| 1. |
- Albåge, Anders, et al.
(författare)
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Long-Term Risk of Ischemic Stroke After the Cox-Maze III Procedure for Atrial Fibrillation
- 2017
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 0003-4975 .- 1552-6259. ; 104:2, s. 523-529
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Tidskriftsartikel (refereegranskat)abstract
- Background The long-term risk of stroke after surgical treatment of atrial fibrillation is not well known. We performed an observational cohort study with long follow-up after the “cut-and-sew” Cox-maze III procedure (CM-III), including left atrial appendage excision. The aim was to analyze the incidence of stroke/transient ischemic attack (TIA) and the association to preoperative CHA2DS2-VASc (age in years, sex, congestive heart failure history, hypertension history, stroke/TIA, thromboembolism history, vascular disease history, diabetes mellitus) score. Methods Preoperative and perioperative data were collected in 526 CM-III patients operated in four centers 1994 to 2009, 412 men, mean age of 57.1 ± 8.3 years. The incidence of any stroke/TIA was identified through analyses of the Swedish National Patient and Cause-of-Death Registers and from review of individual patient records. The cumulative incidence of stroke/TIA and association with CHA2DS2-VASc score was estimated using methods accounting for the competing risk of death. Results Mean follow-up was 10.1 years. There were 29 patients with any stroke/TIA, including 6 with intracerebral bleedings (2 fatal) and 4 with perioperative strokes (0.76%). The remaining 13 ischemic strokes and six TIAs occurred at a mean of 7.1 ± 4.0 years postoperatively, with an incidence of 0.36% per year (19 events per 5,231 patient-years). In all CHA2DS2-VASc groups, observed ischemic stroke/TIA rate was lower than predicted. A higher risk of ischemic stroke/TIA was seen in patients with CHA2DS2-VASc score 2 or greater compared with score 0 or 1 (hazards ratio 2.15, 95% confidence interval: 0.87 to 5.32) but no difference by sex or stand-alone versus concomitant operation. No patient had ischemic stroke as cause of death. Conclusions This multicenter study showed a low incidence of perioperative and long-term postoperative ischemic stroke/TIA after CM-III. Although general risk of ischemic stroke/TIA was reduced, patients with CHA2DS2-VASc score 2 or greater had a higher risk compared with score 0 or 1. Complete left atrial appendage excision may be an important reason for the low ischemic stroke rate.
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| 2. |
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| 3. |
- Ghaidan, Haider
(författare)
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Clinical and Preclinical Lung Transplantation in the aspects of improving outcome
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lung transplantation (LTx) is an established therapeutic option for end-stage pulmonary disease. However, it remains restricted by donor lung scarcity. Donor's lungs are rejected frequently due to severe lung damage caused by aspiration or neurogenic pulmonary oedema that can all lead to acute lung injury (ALI), and more severe acute respiratory distress syndrome (ARDS). Lung transplant patients face poor survival rates in comparison with other solid organ transplantations. This is primarily due to a high incidence of postoperative complications, such as primary graft dysfunction (PGD) and chronic lung allograft dysfunction (CLAD), especially bronchiolitis obliterans syndrome (BOS). The aim of this thesis was to expand the availability of a donor's lungs for transplantation. We sought to increase the chances of a lifesaving opportunity for recipients who may otherwise have remained on the transplant waiting list for years. We did this preclinically by utilising a variety of techniques to regain lung function in discarded lungs, thus increasing the donor pool. We investigated the role of cytokine adsorption during ex vivo lung perfusion (EVLP), and extracorporeal haemofiltration post-transplant as a means of treating and restoring the ARDS-damaged lungs and reducing the incidence of PGD post-transplantation. The lungs were evaluated regarding the development of primary graft dysfunction (PGD) in which cytokines seem to be an essential target given the outcome of significantly less PGD in the group receiving cytokine adsorption. We suggest this treatment method will increase the availability of the donor's lungs and increase the tolerability of the donor's lungs in the recipient. The results of this study formed the basis for our idea to investigate the effect of mesenchymal stromal cell (MSC) therapy to restore gastric content aspirations damaged lungs and reduce the incidence of PGD at 72 hours’ post-transplantation. Furthermore, we explored pulmonary function, survival, and the incidence of CLAD between patients receiving marginal lungs after ex vivo lung perfusion (EVLP) reconditioning and patients receiving clinically standard lungs (conventional lungs) at our centre. These patients were followed for over 10 years. We did not find any difference in pulmonary function, survival, or incidence of CLAD, indicating that EVLP is safe to use and does not increase mortality. We also explored the impact of allograft ischaemic time (IT) in lung transplantation survival rate which showed superior outcomes for IT between 120 and 240 minutes. Every 2-hour increase in IT was equivalent to an increased mortality of up to 24% within 5 years. This indicates that IT has a key role in improving LTx outcomes. We explored the role of plasma biomarkers in the largest subgroup of CLAD, patients with BOS. Plasma from lung- transplanted patients with different BOS grades was analysed for protein biomarkers using Olink proteomics. A selective number of biomarkers were then validated using an enzyme-linked immunosorbent assay (ELISA) at baseline and after 1 year. Corticotropin-releasing hormone (CRH) levels were found to be related to different stages of BOS which identified CRH as a potential marker in a novel diagnostic tool to detect BOS. In conclusion, using EVLP is a safe effective platform for cytokine adsorption therapy and MSC therapy which can restore pulmonary function in damaged donor lungs, thus increasing the donor pool. CRH is a novel potential biomarker in the progression of post-transplantation BOS grades.
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| 4. |
- Ghaidan, Haider, et al.
(författare)
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Impact of allograft ischemic time on long-term survival in lung transplantation : a Swedish monocentric study
- 2020
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 54:5, s. 322-329
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The influence of allograft ischemic time (IT) on short- and long-term mortality remains under debate in lung transplantation (LTx). Due to a scarcity in donors, better understanding of IT might improve the outcome after LTx. Methods: Between January 1990 and June 2016; 307 patients underwent LTx at Lund university hospital, Sweden. The end-point used was death/Re-LTx assessed by Cox regression and Kaplan–Meier survival. Results: Kaplan–Meier survival for mean IT (min) between subgroups ≤120, 121–240, 241–360 and 361+ showed significant difference for pairwise-comparisons with superior outcome for IT between ≤120 and 240 min. Cox regression analyses for each hour of IT in patients with a limited survival up to 1- and 5-year had a hazard ratio (HR) of 1.119 and 1.063 respectively (p <.05). Conclusions: In LTx, every 2-hour increase of IT is equivalent to an increased mortality of up to 24% within 5 years. LTx with an IT of ≤120 min had a superior survival in both 1- and 5 years in comparison to an IT of up to 360 min. Better application of IT provides a key role in improving LTx outcome.
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| 5. |
- Ghaidan, Haider, et al.
(författare)
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Reduction of primary graft dysfunction using cytokine adsorption during organ preservation and after lung transplantation
- 2022
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Despite improvements, lung transplantation remains hampered by both a scarcity of donor organs and by mortality following primary graft dysfunction (PGD). Since acute respiratory distress syndrome (ARDS) limits donor lungs utilization, we investigated cytokine adsorption as a means of treating ARDS donor lungs. We induced mild to moderate ARDS using lipopolysaccharide in 16 donor pigs. Lungs were then treated with or without cytokine adsorption during ex vivo lung perfusion (EVLP) and/or post-transplantation using extracorporeal hemoperfusion. The treatment significantly decreased cytokine levels during EVLP and decreased levels of immune cells post-transplantation. Histology demonstrated fewer signs of lung injury across both treatment periods and the incidence of PGD was significantly reduced among treated animals. Overall, cytokine adsorption was able to restore lung function and reduce PGD in lung transplantation. We suggest this treatment will increase the availability of donor lungs and increase the tolerability of donor lungs in the recipient.
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| 6. |
- Ghaidan, Haider, et al.
