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Sample records for adult lung transplant

  1. Lung transplantation

    PubMed Central

    Afonso, José Eduardo; Werebe, Eduardo de Campos; Carraro, Rafael Medeiros; Teixeira, Ricardo Henrique de Oliveira Braga; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a globally accepted treatment for some advanced lung diseases, giving the recipients longer survival and better quality of life. Since the first transplant successfully performed in 1983, more than 40 thousand transplants have been performed worldwide. Of these, about seven hundred were in Brazil. However, survival of the transplant is less than desired, with a high mortality rate related to primary graft dysfunction, infection, and chronic graft dysfunction, particularly in the form of bronchiolitis obliterans syndrome. New technologies have been developed to improve the various stages of lung transplant. To increase the supply of lungs, ex vivo lung reconditioning has been used in some countries, including Brazil. For advanced life support in the perioperative period, extracorporeal membrane oxygenation and hemodynamic support equipment have been used as a bridge to transplant in critically ill patients on the waiting list, and to keep patients alive until resolution of the primary dysfunction after graft transplant. There are patients requiring lung transplant in Brazil who do not even come to the point of being referred to a transplant center because there are only seven such centers active in the country. It is urgent to create new centers capable of performing lung transplantation to provide patients with some advanced forms of lung disease a chance to live longer and with better quality of life. PMID:26154550

  2. Lung transplant

    MedlinePlus

    Solid organ transplant - lung ... the new lung Have severe disease of other organs Cannot reliably take their medicines Are unable to ... medicines Damage to your kidneys, liver, or other organs from anti-rejection medicines Future risk of certain ...

  3. Risk of Post-Lung Transplant Renal Dysfunction in Adults With Cystic Fibrosis

    PubMed Central

    Mayer-Hamblett, Nicole; Aitken, Moira L.; Goss, Christopher H.

    2012-01-01

    Background: Cystic fibrosis (CF) is one of the leading indications for lung transplantation. The incidence and pre-lung transplant risk factors for posttransplant renal dysfunction in the CF population remain undefined. Methods: We conducted a cohort study using adults (≥ 18 years old) in the CF Foundation Patient Registry from 2000 to 2008 to determine the incidence of post-lung transplant renal dysfunction, defined by an estimated glomerular filtration rate of < 60 mL/min/1.73 m2. Multivariable Cox proportional hazards modeling was used to identify independent pretransplant risk factors for post-lung transplant renal dysfunction. Results: The study cohort included 993 adult lung transplant recipients with CF, with a median follow-up of 2 years. During the study period, 311 individuals developed renal dysfunction, with a 2-year risk of 35% (95% CI, 32%-39%). Risk of posttransplant renal dysfunction increased substantially with increasing age (25 to < 35 years vs 18 to < 25 years: hazard ratio [HR], 1.60; 95% CI, 1.15-2.23; vs ≥ 35 years: HR, 2.45; 95% CI, 1.73-3.47) and female sex (HR, 1.56; 95% CI, 1.22-1.99). CF-related diabetes requiring insulin therapy (HR, 1.30; 95% CI, 1.02-1.67) and pretransplant renal function impairment (estimated glomerular filtration rate, 60-90 mL/min/m2 vs > 90 mL/min/m2: HR, 1.58; 95% CI, 1.19-2.12) also increased the risk of posttransplant renal dysfunction. Conclusions: Renal dysfunction is common following lung transplant in the adult CF population. Increased age, female sex, CF-related diabetes requiring insulin, and pretransplant renal impairment are significant risk factors. PMID:22222189

  4. Liver and lung transplantation in cystic fibrosis: an adult cystic fibrosis centre's experience.

    PubMed

    Sivam, S; Al-Hindawi, Y; Di Michiel, J; Moriarty, C; Spratt, P; Jansz, P; Malouf, M; Plit, M; Pleass, H; Havryk, A; Bowen, D; Haber, P; Glanville, A R; Bye, P T P

    2016-07-01

    Liver disease develops in one-third of patients with cystic fibrosis (CF). It is rare for liver disease to have its onset after 20 years of age. Lung disease, however, is usually more severe in adulthood. A retrospective analysis was performed on nine patients. Three patients required lung transplantation approximately a decade after liver transplant, and another underwent combined liver and lung transplants. Four additional patients with liver transplants are awaiting assessment for lung transplants. One patient is awaiting combined liver and lung transplants. With increased survival in CF, several patients may require more than single organ transplantation. PMID:27405894

  5. Who Needs a Lung Transplant?

    MedlinePlus

    ... from the NHLBI on Twitter. Who Needs a Lung Transplant? Your doctor may recommend a lung transplant ... lungs to pick up oxygen. Applying to a Lung Transplant Program Lung transplants are done in medical ...

  6. Pediatric lung transplantation: 10 years of experience

    PubMed Central

    Camargo, Priscila C. L. B.; Pato, Eduardo Z. S.; Campos, Silvia V.; Afonso, José E.; Carraro, Rafael M.; Costa, André N.; Teixeira, Ricardo H. O. B.; Samano, Marcos N.; Pêgo-Fernandes, Paulo M.

    2014-01-01

    Lung transplantation is a well-established treatment for advanced lung diseases. In children, the diseases that most commonly lead to the need for a transplantation are cystic fibrosis, pulmonary hypertension, and bronchiolitis. However, the number of pediatric lung transplantations being performed is low compared with the number of transplants performed in the adult age group. The objective of this study was to demonstrate our experience with pediatric lung transplants over a 10-year period in a program initially designed for adults. PMID:24860860

  7. Lung transplantation at Duke

    PubMed Central

    Gray, Alice L.; Hartwig, Matthew G.

    2016-01-01

    Lung transplantation represents the gold-standard therapy for patients with end-stage lung disease. Utilization of this therapy continues to rise. The Lung Transplant Program at Duke University Medical Center was established in 1992, and since that time has grown to one of the highest volume centers in the world. The program to date has performed over 1,600 lung transplants. This report represents an up-to-date review of the practice and management strategies employed for safe and effective lung transplantation at our center. Specific attention is paid to the evaluation of candidacy for lung transplantation, donor selection, surgical approach, and postoperative management. These evidence-based strategies form the foundation of the clinical transplantation program at Duke. PMID:27076968

  8. Intrapulmonary Pharmacokinetics and Pharmacodynamics of Micafungin in Adult Lung Transplant Patients▿

    PubMed Central

    Walsh, Thomas J.; Goutelle, Sylvain; Jelliffe, Roger W.; Golden, Jeffrey A.; Little, Emily A.; DeVoe, Catherine; Mickiene, Diana; Hayes, Maggie; Conte, John E.

    2010-01-01

    Invasive pulmonary aspergillosis is a life-threatening infection in lung transplant recipients; however, no studies of the pharmacokinetics and pharmacodynamics (PKPD) of echinocandins in transplanted lungs have been reported. We conducted a single-dose prospective study of the intrapulmonary and plasma PKPD of 150 mg of micafungin administered intravenously in 20 adult lung transplant recipients. Epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage performed 3, 5, 8, 18, or 24 h after initiation of infusion. Micafungin concentrations in plasma, ELF, and ACs were determined using high-pressure liquid chromatography. Noncompartmental methods, population analysis, and multiple-dose simulations were used to calculate PKPD parameters. Cmax in plasma, ELF, and ACs was 4.93, 1.38, and 17.41 μg/ml, respectively. The elimination half-life in plasma was 12.1 h. Elevated concentrations in ELF and ACs were sustained during the 24-h sampling period, indicating prolonged compartmental half-lives. The mean micafungin concentration exceeded the MIC90 of Aspergillus fumigatus (0.0156 μg/ml) in plasma (total and free), ELF, and ACs throughout the dosing interval. The area under the time-concentration curve from 0 to 24 h (AUC0-24)/MIC90 ratios in plasma, ELF, and ACs were 5,077, 923.1, and 13,340, respectively. Multiple-dose simulations demonstrated that ELF and AC concentrations of micafungin would continue to increase during 14 days of administration. We conclude that a single 150-mg intravenous dose of micafungin resulted in plasma, ELF, and AC concentrations that exceeded the MIC90 of A. fumigatus for 24 h and that these concentrations would continue to increase during 14 days of administration, supporting its potential activity for prevention and early treatment of pulmonary aspergillosis. PMID:20439610

  9. Evidence for tissue-resident mesenchymal stem cells in human adult lung from studies of transplanted allografts.

    PubMed

    Lama, Vibha N; Smith, Lisa; Badri, Linda; Flint, Andrew; Andrei, Adin-Cristian; Murray, Susan; Wang, Zhuo; Liao, Hui; Toews, Galen B; Krebsbach, Paul H; Peters-Golden, Marc; Pinsky, David J; Martinez, Fernando J; Thannickal, Victor J

    2007-04-01

    The origin and turnover of connective tissue cells in adult human organs, including the lung, are not well understood. Here, studies of cells derived from human lung allografts demonstrate the presence of a multipotent mesenchymal cell population, which is locally resident in the human adult lung and has extended life span in vivo. Examination of plastic-adherent cell populations in bronchoalveolar lavage samples obtained from 76 human lung transplant recipients revealed clonal proliferation of fibroblast-like cells in 62% (106 of 172) of samples. Immunophenotyping of these isolated cells demonstrated expression of vimentin and prolyl-4-hydroxylase, indicating a mesenchymal phenotype. Multiparametric flow cytometric analyses revealed expression of cell-surface proteins, CD73, CD90, and CD105, commonly found on mesenchymal stem cells (MSCs). Hematopoietic lineage markers CD14, CD34, and CD45 were absent. Multipotency of these cells was demonstrated by their capacity to differentiate into adipocytes, chondrocytes, and osteocytes. Cytogenetic analysis of cells from 7 sex-mismatched lung transplant recipients harvested up to 11 years after transplant revealed that 97.2% +/- 2.1% expressed the sex genotype of the donor. The presence of MSCs of donor sex identity in lung allografts even years after transplantation provides what we believe to be the first evidence for connective tissue cell progenitors that reside locally within a postnatal, nonhematopoietic organ.

  10. Xenogeneic lung transplantation models

    PubMed Central

    Burdorf, Lars; Azimzadeh, Agnes M.; Pierson, Richard N.

    2014-01-01

    Summary Study of lung xenografts has proven useful to understand the remaining barriers to successful transplantation of other organ xenografts. In this chapter, the history and current status of lung xenotransplantation will be briefly reviewed and two different experimental models, the ex vivo porcine-to-human lung perfusion and the in vivo xenogeneic lung transplantation, will be presented. We will focus on the technical details of these lung xenograft models in sufficient detail, list the needed materials and mention analysis techniques to allow others to adopt them with minimal learning curve. PMID:22565996

  11. Lung transplantation in children. Specific aspects.

    PubMed

    Moreno Galdó, Antonio; Solé Montserrat, Juan; Roman Broto, Antonio

    2013-12-01

    Lung transplantation has become in recent years a therapeutic option for infantswith terminal lung disease with similar results to transplantation in adults.In Spain, since 1996 114 children lung transplants have been performed; this corresponds to3.9% of the total transplant number.The most common indication in children is cystic fibrosis, which represents between 70-80% of the transplants performed in adolescents. In infants common indications areinterstitial lung disease and pulmonary hypertension.In most children a sequential double lung transplant is performed, generally with the help ofextracorporeal circulation. Lung transplantation in children presents special challenges in monitoring and follow-up, especially in infants, given the difficulty in assessing lung function and performing transbronchial biopsies.There are some more specific complications in children like postransplant lymphoproliferative syndrome or a greater severity of respiratory virus infections .After lung transplantation children usually experiment a very important improvement in their quality of life. Eighty eight per cent of children have no limitations in their activity after 3 years of transplantation.According to the registry of the International Society for Heart & Lung Transplantation (ISHLT) survival at 5 years of transplantation is 54% and at 10 years is around 35%. PMID:24239132

  12. Overview of Clinical Lung Transplantation

    PubMed Central

    Yeung, Jonathan C.; Keshavjee, Shaf

    2014-01-01

    Since the first successful lung transplant 30 years ago, lung transplantation has rapidly become an established standard of care to treat end-stage lung disease in selected patients. Advances in lung preservation, surgical technique, and immunosuppression regimens have resulted in the routine performance of lung transplantation around the world for an increasing number of patients, with wider indications. Despite this, donor shortages and chronic lung allograft dysfunction continue to prevent lung transplantation from reaching its full potential. With research into the underlying mechanisms of acute and chronic lung graft dysfunction and advances in personalized diagnostic and therapeutic approaches to both the donor lung and the lung transplant recipient, there is increasing confidence that we will improve short- and long-term outcomes in the near future. PMID:24384816

  13. Lung Transplantation for Cystic Fibrosis

    PubMed Central

    Adler, Frederick R.; Aurora, Paul; Barker, David H.; Barr, Mark L.; Blackwell, Laura S.; Bosma, Otto H.; Brown, Samuel; Cox, D. R.; Jensen, Judy L.; Kurland, Geoffrey; Nossent, George D.; Quittner, Alexandra L.; Robinson, Walter M.; Romero, Sandy L.; Spencer, Helen; Sweet, Stuart C.; van der Bij, Wim; Vermeulen, J.; Verschuuren, Erik A. M.; Vrijlandt, Elianne J. L. E.; Walsh, William; Woo, Marlyn S.; Liou, Theodore G.

    2009-01-01

    Lung transplantation is a complex, high-risk, potentially life-saving therapy for the end-stage lung disease of cystic fibrosis (CF). The decision to pursue transplantation involves comparing the likelihood of survival with and without transplantation as well as assessing the effect of wait-listing and transplantation on the patient's quality of life. Although recent population-based analyses of the US lung allocation system for the CF population have raised controversies about the survival benefits of transplantation, studies from the United Kingdom and Canada have suggested a definite survival advantage for those receiving transplants. In response to these and other controversies, leaders in transplantation and CF met together in Lansdowne, Virginia, to consider the state of the art in lung transplantation for CF in an international context, focusing on advances in surgical technique, measurement of outcomes, use of prognostic criteria, variations in local control over listing, and prioritization among the United States, Canada, the United Kingdom, and The Netherlands, patient adherence before and after transplantation and other issues in the broader context of lung transplantation. Finally, the conference members carefully considered how efforts to improve outcomes for lung transplantation for CF lung disease might best be studied. This Roundtable seeks to communicate the substance of our discussions. PMID:20008865

  14. What to Expect During a Lung Transplant

    MedlinePlus

    ... NHLBI on Twitter. What To Expect During a Lung Transplant Just before lung transplant surgery, you will ... airway and its blood vessels to your heart. Lung Transplant The illustration shows the process of a ...

  15. The lung microbiome after lung transplantation.

    PubMed

    Becker, Julia; Poroyko, Valeriy; Bhorade, Sangeeta

    2014-04-01

    Lung transplantation survival remains significantly impacted by infections and the development of chronic rejection manifesting as bronchiolitis obliterans syndrome (BOS). Traditional microbiologic data has provided insight into the role of infections in BOS. Now, new non-culture-based techniques have been developed to characterize the entire population of microbes resident on the surfaces of the body, also known as the human microbiome. Early studies have identified that lung transplant patients have a different lung microbiome and have demonstrated the important finding that the transplant lung microbiome changes over time. Furthermore, both unique bacterial populations and longitudinal changes in the lung microbiome have now been suggested to play a role in the development of BOS. In the future, this technology will need to be combined with functional assays and assessment of the immune responses in the lung to help further explain the microbiome's role in the failing lung allograft.

  16. Lung Transplantation for Hypersensitivity Pneumonitis

    PubMed Central

    Singer, Jonathan P.; Koth, Laura; Mooney, Joshua; Golden, Jeff; Hays, Steven; Greenland, John; Wolters, Paul; Ghio, Emily; Jones, Kirk D.; Leard, Lorriana; Kukreja, Jasleen; Blanc, Paul D.

    2015-01-01

    BACKGROUND: Hypersensitivity pneumonitis (HP) is an inhaled antigen-mediated interstitial lung disease (ILD). Advanced disease may necessitate the need for lung transplantation. There are no published studies addressing lung transplant outcomes in HP. We characterized HP outcomes compared with referents undergoing lung transplantation for idiopathic pulmonary fibrosis (IPF). METHODS: To identify HP cases, we reviewed records for all ILD lung transplantation cases at our institution from 2000 to 2013. We compared clinical characteristics, survival, and acute and chronic rejection for lung transplant recipients with HP to referents with IPF. We also reviewed diagnoses of HP discovered only by explant pathology and looked for evidence of recurrent HP after transplant. Survival was compared using Kaplan-Meier methods and Cox proportional hazard modeling. RESULTS: We analyzed 31 subjects with HP and 91 with IPF among 183 cases undergoing lung transplantation for ILD. Survival at 1, 3, and 5 years after lung transplant in HP compared with IPF was 96%, 89%, and 89% vs 86%, 67%, and 49%, respectively. Subjects with HP manifested a reduced adjusted risk for death compared with subjects with IPF (hazard ratio, 0.25; 95% CI, 0.08-0.74; P = .013). Of the 31 cases, the diagnosis of HP was unexpectedly made at explant in five (16%). Two subjects developed recurrent HP in their allografts. CONCLUSIONS: Overall, subjects with HP have excellent medium-term survival after lung transplantation and, relative to IPF, a reduced risk for death. HP may be initially discovered only by review of the explant pathology. Notably, HP may recur in the allograft. PMID:25412059

  17. [Current status and future of lung transplantation].

    PubMed

    Date, Hiroshi

    2011-10-01

    Lung transplantation has been a widely accepted treatment modality for patients with end-stage chronic obstructive lung disease (COPD). COPD is the most frequent indication for lung transplantation according to the report from International Society for Lung and Heart Transplantation. However, it is a minor population in Japan. A total of 204 lung transplants have been performed in Japan to date. Among them, 10 patients were suffering from severe COPD. Nine of them received cadaveric lung transplantation and one received living-donor lobar lung transplantation. All are currently alive during follow-up period of 3-87 months.

  18. What To Expect Before a Lung Transplant

    MedlinePlus

    ... NHLBI on Twitter. What To Expect Before a Lung Transplant If you get into a medical center's ... friends also can offer support. When a Donor Lung Becomes Available OPTN matches donor lungs to recipients ...

  19. Technology and Outcomes Assessment in Lung Transplantation

    PubMed Central

    Yusen, Roger D.

    2009-01-01

    Lung transplantation offers the hope of prolonged survival and significant improvement in quality of life to patients that have advanced lung diseases. However, the medical literature lacks strong positive evidence and shows conflicting information regarding survival and quality of life outcomes related to lung transplantation. Decisions about the use of lung transplantation require an assessment of trade-offs: do the potential health and quality of life benefits outweigh the potential risks and harms? No amount of theoretical reasoning can resolve this question; empiric data are needed. Rational analyses of these trade-offs require valid measurements of the benefits and harms to the patients in all relevant domains that affect survival and quality of life. Lung transplant systems and registries mainly focus outcomes assessment on patient survival on the waiting list and after transplantation. Improved analytic approaches allow comparisons of the survival effects of lung transplantation versus continued waiting. Lung transplant entities do not routinely collect quality of life data. However, the medical community and the public want to know how lung transplantation affects quality of life. Given the huge stakes for the patients, the providers, and the healthcare systems, key stakeholders need to further support quality of life assessment in patients with advanced lung disease that enter into the lung transplant systems. Studies of lung transplantation and its related technologies should assess patients with tools that integrate both survival and quality of life information. Higher quality information obtained will lead to improved knowledge and more informed decision making. PMID:19131538

  20. Current status and problems of lung transplantation in Japan

    PubMed Central

    2016-01-01

    Lung transplantation has been performed worldwide and recognized as an effective treatment for patients with various end-stage lung diseases. Shortage of lung donors is one of the main obstacles in most of the countries, especially in Japan. Every effort has been made to promote organ donation during the past 20 years. In 2010, Japanese transplant low was revised so that the family of the brain dead donors can make a decision for organ donation. Since then, the number of cadaveric lung donor has increased by 5-fold. However, the average waiting time is still more than 800 days resulting in considerable number of deaths on the waiting list. Lung transplantation in the use of donation after cardiac death (DCD) has now been increasingly performed in Europe, Australia and North America with promising results. However, controlled death is not permitted in Japan making it difficult to accept this strategy. Use of marginal donors is one of the strategies for organ shortage. In Japan, the rate of lung usage is now well over 60% because of careful donor management by medical consultants and aggressive use of marginal donors. Living-donor lobar lung transplantation (LDLLT) has been developed to offset the mismatch between supply and demand for those patients awaiting cadaveric lung transplantation (CLT) and it is often the most realistic option for very ill patients. Between 1998 and 2015, lung transplantation has been performed in 464 patients (55 children, 419 adults) at 9 lung transplant centers in Japan. CLT was performed in 283 patients (61%) and LDLLT was performed in 181 patients (39%). The 5-year survival was 72.3% and 71.6%, respectively. Of note, only seven children received CLT. In conclusion, lung transplantation in Japan has grown significantly with excellent results but the shortage of cadaveric lung donor remains to be an important unsolved problem. LDLLT is often the only realistic option for very ill patients especially for children. PMID:27651939

  1. Current status and problems of lung transplantation in Japan

    PubMed Central

    2016-01-01

    Lung transplantation has been performed worldwide and recognized as an effective treatment for patients with various end-stage lung diseases. Shortage of lung donors is one of the main obstacles in most of the countries, especially in Japan. Every effort has been made to promote organ donation during the past 20 years. In 2010, Japanese transplant low was revised so that the family of the brain dead donors can make a decision for organ donation. Since then, the number of cadaveric lung donor has increased by 5-fold. However, the average waiting time is still more than 800 days resulting in considerable number of deaths on the waiting list. Lung transplantation in the use of donation after cardiac death (DCD) has now been increasingly performed in Europe, Australia and North America with promising results. However, controlled death is not permitted in Japan making it difficult to accept this strategy. Use of marginal donors is one of the strategies for organ shortage. In Japan, the rate of lung usage is now well over 60% because of careful donor management by medical consultants and aggressive use of marginal donors. Living-donor lobar lung transplantation (LDLLT) has been developed to offset the mismatch between supply and demand for those patients awaiting cadaveric lung transplantation (CLT) and it is often the most realistic option for very ill patients. Between 1998 and 2015, lung transplantation has been performed in 464 patients (55 children, 419 adults) at 9 lung transplant centers in Japan. CLT was performed in 283 patients (61%) and LDLLT was performed in 181 patients (39%). The 5-year survival was 72.3% and 71.6%, respectively. Of note, only seven children received CLT. In conclusion, lung transplantation in Japan has grown significantly with excellent results but the shortage of cadaveric lung donor remains to be an important unsolved problem. LDLLT is often the only realistic option for very ill patients especially for children.

  2. Current status and problems of lung transplantation in Japan.

    PubMed

    Date, Hiroshi

    2016-08-01

    Lung transplantation has been performed worldwide and recognized as an effective treatment for patients with various end-stage lung diseases. Shortage of lung donors is one of the main obstacles in most of the countries, especially in Japan. Every effort has been made to promote organ donation during the past 20 years. In 2010, Japanese transplant low was revised so that the family of the brain dead donors can make a decision for organ donation. Since then, the number of cadaveric lung donor has increased by 5-fold. However, the average waiting time is still more than 800 days resulting in considerable number of deaths on the waiting list. Lung transplantation in the use of donation after cardiac death (DCD) has now been increasingly performed in Europe, Australia and North America with promising results. However, controlled death is not permitted in Japan making it difficult to accept this strategy. Use of marginal donors is one of the strategies for organ shortage. In Japan, the rate of lung usage is now well over 60% because of careful donor management by medical consultants and aggressive use of marginal donors. Living-donor lobar lung transplantation (LDLLT) has been developed to offset the mismatch between supply and demand for those patients awaiting cadaveric lung transplantation (CLT) and it is often the most realistic option for very ill patients. Between 1998 and 2015, lung transplantation has been performed in 464 patients (55 children, 419 adults) at 9 lung transplant centers in Japan. CLT was performed in 283 patients (61%) and LDLLT was performed in 181 patients (39%). The 5-year survival was 72.3% and 71.6%, respectively. Of note, only seven children received CLT. In conclusion, lung transplantation in Japan has grown significantly with excellent results but the shortage of cadaveric lung donor remains to be an important unsolved problem. LDLLT is often the only realistic option for very ill patients especially for children. PMID:27651939

  3. [Lung transplantation program for Hungarian patients].

    PubMed

    Lang, György; Czebe, Krisztina; Gieszer, Balázs; Rényi-Vámos, Ferenc

    2013-06-01

    When conservative treatment fails, lung transplantation often remains the only therapeutic option for patients with end stage parenchymal or vascular lung diseases. According to the statistics of the International Society for Heart and Lung Transplantation, in 2010 more than 3500 lung transplantations have been performed worldwide. The Department of Thoracic Surgery at the University of Vienna is considered to be one of the world's leading lung transplantation centres; in the last year 115, since 1989 more than 1500 lung transplantation procedures under the supervision of Prof. Dr. Walter Klepetko. Similar to other Central-European countries, lung transplantation procedures of Hungarian patients have also been performed in Vienna whithin the framework of a twinning aggreement. However, many crucial tasks in the process, such indication and patient selection preoperative rehabilitation organ procurement and long term follow-up care have been stepwise taken over by the Hungarian team. Although the surgery itself is still preformed in Vienna, professional experience is already available in Hungary, since the majority of Hungarian recipients have been transplanted by hungarian surgeons who are authors of this article the professional and personal requirements of performing lung transplantations are already available in Hungary. The demand of performing lung transplantation in Hungary has been raising since 1999 and it soon reaches the extent which justifies launching of an individual national program. Providing the technical requirements is a financial an organisational issue. In order to proceed, a health policy decision has to be made.

  4. [Lung hyperinflation after single lung transplantation to treat emphysema].

    PubMed

    Samano, Marcos Naoyuki; Junqueira, Jader Joel Machado; Teixeira, Ricardo Henrique de Oliveira Braga; Caramori, Marlova Luzzi; Pêgo-Fernandes, Paulo Manuel; Jatene, Fabio Biscegli

    2010-01-01

    Despite preventive measures, lung hyperinflation is a relatively common complication following single lung transplantation to treat pulmonary emphysema. The progressive compression of the graft can cause mediastinal shift and respiratory failure. In addition to therapeutic strategies such as independent ventilation, the treatment consists of the reduction of native lung volume by means of lobectomy or lung volume reduction surgery. We report two cases of native lung hyperinflation after single lung transplantation. Both cases were treated by means of lobectomy or lung volume reduction surgery.

