allograft dysfunction
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2022 ◽  
pp. 00583-2021
Author(s):  
Christoffer Stark ◽  
Juha W. Koskenvuo ◽  
Antti Nykänen ◽  
Eija H. Seppälä ◽  
Samuel Myllykangas ◽  
...  

Question addressed by the studyThe prevalence of monogenic disease-causing gene variants in lung-transplant recipients with idiopathic pulmonary fibrosis is not fully known. Their impact on clinical outcomes before and after transplantation requires more evidence.Patients and MethodsWe retrospectively performed sequence analysis of genes associated with pulmonary fibrosis in a cohort of 23 patients with histologically confirmed usual interstitial pneumonia that had previously undergone double lung transplantation. We evaluated the impact of confirmed molecular diagnoses on disease progression, clinical outcomes and incidence of acute rejection or chronic lung allograft dysfunction after transplantation.ResultsFifteen patients out of 23 (65%) had a variant in a gene associated with interstitial lung disease. Eleven patients (48%) received a molecular diagnosis, of which nine involved genes for telomerase function. Five diagnostic variants were found in the gene for Telomerase reverse transcriptase. Two of these variants, p.(Asp684Gly) and p.(Arg774*), seemed to be enriched in Finnish lung-transplant recipients. Disease progression and the incidence of acute rejection and chronic lung allograft dysfunction was similar between patients with telomere-related disease and the rest of the study population. The incidence of renal or bone marrow insufficiency or skin malignancies did not differ between the groups.Answer to the questionGenetic variants are common in lung transplant recipients with pulmonary fibrosis and are most often related to telomerase function. A molecular diagnosis for telomeropathy does not seem to impact disease progression or the risk of complications or allograft dysfunction after transplantation.


2022 ◽  
Vol 35 ◽  
Author(s):  
Naofumi Miyahara ◽  
Alberto Benazzo ◽  
Felicitas Oberndorfer ◽  
Akinori Iwasaki ◽  
Viktoria Laszlo ◽  
...  

Background: Micro-RNA-21 (miR-21) is a post-translational regulator involved in epithelial-to-mesenchymal transition (EMT). Since EMT is thought to contribute to chronic lung allograft dysfunction (CLAD), we aimed to characterize miR-21 expression and distinct EMT markers in CLAD.Methods: Expression of miR-21, vimentin, Notch intracellular domain (NICD) and SMAD 2/3 was investigated in explanted CLAD lungs of patients who underwent retransplantation. Circulating miR-21 was determined in collected serum samples of CLAD and matched stable recipients.Results: The frequency of miR-21 expression was higher in restrictive allograft syndrome (RAS) than in bronchiolitis obliterans syndrome (BOS) specimens (86 vs 30%, p = 0.01); Vimentin, NICD and p-SMAD 2/3 were positive in 17 (100%), 12 (71%), and 7 (42%) BOS patients and in 7 (100%), 4 (57%) and 4 (57%) RAS cases, respectively. All four markers were negative in control tissue from donor lungs. RAS patients showed a significant increase in serum concentration of miR-21 over time as compared to stable recipients (p = 0.040).Conclusion: To the best of our knowledge this is the first study highlighting the role miR-21 in CLAD. Further studies are necessary to investigate the involvement of miR-21 in the pathogenesis of CLAD and its potential as a therapeutic target.


Author(s):  
Ji‐wen Fan ◽  
Lin Yan ◽  
Xue‐qiao Wang ◽  
Ya‐mei Li ◽  
Yang‐juan Bai ◽  
...  

PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260881
Author(s):  
Jens Gottlieb ◽  
Geert M. Verleden ◽  
Michael Perchl ◽  
Christina Valtin ◽  
Alexander Vallee ◽  
...  

Background Chronic Lung Allograft Dysfunction (CLAD) is a major obstacle for long term survival after lung transplantation (LTx). Besides Bronchiolitis Obliterans Syndrome, two other phenotypes of CLAD, restrictive allograft syndrome (RAS) and mixed phenotype, have been described. Trials to test in these conditions are desperately needed and analyzing natural outcome to plan such trials is essential. Methods We performed a retrospective analysis of functional outcome in bilateral LTx recipients with RAS and mixed phenotype, transplanted between 2009 and 2018 in five large European centers with follow- up spirometry up to 12 months after diagnosis. Based on these data, sample size and power calculations for randomized therapeutic trial was estimated using two imputation methods for missing values. Results Seventy patients were included (39 RAS and 31 mixed phenotype), median 3.1 years after LTx when CLAD was diagnosed. Eight, 13 and 25 patients died within 6, 9 and 12 months after diagnosis and a two patients underwent re-transplantation within 12 months leading to a graft survival of 89, 79 and 61% six, nine and 12 months after diagnosis, respectively. Observed FEV1 decline was 451 ml at 6 months and stabilized at 9 and 12 months, while FVC showed continuous decline. Using two methods of imputation, a progressive further decline after 6 months for FEV1 was noted. Conclusion The poor outcome of these two specific CLAD phenotypes suggests the urgent need for future therapeutic randomized trials. The number of missing values in a potential trial seems to be high and most frequently attributed to death. Survival may be used as an endpoint in clinical trials in these distinct phenotypes and imputation techniques are relevant if graft function is used as a surrogate of disease progression in future trials.


2021 ◽  
pp. 2101652
Author(s):  
Micheal C. McInnis ◽  
Jin Ma ◽  
Gauri Rani Karur ◽  
Christian Houbois ◽  
Liran Levy ◽  
...  

