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Long-term continuous-flow left ventricular assist device (CFLVAD) therapy is limited by complications. Compared with stroke and renal dysfunction, post-CFLVAD bowel ischemia is poorly characterized. Adult patients who underwent first-time durable CFLVAD implantation at our institution between 2008 and 2018 were identified and screened for bowel ischemia using Current Procedural Terminology codes for abdominal surgical exploration and International Classification of Disease codes for intestinal vascular insufficiency. Patients who developed biopsy-proven bowel ischemia (cases) were matched to controls (1:1, nearest neighbor, caliper = 0.29) based on preoperative characteristics. Incidences of postoperative right heart failure and renal replacement therapy were compared using McNemar's test. One year survival was estimated using the Kaplan-Meier method. Overall, 711 patients underwent CFLVAD implantation. Nineteen (2.7%) developed bowel ischemia (cases) median 17 days postimplantation (IQR 8-71). The majority of cases were male (78.9%), Black (63.2%), received HeartMate II (57.9%), treated as destination therapy (78.9%), and had a history of hypertension (89.5%), chronic kidney disease (84.2%), hyperlipidemia (84.2%), smoking (78.9%), and atrial fibrillation (57.9%). Post-LVAD, case patients were more likely to develop moderate-severe right heart failure (89.5% vs. 68.4%, p = 0.005), require renal replacement therapy (21.1% vs. 0%, p < 0.001), and less likely to survive to discharge (52.6% vs. 89.5%, p = 0.02) compared with controls. Case subjects demonstrated worse 1 year survival. While less common than stroke and renal dysfunction, post-CFLVAD bowel ischemia is associated with high 1 year mortality. Multi-institutional registries should consider reporting abdominal complications such as bowel ischemia as an adverse event to further investigate these trends and identify predictors of this complication to reduce patient mortality.

Sensitized kidney transplant recipients experience high rates of antibody-mediated rejection due to the presence of donor-specific antibodies and immunologic memory. Here we show that transient peri-transplant treatment with the central complement component C3 inhibitor Cp40 significantly prolongs median allograft survival in a sensitized nonhuman primate model. Despite donor-specific antibody levels remaining high, fifty percent of Cp40-treated primates maintain normal kidney function beyond the last day of treatment. Interestingly, presence of antibodies of the IgM class associates with reduced median graft survival (8 vs. 40 days; p = 0.02). Cp40 does not alter lymphocyte depletion by rhesus-specific anti-thymocyte globulin, but inhibits lymphocyte activation and proliferation, resulting in reduced antibody-mediated injury and complement deposition. In summary, Cp40 prevents acute antibody-mediated rejection and prolongs graft survival in primates, and inhibits T and B cell activation and proliferation, suggesting an immunomodulatory effect beyond its direct impact on antibody-mediated injury. Donor-specific antibodies in sensitized recipients may cause kidney transplant rejection. Here the authors show that complement component C3 inhibition prolongs graft survival by inhibiting T and B cell proliferation/activation and hence tissue injury, despite antibody levels remaining unaffected.

BACKGROUND: Magnetic sphincter augmentation (MSA) is a promising minimally invasive surgical technique for management of gastroesophageal reflux disease (GERD); however, device implantation after transplantation has not been studied and may be concerning in these immunosuppressed patients. We explored the safety of the LINX Reflux Management System (MSA device) for management of GERD following lung transplantation (LTx). METHODS: Lung transplant recipients who underwent LINX implantation at our institution between 2017 and 2019 were followed prospectively in the Reflux Following Lung Transplantation and Associated Treatment Registry. Ambulatory pH testing and acid-suppressing medication use were compared before and after LINX implantation. One-year outcomes and change in pulmonary function were compared between matched LINX and fundoplication groups. RESULTS: Of 17 patients who underwent post-lung transplant LINX implantation, 8 (47.1%) agreed to undergo post-LINX pH testing. Three/eight (37.5%) patients achieved normal esophageal acid exposure time; 14 (82.4%) remained on acid-suppressing medication at one-year under the direction of their transplant teams. One-year patient survival and change in pulmonary function were similar between groups. LINX patients experienced more early side effects. CONCLUSIONS: Use of the LINX MSA device in a cohort of lung transplant recipients at our institution was associated with similar short-term safety compared to traditional fundoplication, however assessment of efficacy was limited. Further investigation is needed to characterize the long-term efficacy of LINX implantation after LTx.

