questionnaire distributed through not-for-profit stakeholder organizations and social media plat-forms. RESULTS: With a total of 55 respondents (n = 55), most women with phenotypic and/or genotypic evidence of CHM (76%) reported a change in their visual acuity. When assessing its impact on ADLs, Pearson's correlation coefficient showed a negative correlation between driving (p = 0.046) and mobility capabil-ities (0.046) with the respondent's age. More than half of women reported being afraid, anxious, and stressed, with women below the age of 50 years old reporting a significantly higher level of distress and hopelessness (p = 0.003), anxiety (p = 0.00007), issues with relaxing (p = 0.025), and negative personal thoughts (p = 0.042). CONCLUSION: Overall, this survey outlines both physical and psychological burden of being a woman with phenotypic and/or genotypic evidence of CHM. Given the limited clinical research in females affected by CHM, this patient-centered survey is a crucial advocacy tool for these individuals.

Correlation between Neutrophil Extracellular Traps (NETs) Expression and Primary Graft Dysfunction Following Human Lung Transplantation.

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.

The treatment of end-stage corneal disease: penetrating keratoplasty compared with Boston type 1 keratoprosthesis.

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.

Effect of a surgical observership on the perceptions and career choices of preclinical medical students: a mixed-methods study.

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.

Angiopoietin 1 release from human neutrophils is independent from neutrophil extracellular traps (NETs).

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.