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Sommer W, Franz M, Aburahma K, Saipbaev A, Flöthmann K, Yablonski P, Avsar M, Tudorache I, Greer M, Haverich A, Welte T, Kuehn C, Salman J, Warnecke G, Ius F. Lungs From Donors ≥70 Years of Age for Transplantation-Do Long-Term Outcomes Justify Their Use? Transpl Int 2023; 36:11071. [PMID: 37125386 PMCID: PMC10133456 DOI: 10.3389/ti.2023.11071] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 03/23/2023] [Indexed: 05/02/2023]
Abstract
Donor shortages have led transplant centers to extend their criteria for lung donors. Accepting lung donors ≥70 years of age has previously shown good short-term outcomes; however, no mid- and long-term outcome data on these extended criteria donors has been published to date. In this study, all patients who underwent lung transplantation between 06/2010 and 12/2019 were included in the analysis, and the outcomes were compared between patients receiving organs from donors <70 years of age and patients transplanted with lungs from donors ≥70 years of age. Among the 1,168 lung-transplanted patients, 62 patients received lungs from donors ≥70 years of age. The recipient age of those receiving older organs was significantly higher, and they were more likely to suffer from obstructive lung disease. Older donors were exposed to significantly shorter periods of mechanical ventilation prior to donation, had higher Horowitz indices, and were less likely to have smoked. The postoperative time on mechanical ventilation, time on ICU, and total hospital stay were comparable. The overall survival as well as CLAD-free survival showed no differences between both groups in the follow-up period. Utilization of lungs from donors ≥70 years of age leads to excellent mid- and long-term results that are similar to organs from younger donors when the organs from older donors are carefully preselected.
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Affiliation(s)
- Wiebke Sommer
- Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
- German Center for Lung Research, Deutsches Zentrum Lungenforschung (DZL), BREATH, Hannover, Germany
| | - Maximilian Franz
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Khalil Aburahma
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Akylbek Saipbaev
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Katharina Flöthmann
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Pavel Yablonski
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Murat Avsar
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Igor Tudorache
- Department of Cardiac Surgery, University of Duesseldorf, Duesseldorf, Germany
| | - Mark Greer
- Department of Pulmonology, Hannover Medical School, Hannover, Germany
| | - Axel Haverich
- German Center for Lung Research, Deutsches Zentrum Lungenforschung (DZL), BREATH, Hannover, Germany
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Tobias Welte
- German Center for Lung Research, Deutsches Zentrum Lungenforschung (DZL), BREATH, Hannover, Germany
- Department of Pulmonology, Hannover Medical School, Hannover, Germany
| | - Christian Kuehn
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Jawad Salman
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
| | - Gregor Warnecke
- Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany
- German Center for Lung Research, Deutsches Zentrum Lungenforschung (DZL), BREATH, Hannover, Germany
| | - Fabio Ius
- German Center for Lung Research, Deutsches Zentrum Lungenforschung (DZL), BREATH, Hannover, Germany
- Department of Cardiothoracic, Vascular and Transplantation Surgery, Hannover Medical School, Hannover, Germany
- *Correspondence: Fabio Ius,
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Response to Comment on "Lung Transplantation for Elderly Patients With End-stage COVID-19 Pneumonia". Ann Surg 2022; 276:e66-e67. [PMID: 33605585 PMCID: PMC9213061 DOI: 10.1097/sla.0000000000004414] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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Peterson DM, Beal EW, Reader BF, Dumond C, Black SM, Whitson BA. Electrical Impedance as a Noninvasive Metric of Quality in Allografts Undergoing Normothermic Ex Vivo Lung Perfusion. ASAIO J 2022; 68:964-971. [PMID: 35067581 PMCID: PMC9247000 DOI: 10.1097/mat.0000000000001591] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Ex vivo lung perfusion (EVLP) increases the pool of suitable organs for transplant by facilitating assessment and repair at normothermia, thereby improving identification of quality of marginal organs. However, there exists no current objective approach for assessing total organ edema. We sought to evaluate the use of electrical impedance as a metric to assess total organ edema in lungs undergoing EVLP. Adult porcine lungs (40 kg) underwent normothermic EVLP for 4 hours. To induce varying degrees of lung injury, the allografts were perfused with either Steen, a modified cell culture media, or 0.9% normal saline. Physiologic parameters (peak airway pressure and compliance), pulmonary artery and left atrial blood gases, and extravascular lung water measurements were evaluated over time. Wet-to-dry ratios were evaluated postperfusion. Modified Murray scoring was used to calculate lung injury. Impedance values were associated with lung injury scores ( p = 0.007). Peak airway pressure ( p = 0.01) and PaO 2 /FiO 2 ratios ( p = 0.005) were both significantly associated with reduced impedance. Compliance was not associated with impedance ( p = 0.07). Wet/dry ratios were significantly associated with impedance and Murray Scoring within perfusion groups of Steen, Saline, and Modified Cell Culture ( p = 0.0186, 0.0142, 0.0002, respectively). Electrical impedance offers a noninvasive modality for measuring lung quality as assessed by tissue edema in a porcine model of normothermic EVLP. Further studies evaluating the use of impedance to assess organ edema as a quality marker in human clinical models and abdominal organs undergoing ex vivo perfusion warrant investigation.