Objective The objective of this study was to examine early lung transplant outcomes following EVLP using a large national transplant registry. Summary of background data Lung transplantation in the United States continues to be constrained by a limited supply of donor organs. EVLP has the potential to significantly increase the available pool of donor lung allografts through the reconditioning of "marginal" organs. Methods The united network for organ sharing registry was queried for all adults (age ≥18) who underwent first-time lung transplantation between March 2018 (when united network for organ sharing began collecting confirmed donor EVLP status) and June 2019. Transplants were stratified by EVLP use. The primary outcome was short-term survival and secondary outcomes included acute rejection before discharge and need for extracorporeal membrane oxygenation support post-transplant. Results A total of 3334 recipients met inclusion criteria including 155 (5%) and 3179 (95%) who did and did not receive allografts that had undergone EVLP, respectively. On unadjusted descriptive analysis, EVLP and non-EVLP cohorts had similar 180-day survival (92% vs 92%, P = 0.9). EVLP use was associated with a similar rate of acute rejection (13% vs 9%, P = 0.08) but increased rate of early extracorporeal membrane oxygenation use (12% vs 7%, P = 0.04). After adjustment, EVLP use was not associated with significantly increased mortality (adjusted hazard ratio 0.99, 95% confidence interval 0.62-1.58) or acute rejection (adjusted odds ratio 0.89, 95% confidence interval 0.40-1.97) compared to non-EVLP use. Conclusions In the largest national series of EVLP lung transplant recipients, EVLP is associated with early recipient outcomes comparable to that of non-EVLP recipients with similar baseline characteristics. Longer term follow-up data is needed to further assess the impact of EVLP on post-lung transplant outcomes.

Preexisting donor-specific antibodies (DSA) to MHC antigens increase the risk of antibody-mediated rejection (AMR) in sensitized transplant recipients and reduces graft survival. Pretransplant desensitization with costimulation blockade and proteasome inhibition has facilitated transplantation in our preclinical nonhuman primate (NHP) model. However, long-term graft survival is limited by rebound of DSA after transplantation. In this study, we performed kidney transplants between highly sensitized, maximally MHC-mismatched NHPs (n=14). At kidney transplantation, primates received T cell depletion with rhesus-specific anti-thymocyte globulin (rhATG; n=10) or monoclonal anti-CD4 and anti-CD8 antibodies (n=4). Maintenance immunosuppression consisted of belatacept and tacrolimus (n=5) or belatacept and rapamycin (n=9) with steroids. Rebound of DSA post–kidney transplantation was significantly reduced compared with maintenance immunosuppression with tacrolimus, mycophenolate, and steroids. Protocol lymph node biopsy specimens showed a decrease in germinal center activity, with low frequencies of T follicular helper cells and class-switched B cells after kidney transplantation. Combined belatacept and rapamycin was superior in controlling viral reactivation, enabling weaning of ganciclovir prophylaxis. Tacrolimus was associated with increased morbidity that included cytomegalovirus and parvovirus viremia and post-transplant lymphoproliferative disorder. All primates in the tacrolimus/belatacept group failed discontinuation of antiviral therapy. Overall, belatacept-based immunosuppression increased AMR-free graft survival by controlling post-transplant humoral responses in highly sensitized NHP recipients and should be further investigated in a human clinical trial.

ImportanceA growing body of literature has been developed with the goal of attempting to understand the experiences of female surgeons. While it has helped to address inequities and promote important programmatic improvements, work remains to be done.ObjectiveTo explore how practicing male and female surgeons’ experiences with gender compare across 5 qualitative/quantitative domains: career aspirations, gender-based discrimination, mentor-mentee relationships, perceived barriers, and recommendations for change.Design, Setting, and ParticipantsThis national concurrent mixed-methods survey of Fellows of the American College of Surgeons (FACS) compared differences between male and female FACS. Differences between female FACS and female members of the Association of Women Surgeons (AWS) were also explored. A randomly selected 3:1 sample of US-based male and female FACS was surveyed between January and June 2020. Female AWS members were surveyed in May 2020.ExposureSelf-reported gender.Main Outcomes and MeasuresSelf-reported experiences with career aspirations (quantitative), gender-based discrimination (quantitative), mentor-mentee relationships (quantitative), perceived barriers (qualitative), and recommendations for change (qualitative).ResultsA total of 2860 male FACS (response rate: 38.1% [2860 of 7500]) and 1070 female FACS (response rate: 42.8% [1070 of 2500]) were included, in addition to 536 female AWS members. Demographic characteristics were similar between randomly selected male and female FACS, with the notable exception that female FACS were less likely to be married (720 [67.3%] vs 2561 [89.5%]; nonresponse-weighted P P Conclusions and RelevanceExperiences with gender are not limited to supportive female surgeons. The results of this study emphasize the importance of recognizing the voices of all stakeholders involved when striving to promote workforce diversity and the related need to develop quality improvement/surgical education initiatives that enhance inclusion through open, honest discourse.

