Relation of body mass index to long-term survival and cardiac remodelling for patients undergoing mitral valve replacement surgery.

BACKGROUND AND AIMS: Studies have demonstrated that obesity is paradoxically associated with reduced mortality following cardiac surgery. However, these studies have treated various types of cardiac surgery as a single entity. With mitral valve (MV) surgeries being the fastest-growing cardiac surgical interventions in North America, the purpose of this study was to identify the impact of body mass index (BMI) on long-term survival and cardiac remodelling of patients undergoing MV replacement (MVR). METHODS AND RESULTS: In this retrospective, single-center study, 1071 adult patients who underwent an MVR between 2004 and 2018 were stratified into five BMI groups (<20, 20-24.9, 25-29.9, 30-34.9, >35). Cox proportional hazard regression models were used to determine the association between BMI and all-cause mortality. Patients who were underweight had significantly higher all-cause mortality rates at the longest follow-up (median 8.2 years) than patients with normal weight (p = 0.01). Patients who were in the obese group had significantly higher readmission rates due to myocardial infarction (MI) at the longest follow-up (p = 0.017). Subgroup analysis revealed a significant increase in long-term all-cause mortality for female patients who were underweight. Significant changes in left atrial size, mitral valve peak and mean gradients were seen in all BMI groups. CONCLUSIONS: For patients undergoing mitral valve replacement, BMI is unrelated to operative outcomes except for patients who are underweight.

Impact of the COVID-19 pandemic on esophageal cancer resource allocation: a systematic review.

Background: The coronavirus disease 2019 (COVID-19) pandemic challenged global infrastructure. Healthcare systems were forced to reallocate resources toward the frontlines. In this systematic review, we analyze the impact of resource reallocation during the COVID-19 pandemic on the diagnosis, management, and outcomes of esophageal cancer (EC) patients. Methods: PubMed and Embase were systematically searched for articles investigating the impact of the COVID-19 pandemic on EC patients. Of the 1,722 manuscripts initially screened, 23 met the inclusion criteria. Results: Heterogeneity of data and outcomes reporting prohibited aggregate analysis. Reduced detection of EC and considerable variability in disease stage at presentation were noted during the COVID-19 pandemic. EC patients experienced delays in diagnostic and preoperative staging investigations but surgical resection was not associated with greater short-term morbidity or mortality. Modeling the impact of pandemic-related delays in EC care predicts significant reductions in survival with associated economic losses in the coming years. Conclusions: Amidst resource scarcity during the COVID-19 pandemic, the multidisciplinary management of patients with EC was affected at multiple stages in the care pathway. Although the complete ramifications of reductions in EC diagnosis and delays in care remain unclear, EC surgery was able to safely continue as a result of collaboration between centers, strict adherence to COVID-19 protective measures, and reallocation of healthcare resources towards the same. Ultimately, when healthcare systems are pushed to the brink, the downstream consequences of resource reallocation require judicious analysis to optimize overall patient outcomes.

The Effects of Oxygen-Derived Free-Radical Scavengers During Normothermic Ex-Situ Heart Perfusion.

Oxidative stress occurs during ex-situ heart perfusion (ESHP) and may negatively affect functional preservation of the heart. We sought to assess the status of key antioxidant enzymes during ESHP, and the effects of augmenting these antioxidants on the attenuation of oxidative stress and improvement of myocardial and endothelial preservation in ESHP. Porcine hearts were perfused for 6 hours with oxygen-derived free-radical scavengers polyethylene glycol (PEG)-catalase or PEG-superoxide dismutase (SOD) or with naive perfusate (control). The oxidative stress-related modifications were determined in the myocardium and coronary vasculature, and contractile function, injury, and endothelial integrity were compared between the groups. The activity of key antioxidant enzymes decreased and adding catalase and SOD restored the enzyme activity. Cardiac function and endothelial integrity were preserved better with restored catalase activity. Catalase and SOD both decreased myocardial injury and catalase reduced ROS production and oxidative modification of proteins in the myocardium and coronary vasculature. The activity of antioxidant enzymes decrease in ESHP. Catalase may improve the preservation of cardiac function and endothelial integrity during ESHP. While catalase and SOD may both exert cardioprotective effects, unbalanced SOD and catalase activity may paradoxically increase the production of reactive species during ESHP.

