Andrea J. Carpenter

Envisioning simulation in the future of thoracic surgical education

T he Visioning Simulation Conference (VSC), convened in Cambridge, Mass, on April 19, 2007, sponsored by the Thoracic Surgery Foundation for Research and Education (TSFRE), was attended by appointed representatives from the Society of Thoracic Surgery (STS), the American Association for Thoracic Surgery (AATS), the American Board of Thoracic Surgery (ABTS), the Thoracic Surgery Directors Association (TSDA), the European Association for Cardiothoracic Surgery (EACTS), the American College of Surgeons (ACS), the National Heart, Lung, and Blood Institute (NHLBI), industry partners (Medtronic, Inc, Edwards Lifesciences LLC, and St Jude Medical, Inc), and several attendees with extensive simulation experience and development. The conference began with a simulated operating room (OR) demonstration by live video feed. During the 2-day conference, speakers discussed simulation use in anesthesia, the airline industry, and congenital heart disease, with the goal of demonstrating what technology is currently available and stimulating thought among the participants regarding future needs. The primary working function of the conference centered on a series of roundtable discussions planned to define how simulation could be applied to cardiothoracic surgical education. This report defines the vision developed during this 2-day conference and recommends actions necessary to bring this vision to reality. Surgical education is becoming a progressively more complex endeavor. In this era of limited work hours for residents and rapidly changing technology, new and creative educational techniques must be used to ensure that surgeons in training achieve proficiency in more complex problems during shorter training periods and that practicing surgeons can be rapidly trained in new technologies. It is clear that simulation will become a required method for demonstrating proficiency, maintaining certification, and introducing new techniques. Evolving requirements for measurable quality indicators will soon mandate that maintenance of certification require the demonstration of proficiency in technical skills, fundamental knowledge, and management of complex clinical situations. The VSC was based on the premise that simulation could be used as a tool to meet these needs in thoracic surgery. Under the auspices of TSFRE and the Joint Council on Thoracic Surgical Education (JCTSE), a committee was formed to plan the VSC. The objective of the conference was to bring together surgeons, professionals with simulation experience, simulation developers, government, and industry funding partners. The committee devised a program that combined simulation demonstrations, lectures by simulation experts, and a series of roundtable discussions. The primary focus of the conference centered on the following questions: How can simulation be used to improve patient safety and transform thoracic surgery in a positive way? What is unique about thoracic surgery as a specialty that makes it appropriate for simulation education? From the Division of Thoracic Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Tex; the Division of Thoracic Surgery, Johns Hopkins Medical Institutions, Baltimore, Md; Central Plains Cardiothoracic Surgery LLC, Wichita, Kans; and the Division of Thoracic Surgery, Department of Surgery, Brigham and Women’s Hospital, Boston, Mass.

Factors affecting interest in cardiothoracic surgery: Survey of North American general surgery residents

BACKGROUND Applications to cardiothoracic surgery (CTS) training programs have declined precipitously. The viewpoints of potential applicants, general surgery residents, have not yet been assessed. Their perceptions are crucial to understanding the cause and formulating appropriate changes in our educational system. METHODS An initial survey instrument was content-validated, and the final instrument was distributed electronically between March 24 and May 2, 2008 through 251 general surgery program directors to all Accreditation Council for Graduate Medical Education-accredited general surgery residents (7508). RESULTS The response rate was 29% (2153 residents; 89% programs). Respondents demographics matched existing data; 6% were committed to CTS, and 26% reported prior or current interest in CTS. Interest waned after postgraduate year 3. Interest correlated with CTS rotation duration. Of the respondents committed to CTS, 76% had mentors (71% were cardiothoracic surgeons). CTS had the most shortcomings among 9 subspecialties. Job security and availability accounted for 46% of reported shortcomings (3 to 14 times higher than other subspecialties). Work schedule accounted for 25%. Length of training was not a very important factor, although it was identified as an option to increase interest in CTS. Residents who were undecided or uninterested in CTS were twice as likely to cite the ability to balance work and personal life as important than residents who chose CTS. CONCLUSIONS The dominant concern documented in the survey is job security and availability. The importance of mentorship and exposure to CTS faculty in promoting interest was also evident. Decision makers should consider these findings when planning changes in education and the specialty.