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Affiliation(s)
- Danielle M Peterson
- From the The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University, Columbus, Ohio
- The Ohio State University College of Medicine, Columbus, Ohio
- Penn State College of Medicine Department of Surgery, Hershey, Pennsylvania
| | - Eliza W Beal
- From the The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University, Columbus, Ohio
- The Ohio State University Wexner Medical Center Department of Surgery, Columbus Ohio
| | - Brenda F Reader
- From the The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University, Columbus, Ohio
- The Ohio State University Wexner Medical Center Department of Surgery, Columbus Ohio
| | - Curtis Dumond
- From the The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University, Columbus, Ohio
- The Ohio State University Wexner Medical Center Department of Surgery, Columbus Ohio
| | - Sylvester M Black
- From the The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University, Columbus, Ohio
- The Ohio State University Wexner Medical Center Department of Surgery, Columbus Ohio
| | - Bryan A Whitson
- From the The Collaboration for Organ Perfusion, Protection, Engineering and Regeneration (COPPER) Laboratory, The Ohio State University, Columbus, Ohio
- The Ohio State University Wexner Medical Center Department of Surgery, Columbus Ohio
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Santos PARD, Teixeira PJZ, Moraes Neto DMD, Cypel M. Donation after circulatory death and lung transplantation. J Bras Pneumol 2022; 48:e20210369. [PMID: 35475865 PMCID: PMC9064622 DOI: 10.36416/1806-3756/e20210369] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Accepted: 12/17/2021] [Indexed: 11/17/2022] Open
Abstract
Lung transplantation is the most effective modality for the treatment of patients with end-stage lung diseases. Unfortunately, many people cannot benefit from this therapy due to insufficient donor availability. In this review and update article, we discuss donation after circulatory death (DCD), which is undoubtedly essential among the strategies developed to increase the donor pool. However, there are ethical and legislative considerations in the DCD process that are different from those of donation after brain death (DBD). Among others, the critical aspects of DCD are the concept of the end of life, cessation of futile treatments, and withdrawal of life-sustaining therapy. In addition, this review describes a rationale for using lungs from DCD donors and provides some important definitions, highlighting the key differences between DCD and DBD, including physiological aspects pertinent to each category. The unique ability of lungs to maintain cell viability without circulation, assuming that oxygen is supplied to the alveoli-an essential aspect of DCD-is also discussed. Furthermore, an updated review of the clinical experience with DCD for lung transplantation across international centers, recent advances in DCD, and some ethical dilemmas that deserve attention are also reported.
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Affiliation(s)
- Pedro Augusto Reck Dos Santos
- . Department of Cardiothoracic Surgery, Mayo Clinic (AZ) USA.,. Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre (RS) Brasil
| | - Paulo José Zimermann Teixeira
- . Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre (RS) Brasil.,. Departamento de Clínica Médica, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre (RS) Brasil
| | | | - Marcelo Cypel
- . Division of Thoracic Surgery, University of Toronto, University Health Network, Toronto (ON) Canada
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Lee J, Balasubramanya S, Agopian VG. Solid Organ Transplantation. Perioper Med (Lond) 2022. [DOI: 10.1016/b978-0-323-56724-4.00035-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
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Lung Transplantation, Pulmonary Endothelial Inflammation, and Ex-Situ Lung Perfusion: A Review. Cells 2021; 10:cells10061417. [PMID: 34200413 PMCID: PMC8229792 DOI: 10.3390/cells10061417] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2021] [Revised: 06/01/2021] [Accepted: 06/02/2021] [Indexed: 12/31/2022] Open
Abstract
Lung transplantation (LTx) is the gold standard treatment for end-stage lung disease; however, waitlist mortality remains high due to a shortage of suitable donor lungs. Organ quality can be compromised by lung ischemic reperfusion injury (LIRI). LIRI causes pulmonary endothelial inflammation and may lead to primary graft dysfunction (PGD). PGD is a significant cause of morbidity and mortality post-LTx. Research into preservation strategies that decrease the risk of LIRI and PGD is needed, and ex-situ lung perfusion (ESLP) is the foremost technological advancement in this field. This review addresses three major topics in the field of LTx: first, we review the clinical manifestation of LIRI post-LTx; second, we discuss the pathophysiology of LIRI that leads to pulmonary endothelial inflammation and PGD; and third, we present the role of ESLP as a therapeutic vehicle to mitigate this physiologic insult, increase the rates of donor organ utilization, and improve patient outcomes.