Randomized trial of routine versus on-demand intraoperative extracorporeal membrane oxygenation in lung transplantation: A feasibility study.

In most centers, extracorporeal membrane oxygenation (ECMO) is the preferred means to provide cardiopulmonary support during lung transplantation. However, there is controversy about whether intraoperative venoarterial (VA) ECMO should be used routinely or selectively. A randomized controlled trial is the best way to address this controversy. In this publication, we describe a feasibility study to assess the practicality of a protocol comparing routine versus selective VA-ECMO during lung transplantation. This prospective, single-center, randomized controlled trial screened all patients undergoing lung transplantation. Exclusion criteria include retransplantation, multiorgan transplantation, and cases where ECMO is mandatory. We determined that the trial would be feasible if we could recruit 19 participants over 6 months with less than 10% protocol violations. Based on the completed feasibility study, we conclude that the protocol is feasible and safe, giving us the impetus to pursue a multicenter trial with little risk of failure due to low recruitment.

The Use of Sodium-Glucose Cotransporter-2 Inhibitors in Coronary Revascularization: Where Are We Now? A Systematic Review.

INTRODUCTION: Diabetes and coronary artery disease are two common conditions that often co-exist. In recent years, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to provide significant cardioprotective benefits, especially among patients with heart failure. OBJECTIVE: In this systematic review, we look to identify the outcomes SGLT2i use in patients undergoing coronary revascularization. METHODS: Pubmed and Embase were systematically searched for articles describing the outcomes of patients taking SGLT2i and undergoing coronary revascularization. 834 titles and abstracts were screened, 42 full texts were reviewed, and 18 studies were found to meet the inclusion criteria and were included in this review. RESULTS: For patients undergoing coronary artery bypass grafting and percutaneous coronary intervention, the use of SGLT2i resulted in reductions in mortality, hospitalization for heart failure, and improved blood glucose; however, these benefits were not consistently reported in the literature. Reduced inflammatory markers and positive cardiac remodeling were identified among patients taking SGLT2i. CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been demonstrated to provide benefits for patients with heart failure along with a host of positive modulatory effects on the cardiovascular system, including reductions in inflammatory properties, hypertension, and left ventricular volume load. Given the clear benefit provided by SGLT2i to patients with cardiovascular disease and a host of positive properties that are expected to be protective for patients with ischemic heart disease, future investigation into the relationship between SGLT2i and outcomes for patients undergoing revascularization is imperative.

Resource allocation during the coronavirus disease 2019 pandemic and the impact on patients with lung cancer: a systematic review.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic resulted in unprecedented tolls on both economies and human life. Healthcare resources needed to be reallocated away from the care of patients and towards supporting the pandemic response. In this systematic review, we explore the impact of resource allocation during the COVID-19 pandemic on the screening, diagnosis, management and outcomes of patients with lung cancer during the pandemic. METHODS: PubMed and Embase were systematically searched for articles investigating the impact of the COVID-19 pandemic on patients with lung cancer. Of the 1605 manuscripts originally screened, 47 studies met the inclusion criteria. RESULTS: Patients with lung cancer during the pandemic experienced reduced rates of screening, diagnostic testing and interventions but did not experience worse outcomes. Population-based modelling studies predict significant increases in mortality for patients with lung cancer in the years to come. CONCLUSIONS: Reduced access to resources during the pandemic resulted in reduced rates of screening, diagnosis and treatment for patients with lung cancer. While significant differences in outcomes were not identified in the short term, ultimately the effects of the pandemic and reductions in cancer screening will likely be better delineated in the coming years. Future consideration of the long-term implications of resource allocation away from patients with lung cancer with an attempt to provide equitable access to healthcare and limited interruptions of patient care may help to provide the best care for all patients during times of limited resources.

Aging Is Associated With Organ-Specific Alterations in the Level and Expression Pattern of von Willebrand Factor.

