Search

Background: Hospitalizations for drug-use associated infective endocarditis (DUA-IE) have led to increasing surgical consultation for valve replacement. Cardiothoracic surgeons' perspectives about the process of decision making around operation for people with DUA-IE are largely unknown., Methods: This multisite semiqualitative study sought to gather the perspectives of cardiothoracic surgeons on initial and repeat valve surgery for people with DUA-IE through purposeful sampling of surgeons at 7 hospitals: University of Alabama, Tufts Medical Center, Boston Medical Center, Massachusetts General Hospital, University of North Carolina-Chapel Hill, Vanderbilt University Medical Center, and Rhode Island Hospital-Brown University., Results: Nineteen cardiothoracic surgeons (53% acceptance) were interviewed. Perceptions of the drivers of addiction varied as well as approaches to repeat valve operations. There were mixed views on multidisciplinary meetings, although many surgeons expressed an interest in more efficient meetings and more intensive postoperative and posthospitalization multidisciplinary care., Conclusions: Cardiothoracic surgeons are emotionally and professionally impacted by making decisions about whether to perform valve operation for people with DUA-IE. The use of efficient, agenda-based multidisciplinary care teams is an actionable solution to improve cross-disciplinary partnerships and outcomes for people with DUA-IE., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: On October 18, 2018, several changes to the donor heart allocation system were enacted. We hypothesize that patients undergoing orthotopic heart transplantation (OHT) under the new allocation system will see an increase in ischemic times, rates of primary graft dysfunction, and 1-year mortality due to these changes., Methods: In this single-center retrospective study, we reviewed the charts of all OHT patients from October 2017 through October 2019. Pre- and postallocation recipient demographics were compared. Survival analysis was performed using the Kaplan-Meier method., Results: A total of 184 patients underwent OHT. Recipient demographics were similar between cohorts. The average distance from donor increased by more than 150 km (p = .006). Patients in the postallocation change cohort demonstrated a significant increase in the rate of severe left ventricle primary graft dysfunction from 5.4% to 18.7% (p = .005). There were no statistically significant differences in 30-day mortality or 1-year survival. Time on the waitlist was reduced from 203.8 to 103.7 days (p = .006)., Conclusions: Changes in heart allocation resulted in shorter waitlist times at the expense of longer donor distances and ischemic times, with an associated negative impact on early post-transplantation outcomes. No significant differences in 30-day or 1-year mortality were observed., (© 2021 Wiley Periodicals LLC.)

Background: Coronavirus disease 2019 (COVID-19) has significantly impacted the healthcare landscape in the United States in a variety of ways including a nation-wide reduction in operative volume. The impact of COVID-19 on the availability of donor organs and the impact on solid organ transplant remains unclear. We examine the impact of COVID-19 on a single, large-volume heart transplant program., Methods: A retrospective chart review was performed examining all adult heart transplants performed at a single institution between March 2020 and June 2020. This was compared to the same time frame in 2019. We examined incidence of primary graft dysfunction, continuous renal replacement therapy (CRRT) and 30-day survival., Results: From March to June 2020, 43 orthotopic heart transplants were performed compared to 31 performed during 2019. Donor and recipient demographics demonstrated no differences. There was no difference in 30-day survival. There was a statistically significant difference in incidence of postoperative CRRT (9/31 vs. 3/43; p = .01). There was a statistically significant difference in race (23 W/8B/1AA vs. 30 W/13B; p = .029)., Conclusion: We demonstrate that a single, large-volume transplant program was able to grow volume with little difference in donor variables and clinical outcomes following transplant. While multiple reasons are possible, most likely the reduction of volume at other programs allowed us to utilize organs to which we would not have previously had access. More significantly, our growth in volume was coupled with no instances of COVID-19 infection or transmission amongst patients or staff due to an aggressive testing and surveillance program., (© 2021 Wiley Periodicals LLC.)

