The Conversional Efficacy of Ex Vivo Lung Perfusion and Clinical Outcomes in Patients Undergoing Transplantation of Donor Lungs by Ex Vivo Lung Perfusion: A Meta-Analysis.

BACKGROUND: Ex vivo lung perfusion (EVLP) is a relatively new technique that can be used to assess and repair the donor lungs, increasing the utilization of high-risk lungs. However, its effect on outcomes of lung transplantation patients is uncertainty. This meta-analysis is conducted to assess the impact of EVLP on donor lungs and outcomes of recipients compared with the standard lung transplantation. MATERIAL/METHODS: We systematically searched for studies comparatively analyzing the efficacy of EVLP and standard cold storage in lung transplantation. The hazard ratio (HR), relative risk (RR), and weighted mean difference (WMD) were used as the effect size (ES) to evaluate the survival outcomes, categorical variables, and continuous variables respectively. RESULTS: A total of 20 published articles (including 2574 donors and 2567 recipients) were eligible. The chest x-ray manifestations and PaO2/FiO2 100% were more deficient in the EVLP group than the standard group. EVLP improved the function of high-risk donor lungs with the conversion rate ranging from 34% to 100%. The EVLP group had a lower incidence of primary graft dysfunction 3, but longer intensive care unit stay. Other clinical outcomes between the 2 groups were similar. CONCLUSIONS: The pooled results indicated that EVLP could be used to assess and improve high-risk donor lungs and had non-inferior postoperative outcomes compared with the standard cold storage. EVLP not only increased the utilization of marginal donors, but also could extend preservation time and reduce the total ischemia time of donors.

Adherence is associated with a favorable outcome after lung transplantation.

Non-adherence to therapy is associated with impaired outcome in solid organ allograft recipients. Outcome data are limited after lung transplantation. In a single-center cohort study, adherence was assessed in 427 patients undergoing lung transplantation from 2010 to 2013. Objective criteria of adherence were judged by health care workers on every visit on a five item Likert scale including trough level monitoring, home spirometry and contact with an overall rating of adherence between 0 and 100%. Cut-off values for good vs. suboptimal adherence were defined retrospectively. Primary outcome was allograft survival, secondary outcomes were patient survival, prevalence of chronic lung allograft dysfunction, hospitalizations, renal function and quality of life. Follow-up ended on 31st December 2018. Median adherence was 86% on 6,623 visits, this cut-off was used as a discriminator between good and suboptimal adherers. Patients with good adherence within the first three years showed better 5-year allograft (74% vs. 60%, p = 0.003) and patient survival (79% vs. 64%, p<0.001) and lower prevalence of chronic allograft dysfunction (33% vs. 45%, p = 0.011) after 5 years compared to patients with suboptimal adherence. A multidimensional adherence score proved to be a simple tool to assess adherence in clinical practice. Suboptimal adherence was associated with impaired outcome in lung transplant patients.

Clinical Result and Feasibility of Transport ECMO in Thoracic Transplantation.

INTRODUCTION: There is an increasing need for transport extracorporeal membrane oxygenation (ECMO) in thoracic transplantation. This study was performed to evaluate the safety and feasibility of transport ECMO in thoracic transplantation. PATIENTS AND METHODS: A total of 24 patients referred from outside hospitals for ECMO treatment used our interhospital ECMO transport system from December 2011 to October 2018. We retrospectively analyzed the clinical data to evaluate the feasibility and safety of transport ECMO for thoracic transplantations. RESULTS: The median transport distance was 34 km (interquartile range [IQR]: 29-45) and the median transport time was 38 minutes (IQR: 26-45). There were no adverse events during transit in any patient. ECMO weaning was possible in 19 patients (79%) and 13 patients (54%) were weaned from mechanical ventilation. Of these patients, only 14 (58%) underwent transplantation, of whom 8 received lung transplants (53%) and 6 received heart transplants (67%). Among the patients receiving transplants, intensive care unit discharge was possible in 9 patients (64%), and 8 patients (57%) were discharged home. CONCLUSIONS: Transport ECMO to the transplantation center is a useful strategy to rescue patients with cardiorespiratory failure who may require transplantation, providing an additional means of improving the chance of survival.