BACKGROUND: VWF (von Willebrand factor) is an endothelial-specific procoagulant protein with a major role in thrombosis. Aging is associated with increased circulating levels of VWF, which presents a risk factor for thrombus formation. METHODS: Circulating plasma, cellular protein, and mRNA levels of VWF were determined and compared in young and aged mice. Major organs were subjected to immunofluorescence analyses to determine the vascular pattern of VWF expression and the presence of platelet aggregates. An in vitro model of aging, using extended culture time of endothelial cells, was used to explore the mechanism of age-associated increased VWF levels. RESULTS: Increased circulating plasma levels of VWF with elevated levels of larger multimers, indicative of VWF functional activity, were observed in aged mice. VWF mRNA and cellular protein levels were significantly increased in the brains, lungs, and livers but not in the kidneys and hearts of aged mice. Higher proportion of small vessels in brains, lungs, and livers of aged mice exhibited VWF expression compared with young, and this was concomitant with increased platelet aggregate formation. Prolonged culture of endothelial cells resulted in increased cell senescence that correlated with increased VWF expression; VWF expression was specifically detected in senescent cultured endothelial cells and abolished in response to p53 knockdown. A significantly higher proportion of VWF expressing endothelial cells in vivo exhibited senescence markers SA-ß-Gal (senescence-associated ß-galactosidase) and p53 in aged mouse brains compared with that of the young. CONCLUSIONS: Aging elicits a heterogenic response in endothelial cells with regard to VWF expression, leading to organ-specific increase in VWF levels and alterations in vascular tree pattern of expression. This is concomitant with increased platelet aggregate formation. The age-associated increase in VWF expression may be modulated through the process of cell senescence, and p53 transcription factor contributes to its regulation.

Relative Lung Perfusion on Ventilation-Perfusion Scans After Double Lung Transplant.

BACKGROUND: Pulmonary blood flow can be assessed on ventilation-perfusion (VQ) scan with relative lung perfusion, with a 55% to 45% (or 10%) right-to-left differential considered normal. We hypothesized that wide perfusion differential on routine VQ studies at 3 mo posttransplant would be associated with an increased risk of death or retransplantation, chronic lung allograft (CLAD), and baseline lung allograft dysfunction. METHODS: We conducted a retrospective cohort study on all patients who underwent double-lung transplant in our program between 2005 and 2016, identifying patients with a wide perfusion differential of >10% on a 3-mo VQ scan. We used Kaplan-Meier estimates and proportional hazards models to assess the association between perfusion differential and time to death or retransplant and time to CLAD onset. We used correlation and linear regression to assess the relationship with lung function at time of scan and with baseline lung allograft dysfunction. RESULTS: Of 340 patients who met inclusion criteria, 169 (49%) had a relative perfusion differential of ≥ 10% on a 3-mo VQ scan. Patients with increased perfusion differential had increased risk of death or retransplantation ( P = 0.011) and CLAD onset ( P = 0.012) after adjustment for other radiographic/endoscopic abnormalities. Increased perfusion differential was associated with lower lung function at time of scan. CONCLUSIONS: Wide lung perfusion differential was common after lung transplant in our cohort and associated with increased risk of death, poor lung function, and CLAD onset. The nature of this abnormality and its use as a predictor of future risk warrant further investigation.

The impact of resource allocation during the COVID-19 pandemic on cardiac surgical practice and patient outcomes: a systematic review.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has shaken the world and placed enormous strain on healthcare systems globally. In this systematic review, we investigate the effect of resource allocation on cardiac surgery programs and the impact on patients awaiting elective cardiac surgery. METHODS: PubMed and Embase were systematically searched for articles published from 1 January 2019 to 30 August 2022. This systematic review included studies investigating the impact of the COVID-19 pandemic on resource allocation and the subsequent influence on cardiac surgery outcomes. A total of 1676 abstracts and titles were reviewed and 20 studies were included in this review. RESULTS: During the COVID-19 pandemic, resources were allocated away from elective cardiac surgery to help support the pandemic response. This resulted in increased wait times for elective patients, increased rates of urgent or emergent surgical intervention and increased rates of mortality or complications for patients awaiting or undergoing cardiac surgery during the pandemic. CONCLUSIONS: While the finite resources available during the pandemic were often insufficient to meet the needs of all patients as well as the influx of new COVID-19 patients, resource allocation away from elective cardiac surgery resulted in prolonged wait times, more frequent urgent or emergent surgeries and negative impacts on patient outcomes. Understanding the impacts of delayed access to care with regards to urgency of care, increased morbidity and mortality and increased utilization of resources per indexed case needs to be considered to navigate through pandemics to minimize the lingering effects that continue to negatively impact patient outcomes.

