A single-centre analysis of lung transplantation outcomes in recipients aged 70 or older.

OBJECTIVES: As life expectancies continue to increase, a greater proportion of older patients will require lung transplants (LTs). However, there are no well-defined age cutoffs for which LT can be performed safely. At our high-volume LT centre, we explored outcomes for LT recipients ≥70 vs <70 years old. METHODS: This is a retrospective single-centre study of survival after LT among older recipients. Data were stratified by recipient age (≥70 vs <70 years old) and procedure type (single versus double LT). Demographics and clinical variables were compared using Chi-square test and 2 sample t-test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching. RESULTS: A total of 988 LTs were performed at our centre over 10 years, including 289 LTs in patients ≥70 years old and 699 LTs in patients <70 years old. The recipient groups differed significantly by race (P < 0.0001), sex (P = 0.003) and disease aetiology (P < 0.0001). Older patients were less likely to receive a double LT compared to younger patients (P < 0.0001) and had lower rates of intraoperative cardiopulmonary bypass (P = 0.019) and shorter length of stay (P = 0.001). Both groups had overall high 1-year survival (85.8% vs 89.1%, respectively). Survival did not differ between groups after propensity matching (P = 0.15). CONCLUSIONS: Our data showed high survival for older and younger LT recipients. There were no statistically significant differences observed in survival between the groups after propensity matching, however, a trend in favour of younger patients was observed.

Cerebral protection strategies for type A aortic dissection repair.

Importance: Techniques to preserve neurological function during type A aortic dissection repairs have been broadly discussed in the literature and heavily debated. Despite the effectiveness of various approaches, a consensus lacks on how to maintain optimal cerebral temperature during surgery. This review examines the three predominant cerebral protection strategies in aortic arch reconstructions: straight deep hypothermic circulatory arrest (sDHCA), retrograde cerebral perfusion (RCP), and antegrade cerebral perfusion (ACP). Observations: The signature characteristics of sDHCA, RCP, and ACP are similar-hypothermia, with or without cerebral perfusion. Employing cerebral perfusion techniques may prolong operative times, while ACP permits operation at higher body temperatures, albeit with restricted operative durations. Conclusion: For type A dissection arch reconstructions, sDHCA, RCP, and ACP can be successfully implemented. Factors such as operative times and individual patient conditions should be considered when choosing a cerebral protection strategy.

Increased-risk versus standard-risk donation in lung transplantation: A United Network of Organ Sharing analysis.

OBJECTIVES: Donors with characteristics that increase risk of hepatitis B virus, hepatitis C virus, and HIV transmission are deemed increased-risk donors (IRDs) per Public Health Service guidelines. Compared with organs from standard-risk donors (SRDs), IRD organs are more frequently declined. We sought to investigate the outcomes of IRD lung transplant recipients following the 2013 guideline change. METHODS: We retrospectively identified lung transplant recipients using the United Network of Organ Sharing registry (February 2014 to March 2020). Patients were divided into 2 cohorts, based on Centers for Disease Control and Prevention risk status of the donor: SRD or IRD. Demographics and clinical parameters were compared across groups. Survival was compared using Kaplan-Meier curves and log-rank tests. Cox proportional hazard model was performed to identify variables associated with survival outcome. RESULTS: We identified 13,205 lung transplant recipients, 9963 who received allografts from SRDs and 3242 who received allografts from IRDs. In both groups, most donors were White, male, and <30 years old. IRDs demonstrated greater rates of heavy alcohol, cigarette, and cocaine use. SRDs had greater rates of cancer, hypertension, previous myocardial infarction, and diabetes. Survival analysis demonstrated no significant difference in 90-day, 1-year, 3-year, or 5-year survival outcome between SRD and IRD recipients (P = .34, P = .67, P = .40, P = .52, respectively). Cox regression demonstrated that double-lung transplants were associated with 13% decreased mortality risk compared with single-lung (P = .0009). CONCLUSIONS: IRD and SRD recipients demonstrated equivalent survival outcomes. Our study suggests that IRDs offer a safe approach to expand the donor pool and increase availability of lungs for transplantation.

