Faculty Bibliography

Lung transplantation is the only potentially curative treatment for end-stage lung failure and successfully improves both long-term survival and quality of life. However, lung transplantation is limited by the shortage of suitable donor lungs. This discrepancy in organ supply and demand has prompted researchers to seek alternative therapies for end-stage lung failure. Tissue engineering (bioengineering) organs has become an attractive and promising avenue of research, allowing for the customized production of organs on demand, with potentially perfect biocompatibility. While breakthroughs in tissue engineering have shown feasibility in practice, they have also uncovered challenges in solid organ applications due to the need not only for structural support, but also vascular membrane integrity and gas exchange. This requires a complex engineered interaction of multiple cell types in precise anatomical locations. In this article, we discuss the process of creating bioengineered lungs and the challenges inherent therein. We summarize the relevant literature for selecting appropriate lung scaffolds, creating decellularization protocols, and using bioreactors. The development of completely artificial lung substitutes will also be reviewed. Lastly, we describe the state of current research, as well as future studies required for bioengineered lungs to become a realistic therapeutic modality for end-stage lung disease. Applications of bioengineering may allow for earlier intervention in end-stage lung disease and have the potential to not only halt organ failure, but also significantly reverse disease progression.

BACKGROUND:Evolution of surgical practice is influenced by publications in the leading journals of that field. If the authorship of a publication lacks geographical diversity, this could create bias and limit generalizability of the evidence. Accordingly, we conducted a geographical analysis of the leading Cardiothoracic Surgery journals worldwide. METHODS:Using 2020 Impact Factor, we searched the leading Cardiothoracic Surgery journals over the past decade. Only original articles were included. Data regarding first, second and last authors were extracted from every article. From this, we analysed country of affiliation, highest academic degree obtained and author location by metropolitan or rural setting. RESULTS:A total of 12,706 original articles were published in the top 5 ranked Cardiothoracic journals between 2011 and 2020. Authors originated from 69 countries, with the majority being from North America and Western Europe. The United States was the most common country of affiliation (42.8%) in all five journals, with New York City the most prominent city. A total of  63.7% of the authorship originated from large metropolitan areas (estimated as population greater than 500,000 residents), and the most common degrees obtained by authors were MD and PhD. CONCLUSION/CONCLUSIONS:The prominent Cardiothoracic authorship is predominantly located in Western countries, most commonly large metropolitan centers in the United States. This raises questions as to whether the literature adequately reflects populations in other geographical areas such as the continents of South America and Africa and rural settings. Leading journals should consider policies which encourage publication by authors from geographical locations that are underrepresented globally.

Objectives/UNASSIGNED:Proning patients with acute respiratory distress syndrome (ARDS) has been associated with increased survival, though little data exists evaluating the safety and feasibility of proning ARDS patients on extracorporeal membrane oxygenation (ECMO). Methods/UNASSIGNED:, 2020 was performed. All proning events were evaluated for complications, as well as change in compliance, sweep, oxygenation and flow. The primary outcome of this study was the rate major morbidity associated with proning while on ECMO. Results/UNASSIGNED:of 86 pre to 103 post (p<0.0001). Mean ECMO flow was unchanged. Conclusions/UNASSIGNED:Proning in patients with ARDS on ECMO is safe with an associated improvement in lung mechanics. With careful planning and coordination, these data support the practice of appropriately proning patients with severe ARDS, even if they are on ECMO.