Background Organ procurement organizations (OPOs) vary in willingness to pursue and utilize non-ideal donor lungs; implications of these practices for lung transplant (LTx) recipients remain unclear. We examined associations between OPO-level behavior toward non-ideal donors and post-LTx outcomes. Methods Adult lung donors and corresponding adult first-time LTx recipients in the 2008-2019 UNOS registry were included. Non-ideal donors had any of age > 50, smoking history ≥20 pack-years, PaO2 /FiO2 ratio ≤350, donation after circulatory death, or increased risk status. OPOs were classified as least, moderately, or most aggressive based on non-ideal donor pursuit, consent attainment, lung recovery, and transplantation. Post-transplant outcomes were compared among aggressiveness strata. Results Of 22,795 recipients, 6229 (27.3%), 8256 (36.2%), and 8310 (36.5%) received lungs from least, moderately, and most aggressive OPOs, respectively. Moderately aggressive OPOs had the highest recipient rates of pre-discharge acute rejection, grade 3 primary graft dysfunction, postoperative extracorporeal membrane oxygenation, and longest lengths of stay. After adjustment, moderately and most aggressive OPOs had similar risks of recipient mortality as least aggressive OPOs. Conclusions The most and least aggressive OPOs achieve similar patient survival and short-term post-LTx outcomes. Aggressive pursuit and utilization of non-ideal donor lungs by less aggressive OPOs would likely expand the donor pool, without compromising recipient outcomes.

BACKGROUND: Donors with characteristics that may increase the likelihood of disease transmission with transplantation are noted as increased risk via Public Health Service criteria. This study aimed to establish the implications of declining an increased-risk donor (IRD) organ offer in lung transplantation. METHODS: Adult candidates waitlisted for isolated lung transplantation in the United States using the Organ Procurement and Transplantation Network/United Network of Organ Sharing registry from 2007 to 2017 were identified. Individual match run files identified candidate recipients who matched to an IRD offer. Competing-risks analysis ascertained the likelihood of survival to transplantation. A stratified Cox model and restricted mean survival times estimated the survival benefit associated with the acceptance of an IRD organ. RESULTS: A total of 6,963 candidates met inclusion criteria, and 1,473 (21.2%) accepted an IRD offer. Candidates who accepted an IRD offer were older, more likely to be male, and had a higher lung allocation score at the time of listing (all p < 0.05). At 1 year after an IRD offer decline, 70.5% of candidates underwent a lung transplant, 13.8% died or decompensated, and 14.9% were still awaiting transplant. Compared with those who declined, candidates who accepted the IRD offer had significantly improved cumulative mortality at 1 year (14.1% vs 23.9%, p < 0.001) and 5 years (48.4% vs 53.8%, p < 0.001). CONCLUSIONS: IRD organ declination is associated with a decreased rate of lung transplantation and worse survival. Overall post-transplant survival rates for those who survive to transplantation are equivalent.

Background The data that exists regarding multiorgan procurement outcomes is conflicted. Given the increasing demand for pulmonary allografts, it is critical to assess the impact of dual procurement on lung transplant recipient outcomes. Methods The United Network for Organ Sharing transplant registry was queried for all first-time adult (age ≥18) lung transplant recipients between 2006 and 2018 and stratified by concurrent heart donor status. Multiorgan transplant recipients and recipients with missing survival time were excluded. Donors were excluded if they were donating after circulatory death, did not consent or were not approached for heart donation, the heart was recovered for nontransplant purposes, or the heart was recovered for transplant but not transplanted. Post-transplant survival was analyzed using the Kaplan–Meier method and multivariable Cox proportional hazards regression. Results A total of 18,641 recipients met inclusion criteria, including 6230 (33.4%) in the nonheart donor group (NHD) and 12,409 (66.6%) in the heart donor group (HD). HD recipients demonstrated longer survival at 10 years posttransplant, with a median survival of 6.5 years as compared with 5.9 years in NHD recipients. On adjusted analysis, HD and NHD recipients demonstrated comparable survival (AHR 0.95, 95% CI 0.90-1.01). Conclusions Concomitant heart and lung procurement was not associated with worse survival. This finding encourages maximizing the number of organs procured from each donor, particularly in the setting of urgency-driven thoracic transplantation.

Lungs from “non-ideal,” but acceptable donors are underutilized, however organ procurement organization (OPO) metrics do not reflect the extent to which OPO-specific practices contribute to these trends. We developed a comprehensive system to evaluate non-ideal lung donor avoidance, or risk aversion among OPOs. Adult donors in the UNOS registry who donated ≥1 organ for transplantation between 2007–2018 were included. Non-ideal donors had any of age>50, smoking history ≥20 pack-years, PaO(2)/FiO(2) ratio ≤350, donation after circulatory death, or increased risk status. OPO-level risk aversion in donor pursuit, consent attainment, lung recovery, and transplantation was assessed. Among 83,916 donors, 70,372 (83.9%) were non-ideal. Unadjusted OPO-level rates of non-ideal donor pursuit ranged from 81–100%. In a three-tier system of overall risk aversion, tier 3 OPOs (least risk-averse) had the highest rates of non-ideal donor pursuit, consent attainment, lung recovery, and transplantation. Tier 1 OPOs (most risk-averse) had the lowest rates of donor pursuit, consent attainment, and lung recovery, but higher rates of transplantation compared to tier 2 OPOs (moderately risk-averse). Risk aversion varies among OPOs and across the donation process. OPO evaluations should reflect early donation process stages to best differentiate over- and underperforming OPOs and encourage optimal OPO-specific performance.