Right Coronary Artery Button Pseudoaneurysm After the Modified Bentall Procedure.

Anastomoses of the coronary buttons are the Achilles' heel of the modified Bentall procedure (MBP) for the repair of the aortic root and ascending aorta. We present a rare case of post-MBP right coronary artery button pseudoaneurysm in a 30-year-old man. The contained leak, attributed to a pseudoknot in the polypropylene suture, was visualized via computed tomography angiography and transesophageal echocardiogram and repaired under deep hypothermic circulatory arrest.

Lung transplant survival with past and concomitant cardiac revascularization.

BACKGROUND: Coronary artery disease is common among lung transplant (LTx) candidates and has historically been viewed as a contraindication to the procedure. Survival outcomes of lung transplant recipients with concomitant coronary artery disease who had prior or perioperative revascularization remain a topic of conversation. METHODS: A retrospective analysis of all single and double lung transplant patients from Feb, 2012 to Aug, 2021 at a single center was performed (n = 880). Patients were split into 4 groups: (1) those who received a preoperative percutaneous coronary intervention, (2) those who received preoperative coronary artery bypass grafting, (3) those who received coronary artery bypass grafting during transplantation, and (4) those who had lung transplantation without revascularization. Groups were compared for demographics, surgical procedure, and survival outcomes using STATA Inc. A p value< 0.05 was considered significant. RESULTS: Most patients receiving LTx were male and white. Pump type (p = 0.810), total ischemic time (p = 0.994), warm ischemic time (p = 0.479), length of stay (p = 0.751), and lung allocation score (p = 0.332) were not significantly different between the four groups. The no revascularization group was younger than the other groups (p<0.01). The diagnosis of Idiopathic Pulmonary Fibrosis was predominant in all groups except the no revascularization group. The pre-coronary artery bypass grafting group had a higher portion of single LTx procedures (p = 0.014). Kaplan-Meier analysis showed no significantly different survival rates after post-LTx between the groups (p = 0.471). Cox Regression analysis showed diagnosis significantly impacted survival rates (p 0.009). CONCLUSIONS: Preoperative or intraoperative revascularization did not affect survival outcomes in lung transplant patients. Selected patients with coronary artery disease may benefit when intervened during lung transplant procedures.

Red Blood Cell Transfusion Prior to Lung Transplantation: Impact on Patient Outcomes.

There is an established association between red blood cell (RBC) transfusion and increased mortality and morbidity in cardiac surgery; however, there is little data demonstrating the influence of blood transfusion while awaiting lung transplantation. Therefore, our study compared the impact of pretransplant RBC transfusion on patient survival and post-transplantation adverse events. Adult lung transplant patient data were extracted retrospectively using the United Network for Organ Sharing thoracic database. Patients were stratified into two groups based on pretransplant transfusion status. In total, 28,217 patients were analyzed in our study (transfused: n = 1,415 and not transfused: n = 26,802). There was an increasing trend in pretransplant transfusion rates from 2006 to 2020. Transfused patients had a higher incidence of adverse events post-transplantation, including dialysis, stroke, and acute organ rejection before discharge. Multivariable survival analysis found an increased mortality risk in patients who required pretransplant transfusion(s) compared to those who did not have a transfusion (hazard ratio [HR]: 1.27; 95% confidence interval [CI]: 1.17-1.41; p < 0.001). There was no significant difference in bronchiolitis obliterans syndrome development between groups (HR: 0.92; 95% CI: 0.82-1.04; p = 0.185). To conclude, our study provides data to suggest that RBC transfusion(s) before lung transplantation are associated with increased patient morbidity and mortality, but have no association with chronic graft rejection development.

Intraoperative Red Blood Cell Transfusion and Primary Graft Dysfunction After Lung Transplantation.