  5. Cardiac transplants. Heart and heart-lung transplantation.

    PubMed

    Holmquist, T; Gamberg, P L

    1992-02-01

    OR nurses play an important role in organ procurement. They are responsible for gathering the necessary equipment, which includes cardioplegia supplies, normal saline, a sterile container for transplantation of the heart, a sterile retractor, vascular clamps, and dissection instruments. Orthotopic heart transplantation involves excision of the recipient heart with placement of the donor heart in a normal anatomic position. Heterotopic transplant, which consists of placing the donor heart in the right side of the chest parallel to the native heart, is rarely used. In heart-lung transplantation procedures, attention is given to the removal of the heart and each lung separately to prevent injury to the vagus, phrenic, and laryngeal nerves.

  6. Donor management and lung preservation for lung transplantation.

    PubMed

    Munshi, Laveena; Keshavjee, Shaf; Cypel, Marcelo

    2013-06-01

    Although lung transplantation has become a life-saving option for patients with end-stage lung disease, this intervention is hampered by a shortage of lungs in view of the growing number of people on the waiting list. Lungs are retrieved from only a small percentage of multiorgan donors, and the transplantation and intensive-care communities have recognised the need to develop innovative methods to expand the donor pool. Advancements in lung-preservation techniques in the preretrieval and postretrieval periods have increased the pool of available donors, and novel research and discoveries in this area have steadily improved post-transplantation adverse events. This Review summarises current best practice and the latest research on intensive-care management of a potential lung donor. We also discuss lung-preservation techniques, including advancements in normothermic ex-vivo lung perfusion, and the potential for a personalised medicine approach to the organ. PMID:24429157

  7. Right and left ventricular performance after single and double lung transplantation. The Toronto Lung Transplant Group.

    PubMed

    Carere, R; Patterson, G A; Liu, P; Williams, T; Maurer, J; Grossman, R

    1991-07-01

    Twelve single lung and nine double lung transplant recipients were studied before transplantation and at 3 months and 1 year after transplantation with serial right and left ventricular radionuclide angiograms. The resting right ventricular ejection fraction increased in the double lung recipients from 31% +/- 5% before transplantation to 43% +/- 11% at 3 months after transplantation (p less than 0.05) and then remained stable to 1 year. The single lung recipients also demonstrated a significant rise in ejection fraction from 25% +/- 11% before transplantation to 36% +/- 12% at 3 months after transplantation. Again, this remained stable to 1 year. The exercise right ventricular ejection fraction also showed a significant posttransplantation rise in the double lung recipients (p less than 0.005) that remained stable to 1 year. In the single lung recipients a trend was seen for a rise in the exercise right ventricular ejection fraction that did not reach statistical significance by 1 year after transplantation. Neither group had a significant change in rest or exercise left ventricular ejection fraction. The systemic blood pressure increased significantly by 1 year after transplantation in both groups. The heart rate increase with exercise at 3 months after transplantation was significantly greater in the single lung group (42 +/- 13 beats/min) than in the double lung group (14 +/- 13 beats/min) (p less than 0.005). These data indicate that a significant improvement in right ventricular function occurs after single and double lung transplantation.

  8. Waiting Narratives of Lung Transplant Candidates

    PubMed Central

    Yelle, Maria T.; Stevens, Patricia E.; Lanuza, Dorothy M.

    2013-01-01

    Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman's concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients' stories and hear what is most meaningful in their lives. PMID:23476760

  9. Leukocyte filtration in lung transplantation.

    PubMed

    Kurusz, Mark; Roach, John D; Vertrees, Roger A; Girouard, Mark K; Lick, Scott D

    2002-05-01

    Controlled reperfusion of the transplanted lung has been used in nine consecutive patients to decrease manifestations of lung reperfusion injury. An extracorporeal circuit containing a roller pump, heat exchanger and leukodepleting filter is primed with substrate-enhanced reperfusion solution mixed with approximately 2000 ml of the patient's blood. This solution is slowly recirculated to remove leukocytes prior to reperfusion. When the pulmonary anastomoses are completed, the pulmonary artery is cannulated through the untied anastomosis using a catheter containing a pressure lumen for measurement of infusion pressure. An atrial clamp is left in place on the patient's native atrial cuff to decrease the risk of systemic air embolism during the brief period of reperfusion from the extracorporeal reservoir. During reperfusion, the water bath to the heat exchanger is kept at 35 degrees C and the flow rate for reperfusion solution is between 150 and 200 m/min, keeping the pulmonary artery pressure <14 mmHg. Eight of nine patients were ventilated on 40% inspired oxygen within a few hours of operation and 7/9 were extubated on or before postoperative day 1. Six of nine patients are long-term survivors.

  10. Leukocyte filtration in lung transplantation.

    PubMed

    Kurusz, Mark; Roach, John D; Vertrees, Roger A; Girouard, Mark K; Lick, Scott D

    2002-05-01

    Controlled reperfusion of the transplanted lung has been used in nine consecutive patients to decrease manifestations of lung reperfusion injury. An extracorporeal circuit containing a roller pump, heat exchanger and leukodepleting filter is primed with substrate-enhanced reperfusion solution mixed with approximately 2000 ml of the patient's blood. This solution is slowly recirculated to remove leukocytes prior to reperfusion. When the pulmonary anastomoses are completed, the pulmonary artery is cannulated through the untied anastomosis using a catheter containing a pressure lumen for measurement of infusion pressure. An atrial clamp is left in place on the patient's native atrial cuff to decrease the risk of systemic air embolism during the brief period of reperfusion from the extracorporeal reservoir. During reperfusion, the water bath to the heat exchanger is kept at 35 degrees C and the flow rate for reperfusion solution is between 150 and 200 m/min, keeping the pulmonary artery pressure <14 mmHg. Eight of nine patients were ventilated on 40% inspired oxygen within a few hours of operation and 7/9 were extubated on or before postoperative day 1. Six of nine patients are long-term survivors. PMID:12009087

  11. Sarcopenia in lung transplantation: a systematic review.

    PubMed

    Rozenberg, Dmitry; Wickerson, Lisa; Singer, Lianne G; Mathur, Sunita

    2014-12-01

    Lung transplant candidates and recipients have significant impairments in skeletal muscle mass, strength and function--individual measures of sarcopenia. Skeletal muscle dysfunction has been observed in the pre-transplant and post-transplant period and could have an important effect on transplant outcomes. A systematic review was performed to characterize the techniques used to study sarcopenia and assess the level of impairment throughout the transplant process. Electronic databases were searched (inception to July 2013) for prospective studies measuring at least 1 element of sarcopenia (muscle mass, strength, or function) in lung transplant patients. Eighteen studies were included, and study quality was assessed using the Downs and Black scale. A variety of measurements were used to evaluate sarcopenia in 694 lung transplant patients. Muscle mass in 7 studies was assessed using bioelectrical impedance (n = 4), computed tomography or magnetic resonance imaging (n = 2), or skin folds (n = 1), and was significantly reduced. Quadriceps strength was examined in 14 studies with computerized dynamometer (n = 10) and hand-held dynamometer (n = 4). Quadriceps strength was reduced in the pre-transplant period (mean range, 49%-86% predicted; n = 455 patients), further reduced immediately after transplant (51%-72%, n = 126), and improved beyond 3 months after transplant (58%-101%, n = 164). Only 2 studies measured lower extremity function (sit-to-stand test). A multitude of measurement techniques have been used to assess individual measures of sarcopenia, with reduced muscle mass and quadriceps strength observed in the pre-transplant and post-transplant period. Further standardization of measurement techniques is needed to assess the clinical effect of sarcopenia in lung transplantation.

  12. Comorbidities impacting on prognosis after lung transplant.

    PubMed

    Vaquero Barrios, José Manuel; Redel Montero, Javier; Santos Luna, Francisco

    2014-01-01

    The aim of this review is to give an overview of the clinical circumstances presenting before lung transplant that may have negative repercussions on the long and short-term prognosis of the transplant. Methods for screening and diagnosis of common comorbidities with negative impact on the prognosis of the transplant are proposed, both for pulmonary and extrapulmonary diseases, and measures aimed at correcting these factors are discussed. Coordination and information exchange between referral centers and transplant centers would allow these comorbidities to be detected and corrected, with the aim of minimizing the risks and improving the life expectancy of transplant receivers.

  13. [Lung transplantation in Hungary (1996-2011)].

    PubMed

    Strausz, János

    2011-10-30

    The 15 years history of lung transplantation in Hungary shows the medical, political and social characteristics of this period. The barely determined, open-ended legal, financial and ethical framework of transplantation has stayed nowadays in the same position. The Hungarian State Audit Office has also noted these problems. Joining of Hungary to Eurotransplant will beneficially influence the whole procedure.

  14. Split liver transplantation in adults.

    PubMed

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-09-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID:27672272

  15. Split liver transplantation in adults

    PubMed Central

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-01-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues.

  16. Split liver transplantation in adults

    PubMed Central

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-01-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues. PMID:27672272

  17. Split liver transplantation in adults.

    PubMed

    Hashimoto, Koji; Fujiki, Masato; Quintini, Cristiano; Aucejo, Federico N; Uso, Teresa Diago; Kelly, Dympna M; Eghtesad, Bijan; Fung, John J; Miller, Charles M

    2016-09-01

    Split liver transplantation (SLT), while widely accepted in pediatrics, remains underutilized in adults. Advancements in surgical techniques and donor-recipient matching, however, have allowed expansion of SLT from utilization of the right trisegment graft to now include use of the hemiliver graft as well. Despite less favorable outcomes in the early experience, better outcomes have been reported by experienced centers and have further validated the feasibility of SLT. Importantly, more than two decades of experience have identified key requirements for successful SLT in adults. When these requirements are met, SLT can achieve outcomes equivalent to those achieved with other types of liver transplantation for adults. However, substantial challenges, such as surgical techniques, logistics, and ethics, persist as ongoing barriers to further expansion of this highly complex procedure. This review outlines the current state of SLT in adults, focusing on donor and recipient selection based on physiology, surgical techniques, surgical outcomes, and ethical issues.

  18. Practical Guidelines: Lung Transplantation in Patients with Cystic Fibrosis

    PubMed Central

    Hirche, T. O.; Knoop, C.; Hebestreit, H.; Shimmin, D.; Solé, A.; Elborn, J. S.; Ellemunter, H.; Aurora, P.; Hogardt, M.; Wagner, T. O. F.; ECORN-CF Study Group

    2014-01-01

    There are no European recommendations on issues specifically related to lung transplantation (LTX) in cystic fibrosis (CF). The main goal of this paper is to provide CF care team members with clinically relevant CF-specific information on all aspects of LTX, highlighting areas of consensus and controversy throughout Europe. Bilateral lung transplantation has been shown to be an important therapeutic option for end-stage CF pulmonary disease. Transplant function and patient survival after transplantation are better than in most other indications for this procedure. Attention though has to be paid to pretransplant morbidity, time for referral, evaluation, indication, and contraindication in children and in adults. This review makes extensive use of specific evidence in the field of lung transplantation in CF patients and addresses all issues of practical importance. The requirements of pre-, peri-, and postoperative management are discussed in detail including bridging to transplant and postoperative complications, immune suppression, chronic allograft dysfunction, infection, and malignancies being the most important. Among the contributors to this guiding information are 19 members of the ECORN-CF project and other experts. The document is endorsed by the European Cystic Fibrosis Society and sponsored by the Christiane Herzog Foundation. PMID:24800072

  19. Novel Technologies for Isolated Lung Perfusion: Beyond Lung Transplant.

    PubMed

    Cypel, Marcelo; Keshavjee, Shaf

    2016-05-01

    Isolated lung perfusion (ILP) has been examined and developed in lung transplantation and thoracic oncology research. In lung transplantation, ILP has been used to assess physiologic integrity of donor lungs after removal from the donor, and it has also been proposed as a method for active treatment and repair of injured unsuitable donor organs ex vivo. ILP is attractive as a concept to deliver high-dose chemotherapy to treat pulmonary metastatic disease, referred to as in vivo lung perfusion. This article focuses on the rationale, technical aspects, and experimental and clinical experience of in vivo lung perfusion. A perspective on the future application of these techniques is described. PMID:27112253

  20. Bronchoscopic procedures and lung biopsies in pediatric lung transplant recipients.

    PubMed

    Wong, Jackson Y; Westall, Glen P; Snell, Gregory I

    2015-12-01

    Bronchoscopy remains a pivotal diagnostic and therapeutic intervention in pediatric patients undergoing lung transplantation (LTx). Whether performed as part of a surveillance protocol or if clinically indicated, fibre-optic bronchoscopy allows direct visualization of the transplanted allograft, and in particular, an assessment of the patency of the bronchial anastomosis (or tracheal anastomosis following heart-lung transplantation). Additionally, bronchoscopy facilitates differentiation of infective processes from rejection episodes through collection and subsequent assessment of bronchoalveolar lavage (BAL) and transbronchial biopsy (TBBx) samples. Indeed, the diagnostic criteria for the grading of acute cellular rejection is dependent upon the histopathological assessment of biopsy samples collected at the time of bronchoscopy. Typically, performed in an out-patient setting, bronchoscopy is generally a safe procedure, although complications related to hemorrhage and pneumothorax are occasionally seen. Airway complications, including stenosis, malacia, and dehiscence are diagnosed at bronchoscopy, and subsequent management including balloon dilatation, laser therapy and stent insertion can also be performed bronchoscopically. Finally, bronchoscopy has been and continues to be an important research tool allowing a better understanding of the immuno-biology of the lung allograft through the collection and analysis of collected BAL and TBBx samples. Whilst new investigational tools continue to evolve, the simple visualization and collection of samples within the lung allograft by bronchoscopy remains the gold standard in the evaluation of the lung allograft. This review describes the use and experience of bronchoscopy following lung transplantation in the pediatric setting.

  1. Broader Geographic Sharing of Pediatric Donor Lungs Improves Pediatric Access to Transplant.

    PubMed

    Tsuang, W M; Chan, K M; Skeans, M A; Pyke, J; Hertz, M I; Israni, A J; Robbins-Callahan, L; Visner, G; Wang, X; Wozniak, T C; Valapour, M

    2016-03-01

    US pediatric transplant candidates have limited access to lung transplant due to the small number of donors within current geographic boundaries, leading to assertions that the current lung allocation system does not adequately serve pediatric patients. We hypothesized that broader geographic sharing of pediatric (adolescent, 12-17 years; child, <12 years) donor lungs would increase pediatric candidate access to transplant. We used the thoracic simulated allocation model to simulate broader geographic sharing. Simulation 1 used current allocation rules. Simulation 2 offered adolescent donor lungs across a wider geographic area to adolescents. Simulation 3 offered child donor lungs across a wider geographic area to adolescents. Simulation 4 combined simulations 2 and 3. Simulation 5 prioritized adolescent donor lungs to children across a wider geographic area. Simulation 4 resulted in 461 adolescent transplants per 100 patient-years on the waiting list (range 417-542), compared with 206 (range 180-228) under current rules. Simulation 5 resulted in 388 adolescent transplants per 100 patient-years on the waiting list (range 348-418) and likely increased transplant rates for children. Adult transplant rates, waitlist mortality, and 1-year posttransplant mortality were not adversely affected. Broader geographic sharing of pediatric donor lungs may increase pediatric candidate access to lung transplant. PMID:26523747

  2. Lung Transplantation in Gaucher Disease: A Learning Lesson in Trying to Avoid Both Scylla and Charybdis.

    PubMed

    de Boer, Geertje M; van Dussen, Laura; van den Toorn, Leon M; den Bakker, Michael A; Hoek, Rogier A S; Hesselink, Dennis A; Hollak, Carla E M; van Hal, Peter Th W

    2016-01-01

    Gaucher disease (GD), a lysosomal storage disorder, may result in end-stage lung disease. We report successful bilateral lung transplantation in a 49-year-old woman with GD complicated by severe pulmonary hypertension and fibrotic changes in the lungs. Before receiving the lung transplant, the patient was undergoing both enzyme replacement therapy (imiglucerase) and triple pulmonary hypertension treatment (epoprostenol, bosentan, and sildenafil). She had a history of splenectomy, severe bone disease, and renal involvement, all of which were related to GD and considered as relative contraindications for a lung transplantation. In the literature, lung transplantation has been suggested for severe pulmonary involvement in GD but has been reported only once in a child. To our knowledge, until now, no successful procedure has been reported in adults, and no reports deal with the severe potential posttransplantation complications specifically related to GD. PMID:26757299

  3. Lung transplantation: overall approach regarding its major aspects

    PubMed Central

    de Camargo, Priscila Cilene León Bueno; Teixeira, Ricardo Henrique de Oliveira Braga; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Afonso, José Eduardo; Costa, André Nathan; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

    2015-01-01

    ABSTRACT Lung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil. PMID:26785965

  4. Probable Phaeoacremonium parasiticum as a cause of cavitary native lung nodules after single lung transplantation.

    PubMed

    Shah, S K; Parto, P; Lombard, G A; James, M A; Beckles, D L; Lick, S; Valentine, V G

    2013-02-01

    Lung nodules after lung transplantation most often represent infection or post-transplant lymphoproliferative disorder in the allograft. Conversely, native lung nodules in single lung transplant recipients are more likely to be bronchogenic carcinoma. We present a patient who developed native lung cavitary nodules. Although malignancy was anticipated, evaluation revealed probable Phaeoacremonium parasiticum infection. Phaeoacremonium parasiticum is a dematiaceous fungus first described as a cause of soft tissue infection in a renal transplant patient. Lung nodules have not been previously described and this is the first case, to our knowledge, of P. parasiticum identified after lung transplantation.

  5. Probable Phaeoacremonium parasiticum as a cause of cavitary native lung nodules after single lung transplantation.

    PubMed

    Shah, S K; Parto, P; Lombard, G A; James, M A; Beckles, D L; Lick, S; Valentine, V G

    2013-02-01

    Lung nodules after lung transplantation most often represent infection or post-transplant lymphoproliferative disorder in the allograft. Conversely, native lung nodules in single lung transplant recipients are more likely to be bronchogenic carcinoma. We present a patient who developed native lung cavitary nodules. Although malignancy was anticipated, evaluation revealed probable Phaeoacremonium parasiticum infection. Phaeoacremonium parasiticum is a dematiaceous fungus first described as a cause of soft tissue infection in a renal transplant patient. Lung nodules have not been previously described and this is the first case, to our knowledge, of P. parasiticum identified after lung transplantation. PMID:23279754

  6. Middle Lobe Torsion after Unilateral Lung Transplant

    PubMed Central

    Cox, Chad S; Decker, Summer J; Rolfe, Mark; Hazelton, Todd R; Rojas, Carlos A

    2016-01-01

    Lobar torsion is well documented after pneumonectomy, but is very rare after lung transplant. To the best of our knowledge, this is the twelfth reported case of lobar torsion after lung transplant. In our case, bronchoscopies and chest radiographs were inconclusive; however, CT scan clearly demonstrated findings consistent with right middle lobe torsion. We review the literature and discuss the epidemiology, clinical presentation, imaging features, and treatment considerations for this condition. We also propose that if a clinical picture could be secondary to torsion and bronchoscopies and chest x ray are inconclusive that a CT scan should be obtained as soon as possible since early recognition increases the likelihood of being able to successfully detorse the lung and avoid lobectomy. PMID:27761176

  7. [Contraindications to lung transplantation: evolving limits?].

    PubMed

    Picard, C; Roux, A

    2014-06-01

    In France, the higher frequency of pulmonary sample in organ donors and the enhancement of surgical and perioperative life support techniques, have increased the number procedures and the short term prognosis of lung transplantation (LT). In this setting, the classical contraindications of LT need to be reconsidered. In this article, some of the classical contraindication of LT are confronted to the experience acquired in other solid organ transplantations or from some LT centers. Specific situations such as LT in patients with previous cancer, HIV infection, viral hepatitis, nutritional disorders, acutely ill LT candidates and aging candidates are addressed. Surgical contraindications are not reviewed.

  8. Changes in lung vascular permeability after heart-lung transplantation.

    PubMed

    Mancini, M C; Borovetz, H S; Griffith, B P; Hardesty, R L

    1985-10-01

    We have employed multiple indicator dilution techniques (MID) in six patients after heart-lung transplantation to assess changes in the lung vascular permeability-surface area product for urea (PS). Serial PS values for the patients when normalized to the predicted total lung capacity (TLC) in liters, ranged between 1.04 and 6.27 ml/sec/TLC (patient 1), 0 and 2.76 ml/sec/TLC (patient 2), 0.59 and 2.88 ml/sec/TLC (patient 3), 0.13 and 1.23 ml/sec/TLC (patient 4). The elevated values for PS in patient 1 exceed the lethal range described by K.L. Brigham et al. (J. Clin. Invest. 72:339, 1983) for severe ARDS. This strongly suggests a severely increased lung microvascular permeability in this patient possibly secondary to rejection as indicated by endomyocardial biopsy. PS values for surviving patients 2-6 fell well below the corresponding lethal value for ARDS patients. We conclude that PS urea derived from MID provides an indicator of the status of lung microvascular integrity in heart-lung transplant recipients.

  9. Primary Graft Dysfunction after Lung Transplantation

    PubMed Central

    Altun, Gülbin Töre; Arslantaş, Mustafa Kemal; Cinel, İsmail

    2015-01-01

    Primary graft dysfunction (PGD) is a severe form of acute lung injury that is a major cause of early morbidity and mortality encountered after lung transplantation. PGD is diagnosed by pulmonary oedema with diffuse alveolar damage that manifests clinically as progressive hypoxemia with radiographic pulmonary infiltrates. Inflammatory and immunological response caused by ischaemia and reperfusion is important with regard to pathophysiology. PGD affects short- and long-term outcomes, the donor organ is the leading factor affecting these adverse ramifications. To minimize the risk of PGD, reduction of lung ischaemia time, reperfusion optimisation, prostaglandin level regulation, haemodynamic control, hormone replacement therapy, ventilator management are carried out; for research regarding donor lung preparation strategies, certain procedures are recommended. In this review, recent updates in epidemiology, pathophysiology, molecular and genetic biomarkers and technical developments affecting PGD are described. PMID:27366539

  10. ICU Care Before and After Lung Transplantation.

    PubMed

    Fuehner, Thomas; Kuehn, Christian; Welte, Tobias; Gottlieb, Jens

    2016-08-01

    Lung transplantation (LTx) has become an accepted treatment for carefully selected patients with end-stage lung disease. Critical care issues have gained importance concerning bridging of candidates by mechanical respiratory support and are involved in the care after transplantation. The nature of respiratory support varies from oxygen supply and noninvasive ventilation, to mechanical respiratory support either by mechanical ventilation and/or extracorporeal life support. Recent innovations in extracorporeal life support technology have resulted in its more widespread use. Retrospective studies have demonstrated promising outcomes in candidates on mechanical respiratory support as a bridge to lung transplantation. The role of mechanical respiratory support has influenced the selection criteria for LTx, although bridging remains technically and ethically challenging. Critical care is integral to manage and prevent postoperative complications of LTx. Primary graft dysfunction and prolonged mechanical ventilation are major obstacles to hospital survival after LTx. Clear evidence is lacking on how to ventilate and optimally manage patients after LTx. Prolonged extracorporeal life support after LTx may improve outcome in selected patients with a primary graft dysfunction. PMID:26953218

  11. Constrictive pericarditis after lung transplantation: an under-recognized complication.

    PubMed

    Karolak, Wojtek; Cypel, Marcelo; Chen, Fengshi; Daniel, Lorretta; Chaparro, Cecilia; Keshavjee, Shaf

    2010-05-01

    Primary graft dysfunction, acute rejection, and infection account for most of the early morbidity after lung transplantation, with bronchiolitis obliterans syndrome accounting for most late morbidity. Mediastinal and pericardial complications, in the form of constriction, are not common. We present 4 patients with constrictive pericarditis after lung transplantation and recommend that constrictive pericarditis be considered in the differential diagnosis in lung transplant recipients who present with signs and symptoms of systemic and pulmonary venous congestion. PMID:20207169

  12. Rehabilitation and transition after lung transplantation in children.

    PubMed

    Burton, J H; Marshall, J M; Munro, P; Moule, W; Snell, G I; Westall, G P

    2009-01-01

    We describe the key components of an outpatient pediatric recovery and rehabilitation program set up within the adult lung transplant service at the Alfred Hospital, Melbourne. Following discharge, pediatric lung transplant recipients and their families participated in an intensive 3-month outpatient rehabilitation program. Weekly sessions included education regarding transplant issues, physiotherapy, and occupational therapy sessions. The overall aim of the program was to comprehensively address physical rehabilitation and psychosocial and educational needs. Sessions tailored to meet the individual needs of the child were presented at an appropriate cognitive level. Education sessions for both the children and parents focused on medications, identification of infection and rejection, nutrition, physiotherapy/rehabilitation, occupational roles and stress management, donor issues, psychosocial readjustment, and transition issues. Physiotherapy included a progressive aerobic and strength training program, postural reeducation, and core stability. We incorporate Age-appropriate play activities: running, dancing, jumping, ball skills, and so on. Occupational therapy sessions addressed the primary roles of patient, students, and player. Transitions such as returning to school, friends, and the community were explored. Issues discussed included adjustment to new health status, strategies to manage side effects of medications, and altered body image issues. Weekly multidisciplinary team meetings were used to discuss and plan the rehabilitation progress. School liaison and visits occurred prior to school commencement with follow-up offered to review the ongoing transition process. Both patients and parents have reported a high level of satisfaction with the rehabilitation program. We plan to formally evaluate the program in the future.