Background: Bundled payments for coronary artery bypass grafting (CABG) provide a single reimbursement for care provided from admission through 90 days post-discharge. We aim to explore the impact of complications on total institutional costs, as well as the drivers of high costs for index hospitalization., Methods: We linked clinical and internal cost data for patients undergoing CABG from 2014 to 2017 at a single institution. We compared unadjusted average variable direct costs, reporting excess cost from an uncomplicated baseline. We stratified by The Society of Thoracic Surgeons preoperative risk and quality outcome measures as well as value-based outcomes (readmission, post-acute care utilization). We performed multivariable linear regression to evaluate drivers of high costs, adjusting for preoperative and intraoperative characteristics and postoperative complications., Results: We reviewed 1789 patients undergoing CABG with an average of 2.7 vessels (SD 0.89). A significant proportion of patients were diabetic (51.2%) and obese (mean body mass index 30.6, SD 6.1). Factors associated with increased adjusted costs were preoperative renal failure (P = .001), diabetes (P = .001) and body mass index (P = .05), and postoperative stroke (P < .001), prolonged ventilation (P < .001), rebleeding requiring reoperation (P < .001) and renal failure (P < .001) with varying magnitude. Preoperative ejection fraction and insurance status were not associated with increased adjusted costs., Conclusions: Preoperative characteristics had less of an impact on costs post-CABG than postoperative complications. Postoperative complications vary in their impact on internal costs, with reoperation, stroke, and renal failure having the greatest impact. In preparation for bundled payments, hospitals should focus on understanding and preventing drivers of high cost., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Increased intravascular volume has been associated with protection from acute kidney injury (AKI), but in patients with congestive heart failure, venous congestion is associated with increased AKI. We tested the hypothesis that intraoperative venous congestion is associated with AKI after cardiac surgery., Methods: In patients enrolled in the Statin AKI Cardiac Surgery trial, venous congestion was quantified as the area under the curve (AUC) of central venous pressure (CVP) >12, 16, or 20 mm Hg during surgery (mm Hg min). AKI was defined using Kidney Disease Improving Global Outcomes (KDIGO) criteria and urine concentrations of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein 7 ([TIMP-2]⋅[IGFBP7]), a marker of renal stress. We measured associations between venous congestion, AKI and [TIMP-2]⋅[IGFBP7], adjusted for potential confounders. Values are reported as median (25th-75th percentile)., Results: Based on KDIGO criteria, 104 of 425 (24.5%) patients developed AKI. The venous congestion AUCs were 273 mm Hg min (81-567) for CVP >12 mm Hg, 66 mm Hg min (12-221) for CVP >16 mm Hg, and 11 mm Hg min (1-54) for CVP >20 mm Hg. A 60 mm Hg min increase above the median venous congestion AUC above each threshold was independently associated with increased AKI (odds ratio=1.06; 95% confidence interval [CI], 1.02-1.10; P=0.008; odds ratio=1.12; 95% CI, 1.02-1.23; P=0.013; and odds ratio=1.30; 95% CI, 1.06-1.59; P=0.012 for CVP>12, >16, and >20 mm Hg, respectively). Venous congestion before cardiopulmonary bypass was also associated with increased [TIMP-2]⋅[IGFBP7] measured during cardiopulmonary bypass and after surgery, but neither venous congestion after cardiopulmonary bypass nor venous congestion throughout surgery was associated with postoperative [TIMP-2]⋅[IGFBP7]., Conclusion: Intraoperative venous congestion was independently associated with increased AKI after cardiac surgery., (Copyright © 2021 British Journal of Anaesthesia. All rights reserved.)

Background: Data on out-of-ice implantation ischemia in heart transplant are scarce. We examined implantation time's impact on allograft dysfunction., Methods: We conducted a single-site retrospective review of all primary adult heart transplants from June 2012 to August 2019 for implantation warm ischemic time (WIT), defined as first atrial stitch to aortic crossclamp removal. Univariate regression was used to assess the relationship of perioperative variables to primary graft dysfunction (PGD) and to pulmonary artery pulsatility index (PAPi) at postoperative hour 24. A threshold of p < .10 was set for the inclusion of covariates in multivariate regression. Secondary analyses evaluated for consistency among alternative criteria for allograft dysfunction. A post hoc subgroup analysis examined WIT effect in prolonged total ischemia of 240 min or longer., Results: Complete data were available for 201 patients. Baseline characteristics were similar between patients who did and did not have WIT documented. In univariate analysis, female gender, longer total ischemic time (TIT), longer bypass time, greater blood transfusions, and pretransplant intensive care unit (ICU) care were associated with PGD, whereas longer bypass time was associated with worse PAPi and pretransplant ICU care was associated with better PAPi. In multivariate analysis, longer bypass time predicted PGD, and worse PAPi and preoperative ICU admission predicted PGD and better PAPi. Results did not differ in secondary or subgroup analyses., Conclusions: This study is one of few examining the functional impact of cardiac implantation ischemia. Results suggest allograft implantation time alone may not impact postoperative graft function, which was driven by intraoperative bypass duration and by preoperative ICU care, instead., (© 2020 Wiley Periodicals LLC.)

Since the 1960s, heart and lung transplantation has remained the optimal therapy for patients with end-stage disease, extending and improving quality of life for thousands of individuals annually. Expanding donor organ availability and immunologic compatibility is a priority to help meet the clinical demand for organ transplant. While effective, current immunosuppression is imperfect as it lacks specificity and imposes unintended adverse effects such as opportunistic infections and malignancy that limit the health and longevity of transplant recipients. In this review, we focus on donor macrophages as a new target to achieve allograft tolerance. Donor organ-directed therapies have the potential to improve allograft survival while minimizing patient harm related to global suppression of recipient immune responses. Topics highlighted include the role of ontogenically distinct donor macrophage populations in ischemia-reperfusion injury and rejection, including their interaction with allograft-infiltrating recipient immune cells and potential therapeutic approaches. Ultimately, a better understanding of how donor intrinsic immunity influences allograft acceptance and survival will provide new opportunities to improve the outcomes of transplant recipients., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Minimally invasive mitral valve surgery (mini-MVS) with hypothermic fibrillatory arrest has been associated with an increased risk of stroke. We aim to investigate the incidence, predictors, and outcomes of stroke in a large cohort of patient who underwent clampless mini-MVS. Between January 2008 and June 2017, we performed 1247 mini-MVSs. The clinical, operative, and postoperative outcomes were analyzed. Univariable and multivariable regression analyses were used to identify predictors of postoperative stroke. The median follow-up was 5.2 years (interquartile range 2.6-7.5). The etiology of mitral valve (MV) disease was degenerative (60.4%, n = 753), functional (12.8%, n = 160), rheumatic (8.7%, n = 109), endocarditis (3.1%, n = 39), and reoperative MV surgery (14.9%, n = 186). The overall incidence of postoperative neurologic event was 2.5% (n = 31/1247). Univariable predictors of stroke were a higher Society of Thoracic Surgeons mortality risk (6.0 ± 11.8% vs 3.3 ± 5.2%, P < 0.001), advanced age, (69.6 ± 12.1 years vs 63.0 ± 13.6 years, P = 0.002), female gender (71.0% vs 46.3%, P = 0.007), and a history of a cerebrovascular accident (22.6% vs 8.7%, P = 0.008). Stroke patients had a higher 30-day mortality (22.6% vs 1.6%, P < 0.001) and a higher risk for long-term mortality (hazard ratio = 5.56, 95% confidence interval [CI] 3.2-9.6, P < 0.001). Advanced age (odds ratio [OR] 2.1; 95% CI 1.1-4.0; P = 0.02), female gender (OR 2.3; 95% CI 0.9-5.2; P = 0.05), and history of cerebrovascular accident (OR 3.1; 95% CI 0.98-10.1; P = 0.05) remained as independent predictors of stroke in the multivariable analysis. Our decade-long experience indicates that clampless mini-MVS is associated with a low incidence of postoperative stroke, and that the predictors of stroke are not specific to this approach., (Published by Elsevier Inc.)

