Interleukin-37 reduces liver inflammatory injury via effects on hepatocytes and non-parenchymal cells.

BACKGROUND AND AIM: The purpose of the present study was to determine the effects of interleukin-37 (IL-37) on liver cells and on liver inflammation induced by hepatic ischemia/reperfusion (I/R). METHODS: Mice were subjected to I/R. Some mice received recombinant IL-37 (IL-37) at the time of reperfusion. Serum levels of alanine aminotransferase, and liver myeloperoxidase content were assessed. Serum and liver tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-2 (MIP-2) and keratinocyte chemokine (KC) were also assessed. Hepatic reactive oxygen species (ROS) levels were assessed. For in vitro experiments, isolated hepatocytes and Kupffer cells were treated with IL-37 and inflammatory stimulants. Cytokine and chemokine production by these cells were assessed. Primary hepatocytes underwent induced cell injury and were treated with IL-37 concurrently. Hepatocyte cytotoxicity and Bcl-2 expression were determined. Isolated neutrophils were treated with TNF-α and IL-37 and neutrophil activation and respiratory burst were assessed. RESULTS: IL-37 reduced hepatocyte injury and neutrophil accumulation in the liver after I/R. These effects were accompanied by reduced serum levels of TNF-α and MIP-2 and hepatic ROS levels. IL-37 significantly reduced MIP-2 and KC productions from lipopolysaccharide-stimulated hepatocytes and Kupffer cells. IL-37 significantly reduced cell death and increased Bcl-2 expression in hepatocytes. IL-37 significantly suppressed TNF-α-induced neutrophil activation. CONCLUSIONS: IL-37 is protective against hepatic I/R injury. These effects are related to the ability of IL-37 to reduce proinflammatory cytokine and chemokine production by hepatocytes and Kupffer cells as well as having a direct protective effect on hepatocytes. In addition, IL-37 contributes to reduce liver injury through suppression of neutrophil activity.

Return to the Real World: A Novel Program to Improve Resident Readiness for the Transplant Surgery Rotation.

OBJECTIVE: We describe a novel didactic program to prepare mid-level residents for the operative complexities of the transplant surgery rotation. DESIGN: A faculty led dry and wet lab experience was held for all residents returning to clinical rotations from a 2-year research experience. Residents were provided instructional video prior to the dry lab and instructed through both labs by transplant faculty and fellows. The culmination of the program entailed a porcine renal autotransplantation. SETTING: The University of Cincinnati, Department of Surgery, Cincinnati, OH. PARTICIPANTS: Incoming third year general surgery residents returning to clinical rotations from a 2-year research experience. RESULTS: This lab was well received by residents and faculty and increased confidence in residents. CONCLUSIONS: This program increased confidence in complex operations seen on the transplant surgery rotation and can be replicated in a cost-effective manner.

See None, Do Some, Teach None: An Analysis of the Contemporary Operative Experience as Nonprimary Surgeon.

OBJECTIVE: The operative experience of today's general surgery resident has changed, but little is known about the modern experience as nonprimary surgeon. We set out to explore changes in the operative experience of general surgery residents as first assistant (FA) and teaching assistant (TA). DESIGN, SETTING, AND PARTICIPANTS: This is a review of ACGME national operative log reports from 1990 to 2018. TA and FA cases were analyzed. Statistical analysis was performed using polynomial regression analysis and Kruskal-Wallis test. Statistical significance was set at p < 0.05. RESULTS: 30,260 individuals completed general surgery residency during the study period with medians of 951 (interquartile range: 929-974) total major, 63 (31-184) FA, and 32 (25-48) TA cases. As a proportion of total cases completed, FA cases decreased from 21.8% of the total operative experience in 1990 to 2.5% in 2018, and TA cases declined from 7.4% of the total operative experience in 1990 to 3.5% in 2018. Regression modeling demonstrated that both operative roles decreased over time, but at a progressively decreasing rate, with FA cases reaching a "floor" around 2010 and TA cases reaching a "breakpoint" in 2008 at which time operative volume rebounded and began to increase. Among the core general surgery domains of abdomen and alimentary tract, compositional analysis revealed a decrease across each of the 11 operative subcategories (all p < 0.05) for FA, and for TA, a decrease in 6 of the 11 operative subcategories (stomach, small intestine, large intestine, anorectal, hernia, and biliary, all p < 0.05). CONCLUSIONS: Over the past 3 decades, the resident operative experience as nonprimary surgeon has decreased dramatically, with today's residents graduating with fewer FA and TA cases. As surgical training has traditionally relied heavily on an apprenticeship model for learning technical skills, it is essential that surgical educators recognize and rectify these trends.