Sensitized patients are difficult to transplant due to pre-formed anti-donor immunity. We have previously reported successful desensitization using carfilzomib and belatacept in a non-human primate (NHP) model. Here we evaluated selective blockade of the co-stimulatory signal (CD28-B7) with Lulizumab, which preserves the co-inhibitory signal (CTLA4-B7). Five maximally MHC-mismatched pairs of NHPs were sensitized to each other with two sequential skin transplants. Individuals from each pair were randomized to either desensitization with once-weekly Carfilzomib (27mg/m(2) IV) and Lulizumab (12.5mg/kg SC) over four weeks, or no desensitization (Control). NHPs then underwent life-sustaining kidney transplantation from their previous skin donor. Rhesus-specific anti-thymocyte globulin was used as induction therapy and immunosuppression maintained with tacrolimus, mycophenolate, and methylprednisolone. Desensitized subjects demonstrated a significant reduction in donor-specific antibody, follicular helper T cells (CD4(+)PD-1(+)ICOS(+)), and proliferating B cells (CD20(+)Ki67(+)) in the lymph nodes. Interestingly, regulatory T cell (CD4(+)CD25(+)CD127(lo)) frequency was maintained after desensitization in addition to increased frequency of naïve CD4 T cells (CCR7(+)CD45RA(+)) and naïve B cells (IgD(+)CD27(−)CD20(+)) in circulation. This was associated with significant prolongation in graft survival (MST = 5.8 ± 4.0 vs. 64.8 ± 36.3; p

SUMMARY There is debate surrounding the appropriate threshold for lymph node harvest during esophagectomy in patients with esophageal cancer, specifically for those receiving preoperative radiation. The purpose of this study was to determine the impact of lymph node yield on survival in patients receiving preoperative chemoradiation for esophageal cancer. The National Cancer Database (NCDB) was utilized to identify patients with esophageal cancer that received preoperative radiation. The cohort was divided into patients undergoing minimal ( 0.05). After adjustment using Cox regression, extensive lymph node yield was associated with survival (hazard ratio 0.80, confidence interval 0.66–0.98, P = 0.03). This study suggests that extensive lymph node yield is advantageous for patients with esophageal cancer undergoing esophagectomy following induction therapy. This most likely reflects improved diagnosis and staging with extensive yield.

OBJECTIVES/GOALS: We sought to examine: 1) variability in center acceptance patterns for heart allografts offered to the highest-priority candidates, 2) impact of this acceptance behavior on candidate survival, and 3) post-transplantation outcomes in candidates who accepted first rank offer vs. previously declined offer. METHODS/STUDY POPULATION: In this retrospective cohort study, the US national transplant registry was queried for all match runs of adult candidates listed for isolated heart transplantation between 2007-2017. We examined center acceptance rates for heart allografts offered to the highest-priority candidates and accounted for covariates in multivariable logistic regression. Competing risks analysis was performed to assess the relationship between center acceptance rate and waitlist mortality. Post-transplantation outcomes (patient survival and graft failure) between candidates who accepted their first-rank offers vs those who accepted previously declined offers were compared using Fine-Gray subdistribution hazards model. RESULTS/ANTICIPATED RESULTS: Among 19,703 unique organ offers, 6,302 (32%) were accepted for first-ranked candidates. After adjustment for donor, recipient, and geographic covariates, transplant centers varied markedly in acceptance rates (12%-62%) of offers made to first-ranked candidates. Lowest acceptance rate centers (

Traditionally, pacing leads are placed transvenously, although smaller pediatric patients who require permanent pacemakers may benefit from delaying tranvenous lead placement until they are larger. Alternative, minimally invasive atrioventricular pacing options have not previously existed for this patient population, leaving many of these children with large sternotomies or thoracotomies. Using three port sites and an adjustable shaft dual-needle suturing device, we placed a steroid-eluting, sew-on epicardial lead on the right atrium of a 9-year-old patient. This is one of the earliest reported cases of a minimally invasive technique for sew-on epicardial lead placement on the atrium of a child. Although based on a single case, we believe that this approach is safe, reliable, and reproducible and that it can be used to place leads on any aspect of the heart. Adoption of this technique will allow for earlier atrioventricular pacing, which may decrease the incidence of pacemaker syndrome, and thus improve overall outcomes in this patient population.

