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- Andersson Sjöland, Annika, et al.
(författare)
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Fibroblast phenotypes and their activity are changed in the wound healing process after lung transplantation.
- 2011
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1557-3117 .- 1053-2498. ; 30, s. 945-954
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Lung transplantation (LTx) is established as a life-saving treatment in end-stage lung disease. However, long-term survival is hampered by the development of chronic rejection, almost synonymous with bronchiolitis obliterans syndrome (BOS). The rejection is characterized by deposition of extracellular matrix in small airways. Fibroblasts/myofibroblasts are the main producers of extracellular matrix molecules such as proteoglycans. This study compared fibroblast phenotype and activity in the wound healing process at different points after LTx in patients who later did, or did not, develop BOS. METHODS: Distally derived fibroblasts from patients 6 and 12 months after LTx and from healthy controls were analyzed for production of the proteoglycans versican, perlecan, biglycan, and decorin, with and without transforming growth factor (TGF)-β(1). Fibroblast migration and proliferation were also studied. RESULTS: At 6 and 12 months after LTx, versican production was higher in fibroblasts from LTx patients (p < 0.01 p < 0.01) than from controls. Fibroblasts from patients who later developed BOS were more responsive to TGF-β(1)-induced synthesis of versican and biglycan than patients without signs of rejection (p < 0.05). Production of perlecan and decorin was negatively correlated with fibroblast proliferation in fibroblasts at 6 months after LTx. In a more detailed case study of 2 patients, one with and one without BOS, the altered proteoglycan profile was associated with impaired lung function. CONCLUSIONS: LTx changes the phenotype of fibroblasts to a non-proliferative but extracellular matrix-producing cell due to wound healing involving TGF-β(1). If not controlled, this may lead to development of BOS.
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- Arora, Satish, et al.
(författare)
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Improvement in renal function after everolimus introduction and calcineurin inhibitor reduction in maintenance thoracic transplant recipients: The significance of baseline glomerular filtration rate
- 2012
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Ingår i: The Journal of Heart and Lung Transplantation. - : Elsevier. - 1053-2498 .- 1557-3117. ; 31:3, s. 259-265
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The NOCTET (NOrdic Certican Trial in HEart and lung Transplantation) trial demonstrated that everolimus improves renal function in maintenance thoracic transplant (FIX) recipients. Nevertheless, introduction of everolimus is not recommended for patients with advanced renal failure. We evaluated NOCTET data to assess everolimus introduction amongst TTx recipients with advanced renal failure. less thanbrgreater than less thanbrgreater thanMETHODS: This 12-month multicenter Scandinavian study randomized 282 maintenance TTx recipients to everolimus introduction with calcineurin inhibitor (CNI) reduction or standard CNI therapy. The measured glomerular filtration rate (mGFR) was noted at baseline and after 1-year using Cr-ethylenediarninetetraacetic acid clearance. less thanbrgreater than less thanbrgreater thanRESULTS: In 21 patients with a baseline mGFR of 20 to 29 ml/min/1.73 m(2), renal function improved in the everolimus group compared with the control group ((Delta mGFR 6.7 +/- 9.0 vs -1.6 +/- 5.1 ml/min/1.73 m(2); p = 0.03). Amongst 173 patients with moderate renal impairment (mGFR 30-59 ml/min/1.73 m(2)), renal function improvement was also greater amongst everolimus patients than in controls (Delta mGFR 5.1 +/- 11.1 vs -0.5 +/- 8.7 ml/min/1.73 m(2); p andlt; 0.01). In 55 patients with mGFR 60 to 89 ml/min/1.73 m(2), mGFR did not change significantly in either group. Improvement in mGFR was limited to patients with a median time since TTx of less than 4.6 years and was also influenced by CM reduction during the study period. less thanbrgreater than less thanbrgreater thanCONCLUSIONS: Everolimus introduction and reduced CNI significantly improved renal function amongst maintenance TTx patients with pre-existing advanced renal failure. This beneficial effect was limited to patients undergoing conversion in less than 5 years after TTx, indicating a window of opportunity that is appropriate for pharmacologic intervention with everolimus.