Organ Transplantation for Cystic Fibrosis.

Cystic fibrosis (CF) remains the most common indication for lung transplantation in children and the third most common in adults and has the highest median survival posttransplant for all pretransplant diagnoses. Criteria for transplant in patients with CF vary widely among transplant centers and early referral to multiple centers may be needed to maximize opportunities for lung transplantation. Comorbidities unique to CF such as resistant and atypical pathogens like Burkholderia and Mycobacterium abscessus, and cirrhosis require special consideration for lung transplantation but should not be considered as absolute contraindications. For those patients who are listed for lung transplantation, mechanical support with extracorporeal membrane oxygenation and mechanical ventilation can be efficacious as bridges to lung transplantation in experienced centers with adequate resources. Liver and pancreas transplantations are also acceptable options for end-organ disease related to CF and can provide improvements in both quantity and quality of life.

Lung transplantation in China between 2015 and 2018.

BACKGROUND: Lung transplantation (LT) has been demonstrated as the only effective therapy for patients with end-stage lung diseases. Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require well-organized programs and registry data collection based on the large population. This study aimed to summarize and analyze the data of LT development in China. METHODS: We retrospectively collected and analyzed data from the China Lung Transplantation Registry (CLuTR). Key data were reported from the registry with transplant types, indications, donor and recipient characteristics, outcomes and survival. The survival <30 days, 1-year and 3-year survival rates were estimated with risk factors identified. RESULTS: CLuTR contained data from 1053 lung transplants performed through January 1st, 2015 to December 31st, 2018 reported by 18 registered transplant centers. The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis. The total <30 days, 1-year and 3-year survival rates in CLuTR were 81.45%, 70.11%, and 61.16% with discrepancy by indications. Large proportion of recipients who were more than 60 years old required higher standard of care. Infection-related complications resulted in more death events in the early post-surgery periods. New York Heart Association grading at listing, extra-corporeal membrane oxygenation usage peri-transplantation, allograft dysfunction (primary graft dysfunction >Grade 0), renal insufficiency (estimated glomerular filtration rate <60 mL·min·1.73 m), were independently associated with a higher risk for 3-year mortality in the entire cohort. CONCLUSIONS: Facing more end-stage of lung diseases and comorbidities, this study analyzed the outcomes and survival of LT recipients in China. Further prospectively stratified analyses with longer follow-up will be needed.

Trasplante pulmonar en pacientes con fibrosis pulmonar idiopática / Lung transplant in patients with idiopathic pulmonary fibrosis

El trasplante pulmonar representa una opción terapéutica en pacientes con fibrosis pulmonar avanzada que presentan un curso progresivo a pesar de tratamiento médico, mejorando su sobrevida y calidad de vida. Es de vital importancia que el neumólogo conozca cuando referir a un paciente y estar familiarizado con los requisitos necesarios y contraindicaciones para enviar un paciente a un centro de trasplante. La derivación oportuna permite realizar un completo estudio, además de identificar las contraindicaciones y condiciones clínicas susceptibles de modificar y/o corregir antes de un trasplante.

Pulmonary transplantation represents a therapeutic option in patients with advanced pulmonary fibrosis who have a progressive course despite medical treatment, improving their survival and quality of life. It is vital that the pulmonologist knows when to refer a patient and be familiar with the requirements and contraindications. Timely referral grants the necessary time for a complete study, in addition to identifying contraindications and clinical conditions that could be modified and / or corrected before a transplant.

Organized Management of Diabetes Mellitus in Lung Transplantation: Study of Glycemic Control and Patient Survival in a Single Center.