Background Patterns of use of older donor lungs within this previously underused donor population are poorly characterized. This study examined factors associated with the use of older donor lung allografts and factors associated with survival in recipients of these lungs. Methods Adult donors in the United Network for Organ Sharing registry who donated 1 or more organs for transplantation between 2006 and 2018 were analyzed and stratified into older (age >55 years) and younger (age ≤55 years) cohorts. Multivariable logistic and Cox regression were used to identify factors associated with transplantation of older donor lungs and factors associated with survival, respectively. Results Overall, 202,477 donors were included and stratified by age (older, 40,406 [20%]; younger, 162,071 [80%]). Compared with younger donors, older donors had an increased rate of consent for donation not requested by organ procurement organizations (7.5% vs 1.7%). Donor factors significantly associated with decreased lung use included male sex, increasing donor age, black race, Hispanic ethnicity, cigarette use, cocaine use, donation after circulatory death status, and PaO2/FiO2 (P/F ratio) lower than 350. In recipients of older donor lungs, increasing donor age (hazard ratio [HR], 1.03; 95% confidence interval [CI], 1.01, 1.05), recipient age 47 years or older (HR 1.03; 95% CI, 1.02, 1.04), and male sex (HR, 1.19; 95% CI, 1.02, 1.39) portended worse survival. Conclusions Barriers in consenting practices, concerns about organ function, and recipient survival prevent the widespread use of aged allografts for lung transplantation. Better understanding of factors associated with worse outcomes of older donors and modification of organ procurement organization consenting practices may increase the use of these higher-risk donor organs.

Our understanding of the role of B cells in organ transplantation remains incomplete and continues to grow. The majority of research has focused on the detrimental role of antibodies that drive the development of pathogenesis of the transplanted organ. However, it has been shown that not all donor-specific antibodies are harmful and in some circumstances can even promote tolerance through the mechanism of accommodation. Furthermore, B cells can have effects on transplanted organs through their interaction with T cells, namely antigen presentation, cytokine production, and costimulation. More recently, the role and importance of Bregs was introduced to the field of transplantation. Due to this functional and ontogenetic heterogeneity, targeting B cells in transplantation may bring undesired immunologic side effects including increased rejection. Therefore, the selective control of B cells that contribute to the humoral response against donor antigens will continue to be an important and challenging area of research and potentially lead to improved long-term transplant outcomes.

Background Constrictive pericarditis is a rare, but increasingly recognized long-term postoperative complication of lung transplantation. Heightened clinical suspicion, improved diagnostic imaging, and effective surgical treatment of the disease have led to progressive awareness of the pathology. We present our institutional experience with constrictive pericarditis after lung transplant in an effort to investigate the cause and natural history of the disease. Methods From October 2005 to October 2018, 1234 patients underwent orthotopic lung transplantation at Duke University Hospital. An institutional database was queried to identify incident patients and determine baseline clinical data. At a median of 11.2 months (interquartile range = 4.6-28.6 mo), 10 patients (0.8%) developed constrictive pericarditis. Simple descriptive statistics were used to describe cohort characteristics and identify variables associated with constrictive pericarditis after lung transplantation. Results The indication for transplantation at index operation was idiopathic pulmonary fibrosis in 8 of 10 patients (1.2% of the 760 restrictive lung disease patients transplanted in the same time period). All 10 patients presented with worsening dyspnea and pleural effusions. Right heart catheterization confirmed constrictive physiology in all cases. Eight patients underwent pericardiectomy with improvement in cardiovascular hemodynamics and resolution of symptoms with no 30-day mortality. Conclusions Diagnosis of constrictive pericarditis should be considered in patients with new-onset heart failure symptoms or recurrent pleural effusions within 2 years of lung transplantation. Idiopathic pulmonary fibrosis may be associated with increased risk for constrictive pericarditis. Pericardiectomy is a safe and effective treatment for posttransplant constrictive pericarditis.

PURPOSE OF REVIEW: Manipulating costimulatory signals has been shown to alter T cell responses and prolong graft survival in solid organ transplantation. Our understanding of and ability to target various costimulation pathways continues to evolve. RECENT FINDINGS: Since the approval of belatacept in kidney transplantation, many additional biologics have been developed targeting clinically relevant costimulation signaling axes including CD40-CD40L, inducible costimulator-inducible costimulator ligand (ICOS-ICOSL), and OX40-OX40L. Currently, the effects of costimulation blockade on posttransplant humoral responses, tolerance induction, and xenotransplantation are under active investigation. Here, we will discuss these pathways as well as preclinical and clinical outcomes of biologics targeting these pathways in organ transplantation. SUMMARY: Targeting costimultion is a promising approach for not only controlling T cell but also B cell responses. Consequently, costimulation blockade shows considerable potential for improving outcomes in antibody-mediated rejection and xenotransplantation.

BACKGROUND Lung transplantation offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which variability in per-center offer acceptance practices impacts candidate survival is not established. The purpose of this study was to determine the degree of variability in per-center rates of lung transplantation offer acceptance and to ascertain the associated contribution to observed differences in per-center waitlist mortality. METHODS We performed a retrospective cohort study of candidates waitlisted for lung transplantation in the US using registry data. Logistic regression was fit to assess the relationship of offer acceptance with donor, candidate, and geographic factors. Listing center was evaluated as a fixed effect to determine the adjusted per-center acceptance rate. Competing risks analysis employing the Fine-Gray model was undertaken to establish the relationship between adjusted per-center acceptance and waitlist mortality. RESULTS Of 15,847 unique organ offers, 4,735 (29.9%) were accepted for first-ranked candidates. After adjustment for important covariates, transplant centers varied markedly in acceptance rate (9%–67%). Higher cumulative incidence of 1-year waitlist mortality was associated with lower acceptance rate. For every 10% increase in adjusted center acceptance rate, the risk of waitlist mortality decreased by 36.3% (sub-distribution hazard ratio 0.637; 95% confidence interval 0.592–0.685). CONCLUSIONS Variability in center-level behavior represents a modifiable risk factor for waitlist mortality in lung transplantation. Further intervention is needed to standardize center-level offer acceptance practices and minimize waitlist mortality.