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- Auråen, Henrik, et al.
(författare)
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Urgent lung allocation system in the Scandiatransplant countries
- 2018
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 37:12, s. 1403-1409
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Throughout the world, the scarcity of donor organs makes optimal allocation systems necessary. In the Scandiatransplant countries, organs for lung transplantation are allocated nationally. To ensure shorter wait time for critically ill patients, the Scandiatransplant urgent lung allocation system (ScULAS) was introduced in 2009, giving supranational priority to patients considered urgent. There were no pre-defined criteria for listing a patient as urgent, but each center was granted only 3 urgent calls per year. This study aims to explore the characteristics and outcome of patients listed as urgent, assess changes associated with the implementation of ScULAS, and describe how the system was utilized by the member centers. METHODS: All patients listed for lung transplantation at the 5 Scandiatransplant centers 5 years before and after implementation of ScULAS were included. RESULTS: After implementation, 8.3% of all listed patients received urgent status, of whom 81% were transplanted within 4 weeks. Patients listed as urgent were younger, more commonly had suppurative lung disease, and were more often on life support compared with patients without urgent status. For patients listed as urgent, post-transplant graft survival was inferior at 30 and 90 days. Although there were no pre-defined criteria for urgent listing, the system was not utilized at its maximum. CONCLUSIONS: ScULAS rapidly allocated organs to patients considered urgent. These patients were younger and more often had suppurative lung disease. Patients with urgent status had inferior short-term outcome, plausibly due to the higher proportion on life support before transplantation.
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- Bergenfeldt, Henrik, et al.
(författare)
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Donor-recipient size matching and mortality in heart transplantation : Influence of body mass index and gender
- 2017
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Ingår i: Journal of Heart and Lung Transplantation. - : Elsevier BV. - 1053-2498. ; 36:9, s. 940-947
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Tidskriftsartikel (refereegranskat)abstract
- Background: The International Society for Heart and Lung Transplantation (ISHLT) guidelines advise against inappropriate weight match (IWM) for heart transplant, defined as donor weight <70% of recipient's weight. Few studies have explored in detail this size-matching recommendation, especially with regard to body mass index (BMI) and gender matching. We aimed to determine whether any difference could be observed between size-matching in obese and non-obese recipients with regard to mortality after cardiac transplantation. Methods: Data from 52,455 adult heart transplants (recipients ≥18 years of age) between 1994 and 2013 were obtained from the ISHLT Registry. We defined the following subgroups of patients based on BMI: underweight, BMI <18.5; non-obese, BMI 18.5 to 30; and obese, BMI >30. The end-points were all-cause 30-day mortality and cumulative mortality. Results: IWM was associated with increased 30-day mortality (odds ratio [OR] = 1.20, 95% confidence interval [CI] 1.01 to 1.43, p = 0.041) and cumulative mortality (hazard ratio [HR] = 1.14, 95% CI 1.07 to 1.22, p < 0.001). In non-obese recipients, IWM was associated with increased 30-day mortality (OR = 1.89, 95% CI 1.48 to 2.41, p < 0.001) as well as cumulative mortality (HR = 1.27, 95% CI 1.15 to 1.41, p < 0.001), whereas, for obese recipients, IWM was not associated with 30-day or cumulative mortality. Male recipients of female allografts (HR = 1.08, 95% CI 1.04 to 1.12, p < 0.001) as well as female recipients of male allografts (HR = 1.07, 95% CI 1.02 to 1.13, p = 0.003) had increased cumulative mortality compared with gender-matched transplants. There was no interaction between IWM and gender mismatch. Conclusions: Our results indicate that donor weight <70% of recipient weight increases mortality in non-obese heart transplant recipients, but not in obese transplant recipients. Gender mismatch increases mortality independently of weight match.
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