Search

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.

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

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.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.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, OOver 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.

Purpose: A difference in the lower body to upper body ratio between similarly heighted individuals could lead to inadequately matched transplants. There has been a perception in clinical circles that body ratio varies between people of different races, and investigating this supposition would prove useful in increasing transplant match accuracy. The investigation’s purpose was to derive an equation with a greater correlation to lung length than height alone. Methods: Lung transplantation donor data for 480 adult patients was obtained and divided by ethnicity—Caucasian, African American, and Hispanic. Height, weight, age, sex, right and left lung length were evaluated for significance. The R2 value of the multiple linear regression with these variables vs. lung length was determined and tested in a separate dataset of 100 patients. Results: Only the distribution of height was significant between the 3 ethnicities ( P = 0.041). None of the ANCOVAs were significant ( P < 0.05) or near significant ( P < 0.10). For the strongest correlation model with lung length, height had a linear fit, weight had a cubic fit, and age had a logistic fit. Multiple regression models were successfully created for right lung (R2 = 0.202) and left lung (R2 = 0.213). Independent testing showed a correlation of 0.131 and 0.136, respectively. Conclusion: Using demographic information from the donor and recipient as proxies for estimating lung size should only serve as a rough guide due to their weak correlation with lung length. As a result, for greater accuracy, donor-recipient matching should be individualized by taking donor and recipient chest X-Rays and/or TLC into consideration.

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.

We present an overview of genetic, metabolomic, proteomic and neurochemical studies done mainly in our laboratories that could improve prediction, mechanistic understanding and possibly extend to diagnostics and treatment of alcoholism and alcohol addiction. Specific polymorphisms in genes encoding for interleukins 2 and 6, catechol-O-methyl transferase (COMT), monaminooxidase B (MAO B) and several other enzymes were identified as associated with altered risks of alcoholism in humans. A polymorphism in the gene for BDNF has been linked to the risk of developing deficiences in colour vision sometimes observed in alcoholics. Metabolomic studies of acute ethanol effects on guinea pig brain cortex in vitro, lead to the identification of specific subtypes of GABA(A) receptors involved in the actions of alcohol at various doses. Acute alcohol affected energy metabolism, oxidation and the production of actaldehyde and acetate; this could have specific consequences not only for the brain energy production/utilization but could influence the cytotoxicity of alcohol and impact the epigenetics (histone acetylation). It is unlikely that brain metabolism of ethanol occurs to any significant degree; the reduction in glucose metabolism following alcohol consumption is due to ethanol effects on receptors, such as α4β3δ GABA(A) receptors. Metabolomics using post-mortem human brain indicated that the catecholaminergic signalling may be preferentially affected by chronic excessive drinking. Changes in the levels of glutathione were consistent with the presence of severe oxidative stress. Proteomics of the post-mortem alcoholic brains identified a large number of proteins, the expression of which was altered by chronic alcohol, with those associated with brain energy metabolism among the most numerous. Neurochemical studies found the increased expression of glutamate transporter GLAST/EAAT1 in brain as one of the largest changes caused by alcoholism. Given that GLAST/EAAT1 is one of the most abundant proteins in the nervous tissue and is intimately associated with the function of the excitatory (glutamatergic) synapses, this may be among the most important effects of chronic alcohol on brain function. It has so far been observed mainly in the prefrontal cortex. We show several experiments suggesting that acute alcohol can translocate GLAST/EAAT1 in astrocytes towards the plasma membrane (and this effect is inhibited by the GABA(B) agonist baclofen) but neither the mechanism nor the specificity (to alcohol) of this phenomenon have been established. Furthermore, as GLAST/EAAT1 is also expressed in testes and sperm (and could also be affected there by chronic alcohol), the levels of GLAST/EAAT1 in sperm could be used as a diagnostic tool in testing the severity of alcoholism in human males. We conclude that the reviewed studies present a unique set of data which could help to predict the risk of developing alcohol dependence (genetics), to improve the understanding of the intoxicating actions of alcohol (metabolomics), to aid in assessing the extent of damage to brain cells caused by chronic excessive drinking (metabolomics and proteomics) and to point to molecular targets that could be used in the treatment and diagnosis of alcoholism and alcohol addiction.

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.