Donor brain death duration (BDD) may impact posttransplant graft function and survival in lung transplant.We queried the 2007 to 2018 United Network for Organ Sharing Registry for adult recipients undergoing first-time isolated lung transplant. Cox proportional hazard modeling with splines enabled identification of 3 donor brain death intervals for subsequent analysis: short (24 hours), reference (24-60 hours), and long (60 hours). The primary outcome was posttransplant survival.In total, 19,721 donors and recipients met inclusion criteria. Median time from donor brain death until cross-clamp was 36.6 hours (interquartile range, 19.5). Unadjusted overall survival between cohorts was equivalent (log-rank P = .42); however, longer BDD was associated with improved bronchiolitis obliterans syndrome (BOS)-free survival (log-rank P.001). On multivariable Cox proportional hazards regression, BDD was not associated with recipient survival (P.05). Similarly, logistic regression did not identify an independent association between BDD and primary graft dysfunction (P .05). Increased BDD was, however, associated with a decreased risk of acute rejection (long vs reference; adjusted odds ratio, 0.78; 95% confidence interval, 0.64-0.94) and improved BOS-free survival (long vs reference; adjusted hazard ratio, 0.88; 95% confidence interval, 0.81-0.96).Donor BDD is not associated with posttransplant survival or primary graft dysfunction. Long donor BDD, however, is associated with a decreased risk for acute rejection and improved BOS-free survival. Therefore, lung allografts from donors with a prolonged length of time from brain death until explant should not be viewed less favorably by donor selection centers.

Central Message: Utilization of donation after circulatory death lungs can be improved with appropriate interventions. International guidelines should be developed to facilitate improved organ recovery. (185/200 characters) Perspective Statement: Waitlist mortality is currently at an all-time high in lung transplantation in the United States. Donation after circulatory death lungs have shown promise in expanding the donor pool, yet the US lags behind several other countries in utilizing these organs. With appropriate interventions such as ex-vivo lung perfusion, many factors that influence these practice patterns can potentially be improved. (402/405 characters); Abstract 250/250 Objective: Despite growing evidence of comparable outcomes in recipients of donation-after-circulatory-death and donation-after-brain-death donor lungs, donation-after-circulatory-death allografts continue to be underutilized nationally. We examined predictors of non-utilization. Methods: All donors who donated at least one organ for transplantation between 2005-2019 were identified in the United Network of Organ Sharing registry and stratified by donation type. The primary outcome of interest was utilization of pulmonary allografts. Organ disposition and refusal reasons were evaluated. Multivariable regression modeling was used to assess the relationship between donor factors and utilization. Results: A total of 15,458 donation-after-circulatory-death donors met inclusion criteria. Of 30,916 lungs, 3.7% (1,158) were utilized for transplantation and 72.8% were discarded primarily due to poor organ function. Consent was not requested in 8.4% of donation-after-circulatory-death offers with donation-after-circulatory-death being the leading reason (73.4%). Non-utilization was associated with smoking history (p 50 (0.75, p=0.031). Recent transplant era was associated with significantly increased utilization (AOR 2.28, p Conclusions: Non-transplantation of donation-after-circulatory-death lungs was associated with potentially modifiable pre-donation factors, including organ procurement organizations’ consenting behavior, and donor factors, including hypoxemia. Interventions to increase consent and standardize donation-after-circulatory-death donor management, including selective use of ex-vivo lung perfusion in the setting of hypoxemia, may increase utilization and the donor pool.

OBJECTIVES/GOALS: Lung transplant (LTx) candidates benefit from use of non-ideal donor organs. Each organ procurement organization (OPO) defines “acceptable” donor organs introducing unmeasured variation in donor pursuit. We characterized non-ideal donor pursuit among OPOs to identify drivers of risk aversion in LTx. METHODS/STUDY POPULATION: We queried the UNOS registry for adult donors who donated ≥1 organ for transplantation from 12/2007-12/2018. Non-ideal donors were those with any of age>50, smoking history ≥20 pack-years, PaO2/FiO2 (P/F) ratioFigure). Of 5 non-ideal characteristics, DCD and IRD status were associated with the most and least risk aversion, respectively. Non-ideal donor pursuit was strongly correlated with overall donor pursuit (r = 0.99). On adjusted analysis, older age (OR 0.15, 95% CI 0.13-0.16), smoking history (OR 0.38, 95% CI 0.34-0.44), low P/F ratio (OR 0.12, 95% CI 0.11-0.14), and DCD status (OR 0.04, 95% CI 0.03-0.04) were all independently associated with significant risk aversion, corresponding to decreased rates of donor pursuit. DISCUSSION/SIGNIFICANCE OF IMPACT: OPOs differ in their levels of risk aversion in LTx and risk aversion is not uniform across selected categories of non-ideal lung donor. Consideration of new OPO performance metrics that encourage the pursuit of non-ideal lung donors is warranted.