BACKGROUND: In this international, multicenter study of patients undergoing lung transplantation (LT), we explored the association between the amount of intraoperative packed red blood cell (PRBC) transfusion and occurrence of primary graft dysfunction (PGD) and associated outcomes. METHODS: The Extracorporeal Life Support in LT Registry includes data on LT recipients from 9 high-volume (>40 transplants/y) transplant centers (2 from Europe, 7 from the United States). Adult patients who underwent bilateral orthotopic lung transplant from January 2016 to January 2020 were included. The primary outcome of interest was the occurrence of grade 3 PGD in the first 72 h after LT. RESULTS: We included 729 patients who underwent bilateral orthotopic lung transplant between January 2016 and November 2020. LT recipient population tertiles based on the amount of intraoperative PRBC transfusion (0, 1-4, and >4 units) were significantly different in terms of diagnosis, age, gender, body mass index, mean pulmonary artery pressure, lung allocation score, hemoglobin, prior chest surgery, preoperative hospitalization, and extracorporeal membrane oxygenation requirement. Inverse probability treatment weighting logistic regression showed that intraoperative PRBC transfusion of >4 units was significantly ( P < 0.001) associated with grade 3 PGD within 72 h (odds ratio [95% confidence interval], 2.2 [1.6-3.1]). Inverse probability treatment weighting analysis excluding patients with extracorporeal membrane oxygenation support produced similar findings (odds ratio [95% confidence interval], 2.4 [1.7-3.4], P < 0.001). CONCLUSIONS: In this multicenter, international registry study of LT patients, intraoperative transfusion of >4 units of PRBCs was associated with an increased risk of grade 3 PGD within 72 h. Efforts to improve post-LT outcomes should include perioperative blood conservation measures.

Lung Transplantation for COVID-19 Pulmonary Sequelae.

BACKGROUND: The role of lung transplantation for coronavirus disease 2019 (COVID-19)-related lung failure is evolving as the pandemic persists. METHODS: From January 2021 to April 2022, 20 patients (median age 62 y; range 31-77) underwent lung transplantation for COVID-related lung failure at our institution. We reviewed their clinical and intraoperative characteristics and early outcomes including postoperative complications. RESULTS: Eleven patients (55%) had chronic lung disease when they contracted COVID-19. All 20 patients required hospitalization for antivirus treatment. Median lung allocation score was 74.7 (33.1-94.0). Thirteen patients (65%) underwent single-lung transplants, and 7 patients (35%) underwent double-lung transplants. Concomitant coronary artery bypass graft surgery was performed in 2 (10%) patients because of severe coronary artery disease. Postoperatively, venovenous extracorporeal membrane oxygenation was needed in 3 patients (15%) because of severe primary graft dysfunction; all were eventually weaned. Ten patients (50%) experienced deep venous thrombosis, and 1 eventually developed a major pulmonary embolus. The median intensive care unit stay and hospital stays were 6.5 d (3-44) and 18 d (7-77), respectively. During a median follow-up of 201 d (47-418), we experienced 1 late mortality due to COVID-19-related myocarditis. Among the 13 patients with single-lung transplant, 5 demonstrated improvement in their native lungs. CONCLUSIONS: Lung transplantation yielded favorable early outcomes in a heterogeneous patient cohort that included older patients, obese patients, and patients with coronary artery disease or preexisting chronic lung disease. Our data also shed light on the transforming role of lung transplantation for the pulmonary sequelae of a complex multisystem COVID-19 disorder.

Two Staged Single Lung Transplants in the Current Era: A United Network for Organ Sharing Study.

BACKGROUND: We hypothesized that outcomes after 2 staged, contralateral single lung transplantation procedures (SSLTs) may be equivalent to those of double lung transplantation (DLT) by capitalizing on the known long-term survival advantages of DLT. METHODS: Using the United Network for Organ Sharing data set (1987-2018), the largest national data set available, the outcomes of 278 SSLTs were retrospectively analyzed and compared with the outcomes of 21,121 standard DLTs. RESULTS: During SSLT, the median interval between the 2 transplants was 960 days, and the indication for the second transplant was most often chronic lung allograft dysfunction (n = 148; 53.2%) or the same disease that necessitated the first transplant (n = 81; 29.1%). The patients who underwent SSLT were significantly older and had a higher baseline creatinine level than the patients who underwent DLT. Most posttransplantation short-term outcomes were equivalent between the second stage of SSLT and DLT, but renal insufficiency requiring hemodialysis was notably higher after SSLT. There were no differences in long-term survival. In multivariate analysis, baseline creatinine, O2 support at rest, ventilator support at the time of the second transplantation, and posttransplantation renal insufficiency requiring dialysis were independent predictors of 1-year mortality after SSLT. CONCLUSIONS: Over a study period of 30 years, long-term survival after SSLT was comparable with survival after DLT. With further analysis of individual risk profiles, including the contributions of preoperative renal function and functional status, SSLT can be a valuable option for patients who would have undergone single lung transplantation to reap the long-term benefits of a second transplant.