  13. Extracorporeal life support as a bridge to lung transplantation.

    PubMed

    Cypel, Marcelo; Keshavjee, Shaf

    2011-06-01

    Patients who are excellent candidates for lung transplantation often die on the waiting list because they are too sick to survive until an organ becomes available. Improvements in lung transplant outcomes, patient selection, and artificial lung device technologies have made it possible to bridge these patients to successful life-saving transplantation. Extracorporeal life support (ECLS) should be tailored to minimize morbidity and provide the appropriate mode and level of cardiopulmonary support for each patient's physiologic requirements. Novel device refinements and further development of ECLS in an ambulatory and simplified manner will help maintain these patients in better condition until transplantation. PMID:21511087

  14. Evolving practice: X-linked agammaglobulinemia and lung transplantation.

    PubMed

    Barnes, S; Kotecha, S; Douglass, J A; Paul, E; Hore-Lacey, F; Stirling, R; Snell, G I; Westall, G P

    2015-04-01

    X-linked agammaglobulinemia (XLA) is a rare primary humoral immunodeficiency syndrome characterized by agammaglobulinemia, recurrent infections and bronchiectasis. Despite the association with end-stage bronchiectasis, the literature on XLA and lung transplantation is extremely limited. We report a series of 6 XLA patients with bronchiectasis who underwent lung transplantation. Short-term outcomes were excellent however long-term outcomes were disappointing with a high incidence of pulmonary sepsis and chronic lung allograft dysfunction (CLAD). PMID:25736826

  15. Retrospective Analysis of Lung Transplant Recipients Found to Have Unexpected Lung Cancer in Explanted Lungs.

    PubMed

    Nakajima, Takahiro; Cypel, Marcelo; de Perrot, Marc; Pierre, Andrew; Waddell, Tom; Singer, Lianne; Roberts, Heidi; Keshavjee, Shaf; Yasufuku, Kazuhiro

    2015-01-01

    Unexpected lung cancer is sometimes found in explanted lungs. The objective of this study was to review these patients and their outcomes to better understand and optimize management protocols for lung transplant candidates with pulmonary nodules. Retrospective analysis of pretransplant imaging and clinicopathologic characteristics of patients who were found to have lung cancer in their explanted lungs was performed. From January 2003 to December 2012, 13 of 853 lung transplant recipients were found to have unexpected lung cancer in their explanted lung (1.52%). Of them, 9 cases were for interstitial lung disease (2.8%; 9/321 recipients) and 4 cases were for chronic obstructive pulmonary disease (1.57%; 4/255 recipients). The median period between computed tomographic scan and lung transplantation was 2.40 months (range: 0.5-19.2). On computed tomographic scan, only 3 cases were shown to possibly have a neoplasm by the radiologist. The staging of these lung cancers was as follows: 3 cases of IA, 1 case of IB, 5 cases of IIA, 1 case of IIIA, and 3 cases of IV. Of 13 cases, 9 died owing to cancer progression. On the contrary, only 1 stage I case with small cell lung cancer showed cancer recurrence. The median survival time was 339 days, and the 3-year survival rate was 11.0%. In conclusion, most of the patients with unexpected lung cancer showed poor prognosis except for the early-stage disease. The establishment of proper protocol for management of such nodules is important to improve the management of candidates who are found to have pulmonary nodules on imaging. PMID:26074103

  16. The role of autophagy in lung ischemia/reperfusion injury after lung transplantation in rats

    PubMed Central

    Liu, Sheng; Zhang, Jun; Yu, Bentong; Huang, Lei; Dai, Bin; Liu, Jichun; Tang, Jian

    2016-01-01

    Background: The aim of this study was to explore the role of autophagy in the cold I/R injury following lung transplantation. Methods: The rat orthotopic lung transplantation model was established to perform the level of autophagy in the cold I/R injury in this study. The pretreatment of inhibitor (3-Methyladenine [3-MA]) and activator (rapamycin [RAPA]) of autophagy were performed to assess the role of autophagy in the cold I/R injury following lung transplantation in rats. Results: After lung transplantation, the autophagy, lung cell apoptosis and lung injury were aggravated and peaked at 6 h following the transplantation. The inhibition of autophagy by 3-MA induced downregulated of autophagy, decreased cell apoptosis. Meanwhile, the lung injury, which was indicated by calculating the peak inspiratory pressure (PIP), pulmonary vein blood gas analysis (PO2) and ratio of wet to dry in lung (W/D), was ameliorated after treatment with 3-MA. The activation of autophagy by RAPA causing the upregulated of autophagy and apoptosis of lung cells, and enhanced the lung injury. Conclusion: All the results suggested that the autophagy was involved in the cold I/R injury in lung transplantation model, and played a potential role on the regulation of I/R injury after lung transplantation. PMID:27648150

  17. The role of autophagy in lung ischemia/reperfusion injury after lung transplantation in rats

    PubMed Central

    Liu, Sheng; Zhang, Jun; Yu, Bentong; Huang, Lei; Dai, Bin; Liu, Jichun; Tang, Jian

    2016-01-01

    Background: The aim of this study was to explore the role of autophagy in the cold I/R injury following lung transplantation. Methods: The rat orthotopic lung transplantation model was established to perform the level of autophagy in the cold I/R injury in this study. The pretreatment of inhibitor (3-Methyladenine [3-MA]) and activator (rapamycin [RAPA]) of autophagy were performed to assess the role of autophagy in the cold I/R injury following lung transplantation in rats. Results: After lung transplantation, the autophagy, lung cell apoptosis and lung injury were aggravated and peaked at 6 h following the transplantation. The inhibition of autophagy by 3-MA induced downregulated of autophagy, decreased cell apoptosis. Meanwhile, the lung injury, which was indicated by calculating the peak inspiratory pressure (PIP), pulmonary vein blood gas analysis (PO2) and ratio of wet to dry in lung (W/D), was ameliorated after treatment with 3-MA. The activation of autophagy by RAPA causing the upregulated of autophagy and apoptosis of lung cells, and enhanced the lung injury. Conclusion: All the results suggested that the autophagy was involved in the cold I/R injury in lung transplantation model, and played a potential role on the regulation of I/R injury after lung transplantation.

  18. Aortic homograft for pulmonary artery augmentation in single lung transplantation.

    PubMed

    Rueda, Pablo; Morales, Jose; Guzman, Enrique; Tellez, Jose L; Niebla, Benito A; Avalos, Alejandro; Patiño, Hilda

    2005-06-01

    We present a case of unilateral lung transplantation in which a segment of the donor's descending aorta was used as a homograft for pulmonary artery augmentation in the donor lung. This technique can be used when the donor's lung artery has been cut at the base of the hilum during the harvesting procedure.

  19. Transfer of peanut allergy following lung transplantation: a case report.

    PubMed

    Schuller, A; Barnig, C; Matau, C; Geny, S; Gosselin, M; Moal, M C; Champion, G; Atal, L; de Blay, F; Massard, G; Kessler, R

    2011-12-01

    This case study describes a patient who developed peanut allergy following lung transplantation. A 54-year-old woman underwent bilateral lung transplantation on June 2009 owing to severe chronic obstructive pulmonary disease. She had no history of food allergy before transplantation. The donor, however, was a 20-year-old man who was fatally injured during an automobile accident; he was allergic to peanuts. At 3 months after transplantation, the lung recipient presented with acute dyspnea and urticaria 15 minutes after consuming food containing peanut derivatives. Pre- and posttransplantation recipient blood samples analyzed for the presence of IgE antibodies specific for peanut allergens confirmed that the allergy had been passively transfered as a consequence of transplantation. Food allergy following solid organ transplantation is thought to be rare, mostly occurring in children. Two mechanisms may explain the observations described for the patient reported in this study: de novo development of peanut allergies after transplantation, or passive transfer of peanut allergies from a peanut-sensitized organ donor. This case report documenting pre- and posttransplantation IgE status in a lung transplantation case suggested that the allergic status of organ donors should be thoroughly assessed before transplantation, and potential allergy transfer risks must be discussed with the transplant team and the patient. PMID:22172896

  20. Burkholderia pyrrocinia in cystic fibrosis lung transplantation: a case report.

    PubMed

    Savi, D; De Biase, R Valerio; Amaddeo, A; Anile, M; Venuta, F; Ruberto, F; Simmonds, N; Cimino, G; Quattrucci, S

    2014-01-01

    Infection with Burkholderia species is typically considered a contraindication leading to transplantation in cystic fibrosis (CF). However, the risks posed by different Burkholderia species on transplantation outcomes are poorly defined. We present the case of a patient with CF who underwent lung transplantation due to a severe respiratory failure from chronic airways infection with Burkholderia pyrrocinia (B. cepacia genomovar IX) and pan-resistant Pseudomonas aeruginosa. The postoperative course was complicated by recurrent B. pyrrocinia infections, ultimately lea ding to uncontrollable sepsis and death. This is the first case report in CF of Burkholderia pyrrocinia infection and lung transplantation, providing further evidence of the high risk nature of the Burkholderia species.

  1. Lung Transplantation for Cystic Fibrosis: Results, Indications, Complications, and Controversies

    PubMed Central

    Lynch, Joseph P.; Sayah, David M.; Belperio, John A.; Weigt, S. Sam

    2016-01-01

    Survival in patients with cystic fibrosis (CF) has improved dramatically over the past 30 to 40 years, with mean survival now approximately 40 years. Nonetheless, progressive respiratory insufficiency remains the major cause of mortality in CF patients, and lung transplantation (LT) is eventually required. Timing of listing for LT is critical, because up to 25 to 41% of CF patients have died while awaiting LT. Globally, approximately 16.4% of lung transplants are performed in adults with CF. Survival rates for LT recipients with CF are superior to other indications, yet LT is associated with substantial morbidity and mortality (~50% at 5-year survival rates). Myriad complications of LT include allograft failure (acute or chronic), opportunistic infections, and complications of chronic immunosuppressive medications (including malignancy). Determining which patients are candidates for LT is difficult, and survival benefit remains uncertain. In this review, we discuss when LT should be considered, criteria for identifying candidates, contraindications to LT, results post-LT, and specific complications that may be associated with LT. Infectious complications that may complicate CF (particularly Burkholderia cepacia spp., opportunistic fungi, and nontuberculous mycobacteria) are discussed. PMID:25826595

  2. Prolonged Use of the Hemolung Respiratory Assist System as a Bridge to Redo Lung Transplantation.

    PubMed

    Bermudez, Christian A; Zaldonis, Diana; Fan, Ming-Hui; Pilewski, Joseph M; Crespo, Maria M

    2015-12-01

    Although extracorporeal membrane oxygenation (ECMO) has been used frequently as a bridge to primary lung transplantation, active centers are conservative with this approach in patients requiring redo lung transplantation. We report the use of extracorporeal carbon dioxide removal, using the Hemolung respiratory assist system, as a prolonged bridge to lung transplantation, and the first use of the Hemolung as a bridge to redo lung transplantation. Hemolung support improved the patient's clinical status and allowed redo lung transplantation.

  3. Imaging in Lung Transplantation: Surgical Considerations of Donor and Recipient.

    PubMed

    Backhus, Leah M; Mulligan, Michael S; Ha, Richard; Shriki, Jabi E; Mohammed, Tan-Lucien H

    2016-03-01

    Modifications in recipient and donor criteria and innovations in donor management hold promise for increasing rates of lung transplantation, yet availability of donors remains a limiting resource. Imaging is critical in the work-up of donor and recipient including identification of conditions that may portend to poor posttransplant outcomes or necessitate modifications in surgical technique. This article describes the radiologic principles that guide selection of patients and surgical procedures in lung transplantation.

  4. Which patients are candidates for lung transplantation? Indications for unilateral, bilateral, and heart-lung procedures.

    PubMed

    Ettinger, N A

    1994-01-01

    Single-lung transplantation, long successful in resolving interstitial lung disease, can now be used in COPD patients and shows promise in managing pulmonary hypertension. The bilateral procedure, which often avoids cardiopulmonary bypass, is preferred when chronic airway infection is present. Heart-lung transplants, now rare, are used when pulmonary hypertension is complicated by congestive cardiomyopathy or irreparable cardiac defects. Mechanical ventilation, prior cardiothoracic surgery, and corticosteroid use no longer constitute absolute contraindications to lung transplantation. The growing scarcity of donor organs is increasing waiting times; thus, earlier recognition of potential recipients is necessary.

  5. Proteome Profiling in Lung Injury after Hematopoietic Stem Cell Transplantation.

    PubMed

    Bhargava, Maneesh; Viken, Kevin J; Dey, Sanjoy; Steinbach, Michael S; Wu, Baolin; Jagtap, Pratik D; Higgins, LeeAnn; Panoskaltsis-Mortari, Angela; Weisdorf, Daniel J; Kumar, Vipin; Arora, Mukta; Bitterman, Peter B; Ingbar, David H; Wendt, Chris H

    2016-08-01

    Pulmonary complications due to infection and idiopathic pneumonia syndrome (IPS), a noninfectious lung injury in hematopoietic stem cell transplant (HSCT) recipients, are frequent causes of transplantation-related mortality and morbidity. Our objective was to characterize the global bronchoalveolar lavage fluid (BALF) protein expression of IPS to identify proteins and pathways that differentiate IPS from infectious lung injury after HSCT. We studied 30 BALF samples from patients who developed lung injury within 180 days of HSCT or cellular therapy transfusion (natural killer cell transfusion). Adult subjects were classified as having IPS or infectious lung injury by the criteria outlined in the 2011 American Thoracic Society statement. BALF was depleted of hemoglobin and 14 high-abundance proteins, treated with trypsin, and labeled with isobaric tagging for relative and absolute quantification (iTRAQ) 8-plex reagent for two-dimensional capillary liquid chromatography (LC) and data dependent peptide tandem mass spectrometry (MS) on an Orbitrap Velos system in higher-energy collision-induced dissociation activation mode. Protein identification employed a target-decoy strategy using ProteinPilot within Galaxy P. The relative protein abundance was determined with reference to a global internal standard consisting of pooled BALF from patients with respiratory failure and no history of HSCT. A variance weighted t-test controlling for a false discovery rate of ≤5% was used to identify proteins that showed differential expression between IPS and infectious lung injury. The biological relevance of these proteins was determined by using gene ontology enrichment analysis and Ingenuity Pathway Analysis. We characterized 12 IPS and 18 infectious lung injury BALF samples. In the 5 iTRAQ LC-MS/MS experiments 845, 735, 532, 615, and 594 proteins were identified for a total of 1125 unique proteins and 368 common proteins across all 5 LC-MS/MS experiments. When comparing IPS to

  6. Pulmonary rehabilitation in patients referred for lung transplantation.

    PubMed

    Jastrzebski, D; Ochman, M; Ziora, D; Labus, L; Kowalski, K; Wyrwol, J; Lutogniewska, W; Maksymiak, M; Ksiazek, B; Magner, A; Bartoszewicz, A; Kubicki, P; Hydzik, G; Zebrowska, A; Kozielski, J

    2013-01-01

    Effectiveness of pulmonary rehabilitation in patients with chronic obstructive lung diseases, cystic fibrosis, and interstitial lung disease is well documented but little is known about the results of pulmonary rehabilitation in patients referred for lung transplantation. The purpose of this study is to prospectively examine the efficacy of Nordic walking, a low cost, accessible, and proven beneficial form of physical exercise, as a form of pulmonary rehabilitation in patients referred for lung transplantation. Twenty-two male patients referred for lung transplantation at the Department of Lung Diseases and Tuberculosis in Zabrze, Poland, were invited to take part in the study. The rehabilitation program, which was conducted for 12 weeks, was based on Nordic walking exercise training with ski poles. Lung function tests (FVC, FEV1), mobility (6 min walking test (6MWT)), rating of dyspnea (Oxygen Cost Index, MRC and Baseline Dyspnea Index), and quality of life assessments (SF-36) were performed before and after the completion of the exercise program. No adverse events were observed after completing the pulmonary rehabilitation program in patients referred for lung transplantation. After 12 weeks of pulmonary rehabilitation with Nordic walking we observed a significant increase in the mean distance walked in the 6MWT (310.2 m vs. 372.1 m, p < 0.05). The results of lung function tests also showed improvement in FVC. There were no significant differences in the perception of dyspnea before and after completing the rehabilitation program. General health and quality of life questionnaire (SF-36) showed improvement in the domain of social functioning (p < 0.05). In conclusion, pulmonary rehabilitation with a Nordic walking program is a safe and feasible physical activity in end-stage lung disease patients referred for lung transplantation and results in improvements in patients' mobility and quality of life. PMID:22826045

  7. Guidelines for the selection of lung transplantation candidates.

    PubMed

    Román, Antonio; Ussetti, Pietat; Solé, Amparo; Zurbano, Felipe; Borro, José M; Vaquero, José M; de Pablo, Alicia; Morales, Pilar; Blanco, Marina; Bravo, Carlos; Cifrian, José; de la Torre, Mercedes; Gámez, Pablo; Laporta, Rosalía; Monforte, Víctor; Mons, Roberto; Salvatierra, Angel; Santos, Francisco; Solé, Joan; Varela, Andrés

    2011-06-01

    The present guidelines have been prepared with the consensus of at least one representative of each of the hospitals with lung transplantation programs in Spain. In addition, prior to their publication, these guidelines have been reviewed by a group of prominent reviewers who are recognized for their professional experience in the field of lung transplantation. Within the following pages, the reader will find the selection criteria for lung transplantation candidates, when and how to remit a patient to a transplantation center and, lastly, when to add the patient to the waiting list. A level of evidence has been identified for the most relevant questions. Our intention is for this document to be a practical guide for pulmonologists who do not directly participate in lung transplantations but who should consider this treatment for their patients. Finally, these guidelines also propose an information form in order to compile in an organized manner the patient data of the potential candidate for lung transplantation, which are relevant in order to be able to make the best decisions possible.

  8. Challenging immunosuppression treatment in lung transplant recipients with kidney failure.

    PubMed

    Högerle, Benjamin A; Kohli, Neeraj; Habibi-Parker, Kirsty; Lyster, Haifa; Reed, Anna; Carby, Martin; Zeriouh, Mohamed; Weymann, Alexander; Simon, André R; Sabashnikov, Anton; Popov, Aron-Frederik; Soresi, Simona

    2016-03-01

    Kidney failure after lung transplantation is a risk factor for chronic kidney disease. Calcineurin inhibitors are immunosuppressants which play a major role in terms of postoperative kidney failure after lung transplantation. We report our preliminary experience with the anti-interleukin-2 monoclonal antibody Basiliximab utilized as a "calcineurin inhibitor-free window" in the setting of early postoperative kidney failure after lung transplantation. Between 2012 and 2015 nine lung transplant patients who developed kidney failure for more than 14 days were included. Basiliximab was administrated in three doses (Day 0, 4, and 20) whilst Tacrolimus was discontinued or reduced to maintain a serum level between 2 and 4 ng/mL. Baseline glomerular filtration rate pre transplant was normal for all patients. Seven patients completely recovered from kidney failure (67%, mean eGFR pre and post Basiliximab: 42.3 mL/min/1.73 m(2) and 69 mL/min/1.73 m(2)) and were switched back on Tacrolimus. Only one of these patients still needs ongoing renal replacement therapy. Two patients showed no recovery from kidney failure and did not survive. Basiliximab might be a safe and feasible therapeutical option in patients which are affected by calcineurin inhibitor-related kidney failure in the early post lung transplant period. Further studies are necessary to confirm our preliminary results.

  9. Interstitial lung disease - adults - discharge

    MedlinePlus

    Diffuse parenchymal lung disease - discharge; Alveolitis - discharge; Idiopathic pulmonary pneumonitis - discharge; IPP - discharge; Chronic interstitial lung - discharge; Chronic respiratory interstitial lung - ...

  10. Ex vivo lung perfusion in clinical lung transplantation--state of the art.

    PubMed

    Andreasson, Anders S I; Dark, John H; Fisher, Andrew J

    2014-11-01

    Ex vivo lung perfusion (EVLP) has emerged as a new technique for assessing and potentially reconditioning human donor lungs previously unacceptable for clinical transplantation with the potential to dramatically push the limits of organ acceptability. With the recent introduction of portable EVLP, a new era in lung preservation may be upon us with the opportunity to also limit organ ischaemic times and potentially improve the outcome of donor lungs already deemed acceptable for transplantation. It took over half a century for the technique to evolve from basic theory to semi-automated circuits fit for clinical use that are now rapidly being adopted in transplant centres across the globe. With this field in constant evolution and many unanswered questions remaining, our review serves as an update on the state of the art of EVLP in clinical lung transplantation.

  11. Successful emergent lung transplantation after remote ex vivo perfusion optimization and transportation of donor lungs.

    PubMed

    Wigfield, C H; Cypel, M; Yeung, J; Waddell, T; Alex, C; Johnson, C; Keshavjee, S; Love, R B

    2012-10-01

    A recent clinical trial provided evidence that ex vivo lung perfusion (EVLP) results in optimized human donor lungs for transplantation. Excellent recipient outcomes were documented after 4 h of normothermic perfusion. We report a clinical case utilizing remote EVLP to assess and improve function of initially otherwise unacceptable injured donor lungs followed by transportation and subsequent bilateral lung transplantation in a patient with virally induced refractory respiratory failure supported with extracorporeal membrane oxygenation. This is the first lung transplantation with the application of remote EVLP, wherein the donor lungs were transported from the donor hospital to a center for EVLP and then transported to another hospital for transplantation. It is also the first case of lung transplantation in the United States utilizing EVLP for functional optimization leading to successful transplantation. Organ procurement data, EVLP assessment, and the pre- and postoperative course of the recipient are presented. The available evidence supporting EVLP, the humanitarian and cooperative utilization of lungs otherwise discarded, are discussed. PMID:23009140

  12. Lung Disease Including Asthma and Adult Vaccination

    MedlinePlus

    ... Healthcare Professionals Lung Disease including Asthma and Adult Vaccination Language: English Español (Spanish) Recommend on Facebook Tweet ... more about health insurance options. Learn about adult vaccination and other health conditions Asplenia Diabetes Heart Disease, ...

  13. A consensus document for the selection of lung transplant candidates: 2014--an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation.

    PubMed

    Weill, David; Benden, Christian; Corris, Paul A; Dark, John H; Davis, R Duane; Keshavjee, Shaf; Lederer, David J; Mulligan, Michael J; Patterson, G Alexander; Singer, Lianne G; Snell, Greg I; Verleden, Geert M; Zamora, Martin R; Glanville, Allan R

    2015-01-01

    The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. A comprehensive search of the medical literature was conducted with the assistance of a medical librarian. Writing Committee members were assigned specific topics to research and discuss. The Chairs of the Writing Committee were responsible for evaluating the completeness of the literature search, providing editorial support for the manuscript, and organizing group discussions regarding its content. The consensus document makes specific recommendations regarding the timing of referral and of listing for lung transplantation. These recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation. In the absence of high-grade evidence to support decision making, these consensus guidelines remain part of a continuum of expert opinion based on available studies and personal experience. Some positions are immutable. Although transplant is rightly a treatment of last resort for end-stage lung disease, early referral allows proper evaluation and thorough patient education. Subsequent waiting list activation implies a tacit agreement that transplant offers a significant individual survival advantage. It is both the challenge and the responsibility of the transplant community globally to ensure organ allocation maximizes the potential benefits of a scarce resource, thereby achieving that advantage. PMID:25085497

  14. Induction Therapy for Lung Transplantation in COPD: Analysis of the UNOS Registry.

    PubMed

    Duffy, Joseph S; Tumin, Dmitry; Pope-Harman, Amy; Whitson, Bryan A; Higgins, Robert S D; Hayes, Don

    2016-10-01

    Although studies demonstrate that induction therapy improves outcomes after lung transplantation, its influence on survival in patients with chronic obstructive pulmonary disease (COPD) is not clear. The United Network for Organ Sharing database was queried to obtain data regarding adult patients with COPD receiving lung transplant between May 2005 and June 2014. Therapies evaluated include anti-thymocyte globulin, anti-lymphocyte globulin, thymoglobulin, basiliximab, and alemtuzumab. Data were categorized based on receiving induction (INDUCED) and no induction (NONE). Kaplan-Meier plots, Cox proportional hazards models of patient survival, and competing-risks regression models for secondary endpoints were utilized. A total of 3,405 patients who underwent lung transplantation for COPD were enrolled with 1,761 (52%) receiving induction therapy. Of INDUCED, 1,146 (65%) received basiliximab, 380 (22%) received alemtuzumab, and 235 (13%) received a polyclonal preparation. The hazard ratio for INDUCED vs. NONE was 0.793 (95% CI = 0.693, 0.909; p = 0.001) in the fully adjusted Cox model. A multivariable competing-risks model also found a protective influence of induction therapy with respect to delayed onset of bronchiolitis obliterans syndrome after transplantation (SHR = 0.801; 95% CI = 0.694, 0.925; p = 0.003). In a cohort of recently transplanted patients with COPD, there appears to be a benefit from contemporary induction agents with no concurrent increase in the risk of death due to infection.

  15. Kidney transplantation in previous heart or lung recipients.

    PubMed

    Lonze, B E; Warren, D S; Stewart, Z A; Dagher, N N; Singer, A L; Shah, A S; Montgomery, R A; Segev, D L

    2009-03-01

    Outcomes after heart and lung transplants have improved, and many recipients survive long enough to develop secondary renal failure, yet remain healthy enough to undergo kidney transplantation. We used national data reported to United Network for Organ Sharing (UNOS) to evaluate outcomes of 568 kidney after heart (KAH) and 210 kidney after lung (KAL) transplants performed between 1995 and 2008. Median time to kidney transplant was 100.3 months after heart, and 90.2 months after lung transplant. Renal failure was attributed to calcineurin inhibitor toxicity in most patients. Outcomes were compared with primary kidney recipients using matched controls (MC) to account for donor, recipient and graft characteristics. Although 5-year renal graft survival was lower than primary kidney recipients (61% KAH vs. 73.8% MC, p < 0.001; 62.6% KAL vs. 82.9% MC, p < 0.001), death-censored graft survival was comparable (84.9% KAH vs. 88.2% MC, p = 0.1; 87.6% KAL vs. 91.8% MC, p = 0.6). Furthermore, renal transplantation reduced the risk of death compared with dialysis by 43% for KAH and 54% for KAL recipients. Our findings that renal grafts function well and provide survival benefit in KAH and KAL recipients, but are limited in longevity by the general life expectancy of these recipients, might help inform clinical decision-making and allocation in this population.

  16. Cavitary lung lesion 6 years after renal transplantation

    PubMed Central

    Subbiah, Arun Kumar; Arava, Sudheer; Bagchi, Soumita; Madan, Karan; Das, Chandan J; Agarwal, Sanjay Kumar

    2016-01-01

    The differential diagnoses of a cavitary lung lesion in renal transplant recipients would include infection, malignancy and less commonly inflammatory diseases. Bacterial infection, Tuberculosis, Nocardiosis, fungal infections like Aspergillosis and Cryptococcosis need to be considered in these patients. Pulmonary cryptococcosis usually presents 16-21 mo after transplantation, more frequently in patients who have a high level of cumulative immunosuppression. Here we discuss an interesting patient who never received any induction/anti-rejection therapy but developed both BK virus nephropathy as well as severe pulmonary Cryptococcal infection after remaining stable for 6 years after transplantation. This case highlights the risk of serious opportunistic infections even in apparently low immunologic risk transplant recipients many years after transplantation. PMID:27358792

  17. Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach.

    PubMed

    Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

    2016-09-24

    Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

  18. Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

    PubMed Central

    Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

    2016-01-01

    Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers.

