Pancreatic ductal adenocarcinoma (PDAC) is associated with a pronounced fibro-inflammatory stromal reaction that contributes to tumor progression. A critical step in invasion and metastasis is the epithelial to mesenchymal transition (EMT), which can be regulated by the Snail family of transcription factors. Overexpression of Snail (Snai1) and mutant KrasG12D in the pancreas of transgenic mice, using an elastase (EL) promoter, resulted in fibrosis. To identify how Snail modulates inflammation in the pancreas, we examined the effect of expressing Snail in ELKrasG12D mice (KrasG12D/Snail) on mast cell infiltration, which has been linked to PDAC progression. Using this animal model system, it was demonstrated that there are increased numbers of mast cells in the pancreas of KrasG12D/Snail mice compared to control KrasG12D mice. In addition, it was revealed that human primary PDAC tumors with increased Snail expression are associated with increased mast cell infiltration and that Snail expression in these clinical specimens positively correlated with the expression of stem cell factor (SCF/KITLG), a cytokine known to regulate mast cell migration. Concomitantly, SCF levels are increased in the KrasG12D/Snail mice compared to control mice. Moreover, overexpression of Snail in PDAC cells increased SCF levels and that the media conditioned by Snail-expressing PDAC cells promoted mast cell migration. Finally, inhibition of SCF using a neutralizing antibody significantly attenuated Snail-induced migration of mast cells. Implications Together, these results elucidate how the EMT regulator Snail contributes to inflammation associated with PDAC tumors.
Background The COVID-19 pandemic has presented new challenges surrounding end-of-life planning and has been associated with increased online discussion about life support. Research Question How has online communication about advance care planning (ACP) and specific life-sustaining interventions (LSIs) changed during the pandemic? Study Design and Methods Conversations on Twitter containing references to LSIs (e.g., ‘ECMO’) or ACP (e.g., ‘DNR/DNI’) were collected from January 2019 to May 2021. User account metadata was used to predict user demographic information and classify users as either organizations, individuals, clinicians, or influencers. We compared the number of impressions across these user categories and analyzed the content of tweets using natural language processing models to identify topics of discussion and associated emotional sentiment. Results There were 202,585 unique tweets about LSIs and 67,162 unique tweets about ACP. Users who were younger, men, or influencers were more likely to discuss LSIs online. Tweets about LSIs were associated with more positive emotional sentiment scores than tweets about ACP (LSIs: 0.3, ACP: -0.2; P < 0.001). Among tweets about ACP, most contained personal experiences related to the death of loved ones (27%) or discussed discrimination through DNR orders directed at the elderly and disabled (19%). Personal experiences had the greatest retweet-to-tweet-ratio (4.7), indicating high levels of user engagement. Tweets about discrimination contained the most negative net sentiment score (-0.5). Interpretation The observed increase in tweets regarding LSIs and ACP suggests that Twitter was consistently utilized to discuss treatment modalities and preferences related to intensive care during the pandemic. Future interventions to increase online engagement with ACP may consider leveraging influencers and personal stories. Finally, we identified DNR-related discrimination as a commonly held public fear, which should be further explored as a barrier to ACP completion and can be proactively addressed by clinicians during bedside goals-of-care discussions.
Background Physicians’ interest in the health and well-being of their patients is a tenet of medical practice. Physicians’ ability to act upon this interest by caring for and about their patients is central to high-quality clinical medicine and may affect burnout. To date, a strong theoretical and empirical understanding of physician caring does not exist. To establish a practical, evidence-based approach to improve health care delivery and potentially address physician burnout, we sought to identify and synthesize existing conceptual models, frameworks, and definitions of physician caring. Methods We performed a scoping review on physician caring. In November 2019 and September 2020, we searched PubMed MEDLINE, Embase, PsycINFO, CINAHL, and CENTRAL Register of Controlled Trials to identify conceptual models, frameworks, and definitions of physician caring. Eligible articles involved discussion or study of care or caring among medical practitioners. We created a content summary and performed thematic analysis of extracted data. Results Of 11,776 articles, we reviewed the full text of 297 articles; 61 articles met inclusion criteria. Commonly identified concepts referenced Peabody’s “secret of care” and the ethics of care. In bioethics, caring is described as a virtue. Contradictions exist among concepts of caring, such as whether caring is an attitude, emotion, or behavior, and the role of relationship development. Thematic analysis of all concepts and definitions identified six aspects of physician caring: (1) relational aspects, (2) technical aspects, (3) physician attitudes and characteristics, (4) agency, (5) reciprocity, and (6) physician self-care. Discussion Caring is instrumental to clinical medicine. However, scientific understanding of what constitutes caring from physicians is limited by contradictions across concepts. A unifying concept of physician caring does not yet exist. This review proposes six aspects of physician caring which can be used to develop evidence-based approaches to improve health care delivery and potentially mitigate physician burnout. Supplementary Information The online version contains supplementary material available at 10.1007/s11606-021-07382-4.
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