(författare)
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Ten year follow-up of lung transplantations using initially rejected donor lungs after reconditioning using ex vivo lung perfusion
- 2019
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Ingår i: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: In 2006 and 2007 we performed double lung transplantation with marginal donor lungs assessed and reconditioned by Ex Vivo Lung Perfusion (EVLP), using a technique developed by Professor Stig Steen. Here we present a 10-year follow-up comparing the outcomes of lung transplantations performed at our clinic using EVLP lungs vs. conventional lungs. Method: Between 2006 and 2007, 21 patients (6 EVLP, 15 conventional) underwent double lung transplantation (LTx) with follow-up on May 2017 at Lund University Hospital, Sweden. Pulmonary function was measured at 3/6/12 months, and annually thereafter for a period of 10 years in addition to survival and freedom from chronic lung allograft dysfunction (CLAD) being analyzed. Results: Regarding Forced Expiratory Volume in 1 s (FEV1) and 6MWT at 3, 6, and 12 months and annually thereafter, no difference in median FEV1 nor 6MWT was found for EVLP-LTx vs. conventional-LTx (p > 0.05). No difference was shown in post-operative survival between EVLP-LTx vs. conventional LTx for patients with an overall survival up to 10-years (p > 0.05). The same pattern was shown in sub analyses for patients with a limited survival up to 1 and 5 years (p > 0.05). Conclusion: No superiority was found in conventional-LTx over EVLP-LTx, neither in long-term survival nor pulmonary function. No difference in CLAD-free survival was seen between the two groups. We believe that EVLP is a safe and effective method to use in LTx, greatly increasing the donor pool by improving marginal lungs and providing an objective assessment of the viability of marginal donor lungs.
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| 7. |
- Niroomand, Anna, et al.
(författare)
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Corticotropin releasing hormone as an identifier of bronchiolitis obliterans syndrome
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12, s. 1-11
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Tidskriftsartikel (refereegranskat)abstract
- Lung transplantion (LTx) recipients have low long-term survival and a high incidence of bronchiolitis obliterans syndrome (BOS), an inflammation of the small airways in chronic rejection of a lung allograft. There is great clinical need for a minimally invasive biomarker of BOS. Here, 644 different proteins were analyzed to detect biomarkers that distinguish BOS grade 0 from grades 1-3. The plasma of 46 double lung transplant patients was analyzed for proteins using a high-component, multiplex immunoassay that enables analysis of protein biomarkers. Proximity Extension Assay (PEA) consists of antibody probe pairs which bind to targets. The resulting polymerase chain reaction (PCR) reporter sequence can be quantified by real-time PCR. Samples were collected at baseline and 1-year post transplantation. Enzyme-linked immunosorbent assay (ELISA) was used to validate the findings of the PEA analysis across both time points and microarray datasets from other lung transplantation centers demonstrated the same findings. Significant decreases in the plasma protein levels of CRH, FERC2, IL-20RA, TNFB, and IGSF3 and an increase in MMP-9 and CTSL1 were seen in patients who developed BOS compared to those who did not. In this study, CRH is presented as a novel potential biomarker in the progression of disease because of its decreased levels in patients across all BOS grades. Additionally, biomarkers involving the remodeling of the extracellular matrix (ECM), such as MMP-9 and CTSL1, were increased in BOS patients.
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| 8. |
- Niroomand, Anna, et al.
(författare)
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Proteomic Analysis of Primary Graft Dysfunction in Porcine Lung Transplantation Reveals Alveolar-Capillary Barrier Changes Underlying the High Particle Flow Rate in Exhaled Breath
- 2024
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Ingår i: Transplant International. - 0934-0874. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Primary graft dysfunction (PGD) remains a challenge for lung transplantation (LTx) recipients as a leading cause of poor early outcomes. New methods are needed for more detailed monitoring and understanding of the pathophysiology of PGD. The measurement of particle flow rate (PFR) in exhaled breath is a novel tool to monitor and understand the disease at the proteomic level. In total, 22 recipient pigs underwent orthotopic left LTx and were evaluated for PGD on postoperative day 3. Exhaled breath particles (EBPs) were evaluated by mass spectrometry and the proteome was compared to tissue biopsies and bronchoalveolar lavage fluid (BALF). Findings were confirmed in EBPs from 11 human transplant recipients. Recipients with PGD had significantly higher PFR [686.4 (449.7–8,824.0) particles per minute (ppm)] compared to recipients without PGD [116.6 (79.7–307.4) ppm, p = 0.0005]. Porcine and human EBP proteins recapitulated proteins found in the BAL, demonstrating its utility instead of more invasive techniques. Furthermore, adherens and tight junction proteins were underexpressed in PGD tissue. Histological and proteomic analysis found significant changes to the alveolar-capillary barrier explaining the high PFR in PGD. Exhaled breath measurement is proposed as a rapid and non-invasive bedside measurement of PGD.