Factors Affecting Interest in Cardiothoracic Surgery: Survey of North American General Surgery Residents

BACKGROUND Applications to cardiothoracic surgery (CTS) training programs have declined precipitously. The viewpoints of potential applicants, general surgery residents, have not yet been assessed. Their perceptions are crucial to understanding the cause and formulating appropriate changes in our educational system. METHODS An initial survey instrument was content-validated, and the final instrument was distributed electronically between March 24 and May 2, 2008 through 251 general surgery program directors to all Accreditation Council for Graduate Medical Education-accredited general surgery residents (7,508). RESULTS The response rate was 29% (2153 residents; 89% programs). Respondents demographics matched existing data; 6% were committed to CTS, and 26% reported prior or current interest in CTS. Interest waned after postgraduate year 3. Interest correlated with CTS rotation duration. Of the respondents committed to CTS, 76% had mentors (71% were cardiothoracic surgeons). CTS had the most shortcomings among 9 subspecialties. Job security and availability accounted for 46% of reported shortcomings (3 to 14 times higher than other subspecialties). Work schedule accounted for 25%. Length of training was not a very important factor, although it was identified as an option to increase interest in CTS. Residents who were undecided or uninterested in CTS were twice as likely to cite the ability to balance work and personal life as important than residents who chose CTS. CONCLUSIONS The dominant concern documented in the survey is job security and availability. The importance of mentorship and exposure to CTS faculty in promoting interest was also evident. Decision makers should consider these findings when planning changes in education and the specialty.

CIKS (Act1 or TRAF3IP2) mediates high glucose-induced endothelial dysfunction.

Hyperglycemia-induced endothelial dysfunction is characterized by enhanced inflammatory cytokine and adhesion molecule expression, and endothelial-monocyte adhesion. The adapter molecule CIKS (connection to IKK and SAPK/JNK; also known as Act1 or TRAF3IP2) is an upstream regulator of NF-κB and AP-1, and plays a role in inflammation and injury. Here we show that high glucose (HG; 25mM vs. 5mM d-glucose)-induced endothelial-monocyte adhesion and inhibition of endothelial cell (EC) migration were both reversed by CIKS knockdown. In EC, HG induced CIKS mRNA and protein expression via DPI-inhibitable Nox4-dependent ROS generation. Further, HG induced CIKS transcription and enhanced CIKS promoter-dependent reporter gene activation via Nox4, ROS, AP-1 and C/EBP. Coimmunoprecipitation and immunoblotting revealed CIKS/IKKβ/JNK physical association under basal conditions that was enhanced by HG treatment. Importantly, CIKS knockdown inhibited HG-induced (i) IKKβ and JNK phosphorylation, (ii) p65 and c-Jun nuclear translocation, and (iii) NF-κB- and AP-1-dependent proinflammatory cytokine, chemokine, and adhesion molecule expression. Similar to HG, the deleterious metabolic products of chronic hyperglycemia, AGE-HSA, AOPPs-HSA and oxLDL, also induced CIKS-dependent endothelial dysfunction. Notably, aortas from streptozotocin-induced and the autoimmune type 1 diabetic NOD and Akita mice showed enhanced DPI-inhibitable ROS generation and CIKS expression. Since CIKS mediates high glucose-induced NF-κB and AP-1-dependent inflammatory signaling and endothelial dysfunction, targeting CIKS may delay progression of vascular diseases during diabetes mellitus and atherosclerosis.