  19. Physical rehabilitation for lung transplant candidates and recipients: An evidence-informed clinical approach

    PubMed Central

    Wickerson, Lisa; Rozenberg, Dmitry; Janaudis-Ferreira, Tania; Deliva, Robin; Lo, Vincent; Beauchamp, Gary; Helm, Denise; Gottesman, Chaya; Mendes, Polyana; Vieira, Luciana; Herridge, Margaret; Singer, Lianne G; Mathur, Sunita

    2016-01-01

    Physical rehabilitation of lung transplant candidates and recipients plays an important in optimizing physical function prior to transplant and facilitating recovery of function post-transplant. As medical and surgical interventions in lung transplantation have evolved over time, there has been a demographic shift of individuals undergoing lung transplantation including older individuals, those with multiple co-morbidites, and candidates with respiratory failure requiring bridging to transplantation. These changes have an impact on the rehabilitation needs of lung transplant candidates and recipients. This review provides a practical approach to rehabilitation based on research and clinical practice at our transplant centre. It focuses on functional assessment and exercise prescription during an uncomplicated and complicated clinical course in the pre-transplant, early and late post-transplant periods. The target audience includes clinicians involved in pre- and post-transplant patient care and rehabilitation researchers. PMID:27683630

  20. Answers about Lung Transplantation for Pulmonary Hypertension

    MedlinePlus

    ... East PH Medical Resources Worldwide Resources in Other Languages Recursos en Español Connect with a Global Community ... essence, when undergoing transplant, a recipient trades their current medical disease for another medical condition that has ...

  1. Risk factors for lung diseases after renal transplantation

    PubMed Central

    Pencheva, Ventsislava P.; Petrova, Daniela S.; Genov, Diyan K.; Georgiev, Ognian B.

    2015-01-01

    Background: Lung diseases are one of the major causes of morbidity and mortality after renal transplantation. The aim of the study is to define the risk factors for infectious and noninfectious pulmonary complications in kidney transplant patients. Materials and Methods: We prospectively studied 267 patients after renal transplantation. The kidney recipients were followed-up for the development of pulmonary complications for a period of 7 years. Different noninvasive and invasive diagnostic tests were used in cases suspected of lung disease. Results: The risk factors associated with the development of pulmonary complications were diabetes mellitus (odds ratio [OR] = 4.60; P = 0.001), arterial hypertension (OR = 1.95; P = 0.015), living related donor (OR = 2.69; P = 0.004), therapy for acute graft rejection (OR = 2.06; P = 0.038), immunosuppressive regimens that includes mycophenolate (OR = 2.40; P = 0.011), azathioprine (OR = 2.25; P = 0.023), and tacrolimus (OR = 1.83; P = 0.041). The only factor associated with the lower risk of complications was a positive serology test for Cytomegalovirus of the recipient before transplantation (OR = 0.1412; P = 0.001). Conclusion: The risk factors can be used to identify patients at increased risk for posttransplant lung diseases. Monitoring of higher-risk patients allow timely diagnosis and early adequate treatment and can reduce the morbidity and mortality after renal transplantation. PMID:26958045

  2. Moving Back to the Future: Use of Organ Care System Lung for Lobectomy Before Lobar Lung Transplantation.

    PubMed

    Sabashnikov, Anton; Zeriouh, Mohamed; Mohite, Prashant N; Patil, Nikhil P; García-Sáez, Diana; Schmack, Bastian; Soresi, Simona; Dohmen, Pascal M; Popov, Aron-Frederik; Weymann, Alexander; Simon, André R; De Robertis, Fabio

    2016-01-01

    BACKGROUND Lung transplantation remains the gold standard treatment for patients with end-stage lung disease. Lobar lung transplantation allows for transplantation of size-mismatch donor lungs in small recipients; however, donor lung volume reduction represents a challenging surgical technique. In this paper we present our initial experience with bilateral lobectomy in donor lungs before lobar lung transplantation using normothermic perfusion on the Organ Care System (OCS) Lung. MATERIAL AND METHODS Specifics of the surgical technique for donor lung instrumentation on the OCS, lobar dissection on the OCS, and right and left donor lobectomies are presented in detail. RESULTS Potential advantages of the use of the OCS for lobectomy for lobar lung transplantation are described in this section. Donor lung volume reduction utilizing OCS appeared to be easier and safer compared to the conventional cold storage technique, due to continuous perfusion of the lungs with blood and well-distended vessels that offer the feel of live lobectomy. Moreover, the OCS represents a platform for donor organ assessment and optimization of its function before transplantation. CONCLUSIONS Donor lung volume reduction was safe and feasible utilizing the OCS, which could be a useful tool for volume reduction in cases of size mismatch. Further research is needed to evaluate early and long-term results after lobar lung transplantation using the OCS in clinical studies. PMID:27425199

  3. Moving Back to the Future: Use of Organ Care System Lung for Lobectomy Before Lobar Lung Transplantation

    PubMed Central

    Sabashnikov, Anton; Zeriouh, Mohamed; Mohite, Prashant N.; Patil, Nikhil P.; García-Sáez, Diana; Schmack, Bastian; Soresi, Simona; Dohmen, Pascal M.; Popov, Aron-Frederik; Weymann, Alexander; Simon, André R.; De Robertis, Fabio

    2016-01-01

    Background Lung transplantation remains the gold standard treatment for patients with end-stage lung disease. Lobar lung transplantation allows for transplantation of size-mismatch donor lungs in small recipients; however, donor lung volume reduction represents a challenging surgical technique. In this paper we present our initial experience with bilateral lobectomy in donor lungs before lobar lung transplantation using normothermic perfusion on the Organ Care System (OCS) Lung. Material/Methods Specifics of the surgical technique for donor lung instrumentation on the OCS, lobar dissection on the OCS, and right and left donor lobectomies are presented in detail. Results Potential advantages of the use of the OCS for lobectomy for lobar lung transplantation are described in this section. Donor lung volume reduction utilizing OCS appeared to be easier and safer compared to the conventional cold storage technique, due to continuous perfusion of the lungs with blood and well-distended vessels that offer the feel of live lobectomy. Moreover, the OCS represents a platform for donor organ assessment and optimization of its function before transplantation. Conclusions Donor lung volume reduction was safe and feasible utilizing the OCS, which could be a useful tool for volume reduction in cases of size mismatch. Further research is needed to evaluate early and long-term results after lobar lung transplantation using the OCS in clinical studies. PMID:27425199

  4. Pulmonary resection after lung transplantation in cystic fibrosis patients.

    PubMed

    Souilamas, Rédha; Saueressig, Mauricio; Boussaud, Véronique; Amrein, Catherine; Guillemain, Romain; Sonett, Joshua

    2011-06-01

    Pulmonary resection after lung transplantation in end-stage cystic fibrosis presents unique challenges, and scant literature exists to guide physicians. We retrospectively reviewed 78 transplants for cystic fibrosis performed between 2003 and 2008. Fourteen patients underwent posttransplantation pulmonary resection. We analyzed the indications, surgical procedures, outcomes, and survival. Three pneumonectomies, 4 lobectomies, and 11 wedge resections were carried out. We identified 2 groups based on indication: a diagnostic group, and a therapeutic group of patients in whom the indications were septic native lung in 2, allograft infection in 2, lobar torsion in 2, pulmonary infarction in 2, and size mismatch in 4. The mean intensive care unit and hospital stays were 29 and 50 days, respectively. Four (28.57%) patients died during follow-up, including 2 who underwent pneumonectomy; 10 (71.43%) are still alive. Survival was 43.43 ± 8.06 months, and it was not significantly different from that in cystic fibrosis patients who had lung transplantation without pulmonary resection. Pulmonary resection following lung transplantation in cystic fibrosis patients showed acceptable survival and surgical risk, but metachronous pneumonectomy was associated with higher mortality.

  5. Pulmonary resection after lung transplantation in cystic fibrosis patients.

    PubMed

    Souilamas, Rédha; Saueressig, Mauricio; Boussaud, Véronique; Amrein, Catherine; Guillemain, Romain; Sonett, Joshua

    2011-06-01

    Pulmonary resection after lung transplantation in end-stage cystic fibrosis presents unique challenges, and scant literature exists to guide physicians. We retrospectively reviewed 78 transplants for cystic fibrosis performed between 2003 and 2008. Fourteen patients underwent posttransplantation pulmonary resection. We analyzed the indications, surgical procedures, outcomes, and survival. Three pneumonectomies, 4 lobectomies, and 11 wedge resections were carried out. We identified 2 groups based on indication: a diagnostic group, and a therapeutic group of patients in whom the indications were septic native lung in 2, allograft infection in 2, lobar torsion in 2, pulmonary infarction in 2, and size mismatch in 4. The mean intensive care unit and hospital stays were 29 and 50 days, respectively. Four (28.57%) patients died during follow-up, including 2 who underwent pneumonectomy; 10 (71.43%) are still alive. Survival was 43.43 ± 8.06 months, and it was not significantly different from that in cystic fibrosis patients who had lung transplantation without pulmonary resection. Pulmonary resection following lung transplantation in cystic fibrosis patients showed acceptable survival and surgical risk, but metachronous pneumonectomy was associated with higher mortality. PMID:21885542

  6. [How to increase availability of grafts in lung transplantion: ex vivo lung reconditioning - cardiac death donors - high emergency list].

    PubMed

    Souilamas, R; Souilamas, J; Saueressig, M; Pison, C; Briot, R

    2010-02-01

    Lung transplantation has become an established treatment for end-stage pulmonary failure refractory to medical management. However, the scarcity of lung grafts and the growing number of candidates has led to an increase in deaths among patients on waiting lists. Despite improvements in donor management, organ preservation, and the use of marginal and cardiac death donors, only about 20% of candidate lungs are currently being transplanted. A new ex vivo "reconditioning" technique is opening up new perspectives. Indeed, a significant number of rejected lungs can now be retrieved and transplanted with acceptable results. Given the longer storage times provided by this technique, transplantation can be programmed, with better surgical efficiency. A new mobile organ-care machine is currently under evaluation. In near future, a pilot laboratory will be created and dedicated to ex vivo reconditionning of all lung grafts before transplantation and grafts will be sent to lung transplant centers after immunologic cross-matching.

  7. [How to increase availability of grafts in lung transplantion: ex vivo lung reconditioning - cardiac death donors - high emergency list].

    PubMed

    Souilamas, R; Souilamas, J; Saueressig, M; Pison, C; Briot, R

    2010-02-01

    Lung transplantation has become an established treatment for end-stage pulmonary failure refractory to medical management. However, the scarcity of lung grafts and the growing number of candidates has led to an increase in deaths among patients on waiting lists. Despite improvements in donor management, organ preservation, and the use of marginal and cardiac death donors, only about 20% of candidate lungs are currently being transplanted. A new ex vivo "reconditioning" technique is opening up new perspectives. Indeed, a significant number of rejected lungs can now be retrieved and transplanted with acceptable results. Given the longer storage times provided by this technique, transplantation can be programmed, with better surgical efficiency. A new mobile organ-care machine is currently under evaluation. In near future, a pilot laboratory will be created and dedicated to ex vivo reconditionning of all lung grafts before transplantation and grafts will be sent to lung transplant centers after immunologic cross-matching. PMID:21353972

  8. What to Expect After a Lung Transplant

    MedlinePlus

    ... recovery. You'll be taught how to do deep breathing exercises with an incentive spirometer (spi-ROM- ... This hand-held device helps you take slow, deep breaths. You also may have lung function tests ...

  9. Solid-organ transplantation in older adults: current status and future research.

    PubMed

    Abecassis, M; Bridges, N D; Clancy, C J; Dew, M A; Eldadah, B; Englesbe, M J; Flessner, M F; Frank, J C; Friedewald, J; Gill, J; Gries, C; Halter, J B; Hartmann, E L; Hazzard, W R; Horne, F M; Hosenpud, J; Jacobson, P; Kasiske, B L; Lake, J; Loomba, R; Malani, P N; Moore, T M; Murray, A; Nguyen, M-H; Powe, N R; Reese, P P; Reynolds, H; Samaniego, M D; Schmader, K E; Segev, D L; Shah, A S; Singer, L G; Sosa, J A; Stewart, Z A; Tan, J C; Williams, W W; Zaas, D W; High, K P

    2012-10-01

    An increasing number of patients older than 65 years are referred for and have access to organ transplantation, and an increasing number of older adults are donating organs. Although short-term outcomes are similar in older versus younger transplant recipients, older donor or recipient age is associated with inferior long-term outcomes. However, age is often a proxy for other factors that might predict poor outcomes more strongly and better identify patients at risk for adverse events. Approaches to transplantation in older adults vary across programs, but despite recent gains in access and the increased use of marginal organs, older patients remain less likely than other groups to receive a transplant, and those who do are highly selected. Moreover, few studies have addressed geriatric issues in transplant patient selection or management, or the implications on health span and disability when patients age to late life with a transplanted organ. This paper summarizes a recent trans-disciplinary workshop held by ASP, in collaboration with NHLBI, NIA, NIAID, NIDDK and AGS, to address issues related to kidney, liver, lung, or heart transplantation in older adults and to propose a research agenda in these areas. PMID:22958872

  10. Survival in sensitized lung transplant recipients with perioperative desensitization.

    PubMed

    Tinckam, K J; Keshavjee, S; Chaparro, C; Barth, D; Azad, S; Binnie, M; Chow, C W; de Perrot, M; Pierre, A F; Waddell, T K; Yasufuku, K; Cypel, M; Singer, L G

    2015-02-01

    Donor-specific HLA antibodies (DSA) have an adverse effect on short-term and long-term lung transplant outcomes. We implemented a perioperative strategy to treat DSA-positive recipients, leading to equivalent rejection and graft survival outcomes. Pretransplant DSA were identified to HLA-A, B, C, DR and DQ antigens. DSA-positive patients were transplanted if panel reactive antibody (PRA) ≥30% or medically urgent and desensitized with perioperative plasma exchange, intravenous immune globulin, antithymocyte globulin (ATG), and mycophenolic acid (MPA). PRA-positive/DSA-negative recipients received MPA. Unsensitized patients received routine cyclosporine, azathioprine and prednisone without ATG. From 2008-2011, 340 lung-only first transplants were performed: 53 DSA-positive, 93 PRA-positive/DSA-negative and 194 unsensitized. Thirty-day survival was 96 %/99%/96% in the three groups, respectively. One-year graft survival was 89%/88%/86% (p = 0.47). DSA-positive and PRA-positive/DSA-negative patients were less likely to experience any ≥ grade 2 acute rejection (9% and 9% vs. 18% unsensitized p = 0.04). Maximum predicted forced expiratory volume (1 s) (81%/74%/76%, p = NS) and predicted forced vital capacity (81%/77%/78%, respectively, p = NS) were equivalent between groups. With the application of this perioperative treatment protocol, lung transplantation can be safely performed in DSA/PRA-positive patients, with similar outcomes to unsensitized recipients. PMID:25612494

  11. [Lung pneumatocele in adult patient - case report].

    PubMed

    Dzian, A; Fúčela, I; Hamžík, J; Huťka, Z; Stiegler, P

    2012-12-01

    Lung pneumatoceles are characterized by a thin-walled air-filled cavity present in lung parenchyma. Mostly they are the result of acute bronchopneumonia after spontaneous drainage of altered lung parenchyma with subsequent development and progression of cavities due to ventile mechanism. This disease is more prevalent in infants and young children, it is rather rare in adults. In the present case report, videothoracoscopy resection of lung pneumatocele of the right lower lobe was performed a 43-years old man. The operation was indicated for the presence of chronic persisting and progressing pneumatocele as a preventive measure of pneumatocele complications. PMID:23448707

  12. Effect of lung transplantation on diaphragmatic function in patients with chronic obstructive pulmonary disease.

    PubMed Central

    Wanke, T.; Merkle, M.; Formanek, D.; Zifko, U.; Wieselthaler, G.; Zwick, H.; Klepetko, W.; Burghuber, O. C.

    1994-01-01

    BACKGROUND--To date there are no data on the effects of lung transplantation on diaphragmatic function in patients with end stage chronic obstructive pulmonary disease (COPD). It is not known whether the relation between the transdiaphragmatic pressure (PDI) and lung volume is altered in recipients after transplantation as a result of changes in diaphragmatic structure caused by chronic hyperinflation. The effect of lung transplantation on diaphragmatic strength was determined in patients with COPD and the relation between postoperative PDI and lung volume analysed. METHODS--Diaphragmatic strength was assessed in eight double lung transplant recipients, six single lung transplant recipients, and in 14 patients with COPD whose lung function was similar to those of the transplant recipients preoperatively. PDI obtained during unilateral and bilateral phrenic nerve stimulation at 1 Hz (twitch PDI) at functional residual capacity (FRC) and during maximal sniff manoeuvres (sniff PDI) at various levels of inspiratory vital capacity (VCin) served as parameters for diaphragmatic strength. Sniff PDI assessed at the various VCin levels were used to analyse the PDI/lung volume relation. RESULTS--Lung transplantation caused a reduction in lung volume, especially in the double lung transplant recipients. As a consequence sniff PDI was higher in the double lung transplant recipients than in the patients with COPD at all levels of VCin analysed. However, sniff PDI values analysed at comparable intrathoracic gas volumes were not reduced in the patients with COPD when compared with those who underwent lung transplantation. Bilateral twitch PDI values were similar in the patients with COPD and in the lung transplant recipients. In the single lung transplant recipients unilateral twitch PDI values were similar on the transplanted and the non-transplanted side. The relation between PDI and lung volume was similar in the patients with COPD and in the lung transplant recipients

  13. Invasive Scedosporium sternal osteomyelitis following lung transplant: Cured.

    PubMed

    Denton, E J; Smibert, O; Gooi, J; Morrissey, C O; Snell, G; McGiffin, D; Paraskeva, M

    2016-06-01

    Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplant but rarely causes invasive infection. Treatment remains challenging, particularly due to inherent resistance to multiple antifungal agents. We present a young man with CF who developed invasive sternal and rib infection 10-months following lung transplant. The infection has been clinically and radiologically cured with extensive surgery and triazole therapy. This case highlights the importance of adjunctive surgery in addition to prolonged triazole treatment to manage invasive Scedosporium infections in immunosuppressed patients. PMID:27595059

  14. Medium-term outcome of fundoplication after lung transplantation.

    PubMed

    Burton, P R; Button, B; Brown, W; Lee, M; Roberts, S; Hassen, S; Bailey, M; Smith, A; Snell, G

    2009-01-01

    Gastroesophageal reflux disease (GERD) in lung transplant recipients has gained increasing attention as a factor in allograft failure. There are few data on the impact of fundoplication on survival or lung function, and less on its effect on symptoms or quality of life. Patients undergoing fundoplication following lung transplantation from 1999 to 2005 were included in the study. Patient satisfaction, changes in GERD symptoms, and the presence of known side effects were assessed. The effect on lung function, body mass index, and rate of progression to the bronchiolitis obliterans syndrome (BOS) were recorded. Twenty-one patients (13 males), in whom reflux was confirmed on objective criteria, were included, with a mean age of 43 years (range 20-68). Time between transplantation and fundoplication was 768 days (range 145-1524). The indication for fundoplication was suspected microaspiration in 13 and symptoms of GERD in 8. There was one perioperative death, at day 17. There were three other late deaths. Fundoplication did not appear to affect progression to BOS stage 1, although it may have slowed progression to stage 2 and 3. Forced expiratory volume-1% predicted was 72.9 (20.9), 6 months prior to fundoplication and 70.4 (26.8), six months post-fundoplication, P= 0.33. Body mass index decreased significantly in the 6 months following fundoplication (23 kg/m(2) vs. 21 kg/m(2), P= 0.05). Patients were satisfied with the outcome of the fundoplication (mean satisfaction score 8.8 out of 10). Prevalence of GERD symptoms decreased significantly following surgery (11 of 14 vs. 4 of 17, P= 0.002). Fundoplication does not reverse any decline in lung function when performed at a late stage post-lung transplantation in patients with objectively confirmed GERD. It may, however, slow progression to the more advanced stages of BOS. Reflux symptoms are well controlled and patients are highly satisfied. Whether performing fundoplication early post-lung transplant in selected

  15. Bronchoscopic lung volume reduction in a single-lung transplant recipient with natal lung hyperinflation: a case report.

    PubMed

    Pato, O; Rama, P; Allegue, M; Fernández, R; González, D; Borro, J M

    2010-06-01

    After single lung transplantation for emphysema native lung hyperinflation is a common complication that may cause respiratory failure. Herein we have reported satisfactory bronchoscopic lung volume reduction in a left single-lung transplant recipient with native lung hyperinflation, who suffered from Medical Research Council (MRC) class 3 dyspnea and chest pain. Three endobronchial valves (Zephyr; Emphasys Medical, Redwood, Calif, United States) were placed into the segmental bronchi of the right upper lobe, using videobronchoscopy under general anesthesia. Postoperative chest computed tomography revealed subsegmental atelectasis in that lobe. The clinical benefit was an improved MRC dyspnea class from 3 to 2, which was still present at 4 months after the procedure, although there were no remarkable changes in spirometric parameters.

  16. Thrombotic microangiopathy associated with tacrolimus in lung transplantation.

    PubMed

    Reig Mezquida, Juan Pablo; Jover, Amparo Solé; Ansótegui Barrera, Emilio; Escrivá Peiró, Juan; Pastor Colom, Maria Desamparados; Pastor Guillem, Juan

    2015-05-01

    Thrombotic microangiopathy (TMA) is a rare complication associated with the use of calcineurin inhibitors in lung transplantation, irrespective of the underlying disease of the graft recipient. It usually occurs in incomplete forms, complicating and delaying diagnosis until damage is already irreversible. It is unrelated to time from transplantation and often presents with concomitant infection, which tends to confound diagnosis. The cases discussed here have a common causative agent and all present with concomitant infection. Treatment recommendations have changed in recent years with the introduction of plasmapheresis or, more recently, the availability of the antibody eculizumab. Notwithstanding, the most cost-effective measure is withdrawal or switching of the calcineurin inhibitor. TMA is an underdiagnosed clinical entity that should be considered in the management of transplantation patients.

  17. Monitoring progress after lung transplantation from home-patient adherence.

    PubMed

    Finkelstein, S M; Snyder, M; Edin-Stibbe, C; Chlan, L; Prasad, B; Dutta, P; Lindgren, B; Wielinski, C; Hertz, M I

    1996-01-01

    A paperless electronic spirometer/diary instrument has been employed in a home monitoring programme for lung and heart-lung transplant patients at the University of Minnesota. The monitoring programme is part of a long term study to develop a system which will detect the earliest signs of developing rejection or infection in the transplanted organs. It is based on patient daily self-measurements of standard spirometry, vital signs, and symptoms recorded at home and transmitted weekly to the study data center over the telephone using a modern built into the instrument. This report summarizes adherence behaviour for 41 subjects enrolled in the study over a 12 month period. The number of subjects from whom home data has been received each week was used to measure adherence at the subject level. The number of records received each week measured adherence at the daily recording level. A data record consists of a daily set of spirometry, vital signs, and symptom values from a given subject. Approximately 82% of subjects transmitted records each week, over the 52 week review period. There was an average of 4.5 records received each week from each subject. Transmitted records had missing vital sign or symptom items in less than 2% of cases, spirometry data was always present. This evaluation showed than lung transplant recipients are willing and able to use a home-monitoring instrument, and that basic spirometry, data entry, and data transmission can be performed satisfactorily.

  18. Hepatic haemangioendothelioma in adults: excellent outcome following liver transplantation.

    PubMed

    Lerut, Jan P; Orlando, Giuseppe; Sempoux, Christine; Ciccarelli, Olga; Van Beers, Bernard E; Danse, Etienne; Horsmans, Yves; Rahier, Jacques; Roggen, Francine

    2004-05-01

    Hepatic epithelioid haemangioendotheliomas (HEHEs) are rare, low-grade vascular tumours. Five adults with HEHEs and one adult with a vascular tumour showing combined features of haemangioma and haemangioendothelioma underwent liver transplantation. Two HEHE patients had extrahepatic metastases at the time of transplantation. Median survival time following diagnosis was 10.7 years (range 40 months to 195 months). One patient needed resection of a HEHE in the breast 13 years post-transplantation. All six patients are surviving free from disease 22 to 166 months after transplantation (median 77 months). One HEHE-patient who had been treated for 8 years for vertebral and cerebral localisations is free of disease without immunosuppression 56 months after transplantation. We can conclude that liver transplantation is a valuable treatment for hepatic haemangioendothelioma, even in cases of extrahepatic localisation of the disease. PMID:15114438

  19. What can happen after lung transplantation and the importance of the time since transplantation: radiological review of post-transplantation complications.

    PubMed

    Daimiel Naranjo, I; Alonso Charterina, S

    2016-01-01

    Lung transplantation is the best treatment option in the final stages of diseases such as cystic fibrosis, pulmonary hypertension, chronic obstructive pulmonary disease, or idiopathic pulmonary fibrosis. Better surgical techniques and advances in immunosuppressor treatments have increased survival in lung transplant recipients, making longer follow-up necessary because complications can occur at any time after transplantation. For practical purposes, complications can be classified as early (those that normally occur within two months after transplantation), late (those that normally occur more than two months after transplantation), or time-independent (those that can occur at any time after transplantation). Many complications have nonspecific clinical and radiological manifestations, so the time factor is key to narrow the differential diagnosis. Imaging can guide interventional procedures and can detect complications early. This article aims to describe and illustrate the complications that can occur after lung transplantation from the clinical and radiological viewpoints so that they can be detected as early as possible.

  20. ST-Elevation Myocardial Infarction 33 Days after Lung Transplant in a Patient with Non-Significant CAD before Transplantation: A Case Report.

    PubMed

    Parsa, Saeed Alipour; Khaheshi, Isa; Dousti, Amir; Naghashzadeh, Farah; Ataeinia, Bahar

    2016-05-01

    Acute myocardial infarction after lung transplantation is not well illustrated in the literature. We present a patient with documented non significant Coronary Artery Disease (CAD) in coronary angiography before lung transplant who was referred to our hospital with acute Myocardial Infarction (MI) 33 days following lung transplantation. PMID:27437285

  1. World Health Organization Pulmonary Hypertension group 2: pulmonary hypertension due to left heart disease in the adult--a summary statement from the Pulmonary Hypertension Council of the International Society for Heart and Lung Transplantation.