Objective: Chest computed tomography (CT) imaging is being increasingly used for potential lung donor assessment. However, the efficacy of CT imaging in this setting remains unknown. We hypothesize that chest CT imaging independently affects the decision-making process in donor lung utilization., Methods: We conducted a retrospective cohort study of all adult donation after brain death donors managed through our local organ procurement organization from June 2011 to November 2016. An experienced thoracic radiologist independently reviewed donor chest CT and chest x-ray images in a blinded, standardized manner to determine the presence of structural lung disease (eg, emphysema, interstitial lung disease [ILD]) and acute abnormalities (eg, traumatic lung injury [TLI]). Distinct models of lung utilization were fit to groups with initial partial pressure of oxygen (iPaO 2 ) ≤300 mm Hg (suboptimal) and iPaO 2 >300 mm Hg (optimal)., Results: The organ procurement organization managed 753 donors during the study period, with a lung utilization rate ([lung donors/all organ donors] × 100) of 36.5% (275 of 753). Four hundred forty-five (59.1%) donors received chest CT imaging, revealing emphysema (13.7%), ILD (2.5%), and TLI (7.2%). In univariate analysis, findings of TLI (odds ratio [OR], 2.23; 95% confidence interval [CI], 1.08-4.61) were positively associated with lung utilization, whereas findings of emphysema (OR, 0.18; CI, 0.08-0.40) were negatively associated with utilization. In multivariate analysis, CT findings of emphysema (OR, 0.21; CI 0.08-0.54) remained negatively associated with utilization. No potential donors with CT findings of ILD became lung donors. After controlling for chest x-ray findings, chest CT imaging findings of structural lung disease remained negatively associated with utilization (P = .0001). Lung utilization rate in the suboptimal and optimal iPaO 2 populations was 35.1% and 41.4%, respectively, and CT findings of emphysema had a significant association with nonutilization in both groups., Conclusions: In the evaluation of potential lung donors, chest CT imaging findings of structural lung disease, such as emphysema and ILD, have a significant negative association with lung utilization. Our findings suggest that chest CT imaging might be an important adjunct to conventional lung donor assessment criteria., (Copyright © 2018 The American Association for Thoracic Surgery. All rights reserved.)

Few studies have evaluated the use of phosphodiesterase-5 inhibitors (PDE5-i) for right ventricular (RV) dysfunction after left ventricular assist device (LVAD) implantation. The study purpose was to examine the impact of postoperative inpatient PDE5-i therapy on clinical outcomes in patients with LVADs. This single-center, retrospective cohort study screened 445 LVAD recipients between January 2011 and May 2015 for eligibility. Subjects receiving post-LVAD PDE5-i were compared with those who did not. The primary outcome was the proportion of all-cause hospital readmission at 30 days. Additional outcomes assessed included duration of intravenous inotrope or inhaled epoprostenol therapy, length of stay, duration of mechanical ventilation, overall survival, and improvement in the degree of postoperative RV dysfunction. Comparative analyses were performed before and after propensity score (PS) matching. Three-hundred and eighteen patients were included; 208 received post-LVAD inpatient PDE5-i and 110 patients did not. There was no difference in the rate of readmission at 30 days before or after PS matching. No significant differences were found between groups with regard to inotrope or epoprostenol duration, lengths of stay, duration of mechanical ventilation, overall survival, or improvement in the degree of RV dysfunction after PS matching. In the current study, the use of PDE5-i for adjunctive treatment of post-LVAD RV dysfunction was not associated with improved clinical outcomes.