OBJECTIVE:Determine the long-term outcome and need for additional therapy after pulmonary endarterectomy (PEA) for segmental chronic thromboembolic pulmonary hypertension. METHODS:Retrospective analysis of a prospective cohort of 401 consecutive Canadian patients undergoing PEA between August 2005 and March 2020 in Toronto. The outcome of segmental disease defined as Jamieson type 3 was compared with more proximal disease defined as Jamieson type 1 and 2. The cohort was divided into 3 intervals to analyze the trend over time: 2005-2010, 2011-2015, and 2016-2020. RESULTS:in type 1 or 2 disease (P = .07). Mortality after PEA was similar between type 3 and type 1 and 2 disease at 30-days (2.8% vs 2.3%; P = .8) and at 1 year (7.7% vs 5.5%; P = .4). At 5 years, the survival was lower in type 3 disease (80% vs 91% in type 1 or 2 disease; P = .002). Type 3 disease was an independent predictor for the initiation of pulmonary hypertension-targeted medical therapy after PEA with a cumulative incidence of 38% at 10 years compared with 20% in type 1 and 2 disease (P < .0001). Post-PEA balloon pulmonary angioplasty was predominantly performed in type 3 disease (8% vs 1% in more type 1 or 2 disease; P = .0002). CONCLUSIONS:PEA achieved excellent early and long-term results in segmental chronic thromboembolic pulmonary hypertension. However, patients with segmental disease are at increased risk of requiring additional therapy after PEA and should be carefully monitored.

Little is known about the effects of hepatitis C viremia on immunologic outcomes in the era of direct-acting antivirals. We conducted a prospective, single-arm trial of lung transplantation from hepatitis C-infected donors into hepatitis C-naïve recipients (n = 21). Recipients were initiated on glecaprevir-pibrentasvir immediately post-transplant and were continued on therapy for a total of 8 weeks. A control group of recipients of hepatitis C-negative lungs were matched 1:1 on baseline variables (n = 21). The primary outcome was the frequency of acute cellular rejection over 1-year post-transplant. Treatment with glecaprevir-pibrentasvir was well tolerated and resulted in viremia clearance after a median of 16 days of therapy (IQR 10-24 days). At one year, there was no difference in incidence of acute cellular rejection (71.4% vs. 85.7%, P = .17) or rejection requiring treatment (33.3% vs. 57.1%, P = .12). Mean cumulative acute rejection scores were similar between groups (.46 [SD ± .53] vs. .52 [SD ± .37], P = .67). Receipt of HCV+ organs was not associated with acute rejection on unadjusted Cox regression analysis (HR .55, 95% CI .28-1.11, P = .09), or when adjusted for risk factors known to be associated with acute rejection (HR .57, 95% CI .27-1.21, P = .14). Utilization of hepatitis C infected lungs with immediate treatment leads to equivalent immunologic outcomes at 1 year.

INTRODUCTION:The COVID-19 pandemic has had a significant impact on global surgery. In particular, deleterious effects of SARS-CoV-2 infection on the heart and cardiovascular system have been described. To inform surgical patients, we performed a systematic review and meta-analysis aiming to characterize outcomes of COVID-19 positive patients undergoing cardiac surgery. METHODS:The study protocol was registered with PROSPERO (CRD42021228533) and conformed with PRISMA 2020 and MOOSE guidelines. PubMed, Ovid MEDLINE and Web of Science were searched between 1 January 2019 to 24 February 2022 for studies reporting outcomes on COVID-19 positive patients undergoing cardiac surgery. Study screening, data extraction and risk of bias assessment were conducted in duplicate. Meta-analysis was conducted using a random-effects model where at least two studies had sufficient data for that variable. RESULTS:Searches identified 4223 articles of which 18 studies were included with a total 44 patients undergoing cardiac surgery. Within these studies, 12 (66.7%) reported populations undergoing coronary artery bypass graft (CABG) surgery, three (16.7%) aortic valve replacements (AVR) and three (16.7%) aortic dissection repairs. Overall mean postoperative length of ICU stay was 3.39 (95% confidence interval (CI): 0.38, 6.39) and mean postoperative length of hospital stay was 17.88 (95% CI: 14.57, 21.19). CONCLUSION:This systematic review and meta-analysis investigated studies of limited quality which characterized cardiac surgery in COVID-19 positive patients and demonstrates that these patients have poor outcomes. Further issues to be explored are effects of COVID-19 on decision-making in cardiac surgery, and effects of COVID-19 on the cardiovascular system at a cellular level.