Giant ventral hernia following left ventricular assist device bridge to heart transplantation.

Ventral hernias following left ventricular assist device (LVAD) placement are rare. With the improvement in technology, and miniaturization of devices associated with intrapericardial placement, these complications have largely been abolished. The mere presence of a large ventral hernia should not exclude recipients from being candidates for orthotopic heart transplantation.

Caught in a vice.

Esophageal dysmotility and dysphagia are well known in patients with scleroderma. Interstitial lung disease (ILD) in these patients is an indication for lung transplantation but is considered high risk in many centers. This report is an attempt to highlight how anatomical causes can contribute to dysphagia in such patients and complicate the post-operative course after lung transplantation. Such a finding is uncommon in this subset of patients and use of suitable imaging can help in arriving at the diagnosis. We present a patient following lung transplantation for scleroderma related ILD with an aberrant right subclavian artery compressing the esophagus in a vice like grip. Imaging is the key to prompt diagnosis and management.

Effect of mode of intraoperative support on primary graft dysfunction after lung transplant.

OBJECTIVE: To clarify the relationship between the use of extracorporeal life support during lung transplantation and severe primary graft dysfunction (PGD), we developed and analyzed a novel multicenter international registry. METHODS: The Extracorporeal Life Support in Lung Transplantation Registry includes double-lung transplants performed at 8 high-volume centers (>40/year). Multiorgan transplants were excluded. We defined severe PGD as grade 3 PGD (PGD3) observed 48 or 72 hours after reperfusion. Modes of support were no extracorporeal life support (off-pump), extracorporeal membrane oxygenation (ECMO), and cardiopulmonary bypass (CPB). To assess the association between mode of support and PGD3, we adjusted for demographic and intraoperative factors with a stepwise, mixed selection, multivariable regression model, ending with 10 covariates in the final model. RESULTS: We analyzed 852 transplants performed between January 2016 and March 2020: 422 (50%) off-pump, 273 (32%) ECMO, and 157 (18%) CPB cases. PGD3 rates at time point 48-72 were 12.1% (51 out of 422) for off-pump, 28.9% for ECMO (79 out of 273), and 42.7% (67 out of 157) for CPB. The adjusted model resulted in the following risk profile for PGD3: CPB versus ECMO odds ratio, 1.89 (95% CI, 1.05-3.41; P = .033), CPB versus off-pump odds ratio, 4.24 (95% CI, 2.24-8.04; P < .001), and ECMO versus off-pump odds ratio, 2.24 (95% CI, 1.38-3.65; P = .001). CONCLUSIONS: Venoarterial ECMO is increasingly used at high-volume centers to support complex transplant recipients during double-lung transplantation. This practice is associated with more risk of PGD3 than off-pump transplantation but less risk than CPB. When extracorporeal life support is required during lung transplantation, ECMO may be the preferable approach when feasible.

Human leukocyte antigen mismatch on lung transplantation outcomes.