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Okahara S, Levvey B, McDonald M, D'Costa R, Opdam H, Pilcher DV, Snell GI. A Retrospective Review of Declined Lung Donors: Estimating the Potential of Ex Vivo Lung Perfusion. Ann Thorac Surg 2020; 112:443-449. [PMID: 33121967 DOI: 10.1016/j.athoracsur.2020.08.042] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2020] [Revised: 07/20/2020] [Accepted: 08/31/2020] [Indexed: 11/30/2022]
Abstract
BACKGROUND Even in the extended-criteria era, the reasons for declining lung donors are not always clear. Furthermore, it has not been determined how many actual declined lungs would be retrieved by ex vivo lung perfusion (EVLP) beyond that already achieved in centers with an existing high utilization rate. METHODS This retrospective study reviewed all lung donor referrals between 2014 and 2018, including detailed formal referrals and preliminary notifications. This study categorized reasons for lung donor non-acceptance and estimated how many declined grafts could have been theoretically retrievable by using EVLP. RESULTS In total, 966 lung donor candidates were referred, including 313 transplanted donors, 336 declined donors after detailed referrals (group A) and 258 preliminary declined. In group A, the primary reasons for refusal were lung quality issues (49%), general medical issues (25%), and organization issues (26%), combined with secondary reasons in many cases. Main lung quality issues were an extensive smoking history, abnormal chest radiography, and underlying lung disease. Although 73 declined lung donors had indications for EVLP, the retrievable lungs decreased to only 30 cases after considering the details of all clinical contraindications and organizational issues. Nevertheless, 59 intended donation after circulatory death donors did not progress to death after withdrawal of cardiorespiratory support in the required timeframe, and EVLP may have an emerging additional role here. CONCLUSIONS Based on commonly cited criteria for EVLP indication, the number of EVLP retrievable lung donors represented only a small portion of declined donor lungs referred to our center from the state donation network.
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Affiliation(s)
- Shuji Okahara
- Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Lung Transplant Service, The Alfred Hospital and Monash University, Melbourne, Australia.
| | - Bronwyn Levvey
- Lung Transplant Service, The Alfred Hospital and Monash University, Melbourne, Australia
| | | | | | - Helen Opdam
- Organ and Tissue Authority, Canberra, Australia
| | - David V Pilcher
- Australian and New Zealand Intensive Care Research Centre, Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia; Department of Intensive Care, The Alfred Hospital, Melbourne, Australia
| | - Gregory I Snell
- Lung Transplant Service, The Alfred Hospital and Monash University, Melbourne, Australia
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Huang J, Pan J, Wang Z, Wang D, Chen J. BLTx Combined With Cardiac Correction in Treatment of PAH in Puerpera: Is It a Feasible Strategy? Ann Thorac Surg 2020; 111:e249-e251. [PMID: 32950491 DOI: 10.1016/j.athoracsur.2020.06.125] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2020] [Accepted: 06/20/2020] [Indexed: 11/17/2022]
Abstract
Though pregnancy is not recommended under current guidelines in pulmonary arterial hypertension, some women insist on parturition. The related surgical treatments are controversial, especially to those complicated with Eisenmenger syndrome. In this report, 2 cases of severe pulmonary arterial hypertension complicated with Eisenmenger syndrome were reviewed. Owing to a lifesaving tenet, bilateral lung transplantation combined with surgical atrioventricular defect correction were performed after careful assessments. Both patients were followed up at 1 year and displayed no obvious complication. It showed that the strategy of bilateral lung transplantation combined with a cardiac correction may be feasible and worthy of further investigation.
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Affiliation(s)
- Jian Huang
- Department of Lung Transplant Center, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Jun Pan
- Department of Thoracic Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University, Nanjing, China
| | - Zitao Wang
- Department of Lung Transplant Center, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China
| | - Dongjin Wang
- Department of Thoracic Surgery, Affiliated Nanjing Drum Tower Hospital of Nanjing University, Nanjing, China
| | - Jingyu Chen
- Department of Lung Transplant Center, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.
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Mulvihill MS, Lee HJ, Weber J, Choi AY, Cox ML, Yerokun BA, Bishawi MA, Klapper J, Kuchibhatla M, Hartwig MG. Variability in donor organ offer acceptance and lung transplantation survival. J Heart Lung Transplant 2020; 39:353-362. [PMID: 32029400 DOI: 10.1016/j.healun.2019.12.010] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Revised: 12/14/2019] [Accepted: 12/29/2019] [Indexed: 10/25/2022] Open
Abstract
BACKGROUND Lung transplantation offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which variability in per-center offer acceptance practices impacts candidate survival is not established. The purpose of this study was to determine the degree of variability in per-center rates of lung transplantation offer acceptance and to ascertain the associated contribution to observed differences in per-center waitlist mortality. METHODS We performed a retrospective cohort study of candidates waitlisted for lung transplantation in the US using registry data. Logistic regression was fit to assess the relationship of offer acceptance with donor, candidate, and geographic factors. Listing center was evaluated as a fixed effect to determine the adjusted per-center acceptance rate. Competing risks analysis employing the Fine-Gray model was undertaken to establish the relationship between adjusted per-center acceptance and waitlist mortality. RESULTS Of 15,847 unique organ offers, 4,735 (29.9%) were accepted for first-ranked candidates. After adjustment for important covariates, transplant centers varied markedly in acceptance rate (9%-67%). Higher cumulative incidence of 1-year waitlist mortality was associated with lower acceptance rate. For every 10% increase in adjusted center acceptance rate, the risk of waitlist mortality decreased by 36.3% (sub-distribution hazard ratio 0.637; 95% confidence interval 0.592-0.685). CONCLUSIONS Variability in center-level behavior represents a modifiable risk factor for waitlist mortality in lung transplantation. Further intervention is needed to standardize center-level offer acceptance practices and minimize waitlist mortality.