    PubMed

    Fang, James C; DeMarco, Teresa; Givertz, Michael M; Borlaug, Barry A; Lewis, Gregory D; Rame, J Eduardo; Gomberg-Maitland, Mardi; Murali, Srinivas; Frantz, Robert P; McGlothlin, Dana; Horn, Evelyn M; Benza, Raymond L

    2012-09-01

    Pulmonary hypertension associated with left heart disease is the most common form of pulmonary hypertension encountered in clinical practice today. Although frequently a target of therapy, its pathophysiology remains poorly understood and its treatment remains undefined. Pulmonary hypertension in the context of left heart disease is a marker of worse prognosis and disease severity, but whether its primary treatment is beneficial or harmful is unknown. An important step to the future study of this important clinical problem will be to standardize definitions across disciplines to facilitate an evidence base that is interpretable and applicable to clinical practice. In this current statement, we provide an extensive review and interpretation of the current available literature to guide current practice and future investigation. At the request of the Pulmonary Hypertension (PH) Council of the International Society for Heart and Lung Transplantation (ISHLT), a writing group was assembled and tasked to put forth this document as described above. The review process was facilitated through the peer review process of the Journal of Heart and Lung Transplantation and ultimately endorsed by the leadership of the ISHLT PH Council. PMID:22884380

  2. Invasive pulmonary Aspergillosis in organ transplants--Focus on lung transplants.

    PubMed

    Geltner, Christian; Lass-Flörl, Cornelia

    2016-03-01

    Infections with filamentous fungi are common in transplant recipients. The risk for aspergillosis and other invasive pulmonary mycosis (IPM) is high in patients undergoing stem cell and lung transplantations. The mortality rates range from 20% to 60% and depend on a number of risk factors. The typical manifestations of IPM are lung infiltrates, consolidations, and fungal tracheobronchitis. The most common infectious agent is Aspergillus fumigatus. Infections caused by non-Aspergillus molds are more frequent for various reasons. The species distribution of non-Aspergillus molds varies in different locations. Furthermore, infections caused by Mucor and Penicillium are increasing, as are infections caused by species resistant to azoles and amphotericin B. Most centers use antifungal prophylaxis with inhaled amphotericin B or oral azoles. Early diagnosis and therapy is crucial. Reliable information on the local microbiological spectrum is a prerequisite for the effective treatment of molds with primary or secondary resistance to antimycotic drugs.

  3. Haploidentical Stem Cell Transplantation in Adult Haematological Malignancies

    PubMed Central

    Parmesar, Kevon; Raj, Kavita

    2016-01-01

    Haematopoietic stem cell transplantation is a well-established treatment option for both hematological malignancies and nonmalignant conditions such as aplastic anemia and haemoglobinopathies. For those patients lacking a suitable matched sibling or matched unrelated donor, haploidentical donors are an alternative expedient donor pool. Historically, haploidentical transplantation led to high rates of graft rejection and GVHD. Strategies to circumvent these issues include T cell depletion and management of complications thereof or T replete transplants with GVHD prophylaxis. This review is an overview of these strategies and contemporaneous outcomes for hematological malignancies in adult haploidentical stem cell transplant recipients. PMID:27313619

  4. An outbreak of chickenpox in adult renal transplant recipients.

    PubMed

    Shahbazian, Heshmatollah; Ehsanpour, Ali

    2007-06-01

    Infection with the varicella-zoster virus, the etiologic agent of chickenpox and herpes zoster, is more serious in immunosuppressed renal transplant recipients than it is in the general population. Chickenpox is a rare infection in adult renal transplant recipients; however, it is significant owing to the severity of its clinical features and its associated high mortality rate. To date, there are no reported outbreaks of primary varicella-zoster virus infection in adult renal transplant recipients. Here, we report 3 patients with chickenpox who presented to our center between May 2006 and June 2006.

  5. A Violaceous Nodule in a Lung-transplant Patient.

    PubMed

    Milford, Emily; Winslow, Caroline; Danhof, Rebecca

    2016-01-01

    Posttransplantation lymphoproliferative disorder (PTLD) is a rare complication of solid organ or allogenic bone marrow transplantation. Cases localized to the skin are even rarer, with only around 100 cases recorded in the literature [2]. We present a case of 60 year-old-woman, a lung transplant recipient, who presented with an asymptomatic violaceous nodule on her left medial calf. Histopathology was consistent with PTLD of the B-cell subtype, EBV negative. This case is unique in that it was of the B cell subtype of cutaneous PTLD, which has been less commonly observed than the T cell subtype. In addition, the case was EBV negative, which is rare in B cell cutaneous PTLD. The patient was treated with rituximab 600 mg IV weekly for four weeks and cytomegalovirus immune globulin (Cytogam) 100 mg/kg once, with resolution of the nodule. PMID:27617611

  6. Bridging to lung transplantation for severe pulmonary hypertension using dual central Novalung lung assist devices.

    PubMed

    Mayes, Jonathan; Niranjan, Gunaratnam; Dark, John; Clark, Stephen

    2016-05-01

    This case describes the technique of using dual Novalungs (a pumpless extracorporeal system) to bridge a patient with idiopathic pulmonary hypertension to bilateral lung transplantation. A 41-year old lady with idiopathic pulmonary hypertension (with a possible veno-occlusive element) presented with symptoms of end-stage heart and lung failure. This was refractory to medical management with iloprost, sildenafil and bosentan. The patient was placed on the urgent waiting list for lung transplantation and central pulmonary artery to left atrial Novalung insertion was performed. Local anaesthetic was given before performing peripheral cardiopulmonary bypass due to the high risk of cardiac arrest. Two days later, donor organs became available and the patient was taken for double-lung transplantation. The pulmonary artery cannula was removed leaving a large defect. This was then closed using a bovine pericardial patch. Due to the damaged right superior pulmonary vein from Novalung cannulation, cardioplegia was given to facilitate an open atrial anastomosis. After 13 days in the intensive therapy unit, she was transferred to the ward. There were no further complications and she has been discharged home. PMID:26819271

  7. Venovenous Extracorporeal Membrane Oxygenation With Atrial Septostomy as a Bridge to Lung Transplantation.

    PubMed

    Kon, Zachary N; Pasrija, Chetan; Shah, Aakash; Griffith, Bartley P; Garcia, Jose P

    2016-03-01

    We report the first successful bridge to lung transplantation using venovenous extracorporeal membrane oxygenation (ECMO) with an atrial septostomy for both pulmonary and right ventricular support. This strategy may provide an alternative to other forms of ECMO support as a bridge to lung transplantation, and potentially allow for ambulation and rehabilitation. PMID:26897198

  8. Automated assessment of split lung functon in post-lung-transplant evaluation

    NASA Astrophysics Data System (ADS)

    Goldin, Jonathan G.; Brown, Matthew S.; McNitt-Gray, Michael F.; Greaser, Lloyd E.; Martin, Katherine; Sayre, James W.; Aberle, Denise R.

    1998-07-01

    The purpose of this work was to develop an automated technique for calculating dynamic lung attenuation changes, through a forced expiratory maneuver, as a measure of split lung function. A total of ten patients post single lung transplantation (SLT) for emphysema were imaged using an Electron Beam CT Scanner; three were studied twice following stent placement. A single-slice flow study, using 100 msec exposures and 3 mm collimation, was performed at the level of the anastomosis during a forced expiration. Images were acquired every 500 msec for the first 3 seconds and every second for the last 4 seconds. An automated, knowledge-based system was developed to segment the chest wall, mediastinum, large airways and lung parenchyma in each image. Knowledge of the expected size, shape, topology and X-ray attenuation of anatomical structures were used to guide image segmentation involving attenuation thresholding, region-growing and morphology. From the segmented left and right parenchyma, the system calculated median attenuation (HU) and cross-sectional areas. These results were plotted against time for both the native and transplanted lungs. In five patients, significant shift of the attenuation/time curve to the right (slower flow) was detected, although the end expiration attenuation was not different. Following stent placement the curve shifted back to the left (faster flow).

  9. Transplantation.

    PubMed

    Faro, Albert; Weymann, Alexander

    2016-08-01

    Despite improvement in median life expectancy and overall health, some children with cystic fibrosis (CF) progress to end-stage lung or liver disease and become candidates for transplant. Transplants for children with CF hold the promise to extend and improve the quality of life, but barriers to successful long-term outcomes include shortage of suitable donor organs; potential complications from the surgical procedure and immunosuppressants; risk of rejection and infection; and the need for lifelong, strict adherence to a complex medical regimen. This article reviews the indications and complications of lung and liver transplantation in children with CF. PMID:27469184

  10. Understanding the Concept of Health Care-Associated Pneumonia in Lung Transplant Recipients

    PubMed Central

    Palacio, Federico; Reyes, Luis F.; Levine, Deborah J.; Sanchez, Juan F.; Angel, Luis F.; Fernandez, Juan F.; Levine, Stephanie M.; Rello, Jordi; Abedi, Ali

    2015-01-01

    BACKGROUND: Limited data are available regarding the etiologic impact of health care-associated pneumonia (HCAP) in lung transplant recipients. Therefore, our aim was to evaluate the microbiologic differences between HCAP and hospital-acquired pneumonia (HAP)/ventilator-associated pneumonia (VAP) in lung transplant recipients with a radiographically confirmed diagnosis of pneumonia. METHODS: We performed a retrospective cohort study of lung transplant recipients with pneumonia at one transplant center over a 7-year period. Eligible patients included lung transplant recipients who developed a first episode of radiographically confirmed pneumonia ≥ 48 h following transplantation. HCAP, HAP, and VAP were classified according to the American Thoracic Society/Infectious Diseases Society of America 2005 guidelines. χ2 and Student t tests were used to compare categorical and continuous variables, respectively. RESULTS: Sixty-eight lung transplant recipients developed at least one episode of pneumonia. HCAP (n = 42; 62%) was most common, followed by HAP/VAP (n = 26; 38%) stratified in HAP (n = 20; 77%) and VAP (n = 6; 23%). Pseudomonas aeruginosa was the predominantly isolated organism (n = 22; 32%), whereas invasive aspergillosis was uncommon (< 10%). Multiple-drug resistant (MDR) pathogens were less frequently isolated in patients with HCAP compared with HAP/VAP (5% vs 27%; P = .009). Opportunistic pathogens were less frequently identified in lung transplant recipients with HCAP than in those with HAP/VAP (7% vs 27%; P = .02). Lung transplant recipients with HCAP had a similar mortality at 90 days (n = 9 [21%] vs n = 4 [15%]; P = .3) compared with patients with HAP/VAP. CONCLUSIONS: HCAP was the most frequent infection in lung transplant recipients. MDR pathogens and opportunistic pathogens were more frequently isolated in HAP/VAP. There were no differences in 30- and 90-day mortality between lung transplant recipients with HCAP and those with HAP/VAP. PMID:25742187

  11. Prolonged Barium-Impaction Ileus in Two Lung Transplant Recipients With Systemic Sclerosis: Case Report.

    PubMed

    Tokman, S; Hays, S R; Leard, L E; Bush, E L; Kukreja, J; Kleinhenz, M E; Golden, J A; Singer, J P

    2015-12-01

    Lung transplantation can be a life-saving measure for people with end-stage lung disease from systemic sclerosis. However, outcomes of lung transplantation may be compromised by gastrointestinal manifestations of systemic sclerosis, which can involve any part of the gastrointestinal tract. Esophageal and gastric disease can be managed by enteral feeding with the use of a gastrojejunal feeding tube. In this report, we describe the clinical courses of 2 lung transplant recipients with systemic sclerosis who experienced severe and prolonged barium-impaction ileus after insertion of a percutaneous gastrojejunal feeding tube.

  12. [Living donor liver transplantation in adults].

    PubMed

    Neumann, U P; Neuhaus, P; Schmeding, M

    2010-09-01

    The worldwide shortage of adequate donor organs implies that living donor liver transplantation represents a valuable alternative to cadaveric transplantation. In addition to the complex surgical procedure the correct identification of eligible donors and recipients plays a decisive role in living donor liver transplantation. Donor safety must be of ultimate priority and overrules all other aspects involved. In contrast to the slightly receding numbers in Europe and North America, in recent years Asian programs have enjoyed constantly increasing living donor activity. The experience of the past 15 years has clearly demonstrated that technical challenges of both bile duct anastomosis and venous outflow of the graft significantly influence postoperative outcome. While short-term in-hospital morbidity remains increased compared to cadaveric transplantation, long-term survival of both graft and patient are comparable or even better than in deceased donor transplantation. Especially for patients expecting long waiting times under the MELD allocation system, living donor liver transplantation offers an excellent therapeutic alternative. Expanding the so-called "Milan criteria" for HCC patients with the option for living donor liver transplantation is currently being controversially debated.

  13. Long term complications following 54 consecutive lung transplants

    PubMed Central

    Tabarelli, Walther; Bonatti, Hugo; Tabarelli, Dominique; Eller, Miriam; Müller, Ludwig; Ruttmann, Elfriede; Lass-Flörl, Cornelia; Larcher, Clara

    2016-01-01

    Background Due to the complex therapy and the required high level of immunosuppression, lung recipients are at high risk to develop many different long term complications. Methods From 1993–2000, a total of 54 lung transplantation (LuTx) were performed at our center. Complications, graft and patient survival of this cohort was retrospectively analyzed. Results One/five and ten-year patient survival was 71.4%, 41.2% and 25.4%; at last follow up (4/2010), twelve patients were alive. Of the 39 deceased patients, 26 died from infectious complications. Other causes of death were myocardial infarction (n=1), progressive graft failure (n=1), intracerebral bleeding (n=2), basilary vein thrombosis (n=1), pulmonary emboli (n=1), others (n=7). Surgical complication rate was 27.7% during the first year and 25% for the 12 long term survivors. Perioperative rejection rate was 35%, and 91.6% for the 12 patients currently alive. Infection incidence during first hospitalization was 79.6% (1.3 episodes per transplant) and 100% for long term survivors. Commonly isolated pathogens were cytomegalovirus (56.8%), Aspergillus (29.4%), RSV (13.7%). Other common complications were renal failure (56.8%), osteoporosis (54.9%), hypertension (45%), diabetes mellitus (19.6%). Conclusions Infection and rejection remain the most common complications following LuTx with many other events to be considered. PMID:27293842

  14. [Nocardia farcinica lung infection in a patient with cystic fibrosis and a lung transplant].

    PubMed

    Chacón, C F; Vicente, R; Ramos, F; Porta, J; Lopez Maldonado, A; Ansotegui, E

    2015-03-01

    Patients with cystic fibrosis have a higher risk of developing chronic respiratory infectious diseases. The Nocardia farcinica lung infection is rare in this group of patients, and there are limited publications about this topic. Its diagnosis is complex, due to the clinical and the radiology signs being non-specific. Identification of the agent responsible in the sputum culture is occasionally negative. It is a slow growing organism and for this reason treatment is delayed, which can lead to an increase in complications, hospitable stays, and mortality. A case is reported on a 26 year-old woman with cystic fibrosis and chronic lung colonization by Nocardia farcinica and Aspergillus fumigatus, on long-term treatment with ciprofloxacin, trimethoprim-sulfamethoxazole, and posaconazole, who was admitted to ICU after bilateral lung transplantation. The initial post-operative progress was satisfactory. After discharge, the patient showed a gradual respiratory insufficiency with new chest X-ray showing diffuse infiltrates. Initially, the agent was not seen in the sputum culture. Prompt and aggressive measures were taken, due to the high clinical suspicion of a Nocardia farcinica lung infection. Treatment with a combination of amikacin and meropenem, and later combined with linezolid, led to the disappearance of the lung infiltrates and a clinical improvement. In our case, we confirm the rapid introduction of Nocardia farcinica in the new lungs. The complex identification and the delay in treatment increased the morbimortality. There is a special need for its eradication in patients with lung transplant, due to the strong immunosuppressive treatment. PMID:25443661

  15. Monitoring of Nonsteroidal Immunosuppressive Drugs in Patients With Lung Disease and Lung Transplant Recipients

    PubMed Central

    Meyer, Keith C; Nathanson, Ian; Angel, Luis; Bhorade, Sangeeta M; Chan, Kevin M; Culver, Daniel; Harrod, Christopher G; Hayney, Mary S; Highland, Kristen B; Limper, Andrew H; Patrick, Herbert; Strange, Charlie; Whelan, Timothy

    2012-01-01

    Objectives: Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. Methods: Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. Conclusions: It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease. PMID:23131960

  16. Pretransplant dyslipidaemia determines outcome in lung transplant recipients

    PubMed Central

    2013-01-01

    Background There is little knowledge about the effect of dyslipidaemia on the outcome after lung transplantation. Thus, the aim of this retrospective single centre study was to analyse the impact of the plasma lipid profile on mortality in lung transplant recipients. From January 2000 to December 2008 the charts of 172 consecutive lung transplantation recipients were analysed. At baseline and after one year lipid profiles were routinely collected. During the follow-up major cardiovascular events (MCE; beginning of dialysis, cerebrovascular insult or myocardial infarction) were recorded. The follow-up period ended December 2010. Findings Over all total cholesterol (4.3 ± 1.6 vs. 5.4 ± 1.3 mmol/l, p < 0.0001), triglycerides (1.2 ± 0.7 vs. 2.4 ± 1.3 mmol/l, p < 0.0001), HDL (1.5 ± 0.6 vs. 1.7 ± 0.6 mmol/l, p = 0.003) and TC/HDL ratio (3.0 ± 1.0 vs. 3.6 ± 1.2, p = 0.002) increased significantly after 1 year. During the observational period 6.9% (10 patients) suffered a major cardiac event. In univariate analysis MCE was associated with baseline TC: on average the event-group had a 33% higher baseline TC (5.6 vs. 4.2 mmol/l, OR 1.6, CI 1.1 – 2.2, p = 0.02). The total mortality in the observational period was 25% (36 patients overall). In univariate analysis mortality was associated with increased TC/HDL ratio. The non-survivors had on average a 22% higher baseline TC/HDL ratio (3.6 vs. 2.8, HR 2.8, CI 1.2 – 3.5, p = 0.001). There was no association between mortality and TC (p = 0.33), triglycerides (p = 0.34), HDL (p = 0.78) and creatinine (p = 0.73). In a multivariate model the hazard ratio was 1.5 (1.2 – 1.9, p = 0.001) per increase of 0.4 TC/HDL ratio. Conclusions This study shows that the total cholesterol before transplantation is associated with the incidence of MCE and the cholesterol/HDL ratio with mortality in lung transplanted recipients. PMID:23617837

  17. Psychological criteria for contraindication in lung transplant candidates: a five-year study*

    PubMed Central

    Hojaij, Elaine Marques; Romano, Bellkiss Wilma; Costa, André Nathan; Afonso, Jose Eduardo; de Camargo, Priscila Cilene Leon Bueno; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Samano, Marcos Naoyuki; Teixeira, Ricardo Henrique de Oliveira Braga

    2015-01-01

    Lung transplantation presents a wide range of challenges for multidisciplinary teams that manage the care of the recipients. Transplant teams should perform a thorough evaluation of transplant candidates, in order to ensure the best possible post-transplant outcomes. That is especially true for the psychologist, because psychological issues can arise at any point during the perioperative period. The objective of our study was to evaluate the psychological causes of contraindication to waiting list inclusion in a referral program for lung transplantation. We retrospectively analyzed data on psychological issues presented by lung transplant candidates, in order to understand these matters in our population and to reflect upon ways to improve the selection process. PMID:26176522

  18. Telephone-Based Coping Skills Training for Patients Awaiting Lung Transplantation

    ERIC Educational Resources Information Center

    Blumenthal, James A.; Babyak, Michael A.; Keefe, Francis J.; Davis, R. Duane; LaCaille, Rick A.; Carney, Robert M.; Freedland, Kenneth E.; Trulock, Elbert; Palmer, Scott M.

    2006-01-01

    Impaired quality of life is associated with increased mortality in patients with advanced lung disease. Using a randomized controlled trial with allocation concealment and blinded outcome assessment at 2 tertiary care teaching hospitals, the authors randomly assigned 328 patients with end-stage lung disease awaiting lung transplantation to 12…

  19. A longitudinal study of patients’ symptoms before and during the first year after lung transplantation

    PubMed Central

    Lanuza, Dorothy M.; Lefaiver, Cheryl A.; Brown, Roger; Muehrer, Rebecca; Murray, Margaret; Yelle, Maria; Bhorade, Sangeeta

    2012-01-01

    Background Lung transplantation provides a viable option for survival of end-stage respiratory disease. In addition to prolonging survival, there is considerable interest in improving patient-related outcomes such as transplant recipients’ symptom experiences. Methods A prospective, repeated measures design was used to describe the symptom experience of 85 lung transplant recipients between 2000–2005. The Transplant Symptom Inventory (TSI) was administered before and at 1, 3, 6, 9, and 12 months post-transplant. Ridit analysis provided a unique method for describing symptom experiences and changes. Results After lung transplantation, significant (p<.05) improvements were reported for the most frequently occurring and most distressing pre-transplant symptoms (e.g., shortness of breath with activity). Marked increases in the frequency and distress of new symptoms, such as tremors were also reported. Patterns of symptom frequency and distress varied with the time since transplant. Conclusion The findings provide data-based information that can be used to inform pre- and post-transplant patient education and also help caregivers anticipate a general time frame for symptom changes in order to prevent or minimize symptoms and their associated distress. In addition, symptoms are described, using an innovative method of illustration which shows “at-a-glance” changes or lack of changes in patients’ symptoms from pre- to post-lung transplant. PMID:22988999

  20. Chronic suppurative lung disease in adults

    PubMed Central

    Mangardich, Antranik

    2016-01-01

    Chronic suppurative lung disease (CSLD), characterized by a bronchiectasis-like syndrome in the absence of bronchial dilatation, is well described in the pediatric literature. In some patients, it may be a precursor of bronchiectasis. In adults, this syndrome has not been well described. We present four adult patients without obvious causative exposures who presented with prolonged cough and purulent sputum. Sputum cultures revealed a variety of Gram negative bacteria, fungi and mycobacteria. High resolution CT scanning did not reveal bronchiectasis. Evaluation revealed underlying causes including immunodeficiency in two, and Mycobacterium avium infection. One patient subsequently developed bronchiectasis. All patients improved with therapy. CSLD occurs in adults and has characteristics that distinguish it from typical chronic bronchitis. These include the lack of causative environmental exposures and infection with unusual pathogens. Evaluation and treatment of these patients similar to bronchiectasis patients may lead to clinical improvement. PMID:27747039

  1. Intermediate-term outcome in lung transplantation from a donor with glioblastoma multiforme.

    PubMed

    Chen, Fengshi; Karolak, Wojtek; Cypel, Marcelo; Keshavjee, Shaf; Pierre, Andrew

    2009-10-01

    A 19-year-old man with cystic fibrosis, who was on extracorporeal membrane oxygenation, underwent bilateral lung transplantation from a donor with glioblastoma multiforme. Because the risk of tumor transmission from donor-related central nervous system malignancies remains unclear, the use of these extended donors remains controversial. In fact, there are few reports on the outcomes of lung transplantation from donors with central nervous system malignancy. This patient was critically ill with extracorporeal membrane oxygenation support before transplantation, but is well without any sign of malignancy 20 months after transplantation. PMID:19782299

  2. Regional pulmonary perfusion following human heart-lung transplantation

    SciTech Connect

    Lisbona, R.; Hakim, T.S.; Dean, G.W.; Langleben, D.; Guerraty, A.; Levy, R.D. )

    1989-08-01

    Ventilation and perfusion scans were obtained in six subjects who had undergone heart-lung transplantation with consequent denervation of the cardiopulmonary axis. Two of the subjects had developed obliterative bronchiolitis, which is believed to be a form of chronic rejection. Their pulmonary function tests demonstrated airflow obstruction and their scintigraphic studies were abnormal. In the remaining four subjects without obstructive airways disease, ventilation and planar perfusion scans were normal. Single photon emission computed tomography imaging of pulmonary perfusion in these patients revealed a layered distribution of blood flow indistinguishable from that of normal individuals. It is concluded that neurogenic mechanisms have little influence on the pattern of local pulmonary blood flow at rest.

  3. Periostitis secondary to prolonged voriconazole therapy in lung transplant recipients.

    PubMed

    Wang, T F; Wang, T; Altman, R; Eshaghian, P; Lynch, J P; Ross, D J; Belperio, J A; Weigt, S S; Saggar, R; Gregson, A; Kubak, B; Saggar, R

    2009-12-01

    We report five cases of possible drug-induced periostitis associated with long-term use of voriconazole therapy after lung transplantation (LT). The diagnosis of periostitis was made by the documentation of bone pain, elevation of serum alkaline phosphatase and characteristic findings on radionuclide bone imaging in the absence of any identifiable rheumatologic disease. This periostitis appears similar to hypertrophic osteoarthopathy (HOA) but does not meet all criteria for HOA. In all patients, the symptoms resolved rapidly after discontinuation of voriconazole therapy. Awareness of this potential syndrome, which manifests as bone pain, elevated serum alkaline phosphatase and a bone scan suggestive of periostitis, is necessary in LT recipients on long-term voriconazole.

  4. Mycobacterium abscessus Complex - a Particular Challenge in the Setting of Lung Transplantation.

    PubMed

    Smibert, O; Snell, G I; Bills, H; Westall, G P; Morrissey, C O

    2016-01-01

    Mycobacterium abscessus complex is an emerging pathogen in lung transplant candidates and recipients. M. abscessus complex is widespread in the environment and can cause pulmonary, skin and soft tissue, and disseminated infection, particularly in lung transplant recipients. It is innately resistant to many antibiotics making it difficult to treat. Herein we describe the epidemiology, clinical manifestations, diagnosis and treatment of M. abscessus with an emphasis on lung transplant candidates and recipients. We also outline the areas where data are lacking and the areas where further research is urgently needed. PMID:26732819

  5. The presence or severity of pulmonary hypertension does not affect outcomes for single-lung transplantation

    PubMed Central

    Julliard, Walker A; Meyer, Keith C; De Oliveira, Nilto C; Osaki, Satoru; Cornwell, Richard C; Sonetti, David A; Maloney, James D

    2016-01-01

    Advanced lung disease (ALD) that requires lung transplantation (LTX) is frequently associated with pulmonary hypertension (PH). Whether the presence of PH significantly affects the outcomes following single-lung transplantation (SLT) remains controversial. Therefore, we retrospectively examined the outcomes of 279 consecutive SLT recipients transplanted at our centre, and the patients were split into four groups based on their mean pulmonary artery pressure values. Outcomes, including long-term survival and primary graft dysfunction, did not differ significantly for patients with versus without PH, even when PH was severe. We suggest that SLT can be performed safely in patients with ALD-associated PH. PMID:26621135

  6. Epigenetic contributions to the developmental origins of adult lung disease.

    PubMed

    Joss-Moore, Lisa A; Lane, Robert H; Albertine, Kurt H

    2015-04-01

    Perinatal insults, including intrauterine growth restriction, preterm birth, maternal exposure to toxins, or dietary deficiencies produce deviations in the epigenome of lung cells. Occurrence of perinatal insults often coincides with the final stages of lung development. The result of epigenome disruptions in response to perinatal insults during lung development may be long-term structural and functional impairment of the lung and development of lung disease. Understanding the contribution of epigenetic mechanisms to life-long lung disease following perinatal insults is the focus of the developmental origins of adult lung disease field. DNA methylation, histone modifications, and microRNA changes are all observed in various forms of lung disease. However, the perinatal contribution to such epigenetic mechanisms is poorly understood. Here we discuss the developmental origins of adult lung disease, the interplay between perinatal events, lung development and disease, and the role that epigenetic mechanisms play in connecting these events.

  7. Transplanted neurons integrate into adult retinas and respond to light

    PubMed Central

    Venugopalan, Praseeda; Wang, Yan; Nguyen, Tu; Huang, Abigail; Muller, Kenneth J.; Goldberg, Jeffrey L.