Pacemaker infections are one of the most distressing and morbid complications for patients and can present a challenging management problem for physicians. Pacemaker leads, especially those that dwell in the venous system and inside the cardiac chambers, are prone to becoming colonized with bacteria owing to their sizeable surface area, the nature of their external exposed materials (usually silicone or polyurethane) that are prone to biofilm formation, and their close association with the skin surface at the level of the pacemaker pocket.1 Leads that cross the tricuspid valve (TV) may be at additional risk for lead-associated endocarditis owing to contact with infected valvular structures, and the local environment of turbulent, high-velocity jets. Leadless pacemakers, on the other hand, have features that may reduce their risk of becoming infected, including a smaller surface area, a metal-only exposed surface, no interaction with the TV, and no component that has proximity to the skin surface. Micra (Medtronic, Minneapolis, MN) is a battery-operated leadless intracardiac pacemaker that was designed to stay anchored inside the right ventricle, thus reducing the infection risk of conventional pacemakers. The cylindrical device is 26 mm long, about the size of a large pill (a volume of 1 cm3), occupying clinically insignificant space within the right ventricular chamber. The Micra leadless pacemaker is placed with a transvenous implantation catheter via the right femoral vein, so no thoracotomy is required for this procedure.2 We present a case where a Micra leadless pacemaker was used to manage a challenging patient with a history of TV endocarditis, complete heart block, and multiple pacemaker system infections. Key Teaching Points • Standard pacemaker leads are prone to bacterial adherence and chronic colonization in the setting of bacteremia and endocarditis. Full extraction of the pacing system is needed as part of curative treatment when lead-associated endocarditis is present. • Multiple episodes of endocarditis over time can mandate sequential removal of transvenous hardware (including pacemaker leads) in order to achieve definitive control of these infections. The need for multiple lead extractions does not preclude the possibility of long-term cure from relapsing endocarditis. • The Micra (Medtronic, Minneapolis, MN) leadless pacemaker has a lower risk of bacterial colonization than standard transvenous pacemaker leads for several reasons, and may be an appropriate choice for chronic pacing in patients at high risk for bacterial endocarditis.

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.

The reform of police investigative practices was one of six key components of the Police Reform Program (PRP) in Bangladesh. The reforms were intended to shifting police investigations from oral to...

BackgroundWhile heart transplantation is increasingly performed in the United States for elderly patients, survival outcomes have primarily been analyzed in single-center studies. The few existing long-term studies have indicated no difference in HTx outcomes between patients ≥70 years and 60-69 years age, but these studies only assessed to 5-years post-transplant and included data from the 1980-90s, introducing significant variance due to poorer outcomes in that era. We analyzed the UNOS database from 1987-2020, stratified by timeframe at 2000, to derive a more representative comparison of modern HTx survival outcomes.MethodsAll UNOS HTx recipients over 18 years of age (n=66,186) were divided into 3 cohorts: 18-59, 60-69 and ≥70 years old. Demographic data as well as perioperative factors were evaluated for significance using Chi-Squared and H-Tests as appropriate. Kaplan-Meier Curve and cox regressions with log-rank tests were used to assess 5 through 10 year survival outcomes.Results45,748 were 18-59 years old, 19,129 were 60-69 years old and 1,309 were ≥70 year old. The distribution of most demographic and perioperative factors significantly differed between cohorts. Pairwise survival analysis involving the 18-59 cohort always indicated significance. While there was no significance between the two older cohorts in the earlier timeframe, there was significance in the later timeframe from 6-10 years post-HTx (pConclusionsThe results indicate that since 2000, recipients 60-69 years of age have better 6 through 10-year post-transplant survival than older recipients, a relationship previously obscured by worse outcomes in early data.

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.

This paper aims to check the dynamic linkages between CO2 emissions and development indicators (per capita Gross Domestic Product (GDP), population density, and urbanisation) of Bangladesh. Using annual data in IPAT model for the period of 1972–2015, we have applied Johansen co-integration and Granger causality tests to examine the long-run co-integration and short-run dynamics of the concerned variables. The obtained results reveal that there is bidirectional causality between CO2 emissions and urbanisation, and CO2 emissions and GDP per capita for the study period in Bangladesh. This implies that GDP growth and urbanisation process are the major sources of CO2 emissions in the country. Therefore, policy makers should take extreme care in designing and implementing the environmental protection policies to curb CO2 emissions with a desired level of economic growth and urbanization.

Procurement of thoracic organs can be divided into two major categories- donation after brain death (DBD) or donation after circulatory determination of death (DCDD). In this section we will focus primarily on DBD, which is the commoner of these two or at times referred to as standard procurement. DCDD is a relatively new and promising field that has helped ameliorate donor shortage, aided by the latest advances in medical technology. However, DBD continues to be the major avenue of organ donation. There are several different combinations of thoracic procurement surgeries: heart, double lung, single lung/ 2-single lungs, heart-lung en bloc for transplantation, Double Lung procurement for Bronchial arterial revascularization, Heart and Lung procurement in DCDD donors with the OCS, NRP or Lungs for EVLP.

