Project description:BackgroundNeurobehavioral functioning is widely recognized as being an important consideration in lung transplant candidates, but little is known about whether these factors are related to clinical outcomes. The present study examined the relationship of neurobehavioral functioning, including measures of executive function and memory, depression, and anxiety, to long-term survival among lung transplant recipients.MethodsThe sample was drawn from 201 patients who underwent transplantation at Duke University and Washington University who participated in a dual-site clinical trial investigating medical and psychosocial outcomes in transplant candidates with end-stage lung disease. All patients completed the Beck Depression Inventory-II (BDI-II) and Spielberger State-Trait Anxiety Inventory at baseline and again after 12 weeks, while a subset of 86 patients from Duke University also completed neurocognitive testing. Patients were followed for survival up to 12 years after completing baseline assessments.ResultsOne hundred eleven patients died over a mean follow-up of 10.8 years (SD=0.8). Baseline depression, anxiety, and neurocognitive function were examined as predictors of posttransplant survival, controlling for age, 6-min walk distance, FEV, and native disease; education and cardiovascular risk factors were also included in the model for neurocognition. Lower executive function (hazard ratio [HR]=1.09, P=.012) and memory performance (HR=1.11, P=.030) were independently associated with greater mortality following lung transplant. Although pretransplant depression and anxiety were not predictive of mortality, patients who scored>13 on the BDI-II at baseline and after 3 months pretransplant had greater mortality (HR=1.85 [95% CI, 1.04, 3.28], P=.036).ConclusionsNeurobehavioral functioning, including persistently elevated depressive symptoms and lower neurocognitive performance, was associated with reduced survival after lung transplantation.Trial registryClinicalTrials.gov; No.: NCT00113139; URL: www.clinicaltrials.gov.
Project description:With an improved median survival of 6.2 years, lung transplantation has become an increasingly acceptable treatment option for end-stage lung disease. Besides survival benefit, improvement of quality of life is achieved in the vast majority of patients. Many developments have taken place in the field of lung transplantation over the past decade. Broadened indication criteria and bridging techniques for patients awaiting lung transplantation have led to increased waiting lists and changes in allocation schemes worldwide. Moreover, the use of previously unacceptable donor lungs for lung transplantation has increased, with donations from donors after cardiac death, donors with increasing age and donors with positive smoking status extending the donor pool substantially. Use of ex vivo lung perfusion further increased the number of lungs suitable for lung transplantation. Nonetheless, the use of these previously unacceptable lungs did not have detrimental effects on survival and long-term graft outcomes, and has decreased waiting list mortality. To further improve long-term outcomes, strategies have been proposed to modify chronic lung allograft dysfunction progression and minimise toxic immunosuppressive effects. This review summarises the developments in clinical lung transplantation over the past decade.
Project description:IntroductionFibrosing interstitial lung diseases (ILDs) often progress despite treatment and become life-threatening, with lung transplant (LTx) remaining the only curative option. Six-minute walk distance (6MWD) is increasingly recognized as reliable predictor of clinical course, especially when longitudinally considered. The use of reference equations to express 6MWD as percent predicted (6MWD%) has not been previously studied in fibrosing ILDs. We sought to investigate whether the prognostic power of 6MWD% is superior to that of 6MWD expressed in meters (6MWD-m).MethodsA retrospective, multicenter cohort analysis was conducted on both idiopathic pulmonary (IPF) and non-IPF fibrosing ILD patients. Patients were divided into a discovery (n = 211) and a validation (n = 260) cohort. Longitudinal changes of 6MWD% and lung function parameters were simultaneously considered. LTx-free survival at 3 years from baseline was the endpoint. Competing risks of death and LTx were considered.ResultsBaseline 6MWD% and its longitudinal changes were significant predictors of LTx-free survival and independent from lung function variables. In both cohorts, on multivariate cox proportional hazard regression analysis, receiver operating characteristics analysis and Kaplan-Meier estimates, 6MWD% was consistently, but only slightly superior to 6MWD-m as a predictor of LTx-free survival.Conclusion6MWD% has only a slight, yet detectable advantage over 6MWD-m as a predictor of survival in fibrosing ILDs. Utilizing 6MWD% may aid in risk stratification, treatment monitoring, and LTx timing optimization. However, available reference equations do have predicting limitations. Refined predictive equations and standardizing reporting practices are therefore needed to further enhance the clinical utility of 6MWD% in fibrosing ILDs.
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:Atrial switch procedures (Senning and Mustard) for transposition of the great arteries have largely been abandoned for arterial switch procedures. The number of surviving patients who have undergone atrial switch procedures is declining. We present a case of the oldest known survivor (aged 67 years) of the Mustard procedure. (Level of Difficulty: Beginner.).
Project description:Background and objectiveDisease-specific outcomes following lung transplantation (LT) in patients with pulmonary Langerhans cell histiocytosis (PLCH) are not well established. We queried the Organ Procurement and Transplantation Network database to identify adult PLCH patients who had undergone LT in the United States.MethodsOverall survival data were analysed with Kaplan-Meier curves. Cox proportional hazard model was used to determine the effect of demographic, clinical and physiological variables on post-transplant survival.ResultsA total of 87 patients with PLCH underwent LT in the United States between October 1987 and June 2017, accounting for 0.25% of the total LT during this period. The mean age at LT for PLCH patients was 49 years (range: 19-67 years), with a near equal gender distribution. Bilateral sequential LT was performed in 71 patients (82%). Pulmonary hypertension was present in 85% of patients, with a mean pulmonary artery pressure of 38.5 ± 14.1 mm Hg. The mean pre-transplant forced expiratory volume in 1 s (FEV1 ) was 41 ± 21% predicted and the mean 6-min walk distance was 221 ± 111 m. Median post-LT survival for PLCH patients was comparable to patients with other lung diseases (5.1 vs 5.5 years, P = 0.76). The actuarial Kaplan-Meier post-LT survival for PLCH patients was 85%, 65%, 49% and 22% at 1, 3, 5 and 10 years, respectively. Female sex (hazard ratio (HR): 0.40, 95% CI: 0.22-0.72), pre-transplant serum bilirubin (HR: 1.66, 95% CI: 1.23-2.26) and serum creatinine (HR: 4.03, 95% CI: 1.01-14.76) were independently associated with post-LT mortality in our cohort.ConclusionPost-LT survival in patients with PLCH is similar to patients with other lung diseases and is significantly affected by patient gender.