OBJECTIVE: To study patient survival and glycemic control before and after lung transplantation (LTx) according to the diabetes status in patients submitted to an organized management of diabetes mellitus (DM) at the Strasbourg University Hospital, France. MATERIAL AND METHODS: Two hundred and sixty-seven LTx recipients were included retrospectively and analyzed according to diabetes status: pretransplant diabetes, new-onset diabetes mellitus after transplant (NODAT) or no diabetes. Organized DM management was coordinated by a diabetologist trained in DM management before and after transplantation and included pretransplant screening, a close monitoring of glycemia after transplant and optimized treatment before and after LTx. RESULTS: DM was well-controlled after transplantation: mean glycosylated hemoglobin and fasting blood glucose levels after LTx were 5.8 ± 0.2% and 5.4 ± 0.1 mmol/L respectively, in pretransplant DM patients and 5.7 ± 0.1% and 5.6 ± 0.2 mmol/L respectively, in NODAT patients. The overall median survival time was 8.3 ± 1.9 years. Pretransplant DM increased the risk of mortality (1.82-fold increase; 95% confidence interval, 1.08-3.06; P = .02) in LTx recipients. CONCLUSIONS: Organized management of diabetes achieved very satisfactory glycemic control in both pretransplant DM and NODAT patients. However, no specific protocols have been created for managing DM following LTx. As DM continues to become an increasing comorbidity in LTx, there exist a significant need of studies in this area.

Continuous-flow mechanical circulatory support is not associated with early graft failure: An analysis of the International Society for Heart and Lung Transplantation registry.

BACKGROUND: Continuous-flow mechanical circulatory support (CF-MCS) is associated with impaired vascular function and increased risk of vasoplegia. One contributing factor to early graft failure (EGF) is severe vasoplegia. We tested the hypothesis that CF-MCS is associated with increased risk of EGF. METHODS: Adult primary heart transplant recipients in the ISHLT Registry from 2005 to 2013 were stratified into three groups based on pre-transplant MCS: No MCS (n = 11 748), pulsatile (P)-MCS (n = 718), and CF-MCS (n = 3818). EGF was defined as death/retransplantation due to graft failure within 30 days after HT. Comparisons were made using descriptive statistics and associations. EGF was assessed with multivariable Cox proportional hazard regression. RESULTS: The incidence of EGF within 30 days was similar between groups (No MCS 2.2%, P-MCS 3.3%, CF-MCS 2.1%, P = .10). Following multivariable adjustment, the risk of EGF was not statistically different for those with CF-MCS compared with P-MCS (HR 0.75, 95% CI 0.46-1.21, P = .24). The risk of EGF was numerically, but not statistically significantly higher for CF-MCS compared with No MCS (HR 1.24, 95% CI 0.92-1.67, P = .16). CONCLUSION: CF-MCS use was not associated with a statistically significant increased risk of EGF resulting in death or retransplantation in the first 30 days after transplant.

Donation after circulatory death in lung transplantation-five-year follow-up from ISHLT Registry.

BACKGROUND: This study aimed to examine intermediate-term outcomes of lung transplantation (LTx) recipients from donors after circulatory death (DCD). METHODS: We examined the International Society for Heart and Lung Transplantation (ISHLT) Thoracic Transplant Registry data for patients transplanted between January 2003 and June 2017 at 22 centers in North America, Europe, and Australia participating in the DCD Registry. The distribution of continuous variables was summarized as median and interquartile range (IQR) values. Wilcoxon rank sum test was used to compare distribution of continuous variables and chi-square or Fisher's exact test for categorical variables. Kaplan-Meier survival rates after LTx from January 2003 to June 2016 were compared between DCD-III (Maastricht category III withdrawal of life-sustaining therapy [WLST]) only and donors after brain death (DBD) using the log-rank test. Risk factors for 5-year mortality were investigated using Cox multivariate proportional-hazards model. RESULTS: The study cohort included 11,516 lung transplants, of which 1,090 (9.5%) were DCD lung transplants with complete data. DCD-III comprised 94.1% of the DCD cohort. Among the participating centers, the proportion of DCD-LTx performed each year increased from 0.6% in 2003 to 13.5% in 2016. DCD donor management included extubation in 91%, intravenous heparin in 53% and pre-transplant normothermic ex vivo donor lung perfusion in 15%. The median time interval from WLST to cardiac arrest was 15 minutes (IQR: 11-22 minutes) and to cold flush 32 minutes (IQR: 26-41minutes). Compared with DBD, donor age was higher in DCD-III donors (46 years [IQR: 34-55] vs 40 years [IQR: 24-52]), bilateral LTx was performed more often (88.3% vs 76.6%), and more recipients had chronic obstructive pulmonary disease and emphysema as their transplant indication. Five-year survival rates were comparable (63% vs 61%, p = 0.72). In multivariable analysis, recipient and donor ages, indication diagnosis, procedure type (single vs bilateral and double LTx), and transplant era (2003-2009 vs 2010-2016) were independently associated with survival (p < 0.001), but donor type was not (DCD-III vs DBD; hazard ratio, 1.04 [0.90-1.19], p = 0.61). CONCLUSION: This ISHLT DCD Registry report with 5-year follow-up demonstrated similar favorable long-term survival in DCD-III and DBD lung donor recipients at 22 experienced centers globally. These data indicate that more extensive use of DCD-LTx would increase donor organ availability and may reduce waiting list mortality.