Persistent methicillin-resistant Staphylococcus aureus bacteremia from an infected superior vena cava thrombus.

Infection is among the leading causes of mortality for patients with end-stage renal disease. The placement of catheters for hemodialysis are common culprits of infection and have been associated with the development of complications such as venous thrombosis, bacteremia and thromboembolism. Calcification of a venous thrombus is a rare complication and infection of a right-sided thrombus can result in life-threatening septicemia and embolic complications. Herein, we describe the case of a 46-year-old patient found to have a calcified superior vena cava thrombus and bacteremia refractory to antibiotic therapy requiring surgical intervention under circulatory arrest to remove the infected thrombus gaining infectious source control and preventing future complications.

Infection is among the leading causes of mortality for patients with end-stage renal disease. The placement of catheters for dialysis are common culprits of infection and have been associated with the development of complications such as blood clotting in the veins and bacteria in the blood. Calcification of a venous blood clot is a rare complication and infection of a venous blood clot can result in life-threatening blood stream infection and dislodgement of clots. Herein, we describe the case of a 46-year-old patient found to have a calcified superior vena cava clot and a blood stream infection resistant to antibiotic therapy requiring surgical intervention to remove the infected clot gaining infectious source control and preventing future complications.

The influence of renal disease on outcomes and cardiac remodeling following surgical mitral valve replacement.

OBJECTIVES: Chronic kidney disease (CKD) is increasingly prevalent in patients undergoing mitral valve replacement (MVR). While CKD is known to result in suboptimal outcomes for patients with mitral valve disease, there is limited literature evaluating the long-term outcomes and cardiac remodeling of patients with CKD undergoing MVR. We present the first analysis coupling long-term outcomes of combined morbidity, mortality, and cardiac remodeling post-MVR in patients with CKD. METHODS: Patients with varying degrees of CKD undergoing MVR from 2004 to 2018 were compared. Patients were grouped by estimated glomerular filtration rate (eGFR) > 90 mL/min/1.73m2 (n = 109), 60-89 mL/min/1.73m2 (450), 30-59 mL/min/1.73m2 (449), < 30 mL/min/1.73m2 (60). The primary outcome was mortality. Secondary outcomes included measures of postoperative morbidity and cardiac remodeling. RESULTS: One-year mortality was significantly increased in patients with eGFR < 30 (p = 0.023). Mortality at 7 years was significantly increased in patients with eGFR < 30 mL/min/1.73m2 (p < 0.001). Multivariable regression analysis of 7-year all-cause mortality indicated an eGFR of 15 mL/min/1.73m2 (HR 4.03, 95% CI 2.54-6.40) and 30 mL/min/1.73m2 (HR 2.17 95% CI 1.55-3.05) were predictive of increased mortality. Reduced eGFR predicted the development of postoperative sepsis (p = 0.002), but not other morbidities. Positive cardiac remodeling of the left ventricle, left atrium, and valve gradients were identified postoperatively for patients with eGFR > 30 mL/min/1.73m2 while patients with eGFR < 30 mL/min/1.73m2 did not experience the same changes. CONCLUSIONS: CKD is predictive of inferior clinical and echocardiographic outcomes in patients undergoing MVR and consequently requires careful preoperative consideration and planning. Further investigation into optimizing the postoperative outcomes of this patient population is necessary.

Quantifying the immune response to a tissue-engineered porcine extracellular matrix.