Introduction: As the prevalence of heart failure increases by age, it is critical we understand the role of heart transplantation (HTx) in older patients. Recent long term studies have indicated no difference in HTx outcomes between recipients 70 years or older and those ages 60-69. But these studies included data from the 1980-90s, introducing significant variance due poorer outcomes across age groups in that era. We analyzed the most recent United Network for Organ Sharing (UNOS) database, stratified by time frames before and after 2000, to demonstrate this statistical discrepancy and derive a more representative comparison of modern survival by age group. Hypothesis: HTx recipients 70+ years old may not actually have comparable survival to those 60-69 years of age, when assessing more recent HTx data. Methods: All UNOS HTx recipients over 60 years of age (n=20,446) were divided into 2 cohorts: those 60-69 and those ≥70 years old, which were analyzed over two time frames: transplant date 1987-1999 and 2000-2019. Demographic data (gender, ethnicity, BMI) as well as peri-operative factors (ICU stay, ischemic time, and length of stay) were evaluated for significance using Chi-Squared and H-Tests as appropriate. Kaplan-Meier Curve with log-rank tests were used to assess 10 year survival outcomes. Results: 19,129 patients were 60-69 years old, and 1,317 were ≥70 years old, with mean ages of 64.0±2.7 and 71.3±1.6 years respectively. The distribution of demographic and peri-operative factors was significantly different between the cohorts, with p Conclusion: The results indicate that since 2000, recipients 60-69 years of age have better 10- year post transplant survival than older recipients, a relationship previously obscured by worse outcomes in early data.

Purpose Whereas double lung transplantation (LTx) is a preferred surgical option for the patients with secondary pulmonary arterial hypertension (SPH: defined as a mean pulmonary artery pressure (mPAP) above 25 mmHg), our institutional experiences have demonstrated the unique values of single LTx for SPH. Here, we review our experiences prioritizing single LTx for SPH in an attempt to optimize their opportunities and decrease mortality while waiting. Methods A retrospective review of the LTx database was used to identify patients who underwent single LTx. SPH patients were stratified into mild SPH (mPAP: 25-40 mmHg) and severe SPH (mPAP > 40 mmHg). Recipients without PH transplanted over the same time period were used as controls. Data are reported as severe SPH vs. mild SPH vs. controls. Results Three hundred eighteen patients received single LTx between January 2017 and December 2019. There were 217 patients with mild SPH (mPAP of 32 mmHg), 59 patients with severe SPH (mPAP of 46 mmHg) and 42 patients without PH (controls). There were no significant differences among the groups in their patients’ characteristics except higher pulmonary vascular resistance noted in severe SPH group and morbid obesity noted in mild and severe SPH groups. While severe SPH group required more intraoperative cardiopulmonary support (37.3% vs. 11.1% vs. 5.0%, p Conclusion Our experience supports the option of single LTx for the patients with even severe SPH by utilizing appropriate mechanical circulatory support intraoperatively. In light of the ongoing donor lung shortage, this strategy should be considered for optimizing organ utilization and decreasing waitlist mortality.

Purpose There is a hesitancy to use older donor lungs in lung transplants, and to perform them in older patients. To invalidate the use of donor and recipient age as relative contraindications for lung transplantation, we examined both, and factored in transplant type, then analyzed their effects on survival outcomes using propensity matching. Methods Patients were stratified by recipient age ( Results Using 743 lung transplant patients at our single center over 8 years (Feb-2012 to Mar-2020) in the pre-propensity match, there was a significant difference in survival outcomes for the group: ≥50 donor age ≥70 recipient age group in survival when looking at single vs. double lung transplant (p = 0.038). There were no other statistically significant differences in survival based on donor and recipient age, or transplant type. Post-propensity matching, there was no difference in survival based on the interplay between donor and recipient age, for donor group ≥50 (p = 0.092), for donor group Conclusion While donor and recipient age are undoubtedly important factors to consider during lung transplantation, neither of these independently affects long-term survival. Upon matching, there was no differences in survival for lung transplant patients based on transplant type. Older lungs and older patients can result in reasonable post-transplant outcomes.

Purpose Currently the continuous suturing technique is used on the bronchial anastomosis during lung transplantation. This study investigated that technique vs. the interrupted suturing technique, comparing survival and occurrence of post-operative bronchial complications to examine if a switch in technique is merited. Methods Survival outcomes of 721 single-center lung transplant recipients over 8 years (Feb-2012 to Mar-2020) were compared. Continuous suturing technique was performed with 3/0 polypropylene suture on an SH needle. Interrupted used the same technique for the membranous portion of the anastomosis and multiple interrupted 2/0 polypropylene sutures for the cartilaginous portion. Clinical parameters and demographics were compared. The two groups were compared for post-operative morbidity and survival was compared using Kaplan-Meier curves. Log-rank tests were performed, as was Cox regression analysis, with p Results Of the 721 patients, 429 received the continuous suturing technique while 292 had interrupted suturing technique. Demographics and clinical parameters compared were: age (p=0.008), gender (p=0.643), race (p=0.268), etiology (p Conclusion Although both techniques showed reasonable post-transplant outcomes, our study indicated better survival and relatively fewer complications when using interrupted suturing technique vs continuous. Further long-term study of similar groups with similar long-term follow up in these two groups should be performed to validate this effect.