    2016-01-01

    Retinal ganglion cells (RGCs) degenerate in diseases like glaucoma and are not replaced in adult mammals. Here we investigate whether transplanted RGCs can integrate into the mature retina. We have transplanted GFP-labelled RGCs into uninjured rat retinas in vivo by intravitreal injection. Transplanted RGCs acquire the general morphology of endogenous RGCs, with axons orienting towards the optic nerve head of the host retina and dendrites growing into the inner plexiform layer. Preliminary data show in some cases GFP+ axons extending within the host optic nerves and optic tract, reaching usual synaptic targets in the brain, including the lateral geniculate nucleus and superior colliculus. Electrophysiological recordings from transplanted RGCs demonstrate the cells' electrical excitability and light responses similar to host ON, ON–OFF and OFF RGCs, although less rapid and with greater adaptation. These data present a promising approach to develop cell replacement strategies in diseased retinas with degenerating RGCs. PMID:26843334

  8. A novel dual ex vivo lung perfusion technique improves immediate outcomes in an experimental model of lung transplantation.

    PubMed

    Tanaka, Y; Noda, K; Isse, K; Tobita, K; Maniwa, Y; Bhama, J K; D'Cunha, J; Bermudez, C A; Luketich, J D; Shigemura, N

    2015-05-01

    The lungs are dually perfused by the pulmonary artery and the bronchial arteries. This study aimed to test the feasibility of dual-perfusion techniques with the bronchial artery circulation and pulmonary artery circulation synchronously perfused using ex vivo lung perfusion (EVLP) and evaluate the effects of dual-perfusion on posttransplant lung graft function. Using rat heart-lung blocks, we developed a dual-perfusion EVLP circuit (dual-EVLP), and compared cellular metabolism, expression of inflammatory mediators, and posttransplant graft function in lung allografts maintained with dual-EVLP, standard-EVLP, or cold static preservation. The microvasculature in lung grafts after transplant was objectively evaluated using microcomputed tomography angiography. Lung grafts subjected to dual-EVLP exhibited significantly better lung graft function with reduced proinflammatory profiles and more mitochondrial biogenesis, leading to better posttransplant function and compliance, as compared with standard-EVLP or static cold preservation. Interestingly, lung grafts maintained on dual-EVLP exhibited remarkably increased microvasculature and perfusion as compared with lungs maintained on standard-EVLP. Our results suggest that lung grafts can be perfused and preserved using dual-perfusion EVLP techniques that contribute to better graft function by reducing proinflammatory profiles and activating mitochondrial respiration. Dual-EVLP also yields better posttransplant graft function through increased microvasculature and better perfusion of the lung grafts after transplantation.

  9. Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations.

    PubMed

    Lane, C Randall; Tonelli, Adriano R

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer. PMID:26491282

  10. Lung transplantation in chronic obstructive pulmonary disease: patient selection and special considerations.

    PubMed

    Lane, C Randall; Tonelli, Adriano R

    2015-01-01

    Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and morbidity. Lung transplantation is one of the few treatments available for end-stage COPD with the potential to improve survival and quality of life. The selection of candidates and timing of listing present challenges, as COPD tends to progress fairly slowly, and survival after lung transplantation remains limited. Though the natural course of COPD is difficult to predict, the use of assessments of functional status and multivariable indices such as the BODE index can help identify which patients with COPD are at increased risk for mortality, and hence which are more likely to benefit from lung transplantation. Patients with COPD can undergo either single or bilateral lung transplantation. Although many studies suggest better long-term survival with bilateral lung transplant, especially in younger patients, this continues to be debated, and definitive recommendations about this cannot be made. Patients may be more susceptible to particular complications of transplant for COPD, including native lung hyperinflation, and development of lung cancer.

  11. [Group therapy following lung transplantation -- first experiences with a theme-centered "life management group"].

    PubMed

    Goetzmann, Lutz; Wagner-Huber, Regula; Andenmatten-Bärenfaller, Manuela; Günthard, Anne; Alfare, Christian; Buddeberg, Claus; Boehler, Annette

    2006-07-01

    Lung transplantation is a drastic life event that usually takes place in the preterminal phase of a lung disease. Although a lung transplantation increases the quality of life considerably, patients still face a range of physical and psychosocial strains. This article presents experiences made with a "Life Management Group" for lung transplantation patients. The aim of the eight group meetings was to encourage the sharing of experiences between patients and to support them in their active and competent realizations of desires and plans. Physical health, self-identity of lung transplant recipients, growing problems financing medical treatment and the forming of doctor-patient-relationships were the important issues. Patients were able to reach a higher level of self efficiency; they could use active coping strategies and develop their social networks. Positive experiences were made with the implementation of group therapy for lung transplantation patients. Lung transplant recipients have to deal with specific problems of identity. On the other hand, there are growing health-economic questions also from the patient's point of view. PMID:16586305

  12. Clinico-pathological Analysis of the Lungs from Patients with Lung Transplantation in a Single Institute in Korea.

    PubMed

    Kim, Hyojin; Jeon, Yoon Kyung; Lee, Hyun Joo; Kim, Young Tae; Chung, Doo Hyun

    2015-10-01

    Recently, the numbers of lung transplantation (LT) has been increased in Korea. However, post-LT outcome has not been successful in all patients, which may be partially affected by the primary lung disease. Therefore comprehensive understanding in original pathological diagnosis of patients with LT would be needed for achieving better clinical outcome. To address this issue, we performed clinico-pathological analysis of the explanted lungs from 29 patients who underwent LT over a 9-yr period in Seoul National University Hospital. Among them, 26 patients received single (1/26) or double (25/26) LT, while heart-lung transplantation was performed in 3 patients. The final clinico-pathological diagnoses were idiopathic pulmonary fibrosis/usual interstitial pneumonia (UIP) (n = 6), acute interstitial pneumonia (AIP)/diffuse alveolar damage (DAD) (n = 4), AIP/non-specific interstitial pneumonia with DAD (n = 1), collagen vascular disease-related interstitial lung disease (CVD-ILD)/DAD (n = 3), CVD-ILD/UIP (n = 1), lymphangioleiomyomatosis (n = 1), bronchiectasis (n = 4), pulmonary arterial hypertension (n = 2), tuberculosis (n = 1), bronchiolitis obliterans (BO) (n = 1), and lung cancer (n = 1). Moreover, 4 patients who had chemotherapy and hematopoietic stem cell transplantation due to hematologic malignancy showed unclassifiable interstitial pneumonia with extensive fibrosis in the lungs. Our study demonstrates that pathology of the explanted lungs from Korean patients with LT is different from that of other countries except for interstitial lung disease and bronchiectasis, which may be helpful for optimization of selecting LT candidates for Korean patients.

  13. Clinical usefulness of oral immunoglobulins in lung transplant recipients with norovirus gastroenteritis: a case series.

    PubMed

    Gairard-Dory, A-C; Dégot, T; Hirschi, S; Schuller, A; Leclercq, A; Renaud-Picard, B; Gourieux, B; Kessler, R

    2014-12-01

    Viral gastroenteritis causing diarrhea is a common complication observed in lung transplant recipients. Differently from the mild and typically self-limited disease seen in immunocompetent subjects, immunocompromised patients frequently have a more severe course. Norovirus and rotavirus are among the leading causes of severe gastroenteritis in transplant recipients. Specific treatment is unavailable, although good supportive treatment can significantly reduce morbidity. Previous studies have suggested that oral immunoglobulins may be used for the treatment of acute viral gastroenteritis after solid-organ transplantation. Herein, we conducted a retrospective chart review of 12 lung transplant recipients with norovirus-induced gastroenteritis who were treated with oral immunoglobulins for 2 days. Eleven patients were successfully treated, whereas 1 subject was only mildly improved. Four patients had at least 1 recurrence. No significant adverse effects were observed. We conclude that oral immunoglobulins may be clinically useful for lung transplant recipients with norovirus-induced gastroenteritis.

  14. Single lung transplantation in a patient with retrospective positive cross-match

    PubMed Central

    Piotrowska, Maria; Dec, Paweł; Wasilewski, Piotr; Kubisa, Anna; Pieróg, Jarosław; Wójcik, Norbert; Czarnecka, Michalina; Kubisa, Bartosz; Grodzki, Tomasz

    2015-01-01

    Lung transplantation is a method useful in such non-malignant end-stage parenchymal and vascular diseases as: chronic obstructive pulmonary disease (COPD), idiopathic interstitial pulmonary fibrosis, cystic fibrosis, or primary pulmonary hypertension. The main aim of this procedure is to extend the patient's lifespan and quality of life. However, the availability of the operation is limited by organ access. In this paper we present the case of a 58-year-old female in the fourth stage of COPD, who was classified to have a single lung transplantation. Because of some technical problems it was decided to transplant a left donor lung in the right recipient lung locus. Positive cross match was demonstrated retrospectively, and we applied five courses of plasmapheresis. Human immunoglobulin and rituximab treatment were performed to decrease the impact of lymphocytotoxic antibodies. The patient survived 498 days after transplantation, 271 in the hospital. PMID:26855654

  15. Disseminated Scedosporium/Pseudallescheria Infection after Double-Lung Transplantation in Patients with Cystic Fibrosis▿

    PubMed Central

    Morio, Florent; Horeau-Langlard, Delphine; Gay-Andrieu, Françoise; Talarmin, Jean-Philippe; Haloun, Alain; Treilhaud, Michelle; Despins, Philippe; Jossic, Frédérique; Nourry, Laurence; Danner-Boucher, Isabelle; Pattier, Sabine; Bouchara, Jean-Philippe; Le Pape, Patrice; Miegeville, Michel

    2010-01-01

    We report a case of disseminated Scedosporium/Pseudallescheria infection due to Pseudallescheria boydii sensu stricto after lung transplantation in a patient with cystic fibrosis. Dissemination occurred under voriconazole. Despite surgery and combination therapy with voriconazole, caspofungin, and terbinafine, the patient died 8 months after transplantation. Previously reported cases are reviewed. PMID:20220160

  16. Donor surfactant protein D (SP-D) polymorphisms are associated with lung transplant outcome.

    PubMed

    Aramini, B; Kim, C; Diangelo, S; Petersen, E; Lederer, D J; Shah, L; Robbins, H; Floros, J; Arcasoy, S M; Sonett, J R; D'Ovidio, F

    2013-08-01

    Chronic lung allograft dysfunction (CLAD) is the major factor limiting long-term success of lung transplantation. Polymorphisms of surfactant protein D (SP-D), an important molecule within lung innate immunity, have been associated with various lung diseases. We investigated the association between donor lung SP-D polymorphisms and posttransplant CLAD and survival in 191 lung transplant recipients consecutively transplanted. Recipients were prospectively followed with routine pulmonary function tests. Donor DNA was assayed by pyrosequencing for SP-D polymorphisms of two single-nucleotide variations altering amino acids in the mature protein N-terminal domain codon 11 (Met(11) Thr), and in codon 160 (Ala(160) Thr) of the C-terminal domain. CLAD was diagnosed in 88/191 patients, and 60/191 patients have died. Recipients of allografts that expressed the homozygous Met(11) Met variant of aa11 had significantly greater freedom from CLAD development and better survival compared to those with the homozygous Thr(11) Th variant of aa11. No significant association was noted for SP-D variants of aa160. Lung allografts with the SP-D polymorphic variant Thr(11) Th of aa11 are associated with development of CLAD and reduced survival. The observed genetic differences of the donor lung, potentially with their effects on innate immunity, may influence the clinical outcomes after lung transplantation.

  17. Lymphoproliferative disease after lung and heart-lung transplantation: first description in Spain.

    PubMed

    Morales, P; Torres, J; Pérez-Enguix, D; Solé, A; Pastor, A; Segura, A; Zurbano, F

    2005-11-01

    Lymphoproliferative syndromes are the most common tumors in transplant recipients. More than 90% of posttransplantation lymphoproliferative syndromes (PTLS) are considered to be associated with Epstein-Barr virus, and 86% are of the B-cell line. Histopathology ranges from polymorphic-reactive to monomorphic forms. Clonality should be studied using molecular biology techniques. Clinically, a differentiation is usually made between early PTLS (occurring within 1 year after transplantation) and late PTLS, which occur as localized or disseminated nodal lymphomas. In localized forms, immunosuppression should be discontinued or decreased, and the involved area should be subsequently resected or irradiated. In disseminated cases, immunosuppression should be decreased and administration of acyclovir/ganciclovir should be considered. If this is not effective, treatment should be started with anti-CD20 monoclonal antibodies (rituximab). If no response occurs, use of chemotherapy, possibly with interferon, should be considered. Our aim was to report the incidence, clinical signs, and treatment in a series of patients undergoing lung transplantation (LTx).

  18. Postinfectious bronchiolitis obliterans in children: lessons from bronchiolitis obliterans after lung transplantation and hematopoietic stem cell transplantation

    PubMed Central

    2015-01-01

    Postinfectious bronchiolitis obliterans (PIBO) is an irreversible obstructive lung disease characterized by subepithelial inflammation and fibrotic narrowing of the bronchioles after lower respiratory tract infection during childhood, especially early childhood. Although diagnosis of PIBO should be confirmed by histopathology, it is generally based on history and clinical findings. Irreversible airway obstruction is demonstrated by decreased forced expiratory volume in 1 second with an absent bronchodilator response, and by mosaic perfusion, air trapping, and/or bronchiectasis on computed tomography images. However, lung function tests using spirometry are not feasible in young children, and most cases of PIBO develop during early childhood. Further studies focused on obtaining serial measurements of lung function in infants and toddlers with a risk of bronchiolitis obliterans (BO) after lower respiratory tract infection are therefore needed. Although an optimal treatment for PIBO has not been established, corticosteroids have been used to target the inflammatory component. Other treatment modalities for BO after lung transplantation or hematopoietic stem cell transplantation have been studied in clinical trials, and the results can be extrapolated for the treatment of PIBO. Lung transplantation remains the final option for children with PIBO who have progressed to end-stage lung disease. PMID:26770220

  19. Review of the International Society for Heart and Lung Transplantation Practice guidelines for management of heart failure in children.

    PubMed

    Colan, Steven D

    2015-08-01

    In 2004, practice guidelines for the management of heart failure in children by Rosenthal and colleagues were published in conjunction with the International Society for Heart and Lung Transplantation. These guidelines have not been updated or reviewed since that time. In general, there has been considerable controversy as to the utility and purpose of clinical practice guidelines, but there is general recognition that the relentless progress of medicine leads to the progressive irrelevance of clinical practice guidelines that do not undergo periodic review and updating. Paediatrics and paediatric cardiology, in particular, have had comparatively minimal participation in the clinical practice guidelines realm. As a result, most clinical practice guidelines either specifically exclude paediatrics from consideration, as has been the case for the guidelines related to cardiac failure in adults, or else involve clinical practice guidelines committees that include one or two paediatric cardiologists and produce guidelines that cannot reasonably be considered a consensus paediatric opinion. These circumstances raise a legitimate question as to whether the International Society for Heart and Lung Transplantation paediatric heart failure guidelines should be re-reviewed. The time, effort, and expense involved in producing clinical practice guidelines should be considered before recommending an update to the International Society for Heart and Lung Transplantation Paediatric Heart Failure guidelines. There are specific areas of rapid change in the evaluation and management of heart failure in children that are undoubtedly worthy of updating. These domains include areas such as use of serum and imaging biomarkers, wearable and implantable monitoring devices, and acute heart failure management and mechanical circulatory support. At the time the International Society for Heart and Lung Transplantation guidelines were published, echocardiographic tissue Doppler, 3 dimensional

  20. Can lungs be taken for transplantation from donors with a significant smoking history?

    PubMed

    Attaran, Saina; Chukwuemeka, Andrew; Anderson, Jon R

    2013-07-01

    A best evidence topic in cardiothoracic surgery was written according to a structured protocol. The question addressed was 'Can lungs be taken for transplantation from donors with a significant smoking history?’. Five papers were found using the reported search that represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. These studies compared the outcome and survival between patients who receive lungs from smokers with those receiving non-smoker lungs. None of these studies were randomized controlled trials. They retrospectively analysed a cohort of patients undergoing lung transplantation for the past 10 years. These studies showed worse outcomes in the early postoperative period, such as longer intensive care unit stay, longer ventilation time and higher early postoperative mortality, with lungs harvested from smokers. Two studies also demonstrated a worse long-term outcome in recipients of lungs from smokers, whereas the other two showed worse results during the early postoperative period only. These latter two studies reported similar survival rates after 3 months and up to 3 years in recipients receiving smoker vs non-smoker lungs. One study, however, showed a better 5-year survival with smoker lungs compared with non-smokers, although in this study, lungs from heavy smokers showed the worse outcome. Despite the difference in long-term results and outcome reported by these authors, all of these studies unanimously indicate that lungs from smokers should not be rejected, as survival in these patients receiving smoker lungs is still significantly higher in 3 and 5 years compared with that in those who remain on the transplant waiting list. In conclusion, the current evidence in the literature suggests that lungs from smokers can be used for transplantation. Patients should, however, be fully informed of

  1. Catheter fragmentation and local lysis in two lung transplant patients with pulmonary embolism.

    PubMed

    Suhling, H; Westerkamp, V; Dinh, Q T; Greer, M; Kempf, T; Simon, A; Gottlieb, J; Welte, T; Schieffer, B

    2010-11-01

    In conjunction with the rising number of lung transplant operations in the past decade, an increased predisposition to venous thrombosis (VT), particularly within the first year posttransplantation has been observed. Previous studies have revealed that between 8.6% and 12% of patients develop VT, which can ultimately result in pulmonary emboli (PE).Transplanted lungs pose a much greater infarction risk due to their lack of collateral vascularisation, relying entirely on the vasa publica--the pulmonary artery--in the absence of vasa privata. Such losses in viable lung parenchyma are always serious, but carry still greater risks for single-lung transplant recipients, an early diagnosis and treatment remain critical. Here we report on two cases of PE after lung transplantation, both of whom were managed with catheter fragmentation and local thrombolysis. In our opinion, this approach represents a viable treatment for symptomatic PE in lung transplant recipients. The benefits and risks of the alternative treatment options in these special cases will be reviewed and the definitive therapy was described. In the patients treated, catheter fragmentation with localized thrombolysis resulted in short term improvements in graft function, but could not prevent later lung infarction in one case.

  2. [The transplantation of revascularized thyroid-trachea-lung complex: the experimental study].

    PubMed

    Parshin, V D; Zhidkov, I L; Bazarov, D V; Parshin, V V; Chernyĭ, S S

    2012-01-01

    The osteoplastic tracheobronchopathy affects the trachea, main, lobar and smaller bronchi, causing their stenosis. Nowadays the mainstay of the treatment of such patients is the cryodestruction, laser destruction and the endoscopic buginage of the trachea and bronchi. The palliative nature and low efficacy of these procedures forces to search new ways of treatment. The traditional lung transplantation or separate trachea and lung transplantation is inappropriate because of the complex affection of both trachea and bronchi. The experimental study aimed the possibility of thyreotracheolung revascularized donor complex transplantation.

  3. Normothermic ex vivo perfusion prevents lung injury compared to extended cold preservation for transplantation.

    PubMed

    Cypel, M; Rubacha, M; Yeung, J; Hirayama, S; Torbicki, K; Madonik, M; Fischer, S; Hwang, D; Pierre, A; Waddell, T K; de Perrot, M; Liu, M; Keshavjee, S

    2009-10-01

    Treatment of injured donor lungs ex vivo to accelerate organ recovery and ameliorate reperfusion injury could have a major impact in lung transplantation. We have recently demonstrated a feasible technique for prolonged (12 h) normothermic ex vivo lung perfusion (EVLP). This study was performed to examine the impact of prolonged EVLP on ischemic injury. Pig donor lungs were cold preserved in Perfadex for 12 h and subsequently divided into two groups: cold static preservation (CSP) or EVLP at 37 degrees C with Steen solution for a further 12 h (total 24 h preservation). Lungs were then transplanted and reperfused for 4 h. EVLP preservation resulted in significantly better lung oxygenation (PaO(2) 531 +/- 43 vs. 244 +/- 49 mmHg, p < 0.01) and lower edema formation rates after transplantation. Alveolar epithelial cell tight junction integrity, evaluated by zona occludens-1 protein staining, was disrupted in the cell membranes after prolonged CSP but not after EVLP. The maintenance of integrity of barrier function during EVLP translates into significant attenuation of reperfusion injury and improved graft performance after transplantation. Integrity of functional metabolic pathways during normothermic perfusion was confirmed by effective gene transfer and GFP protein synthesis by lung alveolar cells. In conclusion, EVLP prevents ongoing injury associated with prolonged ischemia and accelerates lung recovery. PMID:19663886

  4. Endobronchial mucosal blanching due to a post-lung transplantation pulmonary artery stenosis.

    PubMed

    Slebos, Dirk-Jan; Wolff, Rienhart F E; van der Bij, Wim

    2011-03-01

    A 45-year-old woman underwent a bronchoscopy shortly after lung transplantation. The airway mucosal appearance significantly differed between both lungs, with a pale aspect of the left bronchial tree. Computed tomography (CT) and perfusion scan confirmed a left pulmonary artery stenosis, improving with conservative treatment.

  5. Lung transplantation in an intensive care patient with pulmonary alveolar microlithiasis - a case report

    PubMed Central

    Güçyetmez, Bülent; Ogan, Aylin; Çimet Ayyıldız, Aylin; Yalçın Güder, Berrin; Klepetko, Walter

    2014-01-01

    Introduction: Pulmonary alveolar microlithiasis (PAM) is an autosomal recessive disease characterized by the deposition of phosphate and calcium in the alveoli. The disease progresses asymptomatically until later stages. When it becomes symptomatic, lung transplantations performed before the onset of right heart failure may improve life expectancy and quality. Here we present a case report concerning the very first Turkish PAM patient to have undergone lung transplantation surgery. Patient information: A 52 year-old female, Caucasian patient, already diagnosed with PAM in infancy, was admitted to the intensive care unit, diagnosed with pneumonia and hospitalized for 20 days. We decided to refer the patient to a specialized center for lung transplantation. Bilateral lung transplantation was performed in Vienna 14 months later and no recurrence was observed during the first postoperative year. Conclusion: Bilateral lung transplantation may improve both the life expectancy and the quality of life of PAM diagnosed patients with severe respiratory failure who do not suffer from right heart failure. The risk of recurrence should not be considered as a justifying reason to avoid transplantation as a treatment method. PMID:25165536

  6. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient

    PubMed Central

    Bahr, Nathan C.; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S.

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes. PMID:26697244

  7. Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient.

    PubMed

    Bahr, Nathan C; Janssen, Katherine; Billings, Joanne; Loor, Gabriel; Green, Jaime S

    2015-01-01

    Background. De novo and donor-derived invasive fungal infections (IFIs) contribute to morbidity and mortality in solid organ transplant (SOT) recipients. Reporting of donor-derived IFIs (DDIFIs) to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes.