Metformin inhibits aldosterone-induced cardiac fibroblast activation, migration and proliferation in vitro, and reverses aldosterone + salt-induced cardiac fibrosis in vivo

The overall goals of this study were to investigate whether metformin exerts anti-fibrotic effects in aldosterone (Aldo)+salt-treated wild type mouse hearts, and determine the underlying molecular mechanisms in isolated adult cardiac fibroblasts (CF). In vitro, Aldo induced CF activation, migration, and proliferation, and these effects were inhibited by metformin. Further, Aldo induced PPM1A (Protein Phosphatase Magnesium Dependent 1A) activation and inhibited AMPK phosphorylation. At a pharmacologically relevant concentration, metformin restored AMPK activation, and inhibited Aldo-induced Nox4/H2O2-dependent TRAF3IP2 induction, pro-inflammatory cytokine expression, and CF migration and proliferation. Further, metformin potentiated the inhibitory effects of spironolactone, a mineralocorticoid receptor antagonist, on Aldo-induced collagen expression, and CF migration and proliferation. These results were recapitulated in vivo, where metformin reversed Aldo+salt-induced oxidative stress, suppression of AMPK activation, TRAF3IP2 induction, pro-inflammatory cytokine expression, and cardiac fibrosis, without significantly modulating systolic blood pressure. These in vitro and in vivo data indicate that metformin has the potential to reduce adverse cardiac remodeling in hypertensive heart disease.

Down to the Wire: Tricuspid Stenosis in the Setting of Multiple Pacing Leads

Tricuspid stenosis in the setting of endocardial pacing leads is a rare entity, attributed to infection or lead malposition. We report the case of a 37‐year‐old man without these risk factors, who presented with new onset severe tricuspid stenosis in the setting of multiple chronic pacing leads. (PACE 2010; e49–e52)

Diagnostic Techniques in Thoracic Trauma

Diagnosis of thoracic injury begins with a history of events and examination of the patient. Appropriate radiographic studies will be dictated by the findings on history and physical. Procedural examinations, such as endoscopy or angiography, may also be needed for accurate diagnosis.

TRAF3IP2 mediates high glucose-induced endothelin-1 production as well as endothelin-1-induced inflammation in endothelial cells

Hyperglycemia-induced production of endothelin (ET)-1 is a hallmark of endothelial dysfunction in diabetes. Although the detrimental vascular effects of increased ET-1 are well known, the molecular mechanisms regulating endothelial synthesis of ET-1 in the setting of diabetes remain largely unidentified. Here, we show that adapter molecule TRAF3 interacting protein 2 (TRAF3IP2) mediates high glucose-induced ET-1 production in endothelial cells and ET-1-mediated endothelial cell inflammation. Specifically, we found that high glucose upregulated TRAF3IP2 in human aortic endothelial cells, which subsequently led to activation of JNK and IKKβ. shRNA-mediated silencing of TRAF3IP2, JNK1, or IKKβ abrogated high-glucose-induced ET-converting enzyme 1 expression and ET-1 production. Likewise, overexpression of TRAF3IP2, in the absence of high glucose, led to activation of JNK and IKKβ as well as increased ET-1 production. Furthermore, ET-1 transcriptionally upregulated TRAF3IP2, and this upregulation was prevented by pharmacological inhibition of ET-1 receptor B using BQ-788, or inhibition of NADPH oxidase-derived reactive oxygen species using gp91ds-tat and GKT137831. Notably, we found that knockdown of TRAF3IP2 abolished ET-1-induced proinflammatory and adhesion molecule (IL-1β, TNF-α, monocyte chemoattractant protein 1, ICAM-1, VCAM-1, and E-selectin) expression and monocyte adhesion to endothelial cells. Finally, we report that TRAF3IP2 is upregulated and colocalized with CD31, an endothelial marker, in the aorta of diabetic mice. Collectively, findings from the present study identify endothelial TRAF3IP2 as a potential new therapeutic target to suppress ET-1 production and associated vascular complications in diabetes. NEW & NOTEWORTHY This study provides the first evidence that the adapter molecule TRAF3 interacting protein 2 mediates high glucose-induced production of endothelin-1 by endothelial cells as well as endothelin-1-mediated endothelial cell inflammation. The findings presented herein suggest that TRAF3 interacting protein 2 may be an important therapeutic target in diabetic vasculopathy characterized by excess endothelin-1 production.

Simultaneous antegrade and retrograde reperfusion after cardioplegic arrest for coronary artery bypass.