Importance Under the current Centers for Medicare & Medicaid Services guidelines, there is incentivization to optimize posttransplant outcomes regardless of mortality among patients on the waitlist and transplant rates; few data exist with regard to transplant center acceptance practices and survival to heart transplant. Objectives To evaluate the extent of variability in organ acceptance practices in the US and whether this center-level behavior is associated with heart transplant candidate survival. Design, Setting, and Participants In this retrospective cohort study, the US National Transplant Registry was queried for all match runs of adult candidates listed for isolated heart transplant between May 1, 2007, and March 31, 2017. Data analysis was conducted from October 30, 2018, to May 1, 2019. The final cohort included 93 transplant centers, 19 703 donors, and 9628 candidates. Main Outcomes and Measures Center acceptance rates for heart allografts offered to the highest-priority candidates, association between center acceptance rate and mortality among patients on the waitlist, and posttransplant outcomes between candidates who accepted their first-rank offers vs those who accepted previously declined offers. Results Among 19 703 unique organ offers, 6302 hearts (32.0%) were accepted for first-rank candidates. After adjustment for donor, candidate, and geographic covariates, transplant centers varied in acceptance rates (12.3%-61.5%) of offers made to first-rank candidates. Higher acceptance rates were associated with lower cumulative incidence of 1-year mortality among patients on the waitlist. For every 10% increase in adjusted center acceptance rate, the risk of mortality decreased by 27% (subdistribution hazard ratio, 0.73; 95% CI, 0.67-0.80). No statistically significant difference was observed in 5-year adjusted posttransplant patient survival (adjusted hazard ratio, 1.02; 95% CI, 0.94-1.11) and graft failure (subdistribution hazard ratio; 0.95; 95% CI, 0.83-1.09) between hearts accepted at the first-rank compared with lower-rank positions. Conclusions and Relevance Variability in heart allograft acceptance rates appears to exist among transplant centers, with candidates listed at lower acceptance rate centers being more likely to experience mortality while on the waitlist. Comparable posttransplant survival suggests that allografts that were declined as a first offer perform as well as those that were accepted at their first offer. These findings suggest that organ acceptance rate or time to transplant from being added to the waitlist may be an additional measure of heart transplant program performance.

Background Right heart failure occurs in 9% to 44% of left ventricular assist device (LVAD) implants, of which less than 10% require right ventricular assist device (RVAD) support either concurrently with the LVAD or staged, as a delayed procedure. We have reported our outcomes based on whether the RVAD was placed concurrently or staged. Methods Clinical data were obtained from the Duke University Medical Center database. The study focused on all consecutive adult patients who received continuous flow LVAD with either concurrent or staged (within 7 days) extracorporeal, temporary RVAD, between October 2007 and October 2017. Adverse event profiles and ability to wean from RVAD were compared between these two groups. Results Overall, 43 patients required an extracorporeal RVAD; 67% (n = 29) were implanted concurrently and 33% (n = 14) were implanted as staged after the LVAD. In all, 67% of patients (n = 29) could be weaned to an isolated LVAD. The 30-day, inhospital, and total mortality rates for our cohort were 14%, 28%, and 51% respectively. The mortality rate in the study period for the staged implants was 71% versus 45% for the concurrent implants (p = 0.101). In addition, staged RVAD implantation carried a significantly higher rate of postoperative renal failure (64% versus 28%, p = 0.044). Conclusions There was a low incidence of need for RVAD in our cohort. The majority could be weaned to an isolated LVAD. Morbidity and mortality rates of this mode of biventricular support remain high. Early institution of RVAD support was associated with reduced rates of post-LVAD renal failure rates.

Purpose Constrictive pericarditis has become an increasingly recognized long-term post-operative complication of lung transplantation. Heightened clinical suspicion, improved diagnostic imaging and effective surgical treatment of the disease have led to progressive awareness of the pathology. We present our institutional experience with constrictive pericarditis in an effort to investigate the etiology and natural history of the disease. Methods From October 2005 to October 2018, 1,234 patients underwent orthotopic lung transplantation at Duke University Hospital. A prospectively maintained institutional database was queried to identify incident patients and determine baseline clinical data. At a median of 13.8 months (IQR 4.6-124 months), 10 patients (0.8%) developed constrictive pericarditis. Simple descriptive statistics were used to describe cohort characteristics and identify variables associated with constrictive pericarditis after lung transplantation. Results The indication for transplantation at index operation was idiopathic pulmonary fibrosis in 9 of 10 patients (1.2% of the 760 restrictive lung disease patients transplanted in the same time period). All ten patients presented with worsening dyspnea and pleural effusions. Right heart catheterization confirmed constrictive physiology in all cases. Nine patients underwent pericardiectomy with improvement in cardiovascular hemodynamics and resolution of symptoms with no 30-day perioperative mortality. Conclusion Diagnosis of constrictive pericarditis should be considered in patients with new onset heart failure symptoms and/or recurrent pleural effusions within 2 years of lung transplantation. Idiopathic pulmonary fibrosis may be associated with increased risk for constrictive pericarditis. Pericardiectomy is a safe and effective treatment for post-transplant constrictive pericarditis.