Intermediate outcomes of right-to-left inverted living-donor lobar lung transplantation.

OBJECTIVES: Owing to the severe donor shortage in Japan, living-donor lobar lung transplantation (LDLLT) remains a valuable option. As only lobes are implanted in LDLLT, grafts may be too small, especially for adult recipients. To overcome this obstacle, we developed right-to-left inverted LDLLT. In this procedure, the right lower lobe, which is 25% bigger than the left lower lobe, is used as the left-side graft instead of the left lower lobe. This study aimed to investigate the characteristics and intermediate outcomes of right-to-left inverted LDLLT. METHODS: Since the first right-to-left inverted LDLLT performed in 2014, 48 LDLLTs have been performed in our institution, of which 15 were right-to-left inverted LDLLTs. We reviewed their characteristics and intermediate outcomes. RESULTS: The reasons for choosing an inverted procedure instead of the standard LDLLT were small-for-size graft in 11 cases and anatomical variation of donor vessels in 4 cases. The first patient underwent left single LDLLT using a right lower lobe graft, and the following 14 patients underwent bilateral LDLLT using 2 right lower lobe grafts. A native upper lobe-sparing procedure was additionally applied in 2 patients. No complications occurred in the bronchial and vascular anastomoses. No operative mortality occurred, and all the patients were discharged home after LDLLT. The 3-year survival was 92.3%, with a median follow-up time of 40 months. The donor postoperative course was uneventful, and all the donors returned to their regular routine postoperatively. CONCLUSION: Right-to-left inverted LDLLT is a safe and useful option with encouraging intermediate outcome.

Tacrolimus trough monitoring guided by mass spectrometry without accounting for assay differences is associated with acute kidney injury in lung transplant recipients.

PURPOSE: Tacrolimus is a nephrotoxic immunosuppressant historically monitored via enzyme-based immunoassay (IA). After 2011, the 2 largest laboratory companies in the United States implemented tacrolimus quantification by liquid chromatography-mass spectrometry (LC-MS); this method excludes metabolites, potentially resulting in lower quantified drug concentrations. We sought to determine if tacrolimus therapeutic drug monitoring via LC-MS, as performed using trough targets originally derived from IA values, influences clinical outcomes. METHODS: In a single-center retrospective cohort study of lung transplant recipients, risks of acute kidney injury, acute renal failure, and new-onset diabetes after transplantation, as well as chronic lung allograft dysfunction-free survival, were compared in 82 subjects monitored by LC-MS and 102 subjects monitored by IA using Cox proportional hazard models adjusted for age, sex, baseline renal function, and race. RESULTS: LC-MS-based monitoring was associated with a greater risk of acute kidney injury (adjusted hazard ratio, 1.65; 95% confidence interval, 1.02-2.67). No statistically significant differences in risks of acute renal failure and new-onset diabetes after transplantation were observed. CONCLUSION: Although LC-MS provides a more accurate representation of the blood concentration of the parent compound tacrolimus exclusive of metabolite, established cut points for tacrolimus dosing may need to be adjusted to account for the increased risk of renal injury.