Retrograde coronary sinus reperfusion with warm blood during proximal anastomoses permits completion of myocardial revascularization under a single cross‐clamp application. Reperfusion with both antegrade (via arterial and vein grafts) and retrograde (via coronary sinus catheter) warm blood has raised concerns about maldistribution of perfusate or overpressurization of capillary beds. This prospective, randomized design compares post‐cardioplegic myocardial recovery among patients receiving retrograde reperfusion only and patients receiving simultaneous antegradelretrograde reperfusion. Twenty‐four patients were selected among all presenting as outpatients for elective coronary artery bypass (CAB). Each patient underwent CAB with cardioplegic arrest and single cross‐clamp technique. During proximal anastomoses the heart was reperfused with warm blood from the cardiopul‐monary bypass (CPB) circuit. Twelve received retrograde reperfusion only, and 12 received simultaneous antegradelretrograde reperfusion via an internal mammary artery (IMA) graft, all vein grafts, and the coronary sinus catheter. Vein graft perfusion was interrupted in each vein as the proximal anastomosis was performed. Myocardial recovery time (interval from initiating reperfusion until electrical and mechanical activity), cardioversion incidence, requirement for inotropic support, and Swan‐Ganz hemodynamic parameters measured immediately 6 and 24 hours postoperatively were compared between groups. There were no differences between groups in age, ventricular function, number of grafts, or CPB time. Also, there were no differences in cardioversion, inotropic need, or postoperative hemodynamic performance. Myocardial recovery time was reduced in patients receiving simultaneous antegradehetrograde reperfusion (13.9 ± 7.0 vs 2.6 ± 2.1 minutes). Simultaneous reperfusion of warm blood antegrade and retrograde is not deleterious to the myocardium. More rapid recovery of myocardial function may represent a shorter period of warm ischemia but does not appear to translate to improved postoperative myocardial performance.

TRAF3IP2 mediates TWEAK/TWEAKR-induced pro-fibrotic responses in cultured cardiac fibroblasts and the heart

Persistent inflammation promotes development and progression of heart failure (HF). TWEAK (TNF-Related WEAK Inducer Of Apoptosis), a NF-κB- and/or AP-1-responsive proinflammatory cytokine that signals via TWEAK receptor (TWEAKR), is expressed at high levels in human and preclinical models of HF. Since the adapter molecule TRAF3IP2 (TRAF3 Interacting Protein 2) is an upstream regulator of various proinflammatory pathways, including those activated by NF-κB and AP-1, we hypothesized that targeting TRAF3IP2 inhibits TWEAK-induced proinflammatory and pro-fibrotic responses in vitro and in vivo. Consistent with the hypothesis, forced expression of TRAF3IP2 upregulated TWEAK and its receptor expression in cultured adult mouse cardiac fibroblasts (CF). Further, exogenous TWEAK upregulated TRAF3IP2 expression in a time- and dose-dependent manner, suggesting a positive-feedback regulation of TRAF3IP2 and TWEAK. TWEAK also promoted TRAF3IP2 nuclear translocation. Confirming its critical role in TWEAK signaling, silencing TRAF3IP2 inhibited TWEAK autoregulation, TWEAKR upregulation, p38 MAPK, NF-κB and AP-1 activation, inflammatory cytokine expression, MMP and TIMP1 activation, collagen expression and secretion, and importantly, proliferation and migration. Recapitulating these in vitro results, continuous infusion of TWEAK for 7 days increased systolic blood pressure (SBP), upregulated TRAF3IP2 expression, activated p38 MAPK, NF-κB and AP-1, induced the expression of multiple proinflammatory and pro-fibrotic mediators, and interstitial fibrosis in hearts of wild type mice. These proinflammatory and pro-fibrotic changes occurred in conjunction with myocardial hypertrophy and contractile dysfunction. Importantly, genetic ablation of TRAF3IP2 inhibited these TWEAK-induced adverse cardiac changes independent of increases in SBP, indicating that TRAF3IP2 plays a causal role, and thus a therapeutic target, in chronic inflammatory and fibro-proliferative diseases.