Patients supported with extracorporeal life support (ECLS) can experience severe complications from increased left ventricular afterload. The intra-aortic balloon pump (IABP) is thought to unload the left ventricle (LV) and is routinely used with ECLS despite conflicting evidence of its clinical benefit. This retrospective, single-center study examined the effect of the simultaneous use of IABP and centrally cannulated ECLS on patient outcomes and provides new insights into IABP-mediated LV unloading. Thirty patients supported with central ECLS and IABP (extracorporeal life support-IABP group, ECLS-I) were compared with 30 patients with central ECLS alone (ECLS) for cardiogenic shock. Rates of survival to 30 days (p = 0.06) and intensive care unit (ICU) discharge (p = 0.17), and clinical outcomes were not significantly different between the two groups. In patients with pulmonary artery pressure monitoring, mean pulmonary artery (PA) pressure was significantly reduced after 24 (p = 0.007) and 48 hours (p = 0.002) in the ECLS-I group. No significant difference in PA pressure was observed in the ECLS group after 24 or 48 hours. The IABP has the ability to reduce pulmonary artery pressure in patients supported by central ECLS. However, this did not translate into improved survival or clinical outcomes in our population.

Although the incidence of driveline failure has been significantly reduced with the major modification to the driveline connection to the HeartMate II left ventricular assist device (LVAD), internal and external driveline damage continues to be a major reason for pump exchange or driveline repair. We report three cases of internal driveline damage under the costal margin and in the adjacent abdominal wall. All three cases developed occasional electrical disruptions 2-5 years after the original LVAD implant through the median sternotomy. Two patients underwent subcostal LVAD exchange and one had driveline externalization and repair. The driveline velour was well adhered to the costal margin and wire damage was found at the costal margin as well as the subsequent segment in the abdominal wall. Repeated ante-flex bending of the abdominal wall over years appeared to cause the chronic wear and tear of the vertically located driveline under the costal margin. This report will confirm a pitfall of the LVAD driveline location which can potentially cause driveline damage in the mid-to-long term.

Objective: Over the past 30 years, lung transplantation has emerged as the definitive treatment for end-stage lung disease. In 2005, the lung allocation score (LAS) was introduced to allocate organs according to disease severity. The number of transplants performed annually in the United States continues to increase as centers have become more comfortable expanding donor and recipient criteria and have become more facile with the perioperative and long-term management of these patients. We report a single-center experience with lung transplants, looking at patients before and after the introduction of LAS., Methods: We retrospectively reviewed 1500 adult lung transplants at a single center performed between 1988 and 2016. Patients were separated into 2 groups, before and after the introduction of LAS: group 1 (April 1988 to April 2005; 792 patients) and group 2 (May 2005 to September 2016; 708 patients)., Results: Differences in demographic data were noted over these periods, reflecting changes in allocation of organs. Group 1 patient average age was 48 ± 13 years, and 404 subjects (51%) were male. Disease processes included emphysema (52%; 412), cystic fibrosis (18.2%; 144), pulmonary fibrosis (16.1%; 128) and pulmonary vascular disease (7.2%; 57). Double lung transplant (77.7%; 615) was performed more frequently than single lung transplant (22.3%; 177). Group 2 average age was 50 ± 14 years, and 430 subjects (59%) were male. Disease processes included pulmonary fibrosis (46%; 335), emphysema (25.8%; 188), cystic fibrosis (17.7%; 127) and pulmonary vascular disease (1.6%; 11). Double lung transplant (96.2%; 681) was performed more frequently than single lung transplant (3.8%; 27). Overall incidence of grade 3 primary graft dysfunction (PGD) in group 1 was significantly lower at 22.1% (175) than in group 2 at 31.6% (230) (P < .001). Nonetheless, overall hospital mortality was not statistically different between the 2 groups (4.4% vs 3.5%; P < .4). Most notably, survival at 1 year was statistically different at 646 (81.6%) for group 1 and 665 (91.4%) for group 2 (P < .02)., Conclusions: Patient demographics over the study period have changed with an increased number of fibrotic patients transplanted. In addition, more aggressive strategies with donor/recipient selection appear to have resulted in a higher incidence of primary graft dysfunction. This does not, however, appear to affect patient survival on index hospitalization or at 1 year. In fact, we have observed a significant improvement in survival at 1 year in the more recent era. This observation suggests that continued expansion of possible donors and recipients, coupled with a more sophisticated understanding of primary graft dysfunction and long-term chronic rejection, can lead to increased transplant volume and prolonged survival., (Copyright © 2018 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Lung procurement for transplantation occurs in approximately 20% of brain dead donors and is a major impediment to wider application of lung transplantation. We investigated the effect of lung protective management at a specialized donor care facility on lung procurement rates from brain dead donors., Methods: Our local organ procurement organization instituted a protocol of lung protective management at a freestanding specialized donor care facility in 2008. Brain dead donors from 2001 to 2007 (early period) were compared with those from 2009 to 2016 (current period) for lung procurement rates and other solid-organ procurement rates using a prospectively maintained database., Results: An overall increase occurred in the number of brain dead donors during the study period (early group, 791; late group, 1,333; p < 0.0001). The lung procurement rate (lung donors/all brain dead donors) improved markedly after the introduction of lung protective management (early group, 157 of 791 [19.8%]; current group, 452 of 1,333 [33.9%]; p < 0.0001). The overall organ procurement rate (total number of organs procured/donor) also increased during the study period (early group, 3.5 organs/donor; current group, 3.8 organs/donor; p = 0.006)., Conclusions: Lung protective management in brain dead donors at a specialized donor care facility is associated with higher lung utilization rates compared with conventional management. This strategy does not adversely affect the utilization of other organs in a multiorgan donor., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: Surgery for type A aortic dissection is associated with a high operative mortality, and a variety of predictive risk factors have been reported. We hypothesized that a combination of risk factors associated with organ malperfusion and severe acidosis that are not currently documented in databases would be associated with a level of extreme operative risk that would warrant the consideration of treatment paradigms other than immediate ascending aortic surgery., Methods: Charts of patients undergoing repair of acute type A aortic dissection between January 1, 1996, and May 1, 2016, were queried for preoperative malperfusion, preoperative base deficit, pH, bicarbonate, cardiopulmonary resuscitation, severe aortic insufficiency, redo status, and preoperative intubation. Multivariable logistic analyses were considered to evaluate interested variables and operative mortality., Results: Between January 1, 1996, and May 1, 2016, 282 patients underwent surgical repair of type A aortic dissection. A total of 66 patients had a calculated base deficit -5 or greater. Eleven of 12 patients (92%) with severe acidosis (base deficit ≥-10) with malperfusion had operative mortality. No patient with severe acidosis with abdominal malperfusion survived. Multivariable analyses identified base deficit, intubation, congestive heart failure, dyslipidemia/statin use, and renal failure as predictors of operative death. The most significant predictor was base deficit -10 or greater (odds ratio, 9.602; 95% confidence interval, 2.649-34.799)., Conclusions: The combination of severe acidosis (base deficit ≥-10) with abdominal malperfusion was uniformly fatal. Further research is needed to determine whether the identification of extreme risk warrants consideration of alternate treatment options to address the cause of severe acidosis before ascending aortic procedures., (Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Patients supported with extracorporeal life support (ECLS) can experience severe complications from increased left ventricular (LV) afterload. The Impella (Abiomed, Danvers, MA) percutaneous ventricular assist device (PVAD) may offer an attractive option for unloading the LV in these patients. This study describes the efficacy and outcomes of PVAD use during ECLS compared with surgically placed LV vent., Methods: In this retrospective study, we reviewed patients supported by ECLS with PVAD or surgical LV vent for cardiogenic shock between April 2010 and May 2016. Included were 23 patients with PVADs and 22 with surgical vents. Patients' baseline characteristics, hemodynamic data, and outcomes were collected immediately preceding combined support initiation, at 48 hours, intensive care unit discharge, and 30 days., Results: After 48 hours, pulmonary artery diastolic pressure was significantly reduced in the PVAD (23.3 ± 8.4 vs 15.6 ± 4.2, p = 0.02) and surgical vent groups (20.1 ± 5.9 vs 15.6 ± 5.4, p = 0.01), and radiographic evidence of pulmonary edema was reduced or unchanged in 90% of PVAD patients and in 76% of surgical vent patients. The primary end points of survival to 30 days (43% vs 32%, p = 0.42) and intensive care unit discharge (35% vs 23%, p = 0.37) were not different between the two methods of support. The PVAD and surgical vent groups were also not significantly different in the rate of vascular complications or in the number decannulated from ECLS and transitioned to durable LV assist device., Conclusions: PVAD use in ECLS patients is an effective means of LV unloading and preventing worsened pulmonary edema, with outcomes and complications that are comparable to surgical LV vent., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We present the case of a 57 year old woman who developed pan-left ventricular thrombus while being supported with central extracorporeal membrane oxygenation support for cardiogenic shock. The left heart thrombus was evacuated emergently through the aortic valve, left atriotomy, and left ventriculotomy. The cannulation was then revised with the addition of a 36 French angled cannula in the apex of the left ventricle to decompress the ventricle, minimize stasis, and allow for any residual microthrombus to be trapped in the oxygenator membrane, not causing embolization. Once her neurological status was confirmed intact, a durable device was implanted. She recovered well without any neurological injury.