Aim: Structural valvular deterioration of xenogenic heart valve replacements is thought to be due to a chronic immune response. We sought to engineer porcine extracellular matrix that elicits minimal inflammatory immune response. Materials & methods: Whole blood, bone marrow and pericardium were collected from patients undergoing elective cardiac surgery. Porcine extracellular matrix was decellularized, reseeded with homologous mesenchymal stem cells and exposed to whole blood. Results: DAPI stain confirmed the absence of cells after decellularization, and presence of mesenchymal stem cells after recellularization. There was a significant reduction in IL-1ß and TNF-α production in the recellularized matrix. Conclusion: Recellularization of porcine matrix is successful at attenuating the xenogenic immune response and may provide a suitable scaffold to address the current limitations of prosthetic heart valve replacements.

Deterioration of tissue heart valve replacements is thought to be due to a chronic immune response. We sought to remove cells from a pig derived tissue and replace those cells with human stem cells to create a scaffold that results in a reduced immune response. Whole blood, bone marrow and pericardium were collected from patients undergoing elective cardiac surgery. The pig derived tissue had the cells removed, were replaced with human stem cells and exposed to whole blood. Tissue stain confirmed the absence of cells after removal, and presence of stem cells after replacement of cells. There was a significant reduction in markers of immune response in the recellularized tissue. Removal of cells from pig derived tissue and replacement with human stem cells is successful at reducing the immune response to animal tissue and may provide a suitable scaffold to address the current limitations of heart valve replacement options.

Anomalous left anterior descending coronary artery arising from the right coronary artery: a case report.

Congenital anomalous coronary artery origins are rare, with a prevalence of 0.24-1.6%. Common configurations include left circumflex arising from the right coronary (RCA), left main coronary arising from the right coronary sinus and independent ostia for the left anterior descending (LAD) and left circumflex. One rare configuration that is not well described is the LAD arising from the RCA. A 68-year-old patient presented with non-ST elevation myocardial infarction, underwent coronary artery bypass grafting and was found to have a patent LAD arising from the RCA. In patients presenting with coronary artery disease and anomalous coronary anatomy, careful preoperative planning and intraoperative attention to patient anatomy is essential in identifying high-risk coronary anomalies and providing the correct and optimal treatments for these patients.

Abnormal origins of the heart arteries are rare, affecting an estimated 0.24­1.6% of the general population. The two main coronary arteries are the right coronary artery (RCA) and left main coronary artery, which branches into the left anterior descending (LAD) and left circumflex artery. While several configurations have been described, one exceedingly rare configuration is the LAD arising from the RCA. A 68-year-old patient presenting with an acute coronary event undergoing coronary artery bypass grafting was found to have an LAD arising from the RCA. Patients presenting with coronary artery disease and abnormal coronary anatomy require careful preoperative planning and intraoperative attention to patient anatomy to identify high-risk coronary abnormalities and providing the optimal treatments for these patients.

Safety of Crossing Donor-specific Antibodies in Lung Transplantation.

BACKGROUND: Donor-specific antibodies (DSAs) have been associated with antibody-mediated rejection, chronic lung allograft dysfunction (CLAD), and increased mortality in lung transplant recipients. Our center performs transplants in the presence of DSA, and we sought to evaluate the safety of this practice with respect to graft loss, CLAD onset, and primary graft dysfunction (PGD). METHODS: We reviewed recipients transplanted from 2010 to 2017, classifying them as DSA positive (DSA + ) or negative. We used Kaplan-Meier estimation to test the association between DSA status and time to death or retransplant and time to CLAD onset. We further tested associations with severe PGD and rejection in the first year using logistic regression and Fisher exact testing. RESULTS: Three hundred thirteen patients met inclusion criteria, 30 (10%) of whom were DSA + . DSA + patients were more likely to be female, bridged to transplant, and receive induction therapy. There was no association between DSA status and time to death or retransplant (log rank P = 0.581) nor death-censored time to CLAD onset (log rank P = 0.278), but DSA + patients were at increased risk of severe PGD (odds ratio 2.88; 95% confidence interval, 1.10-7.29; P = 0.031) and more frequent antibody-mediated rejection in the first posttransplant year. CONCLUSIONS: Crossing DSA at time of lung transplant was not associated with an increased risk of death or CLAD in our cohort, but patients developed severe PGD and antibody-mediated rejection more frequently. However, these risks are likely manageable when balanced against the benefits of expanded access for sensitized candidates.