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Affiliation(s)
- Michael S Mulvihill
- Division of Cardiovascular and Thoracic Surgery, Duke University, Durham, North Carolina.
| | - Hui J Lee
- Surgical Center for Outcomes Research, Durham, North Carolina; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina
| | - Jeremy Weber
- Duke Clinical Research Institute, Durham, North Carolina
| | - Ashley Y Choi
- Duke University School of Medicine, Durham, North Carolina
| | - Morgan L Cox
- Division of Cardiovascular and Thoracic Surgery, Duke University, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina
| | - Babatunde A Yerokun
- Division of Cardiovascular and Thoracic Surgery, Duke University, Durham, North Carolina; Duke Clinical Research Institute, Durham, North Carolina
| | - Muath A Bishawi
- Division of Cardiovascular and Thoracic Surgery, Duke University, Durham, North Carolina
| | - Jacob Klapper
- Division of Cardiovascular and Thoracic Surgery, Duke University, Durham, North Carolina
| | - Maragatha Kuchibhatla
- Surgical Center for Outcomes Research, Durham, North Carolina; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, North Carolina
| | - Matthew G Hartwig
- Division of Cardiovascular and Thoracic Surgery, Duke University, Durham, North Carolina
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Hu CX, Chen WH, He JX, Jiang GN, Li XS, Wei D, Wu B, Zhang J, Wang C, Chen JY. Lung transplantation in China between 2015 and 2018. Chin Med J (Engl) 2019; 132:2783-2789. [PMID: 31856048 PMCID: PMC6940083 DOI: 10.1097/cm9.0000000000000543] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2019] [Indexed: 12/17/2022] Open
Abstract
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.
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Affiliation(s)
- Chun-Xiao Hu
- Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu 214043, China
- Chinese Lung Transplantation Quality Management and Control Center, Wuxi, Jiangsu 214043, China
- Chinese Lung Transplantation Registry and Data Management Center, Wuxi, Jiangsu 214043, China
| | - Wen-Hui Chen
- Center for Lung Transplantation, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jian-Xing He
- Department of Thoracic Surgery/Oncology State Key Laboratory and National Clinical Research Center for Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, China
| | - Ge-Ning Jiang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, China
| | - Xiao-Shan Li
- Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu 214043, China
- Chinese Lung Transplantation Quality Management and Control Center, Wuxi, Jiangsu 214043, China
- Chinese Lung Transplantation Registry and Data Management Center, Wuxi, Jiangsu 214043, China
| | - Dong Wei
- Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu 214043, China
- Chinese Lung Transplantation Quality Management and Control Center, Wuxi, Jiangsu 214043, China
- Chinese Lung Transplantation Registry and Data Management Center, Wuxi, Jiangsu 214043, China
| | - Bo Wu
- Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu 214043, China
| | - Ji Zhang
- Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu 214043, China
| | - Chen Wang
- Center for Lung Transplantation, China-Japan Friendship Hospital, Beijing 100029, China
| | - Jing-Yu Chen
- Wuxi Lung Transplant Center, Wuxi People's Hospital affiliated to Nanjing Medical University, Wuxi, Jiangsu 214043, China
- Chinese Lung Transplantation Quality Management and Control Center, Wuxi, Jiangsu 214043, China
- Chinese Lung Transplantation Registry and Data Management Center, Wuxi, Jiangsu 214043, China
- Center for Lung Transplantation, China-Japan Friendship Hospital, Beijing 100029, China
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Schiavon M, Faggi G, Rosso L, Luzzi L, Comacchio GM, Gregori D, Nosotti M, Damarco F, Dell’Amore A, Bennet D, Fossi A, Paladini P, Santambrogio L, Rea F. Outcomes and risk factors identification in urgent lung transplantation: a multicentric study. J Thorac Dis 2019; 11:4746-4754. [PMID: 31903264 PMCID: PMC6940257 DOI: 10.21037/jtd.2019.10.55] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 08/26/2019] [Indexed: 01/06/2023]
Abstract
BACKGROUND In rapidly lung deteriorating patients, urgent lung transplantation (ULT) seems the only definitive therapy. Few publications on this topic report conflicting results, putting a word of caution about ULT programs. METHODS A national ULT program was introduced in 2010: patients on mechanical support may be transplanted with the first available graft. We reviewed the experience of three national center, focusing on post-operative outcomes after ULT. RESULTS Ten patients (17.5%) died awaiting transplantation, while 47 underwent LT with a median urgent waiting list time of 6 days. Pre-operatively, 4.3% of patients were supported only by mechanical ventilation (MV), 55.3% by extracorporeal membrane oxygenation (ECMO) and the remaining 40.4% by both. The main indication was cystic fibrosis (64%). Median recipient lung allocation score was 72. In-hospital mortality was 19%. MV and ECMO median duration of 7 and 3 days, respectively while intensive care unit (ICU) and hospital stay were 20 and 46 days, respectively. At long-term, 1- and 3-year survival rate were 74% and 70%, respectively. Highly impact risk factors for in-hospital mortality were both presence and duration of preoperative veno-arterial ECMO and pre-transplant C-reactive protein level. CONCLUSIONS ULT program allows transplantation in a significant percentage of patients with acceptable results. Pre-operative recipient selection is mandatory to improve clinical outcomes.