Purpose Donation after circulatory death (DCD) is propagated to expand the lung transplant (LTx) organ donor pool. Using the International ECLS Registry database, we compared DCD vs DBD LTx survival in the context of intraoperative extracorporeal life support (ECLS). We hypothesize comparable survival outcomes and ECLS usage between donor groups. Methods Patients undergoing double-lung transplant were included from multiple institutions in US & Europe. Patients were stratified by donor type (DCD, DBD). Differences between groups in ECLS usage (yes/no) were analyzed with Chi-square testing or Fisher's exact test. Donor, recipient, and procedural characteristics, including the primary outcome of post-operative survival, were analyzed using Wilcoxon rank sum test or Chi-square testing. Propensity matching was used with Kaplan-Meier survival curves and log-rank testing to assess mortality between groups with and without ECLS. Endpoints Analysis of differences in patient/donor demographics, pre-operative, intra-operative and post-operative ECLS usage, post-operative complications, and patient survival will be used to compare the DCD and DBD donor groups. A total of 866 double lung transplantations (DLT), 72 DCD and 794 DBD cases, were preliminarily analyzed. DCD had older mean donor age (p=0.003), and higher post-operative pneumonia rates in DCD (p=0.01). Groups were different in the type of intra-operative ECLS support required (CPB, ECMO, Modified bypass) (p=0.014), total ischemic time (p=0.0001), and post-op ECMO (p=0.06). Mortality analysis showed no increased risk for DCD vs DBD groups before discharge (HR 1.31; CI- 0.43, 3.96; p=0.63), at 90-days (HR 1.49; CI- 0.35, 6.31; p=0.58), and 1-year (HR 0.93, CI-0.33, 2.60; p=0.89). Figure shows KM curves before and after propensity matching with/without ECLS. Further analysis will be done as the ECLS Registry patient volume increases.

Purpose Donor after cardiac death (DCD) is an organ procurement method that is being increasingly used to expand the current lung donor pool. We hypothesize that in our single-center study, DCD and donor after brain death (DBD) groups would have similar survival rates as found in previous studies. Methods A retrospective analysis was performed at a single center which identified 801 lung transplants completed between March 2012 and September 2020. DCD LTx patients (n=18) were matched by propensity scores with donors after brain death DBD recipients. Propensity scores (PS) were determined using patient age, sex, race diagnosis, BMI, and donor age. PS matching was done by comparing 1:1, 1:2, and 1:3 pooled groups (DCD:DBD), and performing either chi-squared or t-tests analyses on each variable before and after matching. Survival outcomes were calculated using Kaplan-Meier curves and log-rank tests. Results Of the 801 LTx patients, mean donor age for DCD lungs was 27.59. The PS matched DBD group did not significantly differ from the DCD group in age (p=0.6339), sex (p=0.401), race (p=0.846), diagnosis (p=0.102), pump use (p=0.867), BMI (p=0.0467) or donor age (p=0.8275). Log-rank testing with Kaplan-Meier curves of pre-PS matching revealed no significant survival difference between DCD and DBD groups (p=0.38). The PS matched data similarly found no significant difference in patient survival (p=0.26) which was consistent across the 1:1, 1:2 and 1:3 matched groups. Conclusion Our study found both DBD and DCD donor lungs provide comparable short-term survival outcomes. This is in agreement with previous studies, which argue for the viability of DCD donor lungs and for their use to be expanded.

Purpose The lung transplantation (LTx) community continues to investigate single- (SLT) vs. double-lung transplantation (DLT) to predict optimal long-term survival post-LTx. We investigated the survival in younger patients receiving SLT using the current United Network for Organ Sharing (UNOS) database and our single center results. Methods A retrospective analysis of both UNOS and single center databases was performed, investigating patients between ages 18 and 50 who received either a SLT or DLT from August 2005 to March 2020 (n=11156; n=48). Similar patients were matched between the two databases (n=96). Survival outcomes were assessed before and after propensity score matching. P-value Results In the pre-propensity match, the UNOS patient group who received DLT had better survival outcomes than SLT (p Conclusion While debate continues on the validity of SLT vs. DLT continues, transplantation type did not affect long-term survival in any patient group. Upon matching, there was no difference in survival for lung transplant patients based on transplant type. These promising newer results support consideration of the use of SLT, which allows for greater distribution of limited donor organs.

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.