Oxidative stress and related metabolic alterations are induced in ex situ perfusion of donated hearts regardless of the ventricular load or leukocyte depletion.

We sought to determine the role of donor blood circulating leukocytes in mediating oxidative stress and inflammation during normothermic ex situ heart perfusion (ESHP). Normothermic ESHP allows preservation of donated heart in a perfused, dynamic state, preventing ischemia. However, the cardiac function declines during ESHP, limiting the potential of this method for improvement of the outcomes of transplantation and expanding the donor pool. Extracorporeal circulation-related oxidative stress plays a critical role in the functional decline of the donor heart. Hearts from domestic pigs were perfused in working mode (WM, whole blood-based or leukocyte-depleted blood-based perfusate) or nonworking mode. Markers of oxidative stress and responsive glucose anabolic pathways were induced in the myocardium regardless of left ventricular load. Myocardial function during ESHP as well as cardioprotective mechanisms were preserved better in WM. Leukocyte-depleted perfusate did not attenuate tissue oxidative stress or perfusate proinflammatory cytokines and did not improve functional preservation. Although ESHP is associated with ongoing oxidative stress and metabolic alteration in the myocardium, preserved cardioprotective mechanisms in WM may exert beneficial effects. Leukocyte depletion of the perfusate may not attenuate inflammation and oxidative stress effectively or improve the functional preservation of the heart during ESHP.

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Patients With Three Vessel Coronary Artery Disease: A Comparison of Centers in the Same Jurisdiction With Differing Multidisciplinary Heart Team Approaches.

OBJECTIVES: Referral patterns and outcomes of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) were compared between 2 centers within 1 jurisdiction wherein only 1 center utilizes multidisciplinary review for all patients. BACKGROUND: Management of advanced coronary artery disease often involves PCI and CABG for improvements in quality of life and survival. Indications exist for PCI and CABG, with CABG demonstrating benefit in three-vessel disease (TVD). METHODS: A total of 27,961 patients underwent cardiac catheterization in 2 centers within the same single-payer health jurisdiction (Center A and B) from 2017 to 2018. Rates of PCI, CABG, and outcomes of 1-year mortality, rehospitalization, myocardial infarction, and stroke were compared. RESULTS: More patients in Center A received PCI and less received CABG compared with Center B even among patients with TVD ( P <0.001). Multivariable logistic regression identified Center B as protective for mortality for TVD patients ( P <0.001) and those undergoing PCI ( P =0.004), but not CABG ( P =0.06). Center A's 1-year mortality was increased for all patients ( P =0.004) and those with TVD ( P =0.011). CONCLUSION: Discordant outcomes exist between these 2 centers. While patients in Center A were more likely to undergo PCI than Center B and experienced decreased 1-year survival, the difference was not significant for CABG. In part, the differences are attributable to contrasting referral practices and the discrepant rates of PCI and CABG between centers. Review of all coronary artery disease patients with a multidisciplinary Heart Team including a surgical opinion may lead to a more evidence-based referral practice aligned with current clinical guidelines.

The evaluation of constant coronary artery flow versus constant coronary perfusion pressure during normothermic ex situ heart perfusion.

