Objective: We assessed the impact of abdominal aortic aneurysm (AAA)-specific simulation training on resident performance in simulated open AAA repair (SOAAAR) and determined whether simulation training required dedicated faculty instruction.Methods: We randomized 18 residents (postgraduate years 3-5) to an AAA simulation course consisting of two mandatory practice sessions proctored either by a surgical skills lab coordinator (Group A, n = 8) or by a vascular surgery faculty instructor (Group B, n = 10). All residents received a detailed manual and video demonstrating the technique of open AAA repair. Using a validated tool, vascular faculty who were blinded to resident identity, level of training, and randomization status graded SOAAAR performance via videos that were recorded before and after the course.Results: Characteristics and baseline scores between Groups A and B were not different. Postcourse, there was a no significant improvement in performance in Group A. Group B performance was improved significantly from baseline with regard to task-specific checklist scores (44.1 +/- 6.3 vs 34.9 +/- 6.5; P =. 02), global rating scores (28.4 +/- .6 vs 25.3 +/- 5.0; P = .049), and overall assessment of operative competence (P = .02). Time to complete SOAAAR improved in both groups (P = .02). Baseline performance varied significantly with year of training as measured by task-specific checklist scores, global rating scores, final product analysis, time to complete repair, and overall operative competence. Improvement varied inversely with year of training (P < .05) and postcourse scores were equivalent for postgraduate year 3-5 residents.Conclusions: An AAA-specific simulation training course improved resident performance in simulated open AAA repair. Dedicated faculty instruction during the simulation training was required for significant improvement in resident performance. The impact of simulation training was greatest in more junior residents. Procedure-specific simulation training with dedicated faculty can be used to effectively teach simulated open AAA repair.

We assessed the impact of AAA-specific simulation training on resident performance in simulated open abdominal aortic aneurysm repair (SOAAAR) and determined whether simulation training required dedicated faculty instruction. We randomized 18 residents(PGY3-5) to an AAA simulation course consisting of either two mandatory practice sessions proctored by a surgical skills lab coordinator (Group A, n=8) or two sessions led by a vascular faculty instructor (Group B, n=10). All residents received a detailed manual and video demonstrating the technique of open AAA repair. Blinded faculty graded SOAAAR performance at baseline and post-course using a validated tool. Characteristics and baseline scores between Groups A and B were not different. Post-course, there was a trend towards improved performance in Group A as measured by procedural checklist scores(34.8±9.5 vs. 31±12.6, P=.08). Group B performance was improved from baseline with regard to procedural checklist scores (44.1 ± 6.3 vs. 34.9 ± .5, P=.02), global rating scores (28.4 ± .6 vs. 25.3 ± 5.0, P=.049), and overall assessment of operative competence (P=.02), with a trend toward significance in quality of final product (P=.1). Time to complete SOAAAR improved in both groups (P=.02). Baseline performance varied significantly with year of training (PGY3: 42±15 - PGY5: 67±15, P=.008). Improvement varied inversely with year of training (P<.05) and post-course scores were equivalent for PGY3-5 residents. An AAA-specific simulation training course improved resident performance in simulated open AAA repair. Dedicated faculty instruction during the simulation training was required for significant improvement in resident performance. The impact of simulation training was greatest in more junior residents. Procedure-specific simulation training with dedicated faculty can be used to effectively teach operative procedures and should focus on early residency training.