OBJECTIVES: Human leucocyte antigen (HLA) mismatch is a known risk factor for renal transplantation; however, there are conflicting and limited data on its ramifications within lung transplantation (LTx). Therefore, our study evaluated the effects of total HLA, HLA-A, -B and -DR mismatches on LTx outcomes. METHODS: We retrospectively examined the United Network for Organ Sharing database for adult patients who had undergone LTx for the first time between January 2005 and July 2021. Total HLA mismatch (0-3, 4, 5 and 6) and HLA locus mismatch (0-1 and 2) were analysed, with the end points of interest being mortality and bronchiolitis obliterans syndrome (BOS) development. RESULTS: Kaplan-Meier curve analysis found a significant difference in both overall survival (n = 27 651; 11 830 events) and BOS development (n = 25 444; 8901 events) for the total number of HLA (P < 0.001, P < 0.001), HLA-A (P < 0.001, P = 0.006) and HLA-DR (P < 0.001, P < 0.001) mismatches. With reference to 0-3 total HLA mismatches, multivariable Cox regression model found that 6 mismatches had an increased risk of mortality (P = 0.002) while 4 (P = 0.010), 5 (P = 0.007) and 6 (P < 0.001) mismatches had an increased risk of BOS. HLA-B mismatch was not associated with an increased mortality (P = 0.975) or BOS risk (P = 0.512). CONCLUSIONS: This study demonstrates a significant relationship between increased HLA mismatches and BOS development, with decreased overall survival only apparent with 6 mismatches. HLA-A and -DR mismatches were associated with an increased risk of mortality and BOS development compared to groups with at least 1 locus match.

Donor quality assessment and size match in lung transplantation.

Careful donor quality assessment and size match can impact long-term survival in lung transplantation. With this article, we review the conceptual and practical aspects of the preoperative donor lung quality assessment and size matching.

Donor Pulmonary Vein Anomalies: What's in Your Toolbox?

Pulmonary vein anomalies are often unrecognized during donor lung procurement. Consequently, they are at high risk for injury, and this leaves the implanting surgeon with an unpleasant surprise. An innovative approach can help resolve the situation. We wish to highlight our experience with an anomalous left upper pulmonary vein and describe a novel reconstruction technique.

Proximal Anastomotic Device Malfunction: Salvage Using Alternative Option.

Embolic stroke is a major complication of cardiac surgery and there have been multiple methods developed to reduce this risk. Recent technology has produced 2 primary devices for producing a bloodless and clampless field to perform aortocoronary graft anastomosis. We present a case with a Class V aorta, deployment failure of one device after aortic punch, and salvage of the aortotomy with the other device.

Cardiac tamponade masquerading as headache: A diagnostic conundrum.

Cardiac tamponade and its protean presentations are well documented. Tamponade presenting after recent cardiac surgery in a patient on anticoagulation is not unknown. However, severe headache as a presenting feature of tamponade is not documented. We describe how one can be misled into investigating causes of headache while the real cause, tamponade, lies hidden.

Prior and Perioperative Revascularization Does Not Affect Survival in Lung Transplant Patients.

BACKGROUND: Coronary artery disease is common in lung transplant patients and has historically been viewed as a contraindication to the procedure. Although this mindset is changing, the effect of prior or perioperative revascularization on lung transplant survival outcomes is not adequately established. METHODS: We performed a single-center retrospective analysis of all single and double lung transplant patients from 2012 to 2018 (n = 468). Patients were split into 4 groups: (1) patients who received a preoperative percutaneous coronary intervention (n = 34), (2) those who received coronary artery bypass grafting (CABG) before transplantation (n = 25), (3) those that received concomitant CABG during transplantation (n = 29), and (4) those who had lung transplantation with no need for revascularization (n = 380). Groups were compared for demographics, surgical procedure, and survival outcomes. RESULTS: The no-revascularization group was statistically younger than the rest (P = .001). The lung allocation score trended toward being higher in the concomitant coronary artery bypass group (P = .03). All groups were predominantly diagnosed with idiopathic pulmonary fibrosis. The proportion of patients with chronic obstructive pulmonary disease was greatest in the group not requiring revascularization (P = .001). Patients with previous CABG were more likely to receive a single lung transplant than a double one (21 versus 4; P = .054). Length of stay, posttransplant survival, and postoperative adverse events were similar among all groups. CONCLUSIONS: Results suggest that preoperative or intraoperative revascularization does not negatively affect survival in lung transplant patients; lung recipients with coronary artery disease have comparable survival when adequately revascularized.

