Project description:BackgroundDonor selection criteria are crucial for a successful lung transplant outcome. Our objective was to develop a new donor score to predict short- and long-term survival and validate it with five existing lung donor scores (Oto, Eurotransplant, Minnesota, Maryland-UNOS, Louisville-UNOS).MethodsAll 454 adult lung transplants at our center between 1992-2015 were included to develop a new score. Discriminative ability for all scores was calculated by the area under time-dependent receiver operating characteristic curves (time-dependent AUC) at 30-day, 1, 5 and 10-year survival, and their fit compared with Akaike's information criterion. For the new score, five pre-selected donor risk factors were derived: age, diabetes mellitus, smoking history, pulmonary infection, PaO2/FiO2-ratio, weighed via simplification of a multiple Cox model, and shrinkage used to avoid overfitting. The score sub-weighting resulted in a total of 17 points.ResultsThe existing scores showed predictive accuracy better than chance in prediction of survival of 5-year (AUC 0.58-0.60) to 10-year survival (AUC 0.58-0.64). Our new score had better discriminative ability as the existing scores with regard to 1, 5 and 10-year survival (AUC 0.59, 0.64, 0.66, respectively). Additional adjustment for recipient and surgical procedure variables improved the time-dependent AUC's slightly. For the secondary outcomes primary graft dysfunction and bronchiolitis obliterans syndrome, the new score showed also a good predictive accuracy.ConclusionsThe proposed Zurich Donor Score is simple, well adapted for the current urge of extended donors use, and shows higher discriminative ability compared to preexisting donor scores regarding short- to long-term survival.
Project description:PurposesDelayed chest closure (DCC) is a widely accepted procedure in the context of lung transplantation (LTx); yet there are few reports detailing its long-term survival and clinical outcomes.MethodsWe reviewed the medical records of recipients who underwent deceased-donor lung transplantation (LTx) at Tohoku University Hospital. Long-term survival, including overall survival, freedom from chronic lung allograft dysfunction (CLAD), and CLAD-free survival and the clinical outcomes of graft function and physical performance and constitution were reviewed in recipients with DCC.ResultsBetween 2009 and 2022, 116 patients underwent LTx, 33 of whom (28.4%) required DCC. The intra-and post-operative courses of the recipients who required DCC were more complicated than those of the recipients who underwent primary chest closure (PCC), with frequent volume reduction surgery and longer periods of invasive mechanical ventilation. Pulmonary vascular disease was considered a risk factor for these complications and DCC. Nonetheless, long-term survival and graft functions were comparable between the DCC and PCC groups. The physical performance and constitution of recipients who required DCC continued to improve, and by 2 years after transplantation, exhibited almost no difference from those who underwent PCC.ConclusionsIn view of the profoundly complicated intra- and post-operative courses, DCC should be performed cautiously and only when clinically indicated, despite which it can result in equivalent long-term survival and acceptable outcomes to PCC.
Project description:Lung transplantation in mechanically ventilated (MV) patients has been associated with decreased posttransplant survival. Under the Lung Allocation Score (LAS) system, patients at greatest risk of death on the waiting list, particularly those requiring MV, are prioritized for lung allocation. We evaluated whether pretransplant MV is associated with poorer posttransplant survival in the LAS era. Using a national registry, we analyzed all adults undergoing lung transplantation in the United States from 2005 to 2010. Propensity scoring identified nonventilated matched referents for 419 subjects requiring MV at the time of transplantation. Survival was evaluated using Kaplan-Meier methods. Risk of death was estimated by hazard ratios employing time-dependent covariates. We found that pretransplant MV was associated with decreased overall survival after lung transplantation. In the first 6 months posttransplant, ventilated subjects had a twofold higher risk of death compared to nonventilated subjects. However, after 6 months posttransplant, survival did not differ by MV status. We also found that pretransplant MV was not associated with decreased survival in noncystic fibrosis obstructive lung diseases. These results suggest that under the LAS, pretransplant MV is associated with poorer short-term survival posttransplant. Notably, the increased risk of death appears to be strongest the early posttransplant period and limited to certain pretransplant diagnoses.