Acute alcohol binge results in immunosuppression and impaired production of proinflammatory cytokines, including TNF-alpha. TNF-alpha production is induced by LPS, a TLR4 ligand, and is tightly regulated at various levels of the signaling cascade, including the NF-kappa B transcription factor. Here, we hypothesized that acute alcohol induces TLR4/LPS tolerance via Bcl-3, a nuclear protein and member of the NF-kappa B family. We found that acute alcohol pretreatment resulted in the same attenuating effect as LPS pretreatment on TLR4-induced TNF-alpha production in human monocytes and murine RAW 264.7 macrophages. Acute alcohol-induced Bcl-3 expression and IP studies revealed increased association of Bcl-3 with NF-kappa B p50 homodimers in alcohol-treated macrophages and in mice. ChIP assays revealed increased occupancy of Bcl-3 and p50 at the promoter region of TNF-alpha in alcohol-pretreated cells. To confirm that the Bcl-3-p50 complex regulates transcription/production of TNF-alpha during acute alcohol exposure, we inhibited Bcl-3 expression using a targeted siRNA. Bcl-3 knockdown prevented the alcohol-induced inhibition of TNF-alpha mRNA and protein production. In a mouse model of binge alcohol, an increase in Bcl-3 and a concomitant decrease in TNF-alpha but no change in IL-10 production were found in mice that received alcohol followed by LPS challenge. In summary, our novel data suggest that acute alcohol treatment in vitro and in vivo induces molecular signatures of TLR4/LPS tolerance through the induction of Bcl-3, a negative regulator of TNF-alpha transcription via its association with NF-kappa B p50/p50 dimers. J. Leukoc. Biol. 92: 611-620; 2012.

Simulation-based training has become an accepted and increasingly utilized method for surgical skill acquisition. However, validated tools to assess technical performance and provide feedback have not been developed for simulated index vascular surgical procedures. We sought to develop and validate a tool for simulated open abdominal aortic aneurysm repair (SOAAAR). Phase 1: Initial tool development based on current practice and expert consensus. Phase 2: Refinement of the tool based on independent, blinded assessor feedback and psychometric testing including feasibility, reliability (internal consistency, inter-assessor reliability) and construct validity. Phase 1: Three successive iterations of the tool were developed based on expert opinion and psychometric testing. Tool included procedural checklist, global rating score, final product analysis and overall assessment of operative competence. Phase 2: Internal consistency and inter-assessor reliability improved from the first to third version. A trend was also demonstrated for increasing construct validity (intra-class correlation coefficient = 0.72, P=.0008) with the third iteration of the tool. The final SOAAR tool was feasible, reliable (internal consistency using Cronbach's α coefficient = 0.826, inter-assessor reliability using spearman's rho coefficient yielded P<.05), and face and content valid (content validity index=0.94). A psychometrically robust assessment tool for assessing performance of SOAAR was developed and validated. This tool allows for objective assessment of resident performance during open aneurysm repair in the simulated setting. The tool can be used to identify areas for improvement in resident performance and to evaluate and optimize simulation-based training.

Background Hepatitis C Virus (HCV), a single stranded RNA virus, affects millions of people worldwide and leads to chronic infection characterized by chronic inflammation in the liver and in peripheral immune cells. Chronic liver inflammation leads to progressive liver damage. MicroRNAs (miRNA) regulate inflammation (miR-155, -146a and -125b) as well as hepatocyte function (miR-122). Methods Here we hypothesized that microRNAs are dysregulated in chronic HCV infection. We examined miRNAs in the circulation and in peripheral monocytes of patients with chronic HCV infection to evaluate if specific miRNA expression correlated with HCV infection. Results We found that monocytes from chronic HCV infected treatment-naïve (cHCV) but not treatment responder patients showed increased expression of miR-155, a positive regulator of TNFα, and had increased TNFα production compared to monocytes of normal controls. After LPS stimulation, miR-155 levels were higher in monocytes from cHCV patients compared to controls. MiR-125b, which has negative regulatory effects on inflammation, was decreased in cHCV monocytes compared to controls. Stimulation of normal monocytes with TLR4 and TLR8 ligands or HCV core, NS3 and NS5 recombinant proteins induced a robust increase in both miR-155 expression and TNFα production identifying potential mechanisms for in vivo induction of miR-155. Furthermore, we found increased serum miR-155 levels in HCV patients compared to controls. Serum miR-125b and miR-146a levels were also increased in HCV patients. Serum levels of miR-122 were elevated in cHCV patients and correlated with increased ALT and AST levels and serum miR-155 levels. Conclusion In conclusion, our novel data demonstrate that miR-155, a positive regulator of inflammation, is upregulated both in monocytes and in the serum of patients with chronic HCV infection. Our study suggests that HCV core, NS3, and NS5 proteins or TLR4 and TLR8 ligands can mediate increased miR-155 and TNFα production in chronic HCV infection. The positive correlation between serum miR-155 and miR-122 increase in cHCV may be an indicator of inflammation-induced hepatocyte damage.