Left ventricular noncompaction (LVNC) may result in systolic left ventricular (LV) failure resulting in the need for heart transplantation. LV assist devices (LVAD) have been used to bridge these patients to transplantation; however, the extensive trabeculations found in these patients predispose them to thromboembolic events and pump thrombosis. We describe a patient with LVNC in whom an aggressive surgical approach was used to debride the LV cavity of trabeculations to successfully implant an LVAD., (© 2017 Wiley Periodicals, Inc.)

Thoracoscopic lobectomy has become an accepted, safe, and oncologically sound procedure compared with open lobectomy. Several studies have reported that it reduces the length of stay, postoperative pain, and postoperative complications, including air leaks. Although there are specific technical considerations that must be taken into account, it is increasingly becoming the preferred method of anatomic lobectomy. Surgeons should be encouraged to embrace the minimally invasive strategy, which may be learned in courses using novel simulation techniques. Future directions suggest that this technique will be expanded to address even the most challenging thoracic procedures., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Aneurysms of the transverse aortic arch, especially those involving the mid to distal arch, are technically challenging to repair with conventional open techniques. We present our results with a combined open/endovascular approach ("hybrid repair") in such patients., Methods: From August 11, 2005, to September 18, 2008, 28 patients underwent hybrid arch repair. For patients (n = 9) with distal arch aneurysms but 2 cm or more of proximal landing zone (PLZ) distal to the innominate artery, right to left carotid-carotid bypass was performed to create a PLZ by covering the left carotid origin. For patients (n = 12) with mid arch aneurysms but 2 cm or more of PLZ in the ascending aorta, proximal ascending aorta-based arch debranching was performed. For patients (n = 7) with arch aneurysms with no adequate PLZ ("mega aorta") but adequate distal landing zone, a stage 1 elephant trunk procedure was performed to create a PLZ. For the first two groups, endovascular aneurysm exclusion and debranching were performed concomitantly, whereas the procedures were staged for the group undergoing an initial elephant trunk procedure., Results: Mean patient age was 64 +/- 13 years. Primary technical success rate was 100%. Thirty-day/in-hospital rates of death, stroke, and permanent paraplegia/paresis were 0%, 0%, and 3.6% (n = 1), respectively. At a mean follow-up of 14 +/- 11 months, there have been no late aortic-related events. Two patients (7%) required secondary endovascular reintervention for a type 1 endovascular leak. No patient has a type 1 or 3 endovascular leak at latest follow-up., Conclusions: Hybrid repair of transverse aortic arch aneurysms appears safe and effective at midterm follow-up and may represent a technical advance in the treatment of this pathology.