OBJECTIVE:We sought to determine the risk factors associated with late mortality or complications (thoracoabdominal aortic aneurysm [TAAA] life-altering events [TALE]: a composite of mortality, permanent paraplegia, permanent dialysis, and stroke) for patients who had undergone endovascular or open TAAA repair. METHODS:We performed a population-based study of patients who had undergone TAAA repair in Ontario, Canada, from 2006 to 2017. The association of baseline risk factors with mortality and complications after repair was examined using Cox hazards models with hospital-specific random effects. The survival of patients who had undergone TAAA repair was compared with that of controls without TAAAs. The two groups were matched by age, sex, area of residence, and average annual household income. The type of repair (endovascular vs open) was included in all models. RESULTS:We identified 664 adults (mean age, 69.3 ± 10.6 years; 71% men) who had undergone TAAA repair. At 5 and 8 years, survival was 55.0% (95% confidence interval [CI], 49.8%-60.1%) and 44.6% (95% CI, 40.4%-49.6%) for patients who had undergone TAAA repair vs 85.6% (95% CI, 83.9%-87.1%) and 76.3% (95% CI, 73.8%-78.8%) for the control population, respectively (hazard ratio [HR], 1.97; 95% CI, 1.67-2.32; P < .01). For the TAAA group, freedom from TALE was 49.2% (95% CI, 44.7%-53.7%) and 37.3% (95% CI, 33.1%-42.4%) at 5 and 8 years of follow-up, respectively. On multivariable analysis, the risk factors associated with mortality during follow-up included older age (HR, 1.21 per 5-year increase; 95% CI, 1.13-1.28), peripheral artery disease (HR, 1.46; 95% CI, 1.03-2.09), hypertension (HR, 1.58; 95% CI, 1.03-2.43), congestive heart failure (HR, 1.78; 95% CI, 1.34-2.36), and urgent procedures (HR, 2.27; 95% CI, 1.74-3.00). A lower rate of death was observed for those with previous coronary revascularization (HR, 0.63; 95% CI, 0.41-0.96) and those who had undergone repair at high-volume institutions (>60 TAAA repairs during the study period; HR, 0.71; 95% CI, 0.55-0.91). Older age, chronic kidney disease, congestive heart failure, and urgent procedures were associated with a higher rate of TALE. The type of repair (endovascular vs open) was not associated with mortality or TALE. CONCLUSIONS:TAAA repair was associated with reduced long-term survival compared with the general population, regardless of the mode of treatment. Urgent or emergent repair was the most profound risk factor for late adverse events. The type of repair (endovascular vs open) was not a predictor of long-term death or complications. Previous coronary revascularization and treatment performed at a high-volume institution were associated with improved late outcomes for patients undergoing TAAA repair.

BACKGROUND:The novel coronavirus (COVID-19) pandemic has resulted in a severe reduction in operative opportunities for trainees. We hypothesized that augmenting independent practice with a bench model of vascular anastomoses using regular videoconferences and individual feedback would provide a meaningful benefit in the maintenance of technical skills in senior lung transplant surgical fellows. METHODS:A lung transplantation virtual technical skills course was developed, and surgical fellows were provided with a bench model and surgical instruments. Using a virtual communication platform, teaching sessions were held twice weekly, and fellows performed an anastomosis on camera. Video recordings were reviewed and critiqued by attending staff. At the end of the 3-month course, participants were surveyed about their experience. Warm ischemic time was compared between the fellows' 5 most recent cases before and after the pandemic. RESULTS: = .68). CONCLUSIONS:A program of virtual technical skills teaching, individual video coaching, and independent practice has provided a benefit in maintaining technical skills in lung transplant surgical fellows during the COVID-19 pandemic, when equivalent operative experience was unavailable. Lessons learned from this exceptional time can be used to create simulation curricula for senior trainees.