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Affiliation(s)
- Marco Schiavon
- Thoracic Surgery and Lung Transplantation Unit, University-Hospital of Padova, Padova, Italy
| | - Giulio Faggi
- Thoracic Surgery and Lung Transplantation Unit, University-Hospital of Padova, Padova, Italy
| | - Lorenzo Rosso
- Thoracic surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | - Luca Luzzi
- Lung Transplantation Unit, Department of Medical, Surgical and Neurosciences, University of Siena, Siena, Italy
| | | | - Dario Gregori
- Statistic Unit, Department of Cardiac, Thoracic, Vascular Unit and Public Health, University of Padova, Padova, Italy
| | - Mario Nosotti
- Thoracic surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | - Francesco Damarco
- Thoracic surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | - Andrea Dell’Amore
- Thoracic Surgery and Lung Transplantation Unit, University-Hospital of Padova, Padova, Italy
| | - David Bennet
- Lung Transplantation Unit, Department of Medical, Surgical and Neurosciences, University of Siena, Siena, Italy
| | - Antonella Fossi
- Lung Transplantation Unit, Department of Medical, Surgical and Neurosciences, University of Siena, Siena, Italy
| | - Piero Paladini
- Lung Transplantation Unit, Department of Medical, Surgical and Neurosciences, University of Siena, Siena, Italy
| | - Luigi Santambrogio
- Thoracic surgery and Lung Transplantation Unit, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy
| | - Federico Rea
- Thoracic Surgery and Lung Transplantation Unit, University-Hospital of Padova, Padova, Italy
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El biomodelo porcino en la investigación médica traslacional: del biomodelo al humano en trasplante pulmonar. ACTA ACUST UNITED AC 2019; 39:300-313. [DOI: 10.7705/biomedica.v39i3.3820] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2017] [Indexed: 01/05/2023]
Abstract
Introducción. La anatomía humana y porcina son comparables. En consecuencia, el biomodelo porcino tiene el potencial de ser implementado para entrenar al profesional quirúrgico en áreas como el trasplante de órganos sólidos.Objetivo. Describir los procedimientos y hallazgos obtenidos mediante experimentos de medicina respiratoria traslacional con biomodelos porcinos realizados en un laboratorio de experimentación animal, y hacer una revisión comparativa entre el pulmón humano y el porcino.Materiales y métodos. El experimento se llevó a cabo en nueve cerdos de raza híbrida en un laboratorio de cirugía experimental. Se estudiaron la anatomía y la histología de las vías respiratorias mediante fibrobroncoscopia, biopsia bronquial y lavado broncoalveolar. El lavado broncoalveolar se estudió con citología en base líquida y se evaluó con las coloraciones de Papanicolau y hematoxilina y eosina. Se utilizaron técnicas de patología molecular, como inmunohistoquímica, citometría de flujo y microscopía electrónica. Los cerdos se sometieron a neumonectomía izquierda con posterior implante del injerto en otro cerdo experimental.Resultados. Los estudios histopatológicos y moleculares evidenciaron un predominio de macrófagos alveolares (98 %) y linfocitos T (2 %) en el lavado broncoalveolar porcino. En los estudios del parénquima pulmonar porcino se encontró tejido linfoide hiperplásico asociado a las paredes bronquiales. La microscopía electrónica evidenció linfocitos T dentro del epitelio y el diámetro de las cilias porcinas fue similar al de las humanas.Conclusiones. El biomodelo porcino es viable en la investigación traslacional para el entendimiento de la anatomía del sistema respiratorio y el entrenamiento en trasplante pulmonar. La implementación de este modelo experimental podría fortalecer los grupos que planean implementar un programa institucional de trasplante pulmonar en humanos.
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Smail H, Saxena P, Wallinder A, Lin E, Snell GI, Hobson J, Zimmet AD, Marasco SF, McGiffin DC. Donor Lung Procurement by Surgical Fellow With an Expectation of High Rate of Lung Utilisation. Heart Lung Circ 2018. [DOI: 10.1016/j.hlc.2017.12.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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Bozovic G, Adlercreutz C, Björkman-Burtscher IM, Reinstrup P, Ingemansson R, Skansebo E, Geijer M. Impact of donor chest radiography on clinical outcome after lung transplantation. Acta Radiol Open 2018; 7:2058460118781419. [PMID: 29977606 PMCID: PMC6024291 DOI: 10.1177/2058460118781419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Accepted: 05/11/2018] [Indexed: 11/23/2022] Open
Abstract
Background Organ donation guidelines recommend a “clear” conventional bedside chest
radiograph before lung transplantation despite only moderate accuracy for
cardiopulmonary abnormalities. Purpose To evaluate the influence of donor image interpretation on lung
transplantation outcome in recipients by following early and late
complications, one-year survival, and to correlate imaging findings and
blood gas analysis with lung transplantation outcome in recipients. Material and Methods In 35 lung donors from a single institution clinical reports and study
reviews of imaging findings of the mandatory bedside chest radiographs and
blood gas analyses were compared with clinical outcome in 38 recipients.
