Aged polymorphonuclear leukocytes cause fibrotic interstitial lung disease in the absence of regulation by B cells.

Pulmonary immunity requires tight regulation, as interstitial inflammation can compromise gas exchange and lead to respiratory failure. Here we found a greater number of aged CD11bhiL-selectinloCXCR4+ polymorphonuclear leukocytes (PMNs) in lung vasculature than in the peripheral circulation. Using pulmonary intravital microscopy, we observed lung PMNs physically interacting with B cells via ß2 integrins; this initiated neutrophil apoptosis, which led to macrophage-mediated clearance. Genetic deletion of B cells led to the accumulation of aged PMNs in the lungs without systemic inflammation, which caused pathological fibrotic interstitial lung disease that was attenuated by the adoptive transfer of B cells or depletion of PMNs. Thus, the lungs are an intermediary niche in the PMN lifecycle wherein aged PMNs are regulated by B cells, which restrains their potential to cause pulmonary pathology.

Factors Associated With Resident Research Success: An Analysis of Canadian General Surgery Trainees.

OBJECTIVE: Better understanding the research productivity of Canadian general surgery residents and factors associated with success would provide a valuable reference and help inform actions to enable success. We aimed to characterize the research productivity of Canadian general surgery residents and to evaluate factors associated with residents' research quantity and impact. DESIGN: A cross-sectional, observational study was performed using publicly available data evaluating Canadian General Surgery resident research productivity. Research productivity was characterized using measures including publications per postgraduate year (PGY) and CiteScore among others. Residency programs were then comparatively assessed using a multivariable logistic regression to evaluate program and resident factors associated with achieving >50th percentile research productivity. SETTING AND PARTICIPANTS: All General Surgery residents from English speaking Canadian training programs were included in this study, which was completed at the University of Alberta, a tertiary level academic center in Edmonton, Canada. RESULTS: A wide range of resident research productivity was observed across Canada with the median publications per PGY of 0.29, and the median sum of a resident's publication CiteScores of 2.05. The median h-index was 0.90. Graduate degree completion and publication experience prior to residency were significantly associated with higher publications per PGY (OR 2.94 and OR 2.10, respectively), as well as higher mean CiteScore (OR 3.42 and 2.24). The program factors that were assessed, including program size, research blocks, mandatory projects, or higher staff research productivity, did not show significant association with increased research output. CONCLUSIONS: There is a wide range in research output by general surgery residents across the country. Successful completion of graduate degrees and the experience of publication prior to residency are associated with higher research productivity and impact.

Leukotriene B4-Mediated Neutrophil Recruitment Causes Pulmonary Capillaritis during Lethal Fungal Sepsis.

Candida albicans bloodstream infection causes fungal septicaemia and death in over half of afflicted patients. Polymorphonuclear leukocytes (PMN) mediate defense against invasive candidiasis, but their role in protection versus tissue injury and sepsis is unclear. We observe PMN intravascular swarming and subsequent clustering in response to C. albicans yeast in a lethal septic mouse and human pulmonary circulation model. Live C. albicans sequester to the endothelium and are immediately captured by complement-dependent PMN chemotaxis, which is required for host survival. However, complement activation also leads to Leukotriene B4 (LTB4)-mediated intravascular PMN clustering and occlusion, resulting in capillaritis with pulmonary hemorrhage and hypoxemia. This clustering is unique to fungi and triggered by fungal cell wall components. PMN clustering is absent in mice lacking LTB4-receptor, and capillaritis is attenuated upon pharmacological LTB4 blockade without affecting phagocytosis. Therefore, therapeutically disrupting infection-induced capillaritis may limit organ injury without impairing host defense during fungal sepsis.