In lung transplants necessitating cardiopulmonary bypass (CPB), aprotinin has been shown to decrease transfusion requirements. More recently, off-pump transplantation has become the standard of care. The efficacy of aprotinin use in this population has yet to be definitively examined. We completed a retrospective review of all adult OP-BOLTs performed between January 2000 and January 2006 at a single university center (n=215). Aprotinin use was determined by the attending anesthesiologist or surgeon. It was administered at the time of induction. The primary outcome was total blood products utilized in terms of units transfused during postoperative days 0, 1 and 2. One-hundred and one patients received aprotinin and 114 did not. An overall analysis of all of the patients in this study demonstrated a trend towards statistical significance for reduced total blood product transfusion for the aprotinin group compared to the non-aprotinin group (P=0.13). A subgroup analysis was performed in relation to each diagnosis. The use of aprotinin was associated with a significant reduction in peri-operative total blood products transfused in COPD patients (P=0.03) undergoing OP-BOLT. Subgroup analysis demonstrated that the use of aprotinin in the COPD population did result in a statistically significant decrease in total blood products transfused, specifically the total number of units of packed red blood cells given. These findings suggest that aprotinin administration should be considered for all patients undergoing OP-BOLT to reduce exposure to blood products and potential immune sensitization and infectious complications.

Background: Chronic aspiration associated with gastro oesophageal reflux disease (GERD) is thought to play a substantial role in the development of asthma, the incidence of which is dramatically increasing in industrially developed countries. The majority of data examining the association between aspiration and asthma has been obtained from epidemiological studies, which show that between 50 and 90% of individuals with asthma experience some element of GERD. This study describes the effect of chronic aspiration on a model of experimentally induced airway hypersensitivity in Balb/c mice., Materials and Methods: Four experimental groups were utilized: Aspiration/Asthma, Sham/Asthma, Aspiration/Sham and Sham/Sham. Mice were sensitized with aerosolized 1% ovalbumin on days 1 to 10 (sensitization phase), followed by repeated exposure on days 31 to 40 (challenge phase). Aspiration events occurred on days 1, 8,15, 22, 29, 36, 43 and 50. Animals were sacrificed on days 56 and 57., Results: Chronic aspiration of 10 microL of murine gastric fluid per week for eight weeks produced an injury pattern distinct from that of acute aspiration, with lung injury characterized by hyperplasia, neutrophil infiltration of the bronchioles and relative parenchymal sparing. Aspiration during induction of ovalbumin-induced airway hypersensitivity was associated with a trend toward decreased production of antiovalbumin IgG, antiovalbumin IgE, and total IgE. Further, aspiration induced a substantial and significant increase in antiovalbumin IgG1/IgG2a ratios, consistent with a shift toward a predominantly Th2 response., Conclusion: These findings indicate that chronic aspiration has a profound effect on the nature of the immune response to aerosolized allergens in a model of experimentally induced airway hypersensitivity.

Long-term survival of a pulmonary allograft is currently hampered by obliterative bronchiolitis (OB), a form of chronic rejection that is unique to lung transplantation. While tracheobronchial aspiration from gastroesophageal reflux disease (GERD) has clinically been associated with OB, no experimental model exists to investigate this problem. Using a WKY-to-F344 rat orthotopic left lung transplant model, the effects of chronic aspiration on pulmonary allograft were evaluated. Recipients received cyclosporine with or without 8 weekly aspirations of gastric fluid into the allograft. Six (66.7%) of 9 allografts with aspiration demonstrated bronchioles with surrounding monocytic infiltrates, fibrosis and loss of normal lumen anatomy, consistent with the development of OB. In contrast, none of the allografts without aspiration (n = 10) demonstrated these findings (p = 0.002). Of the grafts examined grossly, 83% of the allografts with chronic aspiration but only 20% without aspiration appeared consolidated (p = 0.013). Aspiration was associated with increased levels of IL-1 alpha, IL-1 beta, IL-6, IL-10, TNF-alpha and TGF-beta in BAL and of IL-1 alpha, IL-4 and GM-CSF in serum. This study provides experimental evidence linking chronic aspiration to the development of OB and suggests that strategies aimed at preventing aspiration-related injuries might improve outcomes in clinical lung transplantation.