Introduction: As the prevalence of heart failure increases among older patients, the potential role of heart transplant (HTx) in this demographic demands further investigation. Survival outcome analysis of the elderly has primarily been analyzed in single-center studies, and the few long term studies performed have included a timeframe to the 1980s, introducing substantial variance from much poorer survival outcomes. We investigated the 5 to 10 year survival outcomes of more modern heart transplantation patients by analyzing the UNOS database. Methods: Heart transplantation data for 32,337 patients (2000-2014) was divided into three different age groups- Results: 23,267 were Conclusion: Contrary to prior studies, results indicate a statistically significant difference in survival the older and younger cohorts. This difference is especially prominent at the 10 th year post-transplant, but can be seen even at the 5 th year.

Developing brain cells express many proteins but little is known of how their protein composition responds to chronic exposure to alcohol and/or how such changes might relate to alcohol toxicity. We used cultures derived from embryonic rat brain (previously shown to contain mostly neural stem cells; rat NSC, rNSC), exposed them to ethanol (25-100 mM) for up to 96 h and studied how they reacted. Ethanol (50 and 100 mM) reduced cell numbers indicating either compromised cell proliferation, cytotoxicity or both. Increased lipid peroxidation was consistent with the presence of oxidative stress accompanying alcohol-induced cytotoxicity. Proteomics revealed 28 proteins as altered by ethanol (50 mM for 96 h). Some were constituents of cytoskeleton, others were involved in transcription/translation, signal transduction and oxidative stress. Nucleophosmin (NPM1) and dead-end protein homolog 1 (DND1) were further studied by immunological techniques in cultured neurons and astrocytes (derived from brain tissue at embryonic ages E15 and E20, respectively). In the case of DND1 (but not NPM1) ethanol induced similar pattern of changes in both types of cells. Given the critical role of the protein NPM1 in cell proliferation and differentiation, its reduced expression in the ethanol-exposed rNSC could, in part, explain the lower cells numbers. We conclude that chronic ethanol profoundly alters protein composition of rNSC to the extent that their functioning-including proliferation and survival-would be seriously compromised. Translated to humans, such changes could point the way towards mechanisms underlying the fetal alcohol spectrum disorder and/or alcoholism later in life.

Purpose Following a combined heart/lung transplant (HLTx), UNOS reports a survival rate of 68% at year 1, 58% at year 2, and 53% at year 3. This study aims to compare the survival outcome following HLTx from our medical center with UNOS registry data. Methods We retrospectively studied 12 patients that underwent HLTx at our center between 2012-2020 to assess long-term survival. We analyzed included recipient's age, sex, etiology, lung allocation score (LAS), cardiopulmonary bypass (CPB) time, total/warm ischemic time, procedural approach, induction, donor age/sex, length of stay (LOS), and cause of death. We then assessed the survival outcome of our patients and compared that with the UNOS registry data (n=1295) using a Kaplan-Meier curve and log-rank test (p Results Out of our 12 patients, 8 were male and 4 were female, with the average age 53 ± 10 yrs. From the donors, 7 were male and 5 were female, with an average age of 37 ± 14 yrs. Etiology included PF (50%), sarcoidosis (17%), and pulmonary HTN (17%). Pre-Txp, 2 patients were placed on VA ECMO (1 on ventilation), 1 on VV ECMO, 1 on RVAD, and 1 on HM III. The average LAS was 65 ± 21. All of our patients were put on CPB during operation with an average CPB time of 186 ± 37 min, total ischemic time of 243 ± 68 min for right and 194 ± 60 min for left, and warm ischemic time of 36 ± 10 min for right and 47 ± 11 min for left. In total, 9 had a median sternotomy incision and 3 had a clamshell incision. Campath induction was performed on 7 patients while 5 had Simulect induction. Post-Txp, 2 patients required ECMO. Median LOS was 45 days and mean survival time was 757 ± 945 days. A total of 3 patients died due to infection, MSOF, and bleeding. The log-rank test between the patients from our center compared to the national average showed no significant difference in survivability (p=0.292). Conclusion Although not significant, our HLTx survival outcome was slightly better than the national UNOS survival data. Surgical techniques and careful management may contribute to better survival outcomes in selected patients.

Purpose Idiopathic pulmonary fibrosis (IPF) accounts for the largest proportion of diagnoses on the US lung transplant (LTx) list. LTx type (single vs double) and donor age are associated with differences in outcomes, yet their independent and combined effects in patients with IPF remain unclear and are investigated in this study. Methods This study retrospectively analyzed survival of patients with IPF receiving LTx at a single center from Feb-2012 to Mar-2020. LTx recipients were grouped by single (SLT) or double (DLT) LTx type and donor lung age Results Of 742 LTx patients, 305 (41%) were diagnosed with IPF, of which 204 (67%) were SLT and 97 (32%) were DLT (4 patients underwent either heart-lung transplant or single-sequential LTx and were excluded). There was no significant difference in survival due to LTx type (p=0.368). Similarly, no significant difference in survival was found for patients with donor age Conclusion Demand for donor lungs far exceeds supply, and with IPF accounting for a large percentage of this need, finding effective sources of supply has become increasingly important. Use of SLT and donors aged 50≥ can serve as important supply sources with non-inferior survival outcomes.