Combined Thorax-Abdomen Extraction in Controlled Cardiac Death (Maastricht Type III) Donors.

Donation after circulatory death (DCD) or controlled cardiac death (Maastricht type III donors) is that in which the irreversible cessation of circulatory and respiratory function occurs after the withdrawal of life-sustaining therapies. The shortage of available donor lungs has prompted the development of programs of controlled DCD for lung transplantation. The combined thorax-abdomen extraction in these cases is carried out only in a few centers in Spain, being even more exceptional considering the combined use of super rapid lung extraction with abdominal normothermic regional perfusion. The success achieved with the first cases of combined thorax-abdomen extraction in Maastricht type III donors in Navarra shows that it is a feasible and safe procedure.

Probable progressive multifocal leukoencephalopathy-immune reconstitution inflammatory syndrome with immunosuppressant dose reduction following lung transplantation: a case report and literature review.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a rapidly developing demyelinating disease in the cerebral white matter and is often caused by JC polyomavirus (JCV). PML after lung transplantation is rare and has a poor prognosis, with no established therapies. Reducing the patient's immunosuppressant doses, thereby restoring immunity, could be used to treat PML. However, some patients develop immune reconstitution inflammatory syndrome (IRIS) with this treatment, an immune-induced inflammatory response to JCV that results in serious neuronal damage. We herein report a case of a 60-year-old female who suffered from PML 5 years after lung transplantation, had worsened brain lesions thought to be related to PML-IRIS at the time of immunosuppressant reduction, and missed treatment opportunities. CASE PRESENTATION: A 60-year-old female developed PML 5 years after lung transplantation. Fluid-attenuated inversion recovery and diffusion-weighted brain magnetic resonance imaging (MRI) revealed multiple high-signal lesions, mainly in the cerebral white matter. Polymerase chain reaction found 0.32 million copies/mL of JCV in the cerebrospinal fluid. Thus, she was given a diagnosis of PML. Mycophenolate mofetil and tacrolimus dosages were reduced, and CD4-positive cell counts and the blood concentration of each immunosuppressant were monitored. Mefloquine was also orally administered at a daily dose of 275 mg for 3 days and was then administered at a dose of 275 mg per week. Although the patient's CD4-positive cell counts increased and her immune system recovered, her symptoms and brain MRI findings worsened. We suspected PML progression or a transition to PML-IRIS. Steroid pulse therapy to suppress the inflammatory lesions was not possible but was retrospectively indicated. The patient rapidly began to exhibit akinetic mutism and died 4 months after the onset of neurologic symptoms. CONCLUSIONS: When neurologic symptoms and abnormal brain MRI findings are noted during immune recovery, it is often difficult to distinguish between progressed PML and PML-IRIS. However, the pathogenesis of brain lesions usually involves inflammation and immune-reactive mechanisms for JCV. Steroid pulse therapy, which can reduce inflammation, should thus be administered in organ transplantation cases with differential diagnoses including PML-IRIS.

New-onset asthma in a bilateral lung transplant patient.

We present a case of new-onset asthma in a 35-year-old man who had undergone bilateral lung transplantation 11 years before due to idiopathic bronchiectasis and pulmonary hypertension. He presented with recurrent episodes of breathlessness, wheezing and coughing. Spirometry demonstrated severe airway obstruction. After treatment with systemic and inhaled corticosteroids and long-acting bronchodilators as well as short-acting beta-agonists as needed, his symptoms resolved and his spirometry normalised. A bronchial mannitol challenge test showed significant airway hyperresponsiveness and is thus consistent for a diagnosis of asthma. To our best knowledge, this is the first case of late new-onset asthma in a lung transplant recipient.

New Techniques for Optimization of Donor Lungs/Hearts.