Hospitalization time, peri- and postoperative complications, early
complications (primary graft dysfunction, infection), 30-day and one-year
survival, and forced expiratory volume in 1 s percentage of predicted normal
value (FEV1%) at one-year follow-up were analyzed. Results Findings in clinical reports and study reviews differed substantially, e.g.
regarding reported decompensation, edema, infection, and atelectasis. No
correlation was shown between imaging findings in clinical report or study
review and blood gas analyses in the lung donors compared to postoperative
outcome in recipients. Conclusion The interpretation of the mandatory chest radiograph in its present form does
not influence one-year outcome in lung transplantation. Larger imaging
studies or a change in clinical routine including computed tomography may
provide evidence for future guidelines.
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Affiliation(s)
- Gracijela Bozovic
- Centre for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden
| | | | - Isabella M Björkman-Burtscher
- Centre for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.,Lund University BioImaging Centre, Lund University, Sweden
| | - Peter Reinstrup
- Department of Neurosurgery, Skåne University Hospital, Lund, Sweden
| | - Richard Ingemansson
- Department of Cardiothoracic Surgery, Skåne University Hospital, Lund University, Lund, Sweden
| | - Elin Skansebo
- Department of Thoracic surgery, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Mats Geijer
- Centre for Medical Imaging and Physiology, Skåne University Hospital, Lund, Sweden.,Clinical Sciences Lund, Lund University, Lund, Sweden
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von Dossow V, Costa J, D'Ovidio F, Marczin N. Worldwide trends in heart and lung transplantation: Guarding the most precious gift ever. Best Pract Res Clin Anaesthesiol 2017; 31:141-152. [PMID: 29110788 DOI: 10.1016/j.bpa.2017.08.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2017] [Accepted: 08/03/2017] [Indexed: 01/17/2023]
Abstract
Transplantation is sadly a therapy to die for. The survival of a recipient with end-stage heart or lung disease requires the demise of a human being through brain death or cessation of circulation, with the noblest final act of offering one's organs to another. However, transplantation is constrained by severe hemodynamic, regulatory, inflammatory, and metabolic stresses in the donor, rendering the majority of offered organs unsuitable for transplantation. Coupled with our inability to acquire exact molecular and cellular information and missed opportunities for effectively modulating deteriorations of donors and allografts, anesthesia and critical care contributes to ongoing organ shortages. Progress is made with improving waiting lists by bridging patients for transplantation using mechanical support. However, this represents more complex recipients, higher risk transplant operations, and increased resource utilization. The advent of ex vivo perfusion allows implementing novel diagnostic and therapeutic strategies with real potential of reconditioning less ideal organs. This review advocates a paradigm change in critical care management of the potential donor for improving retrieval practices and for more intellectual involvement of our specialties in organ preservation, ex vivo evaluation and reconditioning, and the need for great advancement in our efficiency in converting unacceptable allografts to suitable donor organs.
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Affiliation(s)
- Vera von Dossow
- Department of Anesthesiology, Ludwig-Maximilians-University of Munich, Germany
| | - Joseph Costa
- Department of Surgery, Division of Cardiothoracic Surgery and Transplantation, Columbia University Medical Center, New York, NY, USA
| | - Frank D'Ovidio
- Department of Surgery, Division of Cardiothoracic Surgery and Transplantation, Columbia University Medical Center, New York, NY, USA
| | - Nandor Marczin
- Section of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK; Department of Anaesthesia, Royal Brompton and Harefield NHS Foundation Trust, Harefield Hospital, Harefield, Middlesex, UK; Centre of Anaesthesia and Intensive Care, Semmelweis University, Budapest, Hungary.
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The University of Minnesota Donor Lung Quality Index: A Consensus-Based Scoring Application Improves Donor Lung Use. Ann Thorac Surg 2016; 102:1156-65. [DOI: 10.1016/j.athoracsur.2016.04.044] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/21/2015] [Revised: 03/16/2016] [Accepted: 04/13/2016] [Indexed: 11/18/2022]
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Pasupneti S, Patel K, Mooney JJ, Chhatwani L, Dhillon G, Weill D. Lung transplantation following death by drowning: a review of the current literature. Clin Transplant 2016; 30:1195-1197. [PMID: 27447443 DOI: 10.1111/ctr.12822] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/18/2016] [Indexed: 12/15/2022]
Abstract
While multiple donor characteristics have been cited as ideal for lung transplantation, there are minimal widely accepted exclusion criteria. One criterion that many centers view with hesitation is death by drowning. However, recent literature suggests such donors may result in acceptable outcomes following transplantation. This review highlights a case of a patient who underwent a successful bilateral lung transplant from a donor following a drowning event. A review of the current literature is presented, concluding with a new proposed set of favorable donor criteria following death by drowning.