  8. Autologous endothelial progenitor cells improve allograft survival in porcine lung transplantation with prolonged ischemia

    PubMed Central

    Yen, Yi-Ting; Roan, Jun-Neng; Fang, Shih-Yuan; Chang, Shi-Wei; Tseng, Yau-Lin

    2016-01-01

    Background As endothelial progenitor cells (EPCs) attenuated acute lung injury (ALI) in rabbit model, we hypothesized that autologous EPCs preserved lung graft function during the acute reperfusion period of lung transplantation and tested the therapeutic potential of EPCs in a porcine model of lung transplantation with prolonged graft ischemia. Methods Day-7 EPCs isolated from the recipient subjects or plain culture media were administered into the left pulmonary artery immediately before restoration of pulmonary blood flow in a porcine lung allotransplantation model, with the transplantation surgeons blinded to the content of injection. Hemodynamics and arterial blood gas were recorded, and the right pulmonary artery was occluded 30 min after reperfusion to evaluate the lung graft function. The lung grafts were sectioned for histological examination at the end of experiments. The total ischemic time for lung graft was approximately 14 h. Results All animals receiving plain medium died within 40 min after reperfusion, but 3 out of 5 (60%) piglets receiving EPCs survived up to 4 h after diversion of the entire cardiac output into the lung graft (P<0.01). The donor body weight, recipient body weight, cold ischemic time, and time for anastomosis were comparable between the EPC and control group (P=0.989, 0.822, 0.843, and 0.452, respectively). The mean aortic pressure decreased, and the cardiac output and mean pulmonary artery pressure elevated after right pulmonary artery occlusion. All these parameters were gradually compensated in the EPC group but decompensated in the control group. Better preservation of gas exchange function, reduced thrombi formation in the terminal pulmonary arterioles, and attenuated interstitial hemorrhage of the lung graft were observed in the EPC group. Conclusions We concluded autologous EPCs significantly enhanced the function of lung allograft and improved survival in a porcine model of lung transplantation with prolonged ischemia

  9. Lung transplantation in idiopathic pulmonary fibrosis: a systematic review of the literature

    PubMed Central

    2014-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is a distinct form of interstitial pneumonia with unknown origin and poor prognosis. Current pharmacologic treatments are limited and lung transplantation is a viable option for appropriate patients. The aim of this review was to summarize lung transplantation survival in IPF patients overall, between single (SLT) vs. bilateral lung transplantation (BLT), pre- and post Lung Allocation Score (LAS), and summarize wait-list survival. Methods A systematic review of English-language studies published in Medline or Embase between 1990 and 2013 was performed. Eligible studies were those of observational design reporting survival post-lung transplantation or while on the wait list among IPF patients. Results Median survival post-transplantation among IPF patients is estimated at 4.5 years. From ISHLT and OPTN data, one year survival ranged from 75% - 81%; 3-year: 59% - 64%; and 5-year: 47% - 53%. Post-transplant survival is lower for IPF vs. other underlying pre-transplant diagnoses. The proportion of IPF patients receiving BLT has steadily increased over the last decade and a half. Unadjusted analyses suggest improved long-term survival for BLT vs. SLT; after adjustment for patient characteristics, the differences tend to disappear. IPF patients account for the largest proportion of patients on the wait list and while wait list time has decreased, the number of transplants for IPF patients has increased over time. OPTN data show that wait list mortality is higher for IPF patients vs. other diagnoses. The proportion of IPF patients who died while awaiting transplantation ranged from 14% to 67%. While later transplant year was associated with increased survival, no significant differences were noted pre vs. post LAS implementation; however a high LAS vs low LAS was associated with decreased one-year survival. Conclusions IPF accounts for the largest proportion of patients awaiting lung transplants, and IPF is associated with

  10. FSGS Recurrence in Adults after Renal Transplantation

    PubMed Central

    Rudnicki, Michael

    2016-01-01

    Recurrence of focal segmental glomerulosclerosis (FSGS) in the allograft occurs in 30–50% of patients, and it is associated with poor renal allograft survival. Major risk factors for recurrence are younger age at diagnosis, rapid progression to end-stage renal disease, white race, and the loss of previous allografts due to recurrence. Recent data support the hypothesis that circulating permeability factors play a crucial role in podocyte injury and progression of FSGS. Due to lack of controlled trials, the management of recurrent FSGS is inconsistent and highly empirical. Prophylactic and perioperative treatment with plasmapheresis and high-dose (intravenous) cyclosporine represent the main cornerstones of immunosuppressive therapy. In recent years, therapy with rituximab has shown promising results. Despite evidence of activation of the renin-angiotensin system (RAS) in recurrent FSGS and its association with progression, only limited data exist on the renoprotective role of RAS blockade in this setting. Further well designed studies are needed on pathogenesis risk factors and therapeutical options in FSGS and its recurrence after transplantation. PMID:27144163

  11. Functional improvement in patients with idiopathic pulmonary fibrosis undergoing single lung transplantation *

    PubMed Central

    Rubin, Adalberto Sperb; Nascimento, Douglas Zaione; Sanchez, Letícia; Watte, Guilherme; Holand, Arthur Rodrigo Ronconi; Fassbind, Derrick Alexandre; Camargo, José Jesus

    2015-01-01

    Abstract Objective: To evaluate the changes in lung function in the first year after single lung transplantation in patients with idiopathic pulmonary fibrosis (IPF). Methods: We retrospectively evaluated patients with IPF who underwent single lung transplantation between January of 2006 and December of 2012, reviewing the changes in the lung function occurring during the first year after the procedure. Results: Of the 218 patients undergoing lung transplantation during the study period, 79 (36.2%) had IPF. Of those 79 patients, 24 (30%) died, and 11 (14%) did not undergo spirometry at the end of the first year. Of the 44 patients included in the study, 29 (66%) were men. The mean age of the patients was 57 years. Before transplantation, mean FVC, FEV1, and FEV1/FVC ratio were 1.78 L (50% of predicted), 1.48 L (52% of predicted), and 83%, respectively. In the first month after transplantation, there was a mean increase of 12% in FVC (400 mL) and FEV1 (350 mL). In the third month after transplantation, there were additional increases, of 5% (170 mL) in FVC and 1% (50 mL) in FEV1. At the end of the first year, the functional improvement persisted, with a mean gain of 19% (620 mL) in FVC and 16% (430 mL) in FEV1. Conclusions: Single lung transplantation in IPF patients who survive for at least one year provides significant and progressive benefits in lung function during the first year. This procedure is an important therapeutic alternative in the management of IPF. PMID:26398749

  12. Acute ischemic optic neuropathy with extended prone position ventilation in a lung transplant recipient.

    PubMed

    Panchabhai, Tanmay S; Bandyopadhyay, Debabrata; Kapoor, Aanchal; Akindipe, Olufemi; Lane, Charles; Krishnan, Sudhir

    2016-01-01

    Prone position ventilation (PPV) improves mortality in severe acute respiratory distress syndrome (ARDS), but outcomes following its use in lung transplant recipients are not known. We report the case of a 42-year-old Caucasian man who presented with severe ARDS from Bordetella pertussis, 5 years after bilateral sequential lung transplant for cystic fibrosis. He was managed with PPV for 22 days and had a prolonged ICU stay complicated by hypoxic ischemic optic neuropathy leading to blindness. Since his discharge from the ICU 6 months ago, his FEV1 has recovered to 47% predicted compared to his pre-ICU peak FEV1 of 85% predicted, suggesting recovery of lung function. This is the first report of optic nerve damage and vision loss in patients undergoing PPV. Our report also suggests that, in appropriately selected lung transplant recipients, severe hypoxemia could potentially be managed with prone ventilation. PMID:27051622

  13. Perioperative management of pulmonary hypertension during lung transplantation (a lesson for other anaesthesia settings).

    PubMed

    Rabanal, J M; Real, M I; Williams, M

    2014-10-01

    Patients with pulmonary hypertension are some of the most challenging for an anaesthesiologist to manage. Pulmonary hypertension in patients undergoing surgical procedures is associated with high morbidity and mortality due to right ventricular failure, arrhythmias and ischaemia leading to haemodynamic instability. Lung transplantation is the only therapeutic option for end-stage lung disease. Patients undergoing lung transplantation present a variety of challenges for anaesthesia team, but pulmonary hypertension remains the most important. The purpose of this article is to review the anaesthetic management of pulmonary hypertension during lung transplantation, with particular emphasis on the choice of anaesthesia, pulmonary vasodilator therapy, inotropic and vasopressor therapy, and the most recent intraoperative monitoring recommendations to optimize patient care.

  14. Perioperative management of pulmonary hypertension during lung transplantation (a lesson for other anaesthesia settings).

    PubMed

    Rabanal, J M; Real, M I; Williams, M

    2014-10-01

    Patients with pulmonary hypertension are some of the most challenging for an anaesthesiologist to manage. Pulmonary hypertension in patients undergoing surgical procedures is associated with high morbidity and mortality due to right ventricular failure, arrhythmias and ischaemia leading to haemodynamic instability. Lung transplantation is the only therapeutic option for end-stage lung disease. Patients undergoing lung transplantation present a variety of challenges for anaesthesia team, but pulmonary hypertension remains the most important. The purpose of this article is to review the anaesthetic management of pulmonary hypertension during lung transplantation, with particular emphasis on the choice of anaesthesia, pulmonary vasodilator therapy, inotropic and vasopressor therapy, and the most recent intraoperative monitoring recommendations to optimize patient care. PMID:25156939

  15. Association of Donor and Recipient Telomere Length with Clinical Outcomes following Lung Transplantation

    PubMed Central

    Courtwright, Andrew M.; Fried, Sabrina; Villalba, Julian A.; Moniodis, Anna; Guleria, Indira; Wood, Isabelle; Milford, Edgar; Mallidi, Hari H.; Hunninghake, Gary M.; Raby, Benjamin A.; Agarwal, Suneet; Camp, Philip C.; Rosas, Ivan O.; Goldberg, Hilary J.; El-Chemaly, Souheil

    2016-01-01

    Background Patients with short telomere syndromes and pulmonary fibrosis have increased complications after lung transplant. However, the more general impact of donor and recipient telomere length in lung transplant has not been well characterized. Methods This was an observational cohort study of patients who received lung transplant at a single center between January 1st 2012 and January 31st 2015. Relative donor lymphocyte telomere length was measured and classified into long (third tertile) and short (other tertiles). Relative recipient lung telomere length was measured and classified into short (first tertile) and long (other tertiles). Outcome data included survival, need for modification of immunosuppression, liver or kidney injury, cytomegalovirus reactivation, and acute rejection. Results Recipient lung tissue telomere lengths were measured for 54 of the 79 patients (68.3%) who underwent transplant during the study period. Donor lymphocyte telomeres were measured for 45 (83.3%) of these recipients. Neither long donor telomere length (hazard ratio [HR] = 0.58, 95% confidence interval [CI], 0.12–2.85, p = 0.50) nor short recipient telomere length (HR = 1.01, 95% CI = 0.50–2.05, p = 0.96) were associated with adjusted survival following lung transplant. Recipients with short telomeres were less likely to have acute cellular rejection (23.5% vs. 58.8%, p = 0.02) but were not more likely to have other organ dysfunction. Conclusions In this small cohort, neither long donor lymphocyte telomeres nor short recipient lung tissue telomeres were associated with adjusted survival after lung transplantation. Larger studies are needed to confirm these findings. PMID:27589328

  16. The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients

    SciTech Connect

    Higenbottam, T.; Jackson, M.; Woolman, P.; Lowry, R.; Wallwork, J.

    1989-07-01

    As a result of clinical heart-lung transplantation, the lungs are denervated below the level of the tracheal anastomosis. It has been questioned whether afferent vagal reinnervation occurs after surgery. Here we report the cough frequency, during inhalation of ultrasonically nebulized distilled water, of 15 heart-lung transplant patients studied 6 wk to 36 months after surgery. They were compared with 15 normal subjects of a similar age and sex. The distribution of the aerosol was studied in five normal subjects using /sup 99m/technetium diethylene triamine pentaacetate (/sup 99m/Tc-DTPA) in saline. In seven patients, the sensitivity of the laryngeal mucosa to instilled distilled water (0.2 ml) was tested at the time of fiberoptic bronchoscopy by recording the cough response. Ten percent of the aerosol was deposited onto the larynx and trachea, 56% on the central airways, and 34% in the periphery of the lung. The cough response to the aerosol was strikingly diminished in the patients compared with normal subjects (p less than 0.001), but all seven patients coughed when distilled water was instilled onto the larynx. As expected, the laryngeal mucosa of heart-lung transplant patients remains sensitive to distilled water. However, the diminished coughing when the distilled water is distributed by aerosol to the central airways supports the view that vagal afferent nerves do not reinnervate the lungs after heart-lung transplantation, up to 36 months after surgery.

  17. Risk factors for fracture in adult kidney transplant recipients

    PubMed Central

    Naylor, Kyla L; Zou, Guangyong; Leslie, William D; Hodsman, Anthony B; Lam, Ngan N; McArthur, Eric; Fraser, Lisa-Ann; Knoll, Gregory A; Adachi, Jonathan D; Kim, S Joseph; Garg, Amit X

    2016-01-01

    AIM: To determine the general and transplant-specific risk factors for fractures in kidney transplant recipients. METHODS: We conducted a cohort study of all adults who received a kidney-only transplant (n = 2723) in Ontario, Canada between 2002 and 2009. We used multivariable Cox proportional hazards regression to determine general and transplant-specific risk factors for major fractures (proximal humerus, forearm, hip, and clinical vertebral). The final model was established using the backward elimination strategy, selecting risk factors with a P-value ≤ 0.2 and forcing recipient age and sex into the model. We also assessed risk factors for other fracture locations (excluding major fractures, and fractures involving the skull, hands or feet). RESULTS: There were 132 major fractures in the follow-up (8.1 fractures per 1000 person-years). General risk factors associated with a greater risk of major fracture were older recipient age [adjusted hazard ratio (aHR) per 5-year increase 1.11, 95%CI: 1.03-1.19] and female sex (aHR = 1.81, 95%CI: 1.28-2.57). Transplant-specific risk factors associated with a greater risk of fracture included older donor age (5-year increase) (aHR = 1.09, 95%CI: 1.02-1.17) and end-stage renal disease (ESRD) caused by diabetes (aHR = 1.72, 95%CI: 1.09-2.72) or cystic kidney disease (aHR = 1.73, 95%CI: 1.08-2.78) (compared to glomerulonephritis as the reference cause). Risk factors across the two fracture locations were not consistent (major fracture locations vs other). Specifically, general risk factors associated with an increased risk of other fractures were diabetes and a fall with hospitalization prior to transplantation, while length of time on dialysis, and renal vascular disease and other causes of ESRD were the transplant-specific risk factors associated with a greater risk of other fractures. CONCLUSION: Both general and transplant-specific risk factors were associated with a higher risk of fractures in kidney transplant

  18. Starting a lung transplant program: a roadmap for long-term excellence.

    PubMed

    Klesney-Tait, Julia; Eberlein, Michael; Geist, Lois; Keech, John; Zabner, Joseph; Gruber, Peter J; Iannettoni, Mark D; Parekh, Kalpaj

    2015-05-01

    Lung transplantation is an effective therapy for many patients with end-stage lung disease. Few centers across the United States offer this therapy, as a successful lung transplant program requires significant institutional resources and specialized personnel. Analysis of the United Network of Organ Sharing database reveals that the failure rate of new programs exceeds 40%. These data suggest that an accurate assessment of program viability as well as a strategy to continuously assess defined quality measures is needed. As part of strategic planning, regional availability of recipient and donors should be assessed. Additionally, analysis of institutional expertise at the physician, support staff, financial, and administrative levels is necessary. In May of 2007, we started a new lung transplant program at the University of Iowa Hospitals and Clinics and have performed 101 transplants with an average recipient 1-year survival of 91%, placing our program among the top in the country for the past 5 years. Herein, we review internal and external factors that impact the viability of a new lung transplant program. We discuss the use of four prospectively identified quality measures: volume, recipient outcomes, financial solvency, and academic contribution as one approach to achieve programmatic excellence. PMID:25940255

  19. High Emergency Lung Transplantation: dramatic decrease of waiting list death rate without relevant higher post-transplant mortality.

    PubMed

    Roux, Antoine; Beaumont-Azuar, Laurence; Hamid, Abdul Monem; De Miranda, Sandra; Grenet, Dominique; Briend, Guillaume; Bonnette, Pierre; Puyo, Philippe; Parquin, François; Devaquet, Jerome; Trebbia, Gregoire; Cuquemelle, Elise; Douvry, Benoit; Picard, Clément; Le Guen, Morgan; Chapelier, Alain; Stern, Marc; Sage, Edouard

    2015-09-01

    Many candidates for lung transplantation (LT) die on the waiting list, raising the question of graft availability and strategy for organ allocation. We report the experience of the new organ allocation program, "High Emergency Lung Transplantation" (HELT), since its implementation in our center in 2007. Retrospective analysis of 201 lung transplant patients, of whom 37 received HELT from 1st July 2007 to 31th May 2012. HELT candidates had a higher impairment grade on respiratory status and higher Lung Allocation Score (LAS). HELT patients had increased incidence of perioperative complications (e.g., perioperative bleeding) and extracorporeal circulatory assistance (75% vs. 36.6%, P = 0.0005). No significant difference was observed between HELT and non-HELT patients in mechanical ventilation duration (15.5 days vs. 11 days, P = 0.27), intensive care unit length of stay (15 days vs. 10 days, P = 0.22) or survival rate at 12 (81% vs. 80%), and 24 months post-LT (72.9% vs. 75.0%). Lastly, mortality on the waiting list was spectacularly reduced from 19% to 2% when compared to the non-HELT 2004-2007 group. Despite a more severe clinical status of patients on the waiting list, HELT provided similar results to conventional LT. These results were associated with a dramatic reduction in the mortality rate of patients on the waiting list.

  20. CNE article: pain after lung transplant: high-frequency chest wall oscillation vs chest physiotherapy.

    PubMed

    Esguerra-Gonzalez, Angeli; Ilagan-Honorio, Monina; Fraschilla, Stephanie; Kehoe, Priscilla; Lee, Ai Jin; Marcarian, Taline; Mayol-Ngo, Kristina; Miller, Pamela S; Onga, Jay; Rodman, Betty; Ross, David; Sommer, Susan; Takayanagi, Sumiko; Toyama, Joy; Villamor, Filma; Weigt, S Samuel; Gawlinski, Anna

    2013-03-01

    Background Chest physiotherapy and high-frequency chest wall oscillation (HFCWO) are routinely used after lung transplant to facilitate removal of secretions. To date, no studies have been done to investigate which therapy is more comfortable and preferred by lung transplant recipients. Patients who have less pain may mobilize secretions, heal, and recover faster. Objectives To compare effects of HFCWO versus chest physiotherapy on pain and preference in lung transplant recipients. Methods In a 2-group experimental, repeated-measures design, 45 lung transplant recipients (27 single lung, 18 bilateral) were randomized to chest physiotherapy (10 AM, 2 PM) followed by HFCWO (6 PM, 10 PM; group 1, n=22) or vice versa (group 2, n=23) on postoperative day 3. A verbal numeric rating scale was used to measure pain before and after treatment. At the end of the treatment sequence, a 4-item patient survey was administered to assess treatment preference, pain, and effectiveness. Data were analyzed with χ(2) and t tests and repeated-measures analysis of variance. Results A significant interaction was found between mean difference in pain scores from before to after treatment and treatment method; pain scores decreased more when HFCWO was done at 10 AM and 6 PM (P =.04). Bilateral transplant recipients showed a significant preference for HFCWO over chest physiotherapy (11 [85%] vs 2 [15%], P=.01). However, single lung recipients showed no significant difference in preference between the 2 treatments (11 [42%] vs 14 [54%]). Conclusions HFCWO seems to provide greater decreases in pain scores than does chest physiotherapy. Bilateral lung transplant recipients preferred HFCWO to chest physiotherapy. HFCWO may be an effective, feasible alternative to chest physiotherapy. (American Journal of Critical Care. 2013;22:115-125).

  1. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    PubMed

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10(-5)) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program. PMID:25637051

  2. T-cell-replete haploidentical transplantation versus autologous stem cell transplantation in adult acute leukemia: a matched pair analysis.

    PubMed

    Gorin, Norbert-Claude; Labopin, Myriam; Piemontese, Simona; Arcese, William; Santarone, Stella; Huang, He; Meloni, Giovanna; Ferrara, Felicetto; Beelen, Dietrich; Sanz, Miguel; Bacigalupo, Andrea; Ciceri, Fabio; Mailhol, Audrey; Nagler, Arnon; Mohty, Mohamad

    2015-04-01

    Adult patients with acute leukemia in need of a transplant but without a genoidentical donor are usually considered upfront for transplantation with stem cells from any other allogeneic source, rather than autologous stem cell transplantation. We used data from the European Society for Blood and Marrow Transplantation and performed a matched pair analysis on 188 T-cell-replete haploidentical and 356 autologous transplants done from January 2007 to December 2012, using age, diagnosis, disease status, cytogenetics, and interval from diagnosis to transplant as matching factors. "Haploidentical expert" centers were defined as having reported more than five haploidentical transplants for acute leukemia (median value for the study period). The median follow-up was 28 months. Multivariate analyses, including type of transplant categorized into three classes ("haploidentical regular", "haploidentical expert" and autologous), conditioning intensity (reduced intensity versus myeloablative conditioning) and the random effect taking into account associations related to matching, showed that non-relapse mortality was higher following haploidentical transplants in expert (HR: 4.7; P=0.00004) and regular (HR: 8.98; P<10(-5)) centers. Relapse incidence for haploidentical transplants was lower in expert centers (HR:0.39; P=0.0003) but in regular centers was similar to that for autologous transplants. Leukemia-free survival and overall survival rates were higher following autologous transplantation than haploidentical transplants in regular centers (HR: 1.63; P=0.008 and HR: 2.31; P=0.0002 respectively) but similar to those following haploidentical transplants in expert centers. We conclude that autologous stem cell transplantation should presently be considered as a possible alternative to haploidentical transplantation in regular centers that have not developed a specific expert program.

  3. Uncontrolled Donation After Circulatory Determination of Death Donors (uDCDDs) as a Source of Lungs for Transplant.

    PubMed

    Egan, T M; Requard, J J

    2015-08-01

    In April 2014, the American Journal of Transplantation published a report on the first lung transplant in the United States recovered from an uncontrolled donation after circulatory determination of death donor (uDCDD), assessed by ex vivo lung perfusion (EVLP). The article identified logistical and ethical issues related to introduction of lung transplant from uDCDDs. In an open clinical trial, we have Food and Drug Administration and Institutional Review Board approval to transplant lungs recovered from uDCDDs judged suitable after EVLP. Through this project and other experiences with lung recovery from uDCDDs, we have identified solutions to many logistical challenges and have addressed ethical issues surrounding lung transplant from uDCDDs that were mentioned in this case report. Here, we discuss those challenges, including issues related to recovery of other solid organs from uDCDDs. Despite logistical challenges, uDCDDs could solve the critical shortage of lungs for transplant. Furthermore, by avoiding the deleterious impact of brain death and days of positive pressure ventilation, and by using opportunities to treat lungs in the decedent or during EVLP, lungs recovered from uDCDDs may ultimately prove to be better than lungs currently being transplanted from conventional brain-dead organ donors. PMID:25873272

  4. Lung transplantation with donation after circulatory determination of death donors and the impact of ex vivo lung perfusion.

    PubMed

    Machuca, T N; Mercier, O; Collaud, S; Tikkanen, J; Krueger, T; Yeung, J C; Chen, M; Azad, S; Singer, L; Yasufuku, K; de Perrot, M; Pierre, A; Waddell, T K; Keshavjee, S; Cypel, M

    2015-04-01

    The growing demand for suitable lungs for transplantation drives the quest for alternative strategies to expand the donor pool. The aim of this study is to evaluate the outcomes of lung transplantation (LTx) with donation after circulatory determination of death (DCDD) and the impact of selective ex vivo lung perfusion (EVLP). From 2007 to 2013, 673 LTx were performed, with 62 (9.2%) of them using DCDDs (seven bridged cases). Cases bridged with mechanical ventilation/extracorporeal life support were excluded. From 55 DCDDs, 28 (51%) underwent EVLP. Outcomes for LTx using DCDDs and donation after neurological determination of death (DNDD) donors were similar, with 1 and 5-year survivals of 85% and 54% versus 86% and 62%, respectively (p = 0.43). Although comparison of survival curves between DCDD + EVLP versus DCDD-no EVLP showed no significant difference, DCDD + EVLP cases presented shorter hospital stay (median 18 vs. 23 days, p = 0.047) and a trend toward shorter length of mechanical ventilation (2 vs. 3 days, p = 0.059). DCDDs represent a valuable source of lungs for transplantation, providing similar results to DNDDs. EVLP seems an important technique in the armamentarium to safely increase lung utilization from DCDDs; however, further studies are necessary to better define the role of EVLP in this context. PMID:25772069

  5. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation.

    PubMed

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-06-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca' Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2 /FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2 /FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40-84] vs. 39 [36-46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953).

  6. Ex vivo lung perfusion to improve donor lung function and increase the number of organs available for transplantation

    PubMed Central

    Valenza, Franco; Rosso, Lorenzo; Coppola, Silvia; Froio, Sara; Palleschi, Alessandro; Tosi, Davide; Mendogni, Paolo; Salice, Valentina; Ruggeri, Giulia M; Fumagalli, Jacopo; Villa, Alessandro; Nosotti, Mario; Santambrogio, Luigi; Gattinoni, Luciano

    2014-01-01

    This paper describes the initial clinical experience of ex vivo lung perfusion (EVLP) at the Fondazione Ca’ Granda in Milan between January 2011 and May 2013. EVLP was considered if donor PaO2/FiO2 was below 300 mmHg or if lung function was doubtful. Donors with massive lung contusion, aspiration, purulent secretions, pneumonia, or sepsis were excluded. EVLP was run with a low-flow, open atrium and low hematocrit technique. Thirty-five lung transplants from brain death donors were performed, seven of which after EVLP. EVLP donors were older (54 ± 9 years vs. 40 ± 15 years, EVLP versus Standard, P < 0.05), had lower PaO2/FiO2 (264 ± 78 mmHg vs. 453 ± 119 mmHg, P < 0.05), and more chest X-ray abnormalities (P < 0.05). EVLP recipients were more often admitted to intensive care unit as urgent cases (57% vs. 18%, P = 0.05); lung allocation score at transplantation was higher (79 [40–84] vs. 39 [36–46], P < 0.05). After transplantation, primary graft dysfunction (PGD72 grade 3, 32% vs. 28%, EVLP versus Standard, P = 1), mortality at 30 days (0% vs. 0%, P = 1), and overall survival (71% vs. 86%, EVLP versus Standard P = 0.27) were not different between groups. EVLP enabled a 20% increase in available donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). PMID:24628890

  7. Anastomotic Airway Complications After Lung Transplant: Clinical, Bronchoscopic and CT Correlation.

    PubMed

    Luecke, Kyle; Trujillo, Camilo; Ford, Jonathan; Decker, Summer; Pelaez, Andres; Hazelton, Todd R; Rojas, Carlos A

    2016-09-01

    The purpose of this article is to review the normal appearance and common complications of the airway anastomosis in lung transplant patients with emphasis on computed tomography images with bronchoscopic correlation. The spectrum of complications will be presented as early (<1 mo after transplant) or late (>1 mo). Variations in surgical technique as well as presentation and management options for airway complications will also be discussed. PMID:27428022

  8. Treatment of bronchus intermedius stenosis in lung transplantation with Montgomery T-tube stent. A novel technique.

    PubMed

    Pinillos Robles, Javier; García Luján, Ricardo; de Pablo Gafas, Alicia; de Miguel Poch, Eduardo

    2015-02-01

    Airway complications after lung transplant are relatively common although the rates vary according to the different studies. Pathogenesis is diverse but the principal mechanism is usually bronchus intermedius ischemia in the post-transplant period. One major complication is bronchial stenosis, with relatively frequent involvement of the bronchus intermedius in the case of right lung transplantation. Various treatments have been proposed for bronchus intermedius stenosis, such as endobronchial balloon dilation, laser, cryosurgery and bronchial stents. We present two cases of lung transplant recipients with bronchus intermedius stenosis treated with a Montgomery stent or T-stent, commonly used for tracheal stenosis, who showed positive clinical and functional response.