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| 9. |
- Niroomand, Anna, et al.
(författare)
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Proteomic changes to immune and inflammatory processes underlie lung preservation using ex vivo cytokine adsorption.
- 2023
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Ingår i: Frontiers in Cardiovascular Medicine. - 2297-055X. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: In recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and clinical studies, with the potential to improve graft quality. Its main benefit is to render marginal and declined donor lungs suitable for transplantation, ultimately increasing the donor pool available for transplantation. In addition, using such therapies in machine perfusion could also increase preservation time, facilitating logistical planning. Cytokine adsorption has been demonstrated as a potentially safe and effective therapy when applied to the EVLP circuit and post-transplantation. However, the mechanism by which this therapy improves the donor lung on a molecular basis is not yet fully understood.METHODS: We hypothesized that there were characteristic inflammatory and immunomodulatory differences between the lungs treated with and without cytokine adsorption, reflecting proteomic changes in the gene ontology pathways and across inflammation-related proteins. In this study, we investigate the molecular mechanisms and signaling pathways of how cytokine adsorption impacts lung function when used during EVLP and post-transplantation as hemoperfusion in a porcine model. Lung tissues during EVLP and post-lung transplantation were analyzed for their proteomic profiles using mass spectrometry.RESULTS: We found through gene set enrichment analysis that the inflammatory and immune processes and coagulation pathways were significantly affected by the cytokine treatment after EVLP and transplantation.CONCLUSION: In conclusion, we showed that the molecular mechanisms are using a proteomic approach behind the previously reported effects of cytokine adsorption when compared to the non-treated transplant recipients undergoing EVLP.
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| 10. |
- Vikholm, Per, 1985-, et al.
(författare)
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Validity of the Swedish Cardiac Surgery Registry
- 2018
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Ingår i: Interactive Cardiovascular and Thoracic Surgery. - : OXFORD UNIV PRESS. - 1569-9293 .- 1569-9285. ; 27:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Our goal was to validate the Swedish Cardiac Surgery Registry by reviewing the reported cardiac operations to assess the completeness and quality of the registered data and the EuroSCORE II variables. METHODS: A total of 5837 cardiac operations were reported to the Swedish Cardiac Surgery Registry in Sweden during 2015. A randomly selected sample of 753 patient records (13%) was scrutinized by 3 surgeons at all 8 units in Sweden performing open cardiac surgery in adults. RESULTS: Coverage was excellent with 99% [95% confidence interval (CI) 98-99%] of the performed procedures found in the registry. Reported waiting times for surgery were correct in 78% (95% CI 76-79%) of the cases. The main procedural code was correctly reported in 96% (95% CI 95-97%) of the cases. The correlation between reported and monitored logistic EuroSCORE II had a coefficient of 0.79 (95% CI 0.76-0.82), and the median difference in EuroSCORE II was 0% (interquartile range -0.4% to 0.4%). The majority of EuroSCORE II variables had good agreement and coherence; however, New York Heart Association functional class, preoperative renal dysfunction, left ventricular ejection fraction, Canadian Cardiovascular Society Class IV angina and poor mobility were less robust Postoperative complications were rare and in general had a high degree of completeness and agreement. CONCLUSIONS: The reliability of the variables in the national Swedish Cardiac Surgery Registry was excellent. Thus, the registry is a valuable source of data for quality studies and research. Some EuroSCORE II variables require improved and stricter definitions to obtain uniform reporting and high validity.
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