Purpose In 2013, the US Public Health Service (PHS) established new guidelines for high risk donor organs and renamed the category “increased risk” (IR). We compared survival outcomes of lung transplant (LTx) patients that received either IR or non-IR donor lungs to determine if IR donor lungs are an underutilized resource. Methods This study retrospectively analyzed and compared survival and utilization rates of IR and non-IR donor lung recipients at a single center from Feb-2012 to Mar-2020. LTx recipients were stratified by PHS IR status of the donor lung(s) received. Survival of IR and non-IR donor lung recipients was assessed using Kaplan-Meier (KM) survival analysis and compared by log-rank test. Cox proportional hazards modeling was used to control for variables significantly associated with IR/non-IR status, including recipient race, average warm ischemic time, transplant type, and donor age. Results Of 742 LTx patients at the center (Feb-2012 to Mar-2020), there were 193 (26%) recipients of IR organs. In 2012 and 2013, 7% and 0% respectively of the lungs transplanted at the institution were IR labeled. After the PHS guidelines were nationally implemented in Feb-2014, the proportion of IR labeled lung transplants rose to 8% (2014), 26% (2015), 40% (2016), 53% (2017), 38% (2018), and 37% (2019). Median survival times were 1.8 years for IR and 2.0 years for non-IR LTx recipients. KM survival analysis and log-rank test comparison showed no statistically significant difference in survival between IR and non-IR donor lung recipients (p = 0.606) over the 8-year period. Cox regression controlling for significant variables suggested none of the covariates significantly affected survival. Conclusion While the 2013 guidelines caused a sharp increase in lungs labeled IR, our survival analysis suggests the criteria may be misleading and of little help when assessing risks and estimating probability of survival. IR designations risk underutilization of viable lungs, a serious concern considering the waitlist demand for donors.

Purpose Cold ischemic time (CIT) may adversely affect clinical outcomes after lung transplantation (LTx). Most centers restrict CIT to less than 6-8 hours. However, to improve donor utilization, centers are increasingly pushing the envelope of CIT. To clarify the effect of CIT on graft function and clinical outcomes, we analyzed the international multicenter ECLS in LTx registry. Methods the ECLS registry collects LTx data from 6 US and 2 European centers between January 2016 and March 2020. Single LTx, ex vivo lung perfusion, and multiple organ transplants were excluded. CIT was analyzed as a continuous variable and divided in balanced tertiles. The reperfusion of the second lung was considered the end of the CIT. Models were adjusted by 11 clinical factors. Our endpoints were PGD at T0, T24, T48 and T72 hours according to the 2016 ISHLT consensus. Length of stay, death within 90 days and at one year of follow-up was investigated. A univariate and multivariate analysis was performed. Pearson correlation analysis was used to assess effect of CIT on length of stay (LOS). Results The inclusion criteria were met by 798 patients. The mean and median CIT was 418 and 397 min, respectively. Adjusted analysis suggests that total CIT was not associated with PGD grade 3 at 48 and 72 hours (OR1.24, 0.87-1.75). However, CIT was associated with several other markers of graft dysfunction and resource utilization including PGD3 T0 (OR1.5, 1.06-2.13), tracheostomy (OR1.93, 1.3-2.87), post-op ECMO (OR3.47, 2.21-5.45), renal failure requiring dialysis (OR1.8, 1.13-2.86), death within 90 days (2.41, 1.42-4.09), death in hospital (OR2.53, 1.47-4.35), and death within one year (OR 2.37, 1.43-3.94). Total ischemic time was also independently associated with LOS (P Conclusion In a multicenter international registry, increasing CIT was associated with increased PGD at T0, higher postoperative morbidity and worse first year survival. Although patients can be transplanted with extended cold ischemic times when absolutely needed, this practice is associated with greater resource utilization and likely impact on survival.

Purpose It remains unclear whether double lung transplantation (DLT) or single lung transplantation (SLT) is preferred for end-stage chronic obstructive pulmonary disease (COPD) patients. The purpose of this study is to examine the interplay between patient age and pulmonary artery pressure on survival after SLT vs DLT for COPD. Methods We performed a single-center retrospective study of lung transplantations for COPD between February 2012 to March 2020 (n=186). Demographics and clinical parameters were compared between patients based on their pulmonary artery pressure (PAP; PAP 65 years old) and PAP were analyzed using Kaplan-Meier curves and log-rank tests. Cox proportional-hazards regression was also performed. P-value less 0.05 was considered significant. Results Of the 186 COPD patients who received lung transplants, 71 (38.2%) received double-lung transplants and 115 (61.8%) received single-lung transplants. Demographics and clinical parameters between the two PAP groups showed significance in: lung allocation score (p=0.002) and BMI at time of transplant (p 65 years (p=0.723). The Cox model itself, also, did not show a statistically significant improvement in evaluating survival outcomes (p=0.126). Conclusion Lung transplantation outcomes in end-stage COPD patients demonstrated non-inferior results with SLT compared to DLT. When patients were differentiated based on PA pressure, adopting SLT or DLT did not show any survival differences.