Injuries sustained by donor heart and lung allografts during the transplantation process are multiple and cumulative. Optimization of allograft function plays an essential role in short- and long-term outcomes after transplantation. Therapeutic targets to prevent or attenuate injury are present in the donor, the preservation process, during transplantation, and in postoperative management of the recipient. The newest and most promising methods of optimizing donor heart and lung allografts are found in alternative preservation strategies, which enable functional assessment of donor organs and provide a modality to initiate therapies for injured allografts or prevent injury during reperfusion in recipients.

Bilateral lung transplantation after caesarean section in pregnancy with severe pulmonary arterial hypertension: A case report.

RATIONALE: Pulmonary arterial hypertension (PAH) can lead to an increase in right ventricular load and subsequently heart failure, making severe PAH a contraindication for pregnancy. In addition, PAH may worsen during pregnancy and puerperium, which requires high-quality critical care. This report is the first instance in which a patient with severe PAH, survived a successful atrial septal defect (ASD) repair and bilateral lung transplantation during puerperium. PATIENT CONCERNS: A 42-year-old pregnant woman with congenital heart disease (CHD) and severe PAH was admitted to our hospital for the management of pregnancy and delivery. The patient was diagnosed with severe PAH in 2013, and no significant improvements or deteriorations were found until this pregnancy-related hospital admission. DIAGNOSIS: The patient was diagnosed with CHD and severe PAH in 2013 with color Doppler echocardiography, right cardiac catheterization, and pulmonary perfusion imaging. The patient's mean pulmonary arterial pressure increased to 140 mm Hg during pregnancy, suggesting an exacerbated PAH with high risks to both her and the unborn child. INTERVENTIONS: The patient was treated with PAH-targeting treprostinil injection to reduce pulmonary artery pressure. Caesarean section was performed at 27 weeks and 5 days of gestation. The patient was put under extracorporeal membrane oxygenation (ECMO) with the help of local anesthesia before the operation. The investigators finally conducted a bilateral lung transplantation with a shell incision of the sternum under cardiopulmonary bypass. OUTCOMES: The mother and the neonate survived and recovered well after the operation, and were discharged from the hospital on the fourth month post-hospitalization. LESSONS: Severe PAH is an absolute contraindication for pregnancy. However, for patients who insist on a pregnancy, it could be plausible to proceed with a targeted drug therapy and ECMO after conducting a cesarean section, and finally, a lung transplantation. Multidisciplinary diagnosis and treatment is the key to the successful treatment of a PAH-complicated pregnancy.

Trends, Determinants, and Impact on Survival of Post-Lung Transplant Weight Changes: A Single-center Longitudinal Retrospective Study.

BACKGROUND: Weight gain is commonly seen in lung transplant (LTx) recipients. Although previous studies have focused on weight changes at fixed time periods and relatively early after transplant, trends over time and long-term weight evolution have not been described in this population. The study objectives were to document weight changes up to 15 years post-LTx and assess the predictors of post-LTx weight changes and their associations with mortality. METHODS: Retrospective cohort study of LTx recipients between January 1, 2000, and November 30, 2016 (n = 502). Absolute weight changes from transplant were calculated at fixed time periods (6 mo, 1, 2, 5, 10, and 15 y), and continuous trends over time were generated. Predictors of weight changes and their association with mortality were assessed using linear and Cox regression analysis. RESULTS: LTx recipients experienced a gradual increase in weight, resulting from the combination of multiple weight trajectories. Interstitial lung disease diagnosis negatively predicted post-LTx weight changes at all time points, whereas transplant body mass index categories were significant predictors at earlier time points. Patients with a weight gain of >10% at 5 years had a better survival (hazard ratio [HR], 0.36; 95% confidence interval [CI], 0.20-0.66), whereas a 10% weight loss at earlier time points was associated with worse survival (1 y: HR, 2.04; 95% CI, 1.22-3.41 and 2 y: HR, 2.37; 95% CI, 1.22-4.58). CONCLUSIONS: Post-LTx weight changes display various trajectories, are predicted to some extent by individual and LTx-related factors, and have a negative or positive impact on survival depending on the time post-LTx. These results may lead to a better individualization of weight management after transplant.