Development of Three Orthogonal Assays Suitable for the Identification and Qualification of PIKfyve Inhibitors.

FYVE-type zinc finger-containing phosphoinositide kinase (PIKfyve) catalyzes the formation of phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2) from phosphatidylinositol 3-phosphate (PI(3)P). PIKfyve has been implicated in multiple cellular processes, and its role in the regulation of toll-like receptor (TLR) pathways and the production of proinflammatory cytokines has sparked interest in developing small-molecule PIKfyve inhibitors as potential therapeutics to treat autoimmune and inflammatory diseases. We developed three orthogonal assays to identify and qualify small-molecule inhibitors of PIKfyve: (1) a purified component microfluidic enzyme assay that measures the conversion of fluorescently labeled PI(3)P to PI(3,5)P2 by purified recombinant full-length human 6His-PIKfyve (rPIKfyve); (2) an intracellular protein stabilization assay using the kinase domain of PIKfyve expressed in HEK293 cells; and (3) a cell-based functional assay that measures the production of interleukin (IL)-12p70 in human peripheral blood mononuclear cells stimulated with TLR agonists lipopolysaccharide and R848. We determined apparent Km values for both ATP and labeled PI(3)P in the rPIKfyve enzyme assay and evaluated the enzyme's ability to use phosphatidylinositol as a substrate. We also tested four reference compounds in the three assays and showed that together these assays provide a platform that is suitable to select promising inhibitors having appropriate functional activity and confirmed cellular target engagement to advance into preclinical models of inflammation.

Anterior Leaflet Augmentation With CorMatrix Porcine Extracellular Matrix in Twenty-Five Patients: Unexpected Patch Failures and Histologic Analysis.

BACKGROUND: This study reported on the treatment of Carpentier type IIIa and type IIIb mitral regurgitation (MR) with a large patch anterior mitral valve leaflet augmentation technique using CorMatrix (CorMatrix Cardiovascular Inc, Alpharetta, GA) extracellular matrix (ECM). METHODS: A single-site chart review was conducted on patients who underwent anterior leaflet augmentation performed with the Da Vinci surgical robot (Intuitive Surgical, Sunnyvale, CA) or through a median sternotomy. Only patients who had anterior leaflet augmentation with porcine intestine ECM or autologous pericardium were included. Follow-up echocardiography was performed on all patients. Histologic specimens were available on ECM patches from a subset of patients who required reoperation. RESULTS: Between August 2011 and April 2014, 44 patients (mean age, 62.6 ± 12.2 years) underwent anterior leaflet augmentation with either porcine intestinal ECM or autologous pericardium at the Temple University Hospital in Philadelphia. Two (4%) late deaths occurred, one in each group. One patient who underwent ECM augmentation died of non-cardiac-related causes 7 months after discharge as a result of complications of chronic renal failure. The second late death occurred 5 months after discharge because of complications of a stroke in a patient in the pericardial augmentation group. Eight (32%) of the patients with ECM had recurrence of severe MR on echocardiography at an average time of 201 ± 98 days. Seven (28%) patients required reoperation because of failure of the ECM patch including perforation (4%), excessive patch dilation (20%), and suture line dehiscence (4%). In contrast, none of the patients with pericardial augmentation developed severe MR or required operation. Statistical analysis of the patients with ECM augmentation demonstrated no correlation of the following: age; sex; comorbid conditions such as diabetes, chronic obstructive pulmonary disease, and hypertension; left ventricular ejection fraction; surgical approach; annuloplasty size; or type of MR with patch failure. A lower body mass index was the only factor associated with recurrent severe regurgitation on univariate analysis (p = 0.039). Histologic study of the four available explants demonstrated intense inflammation without evidence of host integration. The remaining 15 (60%) patients had normal mitral leaflet structure and function on follow-up echocardiograms out to 12 months. CONCLUSIONS: For type III MR, a large anterior leaflet patch technique with porcine ECM was associated with a 32% recurrence rate of severe MR related directly to patch failure. Further research and development should be performed on the use of ECM materials with a goal to decrease the failure rate experienced in this study.