Purpose Coronary artery disease (CAD) is not uncommon among lung transplant (LTx) and has been often carefully evaluated before LTx. Those who undergo these pre- and or post-lung transplantation percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) procedures may be at risk to LTx short-term mortality. The survival outcome of prior or perioperative revascularization has not been adequately established. Methods A single-center retrospective analysis of all single and double LTx patients from Feb-2012 to Mar-2020 (n=748) was performed. Patients were split into 4 groups: (1) patients who received a preoperative PCI (Pre-PCI) (n=55), (2) those who received preoperative CABG (Pre-CABG) (n=38), (3) those who received concomitant CABG during LTx (Con-CABG) (n=47), (4) those who had LTx with no need for revascularization (n=607). Groups were compared for demographics, surgical procedure, and survival outcomes using STATA Inc. P-value Results The no revascularization group was statistically younger than the rest (P Conclusion Our results suggest that 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 procedure.

Purpose Combined heart-lung transplantation remains the only definitive therapy for patients who have both end-stage heart failure and lung failure. We analyzed UNOS data for combined heart-lung transplant data to understand survival outcomes. Methods 1,294 patients underwent simultaneous heart-lung transplantation that were reviewed from the UNOS database between October 1987 and February 2020. Descriptives and frequencies were acquired for the variables height, weight, BMI, gender, ethnicity, age, donor age, ischemic time, length of stay, previous transplant, graft status, and creatinine level at the time of transplant were. Survival outcomes were obtained using a Kaplan-Meier Curve. The impact of all variables on survival outcomes was calculated using a cox regression. Data were expressed as mean ± std (SAS Inc). Results Out of 1,294 patients, 43.6% were male, 76.7% were Caucasian, 9.4% were African American, and 9.0% were Hispanic. 1.2% had experienced a previous transplant and 41.2% had a prior graft. Height was 160.0 ± 23.3 cm, weight was 59.1 ± 20.1 kg, BMI was 22.2 ± 4.9, age was 34.5 ± 15.3 years, donor age was 25.8 ± 14.0 years, ischemic time was 3.7 ± 1.2 hours, creatine levels were 1.0 ± .6 mg/dL, and LOS was a median of 26 days. The Kaplan-Meier Survival Curve showed 1, 3, 5, and 10 year survival outcomes of 68.5%, 53.1%, 44.7%, and 29.8% respectively. The cox regression showed a significant change in survival outcome from the inclusion of all variables (p=0.000). Only the variables graft status (p=0.000), donor age (p=0.002), and LOS (p=0.003) were significant. A prior graft increased the hazard ratio to 1.846, while the hazard ratios for donor age and LOS were 1.015 and 1.003 respectively. Conclusion In selected patients, for the last resort of the patients with end-stage cardiopulmonary failure, combined heart and lung transplantation remains a viable option for excellent outcomes.

Purpose Ex vivo lung perfusion (EVLP) improves organ quality and makes the lungs safe that were previously unsuitable for bilateral lung transplant (BLT). We investigated EVLP utilization in BLT from our ECLS registry and compared the outcome in DCD and DBD. Methods Patient data involving BLT were collected from the National ECLS Registry and stratified by EVLP in DCD and DBD. ECLS usage information was obtained and analyzed with Chi-square testing or Fisher's exact test to determine a relationship with donor groupings in EVLP. Lung transplant procedure details, patient and donor demographics and post-operative survival were analyzed using Wilcoxon rank sum test or Chi-square testing to determine distribution. Kaplan-Meier survival curves with log-rank testing to assess mortality between donor groups with EVLP use. P-values Results Out of 932 BLT, there were total 66 EVLP: 20 DCD and 46 DBD cases. Demographics data showed age:54±14 years, BMI 25 ± 5 kg/m2, 34M, LAS - 44±14, PHTN - 51 patients, prior ECMO - 2, donor age 38 ± 14, donor gender - 38M, total ischemic time - 578±149 min, Use of ECLS - CPB:7, ECMO:26, Modified bypass:8, Off-pump:25, PGD at 48h-72h - 18, Post-op ECMO: VA - 3, VV - 12, VVA - 1. Death before discharge - 9, before 90d - 5, before 1yr - 9. Tracheostomy - 15 patients, post-op pneumonia - 10 patients, median length of stay - 22 days. Unadjusted comparison reveals significant differences in 1yr survival with EVLP vs DBD vs DCD utilization (HR:2.16; CI- 1.00-4.66; p=0.05), but when adjusted, there were no significant differences (HR:0.93; CI- 0.33-2.60; p=0.883). Kaplan-Meier curve showed no statistical significance in DCD and DBD groups when used for EVLP. Conclusion EVLP utilization did not have any significant effect in survival when used in DCD and DBD transplantation. It suggests EVLP can be safely utilized in both groups thereby increasing the donor pool.