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Affiliation(s)
- Shravani Pasupneti
- Department of Pulmonary and Critical Care, Stanford University School of Medicine, Stanford, CA, USA.
| | - Kapil Patel
- Department of Pulmonary and Critical Care, Stanford University School of Medicine, Stanford, CA, USA
| | - Joshua J Mooney
- Department of Pulmonary and Critical Care, Stanford University School of Medicine, Stanford, CA, USA
| | - Laveena Chhatwani
- Department of Pulmonary and Critical Care, Stanford University School of Medicine, Stanford, CA, USA
| | - Gundeep Dhillon
- Department of Pulmonary and Critical Care, Stanford University School of Medicine, Stanford, CA, USA
| | - David Weill
- Department of Pulmonary and Critical Care, Stanford University School of Medicine, Stanford, CA, USA
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Costa J, Sreekanth S, Kossar A, Raza K, Robbins H, Shah L, Sonett JR, Arcasoy S, D'Ovidio F. Donors with a prior history of cardiac surgery are a viable source of lung allografts. Eur J Cardiothorac Surg 2016; 50:822-825. [PMID: 27147626 DOI: 10.1093/ejcts/ezw157] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2015] [Accepted: 04/11/2016] [Indexed: 01/11/2023] Open
Abstract
OBJECTIVES End-stage lung disease continues to rise despite the lack of suitable lung donors, limiting the numbers of lung transplants performed each year. Expanded donor criteria, use of donation after cardiac death donors and the advent of ex vivo lung perfusion have resulted only in a slight increase in donor lung utilization. Organ donors with prior cardiac surgery (DPCS) present risks and technical challenges; however, they may be a potential source of suitable lung allografts with an experienced procurement surgeon. We present our experience having evaluated potential lung donors with a prior history of cardiac surgery, resulting in successful transplant outcomes. METHODS This is a single-institution retrospective review of brain-dead organ donors that were evaluated for lung donation in the period 2012-15. Donor and recipient characteristics were collected. Post-lung transplant survival was recorded. RESULTS From 2012 to 2015, 259 donors were evaluated, 12 with a prior history of cardiac surgery of which 4 had coronary artery bypass, 3 had aortic root replacement, 2 had aortic valve replacement, 1 pulmonary embolectomy, 1 two-time reoperative valve replacement and 1 paediatric congenital ventricular septal defect repair. DPCS, 6/12 (50% dry run) provided suitable allografts generating six single-lung transplants (three right and three left, 1 donor provided twin single-lung transplants) and one double-lung transplant. Interval between cardiac surgery and procurement for those rejected was median 5840 (IQR 2350-8640) days and interval for the donors that provided allografts was median 438 (IQR 336-1095) days (Mann-Whitney, P = 0.07). Recipient 1-year survival from DPCS is 100%. Recipient 1-year survival was 92% in allografts explanted from donors with no prior cardiac surgery (2012-13). CONCLUSION To date, this is the largest single-centre experience using lung allografts from brain-dead DPCS. Our experience shows despite predicted technical difficulties, with good communication between thoracic and abdominal teams, successful transplant outcomes are possible, when surgeons with experience in reoperative cases are sent for lung procurements.
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Affiliation(s)
- Joseph Costa
- Department of Surgery, Division of Cardiac, Vascular and Thoracic Surgery, Columbia University Medical Center, New York, NY, USA
| | - Sowmyashree Sreekanth
- Department of Surgery, Division of Cardiac, Vascular and Thoracic Surgery, Columbia University Medical Center, New York, NY, USA
| | - Alex Kossar
- Department of Surgery, Division of Cardiac, Vascular and Thoracic Surgery, Columbia University Medical Center, New York, NY, USA
| | - Kashif Raza
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, NY, USA
| | - Hilary Robbins
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, NY, USA
| | - Lori Shah
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, NY, USA
| | - Joshua R Sonett
- Department of Surgery, Division of Cardiac, Vascular and Thoracic Surgery, Columbia University Medical Center, New York, NY, USA
| | - Selim Arcasoy
- Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, Columbia University Medical Center, New York, NY, USA
| | - Frank D'Ovidio
- Department of Surgery, Division of Cardiac, Vascular and Thoracic Surgery, Columbia University Medical Center, New York, NY, USA
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Lung Transplantation. PATHOLOGY OF TRANSPLANTATION 2016. [PMCID: PMC7153460 DOI: 10.1007/978-3-319-29683-8_5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
The therapeutic options for patients with advanced pulmonary parenchymal or vascular disorders are currently limited. Lung transplantation remains one of the few viable interventions, but on account of the insufficient donor pool only a minority of these patients actually undergo the procedure each year. Following transplantation there are a number of early and late allograft complications such as primary graft dysfunction, allograft rejection, infection, post-transplant lymphoproliferative disorder and late injury that is now classified as chronic lung allograft dysfunction. The pathologist plays an essential role in the diagnosis and classification of these myriad complications. Although the transplant procedures are performed in selected centers patients typically return to their local centers. When complications arise it is often the responsibility of the local pathologist to evaluate specimens. Therefore familiarity with the pathology of lung transplantation is important.