Background: Gastroesophageal reflux is associated with lung transplantation (LT) and bronchiolitis obliterans syndrome, limiting allograft functional longevity. LT patients may also develop post-operative oropharyngeal dysphagia, exposing the allograft to further risk. However, the magnitude of this problem is unknown. We examined LT recipients post-operatively for swallowing disorders and correlated findings with pre- and post-operative variables., Methods: Two hundred sixty-three LT patients (January 2001 to July 2005) at a single center were retrospectively reviewed. Each underwent clinical swallowing assessment. Provocative swallowing evaluation (SE) was performed in 149 patients (Group 1); 114 patients did not receive formal SE (Group 2). SE studies were considered positive with laryngeal penetration (PEN) or tracheal aspiration (ASP) of thin liquids. Groups were compared with respect to pre-, peri- and post-operative variables using analysis of variance (ANOVA) and chi-square tests., Results: After LT, 56.7% of patients underwent post-operative SE (mean 19 +/- 20 days), most of whom (87.9%) had fiber-optic endoscopic studies. SE was positive for PEN or ASP in 70.5% (n = 105). Aspiration occurred in 63.8% (n = 67) of positive SEs; 77.6% (n = 52) of ASP assessments were clinically silent. Pre-operative gastroesophageal reflux disease (GERD) and post-operative complications, including vocal cord paresis, pleural processes, venous thromboses and severe rejection episodes, were more common among Group 1. Group 2 had a significantly reduced hospital length of stay (p = 0.004)., Conclusions: Prospective SE identified strikingly high rates of dysphagia after LT. Because many of these deficits are silent, aggressive pulmonary toilet is especially important after post-operative LT. Pre-operative SE may clarify those at increased risk for new-onset oropharyngeal dysphagia after LT.

Expression of MHC class II by donor-derived APCs has been shown to be important for allograft rejection. It remains controversial, however, whether nonhemopoietic cells, such as vascular endothelium, possess Ag-presenting capacity to activate alloreactive CD4(+) T lymphocytes. This issue is important in transplantation, because, unlike hemopoietic APCs, allogeneic vascular endothelium remains present for the life of the organ. In this study we report that cytokine-activated vascular endothelial cells are poor APCs for allogeneic CD4(+) T lymphocytes in vitro and in vivo despite surface expression of MHC class II. Our in vitro observations were extended to an in vivo model of allograft rejection. We have separated the allostimulatory capacity of endothelium from that of hemopoietic APCs by using bone marrow chimeras. Hearts that express MHC class II on hemopoietic APCs are acutely rejected in a mean of 7 days regardless of the expression of MHC class II on graft endothelium. Alternatively, hearts that lack MHC class II on hemopoietic APCs are acutely rejected at a significantly delayed tempo regardless of the expression of MHC class II on graft endothelium. Our data suggest that vascular endothelium does not play an important role in CD4(+) direct allorecognition and thus does not contribute to the vigor of acute rejection.

Mesenchymal progenitor cells, isolated from adult bone marrow, have been shown to have utility for autologous tissue engineering. The possibility of isolating from the fetal hematopoietic system a cell population with similar potential, which could be used for autologous reconstruction of prenatally diagnosed congenital anomalies, has not been explored to date. Liver stromal cells isolated from a portion of the right lateral hepatic lobe of midgestation fetal lambs were expanded in vitro. Passage 1 cells displayed a uniform fibroblast-like morphology but could be induced to differentiate into skeletal muscle, adipocytes, chondrocytes, and endothelial cells by selective medium supplementation. By manipulating the extracellular matrix in vitro, spontaneously contracting cardiac myocyte-like cells could be generated as well. Multilineage differentiation was confirmed by morphology, protein expression, and upregulation of lineage-specific mRNA. The potential for engineering myocardial tissue was then investigated by transplanting early-passage progenitor cells, organized on a three-dimensional matrix, into the ventricle of an immunocompromised rat utilizing a previously described model of left ventricular tissue engineering. Survival, incorporation into the host myocardium, and cardiomyocytic differentiation of the transplanted cells were confirmed. We have demonstrated that mesenchymal progenitor cells with multilineage potential can be isolated from the fetal liver and have potential utility for autologous tissue engineering.

Ischemic cardiomyopathy leading to congestive heart failure remains the leading source of morbidity and mortality in Western society and medical management of this condition offers only palliative treatment. While allogeneic heart transplantation can both extend and improve the quality of life for patients with end-stage heart failure, this therapeutic option is limited by donor organ shortage. Even after successful transplantation, chronic cardiac rejection in the form of cardiac allograft vasculopathy can severely limit the lifespan of the transplanted organ. Current experimental efforts focus on cellular cardiomyoplasty, myocardial tissue engineering, and myocardial regeneration as alternative approaches to whole organ transplantation. Such strategies may offer novel forms of therapy to patients with end-stage heart failure within the near future.

Since the finding that the mdx mouse diaphragm, in contrast to limb muscles, undergoes progressive degeneration analogous to that seen in Duchenne muscular dystrophy, the relationship between the workload on a muscle and the pathogenesis of dystrophy has remained controversial. We increased the work performed by the mdx mouse diaphragm in vivo by tracheal banding and evaluated the progression of dystrophic changes in that muscle. Despite the establishment of dramatically increased respiratory workload and accelerated myofiber damage documented by Evans blue dye, no change in the pace of progression of dystrophy was seen in banded animals vs. unbanded, sham-operated controls. At the completion of the study, more centrally nucleated fibers were evident in the diaphragms of banded mdx mice than in sham-operated mdx controls, indicating that myofiber regeneration increases to meet the demands of the work-induced damage. These data suggest that there is untapped regenerative capacity in dystrophin-deficient muscle and validates experimental efforts aimed at augmenting regeneration within skeletal muscle as a therapeutic strategy in the treatment of dystrophinopathies.

