Faculty Bibliography

INTRODUCTION/UNASSIGNED:Variceal hemorrhage is a severe and often fatal consequence of portal hypertension from liver cirrhosis. Although endoscopic and radiographic interventions have largely replaced balloon tamponade, the Sengstaken-Blakemore tube (SBT) remains a critical salvage therapy. However, declining use has led to limited provider experience and familiarity with SBT placement and management. METHODS/UNASSIGNED:We implemented a hands-on, manikin-based simulation program for fellows and attendings from gastroenterology and critical care to improve provider familiarity with SBT placement and management. Standardized SBT kits were developed and distributed across all sites. Annual simulation sessions included presession didactics, live demonstrations, and small-group hands-on practice. Pre- and postsession surveys assessed self-reported confidence in SBT placement, management, and removal using a 5-point Likert scale. A Wilcoxon signed-rank test analyzed changes in confidence. RESULTS/UNASSIGNED:Fifty-four participants participated in 2023. Prior to training, only 20% of participants reported having received any formal instruction on SBT placement or management and 39% had never placed an SBT in a real-life scenario. Confidence in SBT placement (mean 3.00-4.30), management (1.78-4.31), and removal (2.17-4.43) significantly increased after the simulation. DISCUSSION/UNASSIGNED:This simulation-based intervention was associated with improved self-reported confidence in SBT placement, management, and removal for a high-acuity, low-frequency procedure. Given interest, emergency medicine, surgery, and internal medicine were included in subsequent years. Our results underscore the importance of structured training in bridging knowledge and skill gaps across gastroenterology and critical care disciplines. Future work should assess long-term retention and explore curriculum integration.

Inducing long-term protective memory CD8(+) T-cells is a desirable goal for vaccines against intracellular pathogens. However, the mechanisms of differentiation of CD8(+) T-cells into long-lived memory cells capable of mediating protection of immunized hosts remain incompletely understood. We have developed an experimental system using mice immunized with wild type (WT) or mutants of the intracellular bacterium Listeria monocytogenes (Lm) that either do or do not develop protective memory CD8(+) T-cells. We previously reported that mice immunized with Lm lacking functional SecA2, an auxiliary secretion system of gram-positive bacteria, did not differentiate functional memory CD8(+) T-cells that protected against a challenge infection with WT Lm. Herein we hypothesized that the p60 and NamA autolysins of Lm, which are major substrates of the SecA2 pathway, account for this phenotype. We generated Lm genetically deficient for genes encoding for the p60 and NamA proteins, ΔiapΔmurA Lm, and further characterized this mutant. Δp60ΔNamA Lm exhibited a strong filamentous phenotype, inefficiently colonized host tissues, and grew mostly outside cells. When Δp60ΔNamA Lm was made single unit, cell invasion was restored to WT levels during vaccination, yet induced memory T-cells still did not protect immunized hosts against recall infection. Recruitment of blood phagocytes and antigen-presenting cell activation was close to that of mice immunized with ΔActA Lm, which develop protective memory. However, key inflammatory factors involved in optimal T-cell programming such as IL-12 and type I IFN (IFN-I) were lacking, suggesting that cytokine signals may largely account for the observed phenotype. Thus, altogether, these results establish that p60 and NamA secreted by Lm promote primary host cell invasion, the inflammatory response and the differentiation of functional memory CD8(+) T-cells, by preventing Lm filamentation during growth and subsequent triggering of innate sensing mechanisms.

Cells of the innate immune system are essential for host defenses against primary microbial pathogen infections, yet their involvement in effective memory responses of vaccinated individuals has been poorly investigated. Here we show that memory T cells instruct innate cells to become potent effector cells in a systemic and a mucosal model of infection. Memory T cells controlled phagocyte, dendritic cell, and NK or NK T cell mobilization and induction of a strong program of differentiation, which included their expression of effector cytokines and microbicidal pathways, all of which were delayed in nonvaccinated hosts. Disruption of IFN-γ signaling in Ly6C+ monocytes, dendritic cells, and macrophages impaired these processes and the control of pathogen growth. These results reveal how memory T cells, through rapid secretion of IFN-γ, orchestrate extensive modifications of host innate immune responses that are essential for effective protection of vaccinated hosts.