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20
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Salvadori M, Bertoni E. What's new in clinical solid organ transplantation by 2013. World J Transplant 2014; 4:243-266. [PMID: 25540734 PMCID: PMC4274595 DOI: 10.5500/wjt.v4.i4.243] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/22/2014] [Revised: 07/11/2014] [Accepted: 07/27/2014] [Indexed: 02/05/2023] Open
Abstract
Innovative and exciting advances in the clinical science in solid organ transplantation continuously realize as the results of studies, clinical trials, international conferences, consensus conferences, new technologies and discoveries. This review will address to the full spectrum of news in transplantation, that verified by 2013. The key areas covered are the transplantation activity, with particular regards to the donors, the news for solid organs such as kidney, pancreas, liver, heart and lung, the news in immunosuppressive therapies, the news in the field of tolerance and some of the main complications following transplantation as infections and cancers. The period of time covered by the study starts from the international meetings held in 2012, whose results were published in 2013, up to the 2013 meetings, conferences and consensus published in the first months of 2014. In particular for every organ, the trends in numbers and survival have been reviewed as well as the most relevant problems such as organ preservation, ischemia reperfusion injuries, and rejections with particular regards to the antibody mediated rejection that involves all solid organs. The new drugs and strategies applied in organ transplantation have been divided into new way of using old drugs or strategies and drugs new not yet on the market, but on phase Ito III of clinical studies and trials.
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Gilpin SE, Ren X, Okamoto T, Guyette JP, Mou H, Rajagopal J, Mathisen DJ, Vacanti JP, Ott HC. Enhanced lung epithelial specification of human induced pluripotent stem cells on decellularized lung matrix. Ann Thorac Surg 2014; 98:1721-9; discussion 1729. [PMID: 25149047 DOI: 10.1016/j.athoracsur.2014.05.080] [Citation(s) in RCA: 91] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 05/09/2014] [Accepted: 05/13/2014] [Indexed: 12/19/2022]
Abstract
BACKGROUND Whole-lung scaffolds can be created by perfusion decellularization of cadaveric donor lungs. The resulting matrices can then be recellularized to regenerate functional organs. This study evaluated the capacity of acellular lung scaffolds to support recellularization with lung progenitors derived from human induced pluripotent stem cells (iPSCs). METHODS Whole rat and human lungs were decellularized by constant-pressure perfusion with 0.1% sodium dodecyl sulfate solution. Resulting lung scaffolds were cryosectioned into slices or left intact. Human iPSCs were differentiated to definitive endoderm, anteriorized to a foregut fate, and then ventralized to a population expressing NK2 homeobox 1 (Nkx2.1). Cells were seeded onto slices and whole lungs, which were maintained under constant perfusion biomimetic culture. Lineage specification was assessed by quantitative polymerase chain reaction and immunofluorescent staining. Regenerated left lungs were transplanted in an orthotopic position. RESULTS Activin-A treatment, followed by transforming growth factor-β inhibition, induced differentiation of human iPSCs to anterior foregut endoderm as confirmed by forkhead box protein A2 (FOXA2), SRY (Sex Determining Region Y)-Box 17 (SOX17), and SOX2 expression. Cells cultured on decellularized lung slices demonstrated proliferation and lineage commitment after 5 days. Cells expressing Nkx2.1 were identified at 40% to 60% efficiency. Within whole-lung scaffolds and under perfusion culture, cells further upregulated Nkx2.1 expression. After orthotopic transplantation, grafts were perfused and ventilated by host vasculature and airways. CONCLUSIONS Decellularized lung matrix supports the culture and lineage commitment of human iPSC-derived lung progenitor cells. Whole-organ scaffolds and biomimetic culture enable coseeding of iPSC-derived endothelial and epithelial progenitors and enhance early lung fate. Orthotopic transplantation may enable further in vivo graft maturation.
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Affiliation(s)
- Sarah E Gilpin
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Xi Ren
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Tatsuya Okamoto
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Jacques P Guyette
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Hongmei Mou
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Jayaraj Rajagopal
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Douglas J Mathisen
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Joseph P Vacanti
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts
| | - Harald C Ott
- Department of Surgery, Massachusetts General Hospital, and Harvard Medical School, Boston, Massachusetts.
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22
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Andreasson ASI, Dark JH, Fisher AJ. Ex vivo lung perfusion in clinical lung transplantation--State of the art. Eur J Cardiothorac Surg 2014; 46:779-88. [DOI: 10.1093/ejcts/ezu228] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
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Herrmann G, Knudsen L, Madershahian N, Mühlfeld C, Frank K, Rahmanian P, Wahlers T, Wittwer T, Ochs M. Effects of exogenous surfactant on the non-heart-beating donor lung graft in experimental lung transplantation - a stereological study. J Anat 2014; 224:594-602. [PMID: 24527871 DOI: 10.1111/joa.12167] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/21/2014] [Indexed: 11/29/2022] Open
Abstract
The use of non-heart-beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non-SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design-based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham-operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non-SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron-chovascular connective tissue. Regarding intra-alveolar oedema, no statistically significant difference could be found between SF and non-SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart-beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed are limiting factors that need to be addressed in NHBD.
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