BackgroundChronic lung allograft dysfunction (CLAD) is the principal cause of graft failure in lung transplant recipients and prognosis depends on CLAD phenotype. We used machine learning computed tomography (CT) lung texture analysis tool at CLAD diagnosis for phenotyping and prognostication compared to radiologists’ scoring.MethodsThis retrospective study included all adult first double-lung transplant patients (01/2010–12/2015) with CLAD (censored 12/2019) and inspiratory CT near CLAD diagnosis. The machine learning tool quantified ground-glass opacity, reticulation, hyperlucent lung, and pulmonary vessel volume (PVV). Two radiologists scored for ground-glass opacity, reticulation, consolidation, pleural effusion, air trapping and bronchiectasis. Receiver operating characteristic curve analysis was used to evaluate the diagnostic performance of machine learning and radiologist for CLAD phenotype. Multivariable Cox proportional-hazards regression analysis for allograft survival controlled for age, sex, native lung disease, cytomegalovirus serostatus, and CLAD phenotype (bronchiolitis obliterans syndrome [BOS] and restrictive allograft syndrome [RAS]/mixed).Results88 patients were included (57 BOS, 20 RAS/mixed, and 11 unclassified/undefined) with CT a median 9.5 days from CLAD onset. Radiologist and machine learning parameters phenotyped RAS/mixed with PVV as the strongest indicator (AUC 0.85). Machine learning hyperlucent lung phenotyped BOS using only inspiratory CT (AUC=0.76). Radiologist and machine learning parameters predicted graft failure in the multivariable analysis, best with PVV (HR=1.23, 95%CI 1.05–1.44, p=0.01).ConclusionsMachine learning discriminated between CLAD phenotypes on CT. Both radiologist and machine learning scoring were associated with graft failure, independent of CLAD phenotype. PVV, unique to machine learning, was the strongest in phenotyping and prognostication.


Author(s):  
Yu. O. Malinovskaya ◽  
K. Yu. Kokina ◽  
Ya. G. Moysyuk ◽  
O. V. Sumtsova

Introduction. Liver transplantation restores patients' physical and social life, and its quality. The prevalence of low physical activity in liver recipients is unknown as well as the impact of late liver allograft dysfunction on it. Liver transplantation enhances patient's return to the usual physical and social activity and improves the quality of life. However, the prevalence of low physical activity among liver recipients and the impact of the late allograft dysfunction on it, which is a risk factor for obesity and cardiovascular diseases, require studying.The aim of the study was to identify whether the late liver allograft dysfunction influences the physical activity of recipients.Material and methods. The study included 87 liver recipients. We measured anthropometric parameters, physical performance (SPPB, LFI, 6-min walk test), mean step count per day. Late liver allograft dysfunction was determined if elevated transaminases and/or cholestatic enzymes or hepatic failure have been diagnosed later than 3 months posttransplant. Activity trackers were provided to assess physical activity.Results. Median age was 54 years [45;61], 33% were men. The median follow-up period was 36 months [16;64]. The median of the average steps count was 5.9 [4.1;8.7] thousand per day. 60.5% of recipients were sedentary and low active, 24.4% were somewhat active, 15.1% were active. In cases of liver allograft dysfunction, the mean step count was significantly lower than in patients with normal liver function: 4.1 thousand [2.6;5.3] versus 6.8 thousand [4.2;9.4], p=0.003, despite no differences in the physical activity test results.Conclusion. In case of a late liver allograft dysfunction, the physical activity can decrease; 60.5% of liver recipients, in the absence of pathological restriction of movement, have a sedentary and low active lifestyle. Activity trackers may allow identifying patients who need additional check-up or physical training.


2021 ◽  
Vol 8 ◽  
Author(s):  
Qiang Wei ◽  
Junbin Zhou ◽  
Kun Wang ◽  
Xuanyu Zhang ◽  
Junli Chen ◽  
...  

Early allograft dysfunction (EAD) after liver transplantation (LT) accompanies poor prognosis. This study aims to explore the relationship between pretransplant intrahepatic proteins and the incidence of EAD, and the value of combined EAD and protein profiles for predicting recipient and graft survival prognosis. Liver biopsy specimens of 105 pretransplant grafts used for LT were collected and used for immunohistochemistry analysis of 5 proteins. And matched clinical data of donor, recipient, transplantation, and prognosis were analyzed. The incidence of EAD was 41.9% (44/105) in this cohort. Macrovesicular steatosis (P = 0.016), donor body mass index (P = 0.013), recipients' pretransplant serum creatinine (P = 0.036), and intrahepatic expression of heme oxygenase 1 (HO1) (P = 0.015) and tumor necrosis factor α (TNF-α) (P = 0.039) were independent predictors of EAD. Inferior graft and recipient prognosis were observed in patients who experienced EAD (P = 0.028 and 0.031) or received grafts with higher expression of sirtuin 1 (P = 0.005 and 0.013). The graft and recipient survival were worst in patients with both EAD and high expression of sirtuin 1 (P = 0.001 and 0.004). In conclusion, pretransplant intrahepatic expression of HO1 and TNF-α are associated with the incidence of EAD. The combination of EAD and EAD-unrelated proteins showed superiority in distinguishing recipients with worse prognosis.


Author(s):  
Michael Keller ◽  
Junfeng Sun ◽  
Cedric Mutebi ◽  
Pali Shah ◽  
Deborah Levine ◽  
...  

Author(s):  
Michael D Parkes ◽  
Kieran M Halloran ◽  
Alim Hirji ◽  
Shane Pon ◽  
Justin Weinkauf ◽  
...  

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