BACKGROUND: Evidence suggests that hearts that are perfused under ex-situ conditions lose normal coronary vasomotor tone and experience contractile failure over a few hours. We aimed to evaluate the effect of different coronary perfusion strategies during ex situ heart perfusion on cardiac function and coronary vascular tone. METHODS: Porcine hearts (n = 6 each group) were perfused in working mode for 6 hours with either constant aortic diastolic pressure (40 mmHg) or constant coronary flow rate (500 mL/min). Functional and metabolic parameters, cytokine profiles, cardiac and vascular injury, coronary artery function and oxidative stress were compared between groups. RESULTS: Constant coronary flow perfusion demonstrated better functional preservation and less edema formation (Cardiac index: flow control = 8.33 vs pressure control = 6.46 mL·min-1·g-1, p = 0.016; edema formation: 7.92% vs 19.80%, p < 0.0001). Pro-inflammatory cytokines, platelet activation as well as endothelial activation were lower in the flow control group. Similarly, less cardiac and endothelial injury was observed in the constant coronary flow group. Evaluation of coronary artery function showed there was loss of coronary autoregulation in both groups. Oxidative stress was induced in the coronary arteries and was relatively lower in the flow control group. CONCLUSIONS: A strategy of controlled coronary flow during ex situ heart perfusion provides superior functional preservation and less edema formation, together with less myocardial damage, leukocyte, platelet, endothelial activation, and oxidative stress. There was loss of coronary autoregulation and decrease of coronary vascular resistance during ESHP irrespective of coronary flow control strategy. Inflammation and oxidative stress state in the coronary vasculature may play a role.

Recellularized bovine pericardium with autologous mesenchymal stem cells reduces immune activation.

INTRODUCTION: Current bioprosthetic heart valve replacement options are limited by structural valvular deterioration (SVD) due to an immune response to the xenogenic scaffold. Autologous mesenchymal stem cell (MSC) recellularization is a method of concealing xenogenic scaffolds, preventing recipient immune recognition of xenogenic tissue heart valves, and potentially leading to reduction in SVD incidence. The purpose of this study is to examine the effects of autologous MSC recellularized tissue on the immune response of human whole blood to bovine pericardium (BP). We hypothesized that autologous MSC recellularization of BP will result in reduced pro-inflammatory cytokine production equivalent to autologous human pericardium. METHODS: Bone marrow, human pericardium, and whole blood were collected from adult patients undergoing elective cardiac surgery. Decellularized BP underwent recellularization with autologous MSCs, followed by co-incubation with autologous whole blood. Immunohistochemical, microscopic, and quantitative immune analysis approaches were used. RESULTS: We demonstrated that native BP, exposed to human whole blood, results in significant TNF-α and IL1ß production. When decellularized BP is recellularized with autologous MSCs and exposed to whole blood, there is a significant reduction in TNF-α and IL1ß production. Importantly, recellularized BP exposed to whole blood had similar production of TNF-α and IL1ß when compared to autologous human pericardium exposed to human whole blood. CONCLUSION: Our results suggest that preventing initial immune activation with autologous MSC recellularization may be an effective approach to decrease the recipient immune response, preventing recipient immune recognition of xenogeneic tissue engineered heart valves, and potentially leading to reduction in SVD incidence.

Hyperammonemia syndrome post-lung transplantation: Case series and systematic review of literature.

BACKGROUND: Hyperammonemia syndrome (HS) is a rare post-transplant complication associated with high morbidity and mortality. Its incidence appears to be higher in lung transplant recipients and its pathophysiology is not well understood. In addition to underlying metabolic abnormalities, it is postulated that HS may be associated with Ureaplasma or Mycoplasma spp. lung infections. Management of this condition is not standardized and may include preemptive antimicrobials, renal replacement, nitrogen scavenging, and bowel decontamination therapies, as well as dietary modifications. METHODS: In this case series, we describe seven HS cases, five of whom had metabolic deficiencies ruled out. In addition, a literature review was performed by searching PubMed following PRISMA-P guidelines. Articles containing the terms "hyperammonemia" and "lung" were reviewed from 1 January 1997 to 31 October 2021. RESULTS: All HS cases described in our center had positive airway samples for Mycoplasmataceae, neurologic abnormalities and high ammonia levels post-transplant. Mortality in our group (57%) was similar to that published in previous cases. The literature review supported that HS is an early complication post-transplant, associated with Ureaplasma spp. and Mycoplasma hominis infections and of worse prognosis in patients presenting cerebral edema and seizures. CONCLUSION: This review highlights the need for rapid testing for Ureaplasma spp. and M. hominis after lung transplant, as well as the necessity for future studies to explore potential therapies that may improve outcomes in these patients.