Project description:BACKGROUND Kidney transplant recipients have higher life expectancy but may require subsequent transplantations, raising ethical concerns regarding organ allocation. We assessed the safety of multiple kidney transplants through long-term follow-up. MATERIAL AND METHODS A retrospective cohort study was conducted at a single center, categorizing patients based on the number of kidney transplantations received. The primary outcome was the composite of death-censored graft failure and overall mortality. The secondary outcome was death-censored graft failure. RESULTS Between 2000 and 2019, our center performed 2152 kidney transplantations. Patients were divided into 3 groups: A (1 transplant; n=1850), B (2 transplants; n=285), and C (3 or more transplants; n=75). Group C patients were younger, had fewer comorbidities, and received more aggressive induction therapy. The primary outcomes, including death-censored graft loss and overall mortality, showed similar rates across groups (A: 21.3%, B: 25.2%, C: 21.7%, p=0.068). However, the secondary outcome of death-censored graft failure alone was significantly lower in group A compared to the other groups. No significant difference was observed between groups B and C (8% vs 16% and 13%, respectively, p=0.001, p=0.845). Multivariate analysis identified having a living donor as the strongest predictor of patient and graft survival in all study groups. CONCLUSIONS Graft and patient survival rates were similar between first and multiple transplant recipients. Multiple transplant recipients had lower death-censored graft failure risk compared to first transplant recipients. However, the risk did not differ among second and subsequent transplant recipients. Younger patients, especially those with a living donor, should be considered for repeat kidney transplantation.
Project description:Allograft failure remains a major barrier in the field of lung transplantation and results primarily from acute and chronic rejection. To date, standard-of-care immunosuppressive regimens have proven unsuccessful in achieving acceptable long-term graft and patient survival. Recent insights into the unique immunologic properties of lung allografts provide an opportunity to develop more effective immunosuppressive strategies. Here we describe advances in our understanding of the mechanisms driving lung allograft rejection and highlight recent progress in the development of novel, lung-specific strategies aimed at promoting long-term allograft survival, including tolerance.
Project description:The long-term survival after lung transplantation (LT) is favorable in Japan. However, long-term survivors after LT are subject to late complications, including chronic lung allograft dysfunction (CLAD), malignancy, infection, and chronic kidney disease (CKD) because of the need for lifelong immunosuppression. The rates of single cadaveric LT (CLT) and living-donor lobar LT (LDLLT) are higher than that of bilateral CLT in Japan. Here, we will describe the management of late complications and long-term outcome after LT in Japan. Attention should be paid to not only the phenotype of CLAD but also the difference in CLAD after CLT and after LDLLT as well as the timing of lung re-transplantation for advanced CLAD, especially after single CLT. Since post-transplant lymphoproliferative disorder is the most common malignancy after LT, infection monitoring for infection-related malignancies and appropriate screening are keys to the early diagnosis and treatment of malignancy after LT. The long-term management of infection after LT is also important, especially with regard to community-acquired pathogens, Aspergillus, and cytomegalovirus. When providing long-term care after LT, physicians should be aware of CKD and the timing of renal replacement therapy in cases with severe CKD. The widespread use of computed tomography and dialysis in Japan are beneficial for long-term survivors of LT. The similar survival outcomes of single CLT and LDLLT, compared with bilateral CLT, might contribute to improved long-term survival in Japan. Pulmonologists are encouraged to become further involved in long-term management after LT in Japan.