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.

Purpose Prior single center experiences suggest that use of ECLS during lung transplantation (LT) increases the risk of PGD. Here we analyze the effects of intraoperative ECLS time on PGD after LT in a multicenter ECLS registry. Methods The ECLS in LT registry includes data on bilateral LTs from 8 centers (2 from Europe, 6 from United States). The registry excludes single lung transplants and multi-organ transplants and defines primary graft dysfunction according to the ISHLT 2016 consensus statement. Herein, we refer to PGD as a single case developing PGD3 at time 48 and/or 72 hours. We explored the risk of intraoperative ECLS time on the incidence of PGD and death within 90 days using adjusted and unadjusted logistic regression and receiver operating curve (ROC) analysis. Results We identified 297 ECLS patients with intraoperative support times available between January 2016 and August of 2019. Breakdown of cases were as follows: 44% CPB, 66% ECMO (16% VV, 64%VA/VVA, 20% modified bypass-VA). Out of these, 35.6% developed PGD and 6% died within 90 days. Median time of ECLS support was 206 minutes (62-686 minutes). The median time of support was 200 minutes in patients without PGD and 206 minutes in cases with PGD. The median time of support was 202 minutes in patients who survived 90 days compared to 271 minutes in patients who did not survive 90 days. Our unadjusted and adjusted logistic regression analysis showed that time of ECLS was not associated with PGD irrespective of the mode of ECLS (CPB v ECMO). In addition, ROC analysis showed an area under the curve for ECLS time of 0.51 suggesting poor predictability for PGD. Our unadjusted analysis showed that increased time on ECLS was significantly associated with death within 90 days (P=0.014) although this was of borderline significance after adjusting for risk factors (P=0.067). Furthermore, this effect was of borderline significance for CPB (P=0.07) and not significant for ECMO (P=0.17). Conclusion In an international multicenter registry on use of ECLS in LT, the time on ECLS did not alter the risk of PGD with either CPB or ECMO, although it was associated with perioperative death. Surgeons should limit the time spent on ECLS when feasible and consider ECMO for longer procedures.

Purpose Heart transplantation (HTx) is routine in many eligible patients of different ages including elderly. We investigated the 5 year to 10 year survival outcomes of elderly heart transplantation patients by analyzing the UNOS database. Methods 51,899 patients underwent heart transplantation that were reviewed from the UNOS database (1987-2014). HTx patients were divided into two different age groups based on recipient age, Results Out of 51,899 HTx patients, 51,165 were Conclusion Older heart transplant recipients started to showed gradually increasing statistical separation from the 8th year post-HTx, favoring the younger cohort. However, survival of elderly patients (≥70) to estimated 10 years survival is still a fair probability.

Purpose Coronary artery disease (CAD) has been considered a relative contraindication for concomitant cardiac surgery during lung transplantation. We investigated a cohort of older patients who underwent concomitant coronary artery bypass grafting (CABG) with lung transplantation, to determine whether surgical outcomes were acceptable. Methods Lung transplant procedures with concomitant CABG between March 2012 and July 2019 were retrospectively analyzed. The patients investigated were over 70 years of age.Patients were propensity score-matched by pre-transplantation variables. Outcomes between these two groups were then compared; once using the entire cohort, and once using the propensity score-matched patients. Survival was compared by Kaplan-Meier curve and log-rank tests. Results There were 7 patients aged 70 or older that underwent concomitant CABG with lung transplantation. These 7 patients were 1:3 propensity score-matched with 21 of the 166 patients that did not undergo concomitant CABG. There was no statistically significant difference in survival outcomes between patients over 70 that underwent concomitant CABG and patients over 70 that did not undergo concomitant CABG (p=0.77). When analyzing the two groups after propensity score matching, there was still no statistically significant difference in survival outcomes (p=0.73). Overall survival for patients over 70 that underwent concomitant CABG was 100% at 90 days, 86% at 1 year, and 72% at 3 years. Overall survival for patients over 70 that did not undergo concomitant CABG was 93% at 90 days, 85% at 1 year, and 66% at 3 years. Conclusion Patients over 70 that underwent concomitant CABG with lung transplantation showed no significant difference in survival outcomes when compared to patients over 70 that did not undergo concomitant CABG. Considering this data, patients over 70 with CAD would be reasonable candidates for concomitant CABG with lung transplantation in selected cases.