Project description:Patients undergoing lung transplantation (LTx) experience a rapid decline in glomerular filtration rate (GFR) in the acute postoperative period. However, no prospective longitudinal studies directly comparing the performance of equations for estimating GFR in this patient population currently exist. In total, 32 patients undergoing LTx met the study criteria. At pre-LTx and 1-, 3-, and 12-weeks post-LTx, GFR was determined by 51Cr-EDTA and by equations for estimating GFR based on plasma (P)-Creatinine, P-Cystatin C, or a combination of both. Measured GFR declined from 98.0 mL/min/1.73 m2 at pre-LTx to 54.1 mL/min/1.73 m2 at 12-weeks post-LTx. Equations based on P-Creatinine underestimated GFR decline after LTx, whereas equations based on P-Cystatin C overestimated this decline. Overall, the 2021 CKD-EPI combination equation had the lowest bias and highest precision at both pre-LTx and post-LTx. Caution must be applied when interpreting renal function based on equations for estimating GFR in the acute postoperative period following LTx. Simplified methods for measuring GFR may allow for more widespread use of measured GFR in this vulnerable patient population.
Project description:Patients with short telomeres and interstitial lung disease may have decreased chronic lung allograft dysfunction (CLAD)-free survival following lung transplantation. The relationship between post-transplant telomere length and outcomes following lung transplantation has not been characterised among all recipients, regardless of native lung disease. This was a single-centre prospective cohort study. Consenting transplant recipients had their telomere length measured using quantitative real-time PCR assays on peripheral blood collected at the time of surveillance bronchoscopy. We assessed the association between early post-transplant telomere length (as measured in the first 100 days) and CLAD-free survival, time to clinically significant leukopenia, cytomegalovirus (CMV) viraemia, chronic kidney disease, and acute cellular rejection. We also assessed the association between rate of telomere shortening and CLAD-free survival. Telomere lengths were available for 98 out of 215 (45.6%) recipients who underwent lung transplant during the study period (median measurement per patient=2 (interquartile range, 1-3)). Shorter telomere length was associated with decreased CLAD-free survival (hazard ratio (HR)=1.24; 95% CI=1.03-1.48; p=0.02), leukopenia requiring granulocyte colony-stimulating factor (HR=1.17, 95% CI=1.01-1.35, p=0.03), and CMV viraemia among CMV-mismatch recipients (HR=4.04, 95% CI=1.05-15.5, p=0.04). Telomere length was not associated with acute cellular rejection or chronic kidney disease. Recipients with more rapid loss in telomere length (defined as the highest tertile of telomere shortening) did not have worse subsequent CLAD-free survival than those without rapid loss (HR=1.38, 95% CI=0.27-7.01, p=0.70). Shorter early post-transplant telomere length is associated with decreased CLAD-free survival and clinically significant leukopenia in lung transplant recipients, regardless of native lung disease.
Project description:The goal of this study was to apply protein expression profiling tools in cases with lung injury following HSCT or cellular therapy infusion to identify the proteins and biological processes that differentiate IPS from infectious lung injury in HSCT recipients. We performed comprehensive label-based quantitative protein profiling of BALF in patients undergoing HSCT
Project description:Background and purposeCarotid artery intima-media thickness (IMT) and plaque are noninvasive markers of subclinical arterial injury that predict incident cardiovascular disease. We evaluated predictors of longitudinal changes in IMT and new plaque during a decade in a longitudinal multiethnic cohort.MethodsCarotid IMT and plaque were evaluated in Multi-Ethnic Study of Atherosclerosis (MESA) participants at exams 1 and 5, a mean (standard deviation) of 9.4 (0.5) years later. Far wall carotid IMT was measured in both common and internal carotid arteries. A plaque score was calculated from all carotid segments. Mixed-effects longitudinal and multivariate regression models evaluated associations of baseline risk factors and time-updated medication use with IMT progression and plaque formation.ResultsThe 3441 MESA participants were aged 60.3 (9.4) years (53% women; 26% blacks, 22% Hispanic, 13% Chinese); 1620 (47%) had carotid plaque. Mean common carotid artery IMT progression was 11.8 (12.8) μm/year, and 1923 (56%) subjects developed new plaque. IMT progressed more slowly in Chinese (β=-2.89; P=0.001) and Hispanic participants (β=-1.81; P=0.02), and with higher baseline high-density lipoprotein cholesterol (per 5 mg/dL; β=-0.22; P=0.03), antihypertensive use (β=-2.06; P=0.0004), and time on antihypertensive medications (years; β=-0.29; P<0.0001). Traditional risk factors were associated with new plaque formation, with strong associations for cigarette use (odds ratio, 2.31; P<0.0001) and protection by black ethnicity (odds ratio, 0.68; P<0.0001).ConclusionsIn a large, multiethnic cohort with a decade of follow-up, ethnicity was a strong, independent predictor of carotid IMT and plaque progression. Antihypertensive medication use was associated with less subclinical disease progression.