Despite several studies examining the contribution of allorecognition pathways to acute and chronic rejection of vascularized murine allografts, little data describing activation of alloreactive T cells by mouse vascular endothelium exist. We have used primary cultures of resting or IFN-gamma-activated C57BL/6 (H-2(b)) vascular endothelial cells as stimulators and CD8(+) T lymphocytes isolated from CBA/J (H-2(k)) mice as responders. Resting endothelium expressed low levels of MHC class I, which was markedly up-regulated after activation with IFN-gamma. It also expressed moderate levels of CD80 at a resting state and after activation. Both resting and activated endothelium were able to induce proliferation of unprimed CD8(+) T lymphocytes, with proliferation noted at earlier time points after coculture with activated endothelium. Activated endothelium was also able to induce proliferation of CD44(low) naive CD8(+) T lymphocytes. Activated CD8(+) T lymphocytes had the ability to produce IFN-gamma and IL-2, acquired an effector phenotype, and showed up-regulation of the antiapoptotic protein Bcl-x(L). Treatment with CTLA4-Ig led to marked reduction of T cell proliferation and a decrease in expression of Bcl-x(L). Moreover, we demonstrate that nonhemopoietic cells such as vascular endothelium induce proliferation of CD8(+) T lymphocytes in a B7-dependent fashion in vivo. These results suggest that vascular endothelium can act as an APC for CD8(+) direct allorecognition and may, therefore, play an important role in regulating immune processes of allograft rejection.

Background: Cytotoxic T lymphocyte (CTL)-mediated destruction of allogeneic vascular endothelium is important in the pathogenesis of both acute and chronic allograft rejection. Despite the importance of this phenomenon, the effector mechanisms responsible for endothelial cell killing are not well defined, and conflicting conclusions have been reached based on variation in experimental methodology., Methods: We used a recently described method for isolating mouse vascular endothelium to evaluate endothelial cell lysis by CTLs. Endothelial cell destruction was assessed in vitro both by 51Cr release and DNA fragmentation using wild-type and lpr (Fas deficient) endothelium of C3H/HeJ (H2(k)) mice by MHC alloantigen-specific T cells of wild-type, gld (Fas ligand deficient), and perforin-deficient mice on a C57BL/6 (H2(b)) background., Results: Although maximal lysis of 56.6+/-0.8% was seen when using wild-type targets and effectors, only a moderate decrease in apoptosis to 37.6+/-4.0% was detected when the Fas/Fas ligand death receptor pathway was eliminated. This decrease in cytotoxicity occurred despite the preserved functional capacity of this pathway. Alternatively, a significant decrease in cytotoxicity to 17.4+/-4.7% was seen when the perforin/granzyme exocytosis pathway was eliminated., Conclusions: These data indicate that CTLs destroy vascular endothelium primarily by the perforin/granzyme exocytosis pathway with only a minor contribution to apoptosis by the Fas/Fas ligand death receptor pathway. These data are critical for the proper interpretation of studies evaluating acute and chronic allograft rejection and for the design of rational strategies to ameliorate vascular injury concomitant to the rejection process.

Despite evidence that human non-hematopoietic cells, such as vascular endothelium, can activate allogeneic T lymphocytes in vitro, the prevailing view has been that hematopoietic antigen-presenting cells are required to trigger alloimmune responses in vivo. Here we report that mouse non-hematopoietic cells activate alloreactive CD8+ T lymphocytes in vitro and in vivo. We also show that vascularized cardiac allografts are acutely rejected via CD8+ direct allorecognition even if the alloantigen is not presented by hematopoietic professional antigen-presenting cells. Because activation of alloreactive CD8+ T cells by donor-type non-hematopoietic cells can continue for the life of the allograft, these findings present a new clinically relevant mechanism of allorecognition and should be taken into consideration when developing strategies to prevent allograft vasculopathy or to induce tolerance.

Herpes simplex virus type 1 (HSV-1) variant 1716 is deleted in the gene encoding ICP34.5 and is neuroattenuated after intracranial inoculation of mice. Although the mechanism of attenuation is unclear, this property has been exploited to eliminate experimental brain tumours. Previously, it was shown that infectious 1716 was recoverable for up to 3 days after intracranial inoculation suggesting that there may be limited replication in the central nervous system (CNS). Here it is demonstrated that 1716 replicates in specific cell types (predominantly CNS ependymal cells) of BALB/c mice, using immunohistochemical, immunofluorescence, in situ hybridization and virus titration studies. While 1716-infected mice exhibited no overt signs of encephalitis, histological analysis showed a persistent loss of the ependymal lining. Thus, although ICP34.5-deficient viruses are neuroattenuated, they do retain the ability to replicate in and destroy the ependyma of the murine CNS. A detailed understanding of the mechanism(s) of neuroattenuation and limited replication could lead to the rational design of safe HSV vectors for cancer and gene therapy in the CNS.