  9. The "baby lung" became an adult.

    PubMed

    Gattinoni, Luciano; Marini, John J; Pesenti, Antonio; Quintel, Michael; Mancebo, Jordi; Brochard, Laurent

    2016-05-01

    The baby lung was originally defined as the fraction of lung parenchyma that, in acute respiratory distress syndrome (ARDS), still maintains normal inflation. Its size obviously depends on ARDS severity and relates to the compliance of the respiratory system. CO2 clearance and blood oxygenation primarily occur within the baby lung. While the specific compliance suggests the intrinsic mechanical characteristics to be nearly normal, evidence from positron emission tomography suggests that at least a part of the well-aerated baby lung is inflamed. The baby lung is more a functional concept than an anatomical one; in fact, in the prone position, the baby lung "shifts" from the ventral lung regions toward the dorsal lung regions while usually increasing its size. This change is associated with better gas exchange, more homogeneously distributed trans-pulmonary forces, and a survival advantage. Positive end expiratory pressure also increases the baby lung size, both allowing better inflation of already open units and adding new pulmonary units. Viewed as surrogates of stress and strain, tidal volume and plateau pressures are better tailored to baby lung size than to ideal body weight. Although less information is available for the baby lung during spontaneous breathing efforts, the general principles regulating the safety of ventilation are also applicable under these conditions. PMID:26781952

  10. Pleuroparenchymal fibroelastosis: the prevalence of secondary forms in hematopoietic stem cell and lung transplantation recipients

    PubMed Central

    Mariani, Francesca; Gatti, Beatrice; Rocca, Alberto; Bonifazi, Francesca; Cavazza, Alberto; Fanti, Stefano; Tomassetti, Sara; Piciucchi, Sara; Poletti, Venerino; Zompatori, Maurizio

    2016-01-01

    PURPOSE Pleuroparenchymal fibroelastosis (PPFE) is a rare form of interstitial pneumonia, characterized by elastotic fibrosis involving the pleura and subpleural parenchyma, predominantly in the upper lobes. PPFE can be either idiopathic or secondary and mostly occurs as a late complication of lung or hematopoietic stem cell transplantation (HSCT). The aim of this study was to evaluate the prevalence of secondary forms in transplant recipients. METHODS An expert thoracic radiologist retrospectively reviewed high-resolution computed tomography exams of 700 HSCT recipients and 53 lung transplant recipients from the database of the Radiology Department of S. Orsola-Malpighi Hospital dating back from 2007. For each case that radiologically fulfilled PPFE criteria, the following details were retrieved: clinical characteristics, laboratory and functional data, pathologic findings (obtained from one patient) and metabolic data (obtained from three patients). RESULTS Six cases clinically and radiologically consistent with PPFE were identified: two HSCT recipients (0.28%) and four lung transplant recipients (7.54%). CONCLUSION In this study, PPFE was strongly associated with lung transplants as a late complication, with a prevalence of 7.54%. PMID:27460284

  11. Lung transplant for a patient with cystic fibrosis and active Burkholderia Cenocepacia pneumonia.

    PubMed

    Salizzoni, Stefano; Pilewski, Joseph; Toyoda, Yoshiya

    2014-10-01

    Lung transplant for cystic fibrosis has been considered contraindicated in patients who have Burkholderia Cenocepacia infection. A 24-year-old white woman who had cystic fibrosis presented with respiratory failure caused by B. Cenocepacia pneumonia. She was treated with broad-spectrum antibiotics and a double-lung transplant. The chest cavity and both bronchi were irrigated with 0.5% povidone-iodine solution. For immunosuppression, she received induction therapy with alemtuzumab (15 mg) and methylprednisolone and maintenance therapy with tacrolimus, mycophenolate mofetil, and prednisone (5 mg daily). Postoperative antibiotics included intravenous meropenem for 3 weeks; vancomycin for 10 days; and inhaled ceftazidime, oral trimethoprim-sulfamethoxazole, and doxycycline for several months. Follow-up at 25 months after transplant showed that chest radiographs were clear and lung function was normal. At 6 years after transplant, she was working full time and had no recurrence of infection from B. Cenocepacia. This case suggests that patients who have cystic fibrosis and active B. Cenocepacia pneumonia may be successfully treated with a lung transplant. PMID:25299375

  12. Lung function after allogeneic bone marrow transplantation for leukaemia or lymphoma.

    PubMed

    Nysom, K; Holm, K; Hesse, B; Ulrik, C S; Jacobsen, N; Bisgaard, H; Hertz, H

    1996-05-01

    Longitudinal data were analysed on the lung function of 25 of 29 survivors of childhood leukaemia or lymphoma, who had been conditioned with cyclophosphamide and total body irradiation before allogeneic bone marrow transplantation, to test whether children are particularly vulnerable to pulmonary damage after transplantation. None developed chronic graft-versus-host disease. Transfer factor and lung volumes were reduced immediately after bone marrow transplantation, but increased during the following years. However, at the last follow up, 4-13 years (median 8) after transplantation, patients had significantly reduced transfer factor, total lung capacity, and forced vital capacity (-1.0, -1.2, and -0.8 SD score, respectively), and increased ratio of forced expiratory volume in one second to forced vital capacity (+0.9 SD score). None of the patients had pulmonary symptoms, and changes were unrelated to their age at bone marrow transplantation. In conclusion, patients had subclinical restrictive pulmonary disease at a median of eight years after total body irradiation and allogeneic bone marrow transplantation.

  13. Respiratory syncytial virus pneumonia in a lung transplant recipient: case report.

    PubMed

    Doud, J R; Hinkamp, T; Garrity, E R

    1992-01-01

    A 29-year-old man underwent bilateral lung transplantation and received maintenance immunosuppressive therapy. He was readmitted 11 months later with symptoms of cough, sneezing, and rhinorrhea. The physical examination was normal. Laboratory results were significant for a reduction of FEV1 and an interstitial infiltrate on chest films. The patient had recently undergone bronchoscopy for rejection surveillance, and 2 days before admission the bronchoalveolar lavage cultures returned positive for respiratory syncytial virus. The patient was treated with aerosolized ribavirin with complete resolution of symptoms. Respiratory syncytial virus must now be included in the list of pathogens causing pneumonia in the lung transplant recipient. PMID:1540615

  14. Medication-induced periostitis in lung transplant patients: periostitis deformans revisited.

    PubMed

    Chen, Lina; Mulligan, Michael E

    2011-02-01

    We report five cases of diffuse periostitis resembling hypertrophic osteoarthropathy and perostitis deformans in lung transplantation patients on chronic voriconazole, a fluoride-containing compound. Although drug-related periostitis has long been known, the association of lung transplant medication with periostitis was only recently introduced in the literature. To our knowledge, imaging findings have not been fully characterized in the radiology literature. Imaging features along with clinical history help to distinguish this benign condition from other disease entities. In this article, we review the current literature and illustrate the variety of imaging characteristics of this entity so that interpreting radiologists can make accurate diagnoses and avoid unnecessary work up.

  15. Cytokine levels in pleural fluid as markers of acute rejection after lung transplantation*

    PubMed Central

    de Camargo, Priscila Cilene León Bueno; Afonso, José Eduardo; Samano, Marcos Naoyuki; Acencio, Milena Marques Pagliarelli; Antonangelo, Leila; Teixeira, Ricardo Henrique de Oliveira Braga

    2014-01-01

    Our objective was to determine the levels of lactate dehydrogenase, IL-6, IL-8, and VEGF, as well as the total and differential cell counts, in the pleural fluid of lung transplant recipients, correlating those levels with the occurrence and severity of rejection. We analyzed pleural fluid samples collected from 18 patients at various time points (up to postoperative day 4). The levels of IL-6, IL-8, and VEGF tended to elevate in parallel with increases in the severity of rejection. Our results suggest that these levels are markers of acute graft rejection in lung transplant recipients. PMID:25210966

  16. Use of CT densitometry to predict lung toxicity in bone marrow transplant patients

    SciTech Connect

    el-Khatib, E.E.; Freeman, C.R.; Rybka, W.B.; Lehnert, S.; Podgorsak, E.B.

    1989-01-01

    Total body irradiation (TBI) is considered an integral part of the preparation of patients with hematological malignancies for marrow transplantation. One of the major causes of death following bone marrow transplantation is interstitial pneumonia. Its pathogenesis is complex but radiation may play a major role in its development. Computed tomography (CT) has been used in animal and human studies as a sensitive non-invasive method for detecting changes in the lung following radiotherapy. In the present study CT scans are studied before and up to 1 year after TBI. Average lung densities measured before TBI showed large variations among the individual patients. On follow-up scans, lung density decreases were measured for patients who did not develop lung complications. Significant lung density increases were measured in patients who subsequently had lung complications. These lung density increases were observed prior to the onset of respiratory complications and could be correlated with the clinical course of the patients, suggesting the possibility for the usage of CT lung densitometry to predict lung complications before the onset of clinical symptoms.

  17. Multifocal periostitis as a complication of chronic use of voriconazole in a lung transplant recipient.

    PubMed

    Tedja, R; El-Sherief, A; Olbrych, T; Gordon, S

    2013-08-01

    Fungal infections are common in solid organ transplantation. An increasing number of transplant recipients receive antifungal therapy for prolonged duration owing to invasive fungal infections. Herein, we describe a diagnosis of periostitis as a complication of chronic use of voriconazole in a lung transplant recipient. The patient was diagnosed with probable pulmonary aspergillosis and was treated with oral voriconazole for a total of 9 months. Evidence of multifocal periostitis was observed in the axial and appendicular skeleton. Early recognition of this phenomenon is important to prevent unnecessary tests and procedures. Prompt discontinuation of voriconazole should result in improvement of symptoms.

  18. Transfer of peanut allergy from the donor to a lung transplant recipient.

    PubMed

    Khalid, Imran; Zoratti, Edward; Stagner, Lisa; Betensley, Alan D; Nemeh, Hasan; Allenspach, Lisa

    2008-10-01

    Among solid organs, transfer of peanut allergy from donor to recipient has been implicated after liver transplantation. We report the first case in which such transfer occurred after a lung transplant. A 42-year-old woman with history of sarcoidosis underwent a successful bilateral lung transplant from a donor who died from anaphylactic shock after eating peanut-related food. Seven months later, she ate a peanut butter cookie at a transplant support group meeting. Immediately thereafter, she developed an anaphylactic reaction, but survived with prompt treatment. During subsequent follow-up, she could recall three prior episodes of wheezing and difficulty breathing after eating peanut-related foods. The first episode occurred 4 days after the transplant. Prior to her transplant, she never had problems eating peanuts. Skin-prick testing confirmed peanut sensitization. She avoided peanuts and, although her skin-prick test became negative, she still manifested peanut allergy when formally challenged orally with the food. She was advised to continue abstaining from all peanut-related foods. This case emphasizes the importance of considering donor allergy transfer when caring for all solid-organ transplant recipients in order to avoid a life-threatening event.

  19. Single-lung transplantation in emphysema: Retrospective study analyzing survival and waiting list mortality

    PubMed Central

    Borro, José M; Delgado, María; Coll, Elisabeth; Pita, Salvador

    2016-01-01

    AIM: To performed remains a subject of debate and is the principal aim of the study. METHODS: This retrospective analysis included 73 patients with emphysema (2000-2012). The outcomes of patients undergoing single-lung transplantation (SL) (n = 40) or double-lung transplant (DL) (n = 33) were compared in a Cox multivariate analysis to study the impact of the technique, postoperative complications and acute and chronic rejection on survival rates. Patients were selected for inclusion in the waiting list according to the International Society of Heart Lung Transplantation criteria. Pre and postoperative rehabilitation and prophylaxis, surgical technique and immunosuppressive treatment were similar in every patients. Lung transplantation waiting list information on a national level and retrospective data on emphysema patient survival transplanted in Spain during the study period, was obtained from the lung transplantation registry managed by the National Transplant Organization (ONT). RESULTS: Both groups were comparable in terms of gender and clinical characteristics. We found significant differences in the mean age between the groups, the DL patients being younger as expected from the inclusion criteria. Perioperative complications occurred in 27.6% SL vs 54% DL (P = 0.032). Excluding perioperative mortality, median survival was 65.3 mo for SL and 59.4 mo for DL (P = 0.96). Bronchiolitis obliterans and overall 5-year survival were similar in both groups. Bacterial respiratory infection, cytomegalovirus and fungal infection rates were higher but not significant in SL. No differences were found between type of transplant and survival (P = 0.48). To support our results, national data on all patients with emphysema in waiting list were obtained (n = 1001). Mortality on the waiting list was 2.4% for SL vs 6.2% for DL. There was no difference in 5 year survival between 235 SL and 430 DL patients transplanted (P = 0.875). CONCLUSION: Our results suggest that SL

  20. Refractory Pulmonary Edema Caused by Late Pulmonary Vein Thrombosis After Lung Transplantation: A Rare Adverse Event.

    PubMed

    Denton, Eve J; Rischin, Adam; McGiffin, David; Williams, Trevor J; Paraskeva, Miranda A; Westall, Glen P; Snell, Greg

    2016-09-01

    After lung transplantation, pulmonary vein thrombosis is a rare, potentially life-threatening adverse event arising at the pulmonary venous anastomosis that typically occurs early and presents as graft failure and hemodynamic compromise with an associated mortality of up to 40%. The incidence, presentation, outcomes, and treatment of late pulmonary vein thrombosis remain poorly defined. Management options include anticoagulant agents for asymptomatic clots, and thrombolytic agents or surgical thrombectomy for hemodynamically significant clots. We present a rare case highlighting a delayed presentation of pulmonary vein thrombosis occurring longer than 2 weeks after lung transplantation and manifesting clinically as graft failure secondary to refractory pulmonary edema. The patient was treated successfully with surgical thrombectomy and remains well. We recommend a high index of suspicion of pulmonary vein thrombosis when graft failure after lung transplantation occurs and is not responsive to conventional therapy, and consideration of investigation with transesophageal echocardiography or computed tomography with venous phase contrast in such patients even more than 2 weeks after lung transplantation.

  1. The Nitric Oxide/Cyclic GMP Pathway in Organ Transplantation: Critical Role in Successful Lung Preservation

    NASA Astrophysics Data System (ADS)

    Pinsky, David J.; Naka, Yoshifumi; Chowdhury, Nepal C.; Liao, Hui; Oz, Mehmet C.; Michler, Robert E.; Kubaszewski, Eugeniusz; Malinski, Tadeusz; Stern, David M.

    1994-12-01

    Reestablishment of vascular homeostasis following ex vivo preservation is a critical determinant of successful organ transplantation. Because the nitric oxide (NO) pathway modulates pulmonary vascular tone and leukocyte/endothelial interactions, we hypothesized that reactive oxygen intermediates would lead to decreased NO (and hence cGMP) levels following pulmonary reperfusion, leading to increased pulmonary vascular resistance and leukostasis. Using an orthotopic rat model of lung transplantation, a porphyrinic microsensor was used to make direct in vivo measurements of pulmonary NO. NO levels measured at the surface of the transplanted lung plummeted immediately upon reperfusion, with levels moderately increased by topical application of superoxide dismutase. Because cGMP levels declined in preserved lungs after reperfusion, this led us to buttress the NO pathway by adding a membrane-permeant cGMP analog to the preservation solution. Compared with grafts stored in its absence, grafts stored with supplemental 8-Br-cGMP and evaluated 30 min after reperfusion demonstrated lower pulmonary vascular resistances with increased graft blood flow, improved arterial oxygenation, decreased neutrophil infiltration, and improved recipient survival. These beneficial effects were dose dependent, mimicked by the type V phosphodiesterase inhibitor 2-o-propoxyphenyl-8-azapurin-6-one, and inhibited by a cGMP-dependent protein kinase antagonist, the R isomer of 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate. Augmenting the NO pathway at the level of cGMP improves graft function and recipient survival following lung transplantation.

  2. Fractal circuit sensors enable rapid quantification of biomarkers for donor lung assessment for transplantation.

    PubMed

    Sage, Andrew T; Besant, Justin D; Mahmoudian, Laili; Poudineh, Mahla; Bai, Xiaohui; Zamel, Ricardo; Hsin, Michael; Sargent, Edward H; Cypel, Marcelo; Liu, Mingyao; Keshavjee, Shaf; Kelley, Shana O

    2015-08-01

    Biomarker profiling is being rapidly incorporated in many areas of modern medical practice to improve the precision of clinical decision-making. This potential improvement, however, has not been transferred to the practice of organ assessment and transplantation because previously developed gene-profiling techniques require an extended period of time to perform, making them unsuitable in the time-sensitive organ assessment process. We sought to develop a novel class of chip-based sensors that would enable rapid analysis of tissue levels of preimplantation mRNA markers that correlate with the development of primary graft dysfunction (PGD) in recipients after transplant. Using fractal circuit sensors (FraCS), three-dimensional metal structures with large surface areas, we were able to rapidly (<20 min) and reproducibly quantify small differences in the expression of interleukin-6 (IL-6), IL-10, and ATP11B mRNA in donor lung biopsies. A proof-of-concept study using 52 human donor lungs was performed to develop a model that was used to predict, with excellent sensitivity (74%) and specificity (91%), the incidence of PGD for a donor lung. Thus, the FraCS-based approach delivers a key predictive value test that could be applied to enhance transplant patient outcomes. This work provides an important step toward bringing rapid diagnostic mRNA profiling to clinical application in lung transplantation. PMID:26601233

  3. Invasive Fungal Sinusitis Caused by Scytalidium dimidiatum in a Lung Transplant Recipient

    PubMed Central

    Dunn, James J.; Wolfe, Michael J.; Trachtenberg, Joel; Kriesel, John D.; Orlandi, Richard R.; Carroll, Karen C.

    2003-01-01

    We describe a case of invasive fungal sinusitis caused by Scytalidium dimidiatum in a lung transplant recipient. Treatment was complicated by renal failure with amphotericin B therapies. Following 6 months of voriconazole treatment, the patient remained radiographically and clinically stable for a short time before dying of respiratory failure precipitated by graft rejection. PMID:14662991

  4. Fractal circuit sensors enable rapid quantification of biomarkers for donor lung assessment for transplantation

    PubMed Central

    Sage, Andrew T.; Besant, Justin D.; Mahmoudian, Laili; Poudineh, Mahla; Bai, Xiaohui; Zamel, Ricardo; Hsin, Michael; Sargent, Edward H.; Cypel, Marcelo; Liu, Mingyao; Keshavjee, Shaf; Kelley, Shana O.

    2015-01-01

    Biomarker profiling is being rapidly incorporated in many areas of modern medical practice to improve the precision of clinical decision-making. This potential improvement, however, has not been transferred to the practice of organ assessment and transplantation because previously developed gene-profiling techniques require an extended period of time to perform, making them unsuitable in the time-sensitive organ assessment process. We sought to develop a novel class of chip-based sensors that would enable rapid analysis of tissue levels of preimplantation mRNA markers that correlate with the development of primary graft dysfunction (PGD) in recipients after transplant. Using fractal circuit sensors (FraCS), three-dimensional metal structures with large surface areas, we were able to rapidly (<20 min) and reproducibly quantify small differences in the expression of interleukin-6 (IL-6), IL-10, and ATP11B mRNA in donor lung biopsies. A proof-of-concept study using 52 human donor lungs was performed to develop a model that was used to predict, with excellent sensitivity (74%) and specificity (91%), the incidence of PGD for a donor lung. Thus, the FraCS-based approach delivers a key predictive value test that could be applied to enhance transplant patient outcomes. This work provides an important step toward bringing rapid diagnostic mRNA profiling to clinical application in lung transplantation. PMID:26601233

  5. Estradiol worsens the syndrome of ischemia-reperfusion injury in an experimental lung transplantation model.

    PubMed

    Santana-Rodríguez, Norberto; Clavo, Bernardino; Llontop, Pedro; López, Ana; García-Castellano, José Manuel; Machín, Rubén P; Ponce, Miguel A; Fiuza, María D; García-Herrera, Ricardo; Brito, Yanira; Yordi, Nagib Atallah; Chirino, Ricardo

    2011-06-01

    Ischemia-reperfusion injury (IRI) is a common complication after lung transplantation. There is evidence that reactive oxygen species are involved in its pathogenesis. We designed an experimental study to evaluate whether the administration of antioxidants to lung transplantation recipients protects against IRI and early acute rejection (AR). Twenty-five rats received left lung transplants after 6 h of ischemia. Fifty minutes before the reperfusion, groups of five rats received a single dose of desferrioxamine (20 mg/kg), estradiol (25 mg/kg), or melatonin (10 mg/kg). The animals were killed 48 h after surgery and the postoperative outcome, IRI, and AR were evaluated. The frequency of severe injury and of moderate-to-severe edema was higher in animals treated with estradiol than in the control group (P = 0.022 and P = 0.026, respectively). No significant changes in the degree of IRI or AR were observed in the groups treated with desferrioxamine or melatonin. In our study, treatment with the antioxidants melatonin or desferrioxamine before reperfusion had no effects on IRI damage or on AR frequency or severity. However, treatment with estradiol resulted in a worse postoperative outcome and in severe edema. Therefore, despite the antioxidant capacity of estradiol, it is recommended that an evaluation of these adverse effects of estradiol in human lung transplant recipients be performed.

  6. Multifocal nodular periostitis associated with prolonged voriconazole therapy in a lung transplant recipient.

    PubMed

    Ayub, Asad; Kenney, Charles V; McKiernan, Fergus E

    2011-03-01

    We report a case of painful, nodular periostitis in a lung transplant recipient on long-term voriconazole therapy. Symptoms, signs, and laboratory abnormalities resolved quickly after drug withdrawal. The presentation more closely resembles periostitis deformans than hypertrophic osteoarthropathy, suggesting that the fluoride moiety of voriconazole may be pathogenic for this condition. Clinicians should be aware of this association.

  7. Development of transient peanut allergy following lung transplantation: a case report.

    PubMed

    Bhinder, Sacha; Heffer, Matthew J; Lee, Jason K; Chaparro, Cecilia; Tarlo, Susan M

    2011-01-01

    A 47-year-old woman underwent bilateral lung transplantation for nonspecific interstitial pneumonitis and received donor lungs from a 12-year-old patient with a known peanut allergy. Post-transplant, the patient experienced four anaphylaxis-like reactions. A skin prick test to peanut was initially positive; however, it steadily declined over serial assessments and reverted to negative one year post-transplant. The patient subsequently had a negative oral peanut challenge. Transfer of food allergy post-transplantation is theorized to occur via transfer of donor B lymphocytes producing peanut-specific immunoglobulin E into the circulation of the recipient. An alternate mechanism proposes passive transfer of immunoglobulin E-sensitized mast cells and⁄or basophils within the transplanted tissue that subsequently migrate into recipient tissues. The gradual decline in the magnitude of the peanut skin prick test and its return to negative over the course of one year supports the gradual depletion of sensitized cells in the recipient (B lymphocytes and, possibly, mast cells), and supports the initial passive transfer of sensitized cells from donor tissue during transplantation. This should be considered when donor organs are obtained from allergic individuals.

  8. Inhibiting Integrin αvβ5 Reduces Ischemia-Reperfusion Injury in an Orthotopic Lung Transplant Model in Mice.

    PubMed

    Mallavia, B; Liu, F; Sheppard, D; Looney, M R

    2016-04-01

    Primary graft dysfunction after lung transplantation is the leading cause of morbidity and mortality in the immediate posttransplant period and is characterized by endothelial and epithelial barrier disruption and the leakage of protein-rich edema fluid. Integrins are cell surface receptors that have an important role in maintenance of the cell barrier, and inhibition of integrins, such as αvβ5, can diminish alveolar flooding in lung injury models. We hypothesized that inhibition of αvβ5 during donor lung cold ischemia would reduce endothelial permeability during reperfusion. Using an orthotopic single lung transplantation model with and without cold ischemia, donor lungs were perfused with αvβ5-blocking antibody (ALULA) or control antibody at the time of collection, followed by transplantation, 8 h of reperfusion, and the measurement of lung injury parameters. Prolonged cold ischemia (18 h) produced increases in extravascular lung water, protein permeability, and neutrophilic alveolitis and decreased oxygenation compared with lungs without cold ischemia. Perfusion of lungs with αvβ5 antibody versus control antibody protected donor lungs from injury and significantly improved oxygenation. In summary, αvβ5 integrin blockade protects from the development of ischemia-reperfusion lung injury and is a promising approach to preventing primary graft dysfunction in human lung transplant procedures.

  9. HLA-E⁎01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence

    PubMed Central

    Di Cristofaro, Julie; Basire, Agnès; Gomez, Carine; Chiaroni, Jacques; Thomas, Pascal; Reynaud-Gaubert, Martine

    2016-01-01

    Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E⁎01:01 and HLA-E⁎01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E⁎01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E⁎01:01 status (HR: 3.563 (CI 95%, 1.016–12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort. PMID:27493971

  10. Onset of Inflammation With Ischemia: Implications for Donor Lung Preservation and Transplant Survival.

    PubMed

    Tao, J-Q; Sorokina, E M; Vazquez Medina, J P; Mishra, M K; Yamada, Y; Satalin, J; Nieman, G F; Nellen, J R; Beduhn, B; Cantu, E; Habashi, N M; Jungraithmayr, W; Christie, J D; Chatterjee, S

    2016-09-01

    Lungs stored ahead of transplant surgery experience ischemia. Pulmonary ischemia differs from ischemia in the systemic organs in that stop of blood flow in the lung leads to loss of shear alone because the lung parenchyma does not rely on blood flow for its cellular oxygen requirements. Our earlier studies on the ischemia-induced mechanosignaling cascade showed that the pulmonary endothelium responds to stop of flow by production of reactive oxygen species (ROS). We hypothesized that ROS produced in this way led to induction of proinflammatory mediators. In this study, we used lungs or cells subjected to various periods of storage and evaluated the induction of several proinflammatory mediators. Isolated murine, porcine and human lungs in situ showed increased expression of cellular adhesion molecules; the damage-associated molecular pattern protein high-mobility group box 1 and the corresponding pattern recognition receptor, called the receptor for advanced glycation end products; and induction stabilization and translocation of hypoxia-inducible factor 1α and its downstream effector VEGFA, all of which are participants in inflammation. We concluded that signaling with lung preservation drives expression of inflammatory mediators that potentially predispose the donor lung to an inflammatory response after transplant. PMID:26998598

  11. Transbronchial biopsies provide longitudinal evidence for epithelial chimerism in children following sex mismatched lung transplantation

    PubMed Central

    Spencer, H; Rampling, D; Aurora, P; Bonnet, D; Hart, S; Jaffe, A

    2005-01-01

    Background: Recent reports have shown evidence of host derived parenchymal engraftment in several human allografts including the lung, leading to speculation that stem cell therapy may be useful for lung repair in diseases such as cystic fibrosis (CF). To date, previous studies have looked at single surgical or autopsy specimens and no longitudinal studies have been reported. The aim of this study was to assess whether transbronchial biopsies could be used to study the time course of chimerism following lung transplantation. Methods: Specimens of archived transbronchial lung biopsies from five time points taken for clinical purposes from two boys who had received a sex mismatched heart-lung transplant for end stage CF were examined. Sections were dual stained for cytokeratin (epithelium) and a mixture of leucocyte common antigen and CD68 for inflammatory cells. Co-localisation of cells containing a Y chromosome was confirmed by fluorescent in situ hybridisation. Results: Evidence of chimerism was found in up to 6.6% of epithelial cells in bronchial (median 1.4% (range 0–6.6)) and alveolar (median 3.6% (range 2.3–5.5) tissue without apparent evidence of fusion. This engraftment was seen as early as 3 weeks and remained relatively constant up to 37 months. Conclusions: This study has demonstrated proof of principle for long term chimerism in lung epithelium. Transbronchial biopsies may provide a new method for studying the kinetics of stem cell engraftment in the lung. PMID:15618585

  12. Postoperative complications necessitating right lower lobectomy in a heart-lung transplant recipient with previous sternotomy.

    PubMed

    Diethrich, E B; Bahadir, I; Gordon, M; Maki, P; Warner, M G; Clark, R; Siever, J; Silverthorn, A

    1987-09-01

    Heart-lung transplantation for treatment of end-stage cardiopulmonary disease continues to be plagued by many problems. Three primary ones are the technical difficulties that can be encountered, particularly in those patients who have undergone previous cardiac operations, the additional restriction on donor availability imposed by the lack of satisfactory preservation techniques, and the need for lung size compatibility. Two of these difficulties and others surfaced postoperatively in a heart-lung transplant recipient who presented a series of unique operative and therapeutic challenges. A 42-year-old woman with chronic pulmonary hypertension and previous atrial septal defect repair underwent a heart-lung transplantation in August 1985. The operative procedure was expectedly complicated by bleeding from extensive mediastinal adhesions from the previous sternotomy and bronchial collateralization. Excessive chest tube drainage postoperatively necessitated reoperation to control bleeding