Project description:PurposeAllogeneic hematopoietic cell transplantation (HCT) is curative but is associated with life-threatening complications. Most deaths occur within the first 2 years after transplantation. In this report, we examine long-term survival in 2-year survivors in the largest cohort ever studied.Patients and methodsRecords of 10,632 patients worldwide reported to the Center for International Blood and Marrow Transplant Research who were alive and disease free 2 years after receiving a myeloablative allogeneic HCT before 2004 for acute myelogenous or lymphoblastic leukemia, myelodysplastic syndrome, lymphoma, or severe aplastic anemia were reviewed.ResultsMedian follow-up was 9 years, and 3,788 patients had been observed for 10 or more years. The probability of being alive 10 years after HCT was 85%. The chief risk factors for late death included older age and chronic graft-versus-host disease (GVHD). For patients who underwent transplantation for malignancy, relapse was the most common cause of death. The greatest risk factor for late relapse was advanced disease at transplantation. Principal risk factors for nonrelapse deaths were older age and GVHD. When compared with age, sex, and nationality-matched general population, late deaths remained higher than expected for each disease, with the possible exception of lymphoma, although the relative risk generally receded over time.ConclusionThe prospect for long-term survival is excellent for 2-year survivors of allogeneic HCT. However, life expectancy remains lower than expected. Performance of HCT earlier in the course of disease, control of GVHD, enhancement of immune reconstitution, less toxic regimens, and prevention and early treatment of late complications are needed.
Project description:Sarcopenia, the loss of muscle mass and quality, contributes to worse clinical outcome in patients with end-stage liver disease, but its impact on short- and long-term survival remains insufficiently understood. The aim of this study was to evaluate the development of computed tomography (CT) muscle parameters and their impact on short-term and long-term survival after liver transplantation. This retrospective study included patients with liver transplantation between 2011 and 2015 and a pre-transplant CT scan. Clinical characteristics, CT muscle mass and density were assessed pre-transplant, and in available CT scans at short-term (11 months) and long-term follow-up (56 months). Overall, 93/152 (61%) patients (109 male, 55 ± 10 years) suffered from sarcopenia pre-transplant. In short- (n = 50) and long-term follow-up (n = 52) the muscle mass (- 2.65 cm2/m2 95% CI [- 4.52, - 0.77], p = 0.007; - 2.96 cm2/m2 [- 4.7, - 1.23], p = 0.001, respectively), and muscle density (- 3 HU [- 6, - 1], p = 0.007; - 2 HU [- 4, 0], p = 0.069) decreased. Myosteatosis was associated with a higher post-transplant mortality (survival probability: 3 months 72% vs. 95%, 1 year 63% vs. 90%, 5 years 54% vs. 84%, p = 0.001), while muscle mass was not. In conclusion, muscle mass and quality did not improve after transplant. Muscle quality predicts short- and long-term survival and could help to identify a patient's risk profile.
Project description:ObjectiveA small but growing proportion of lung transplant recipients survive longer than a decade post-transplant. The aim of this study was to identify factors associated with survival beyond a decade after lung transplant.MethodsWe queried the United Network for Organ Sharing registry for adult (age ≥18 years) recipients undergoing first-time isolated lung transplantation between the introduction of the Lung Allocation Score in 2005 and 2009. Recipients were stratified into 3 cohorts: those who survived less than 1 year, 1 to 10 years, and greater than 10 years. Multivariable logistic regression was used to identify factors independently associated with early mortality (<1 year) and long-term (>10 years) survival.ResultsA total of 5171 lung transplant recipients and their associated donors met inclusion criteria, including 964 (18.6%) with early mortality, 2843 (55.0%) with intermediate survival, and 1364 (26.3%) long-term survivors. Factors independently associated with early mortality included donor Black race, cigarette use, arterial oxygen partial pressure/fractional inspired oxygen ratio, diabetes, recipient Lung Allocation Score, total bilirubin, extracorporeal membrane oxygenation bridge requirement, single lung transplantation, and annual lung transplant center volume. The only factors independently associated with long-term survival among those who survived at least 1 year was donor age and single lung transplantation.ConclusionsOf patients undergoing lung transplantation after the implementation of the Lung Allocation Score, approximately one-quarter survived 10 years post-transplant. There was minimal overlap between the factors associated with 1-year and 10-year survival. Of note, the Lung Allocation Score was not associated with long-term survival. Further research is needed to better refine patient selection and optimize management strategies to increase the number of long-term survivors.