Purpose Lung transplantation (LTx) offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which center-level variability in organ acceptance impacts candidate survival is not established. Methods We performed a retrospective cohort study of candidates aged ≥ 12 waitlisted for isolated LTx in the US using UNOS/OPTN data from May 2007 to May 2017. Centers that never had candidates ranked first on a match run >10 times in a year were excluded. Logistic regression was fit to assess the relationship of offer acceptance with donor-, candidate-, and geographic factors. Listing center was evaluated as a fixed effect to determine the adjusted per-center acceptance rate. Competing risks analysis employing the Fine-Gray model was undertaken to ascertain the relationship between the adjusted per-center acceptance rate and waitlist mortality. Results Of 15,847 unique organ offers, 4,735 (29.9%) were accepted for the first-ranked patients. After adjustment for important covariates, transplant centers varied markedly in acceptance rate practices (9% to 67%). Higher cumulative incidence of 1-year waitlist mortality was associated with lower acceptance rate (Figure 1). For every 10% increase in adjusted center acceptance rate, the risk of waitlist mortality decreased by 36.3% (subdistribution hazard ratio 0.637; CI 0.592, 0.685). Importantly, high-acceptance centers that accepted ≥ 40% of their first-ranked offers had improved 1-year post-transplant survival compared to centers with adjusted organ acceptance rates Conclusion Variability in center-level behavior potentially represents the largest modifiable risk factor for prolonged waitlist times and mortality in LTx. Further intervention is needed to standardize center-level organ offer acceptance practices and minimize waitlist mortality at the national level.

Purpose Despite growing evidence that donation after circulatory death (DCD) lung transplants have comparable survival outcomes and primary graft dysfunction rates to donation after brain death (DBD), DCD continues to be underutilized in the US. We examined DCD donor characteristics associated with non-utilization. Methods In this retrospective study, all adult (age ≥ 18) DCD donors who donated at least one organ for transplant between 1993 and 2017 were analyzed from the UNOS registry. DBD donors and DCD donors who did not successfully donate any organ were excluded. Organ disposition per lung and reasons for non-use of donor lungs were identified. The primary outcome of interest was donor characteristics that correlated with lower transplant rates. Results A total of 12,627 DCD donors met inclusion criteria. Of 25,254 lungs available for analysis, 2.8% were transplanted and 68% were discarded primarily due to poor organ function and ischemic time constraints. Notably, consent was not requested in 15.3% of DCD offers with non-heart beating donor being the leading reason for consent not requested (77.7%). DCD lungs were less likely to be transplanted if the donor had a higher BMI (mean 26.6 vs. 25.4, p=0.008), smoking history (23.7% vs. 7.5%, p Conclusion The underutilization of DCD lungs in the US remains consistent with prior studies, in contrast with 30-40% utilization in several other countries. The most common reasons for non-transplantation of DCD lungs include modifiable pre-donor factors, such as lack of consent request, as well as donor factors, including hypoxemia. Interventions to increase consent and optimize DCD donor conditions, such as selective use of ex vivo lung perfusion, may increase utilization of DCD organs and expand the donor pool.

OBJECTIVES/SPECIFIC AIMS: The purpose of the study was to describe patient characteristics associated with subsequent development of bowel ischemia. Primary outcomes were survival to discharge, 30-day and 1-year survival in patients with LVAD who subsequently develop bowel ischemia. Secondary outcomes included characteristics of patients who survive to discharge after bowel ischemia and those who do not. These included markers of patient condition prior to surgical/endoscopic intervention such as lactate levels, ICU admission, ventilator dependence, vasopressor and renal replacement requirements, as well as presence of sepsis. Of these, we predicted that lactate levels and white blood cell count would be significantly elevated pre- and post-operatively in patients who do not recover from bowel ischemic event. We used Mann-Whitney U Test to examine lactate levels between the two groups as our sample size was

Protective mucus layers serve as the body’s first line of defense at exposed surfaces of the eyes and respiratory, gastrointestinal, and cervicovaginal tracts. These highly viscoelastic and adhesive mucus gels trap most foreign pathogens and environmental ultrafine particles, which are then removed by mucus clearance mechanisms[1] (on the order of seconds to a few hours, depending on anatomical site). However, mucus also immobilizes and rapidly clears therapeutic nanoparticles, including synthetic drug carriers,[2] and clinically tested viral[3] and nonviral gene vectors[4] and, therefore, represents a critical obstacle to localized drug and gene delivery at mucosal surfaces for the treatment of a variety of diseases.[1b]