Pulmonary fibrosis is a progressive inflammatory disease with high mortality and limited therapeutic options. Previous genetic and immunologic investigations suggest common intersections between idiopathic pulmonary fibrosis (IPF), sarcoidosis, and murine models of pulmonary fibrosis. To identify immune responses that precede collagen deposition, we conducted molecular, immunohistochemical, and flow cytometric analysis of human and murine specimens. Immunohistochemistry revealed programmed cell death-1 (PD-1) up-regulation on IPF lymphocytes. PD-1+CD4+ T cells with reduced proliferative capacity and increased transforming growth factor–β (TGF-β)/interleukin-17A (IL-17A) expression were detected in IPF, sarcoidosis, and bleomycin CD4+T Cells. PD-1+ T helper 17 cells are the predominant CD4+T cell subset expressing TGF-β. Coculture of PD-1+CD4+ T cells with human lung fibroblasts induced collagen-1 production. Strikingly, ex vivo PD-1 pathway blockade resulted in reductions in TGF-β and IL-17A expression from CD4+ T cells, with concomitant declines in collagen-1 production from fibroblasts. Molecular analysis demonstrated PD-1 regulation of the transcription factor STAT3 (signal transducer and activator of transcription 3). Chemical blockade of STAT3, using the inhibitor STATTIC, inhibited collagen-1 production. Both bleomycin administration to PD-1 null mice or use of antibody against programmed cell death ligand 1 (PD-L1) demonstrated significantly reduced fibrosis compared to controls. This work identifies a critical, previously unrecognized role for PD-1+CD4+ T cells in pulmonary fibrosis, supporting the use of readily available therapeutics that directly address interstitial lung disease pathophysiology.
Background:The Plastic Surgery Common Application (PSCA) was introduced as a free and specialty-specific application for plastic surgery applicants in the 2020-2021 cycle. Now in its second year, the PSCA is being piloted by all integrated residency programs with future plans to replace Electronic Residency Application Service (ERAS) in the 2022-2023 cycle. This study aimed to explore applicant perspectives related to the PSCA and ERAS applications. Methods: An anonymous survey was distributed to integrated plastic surgery residency applicants from the 2021-2022 application cycle. Participants were asked to provide basic demographic information, their perspectives of the PSCA, and overall application preference. Results: One hundred forty (43.1%) applicants completed the survey. Nearly, 63% of applicants responded "slightly well" or "not well at all" regarding their ability to highlight at least one aspect of their application. Forty-one percent of applicants believed ERAS best highlighted the strengths of their application compared with 27% who believed their strengths were better highlighted by the PSCA. Seventynine percent reported the cost savings associated with the PSCA were "very" or "extremely important." Overall, 63% of respondents reported a preference to apply with the PSCA alone. Conclusions: This is the first study to provide insight on applicants' perspectives of the PSCA. Although the majority preferred applying with the PSCA, there may be challenges with transitioning to this application solely. Future iterations of the PSCA may aim to ameliorate functionality concerns, optimize application content, and incorporate plastic surgery-specific information that may be important to selection committees.
Background: Free tissue transfer is a valuable surgical option for the reconstruction of a myriad of complex lower extremity defects. Currently, there is a paucity of data that examines the risks of complications for each of these unique indications. Methods: Patients undergoing lower extremity free flap reconstruction from the ACS-NSQIP 2011–2019 database were stratified into groups based on the etiology and indication for reconstruction. Rates of major, surgical wound, and medical complications were compared over the first post-operative month. Multivariable logistic regression was used to identify complication predictors. Results: 425 lower extremity free flaps were analyzed. The most common indications for lower extremity free flap reconstruction were wound-related (29%), malignancy (21%), and trauma (17%). Seventeen percent of free flaps had a major post-operative complication, 9% had a surgical wound complication, and 16% had a medical complication. There were no significant differences in major complications between the indications. However, the independent risk factors for major complications varied widely. Those with an indication of malignancy and those who received a musculocutaneous free flap were significantly more likely to have a surgical wound complication compared to the remaining cohort ( p < 0.05). Those requiring free flap reconstruction for orthopedic hardware related concerns as well as those with wound related indications were significantly more likely to have a post-operative medical complication ( p < 0.05). Conclusion: Understanding the unique risk profiles between the various indications and populations of patients undergoing lower extremity free flap reconstruction is critical for providing accurate risk estimations and optimizing post-operative outcomes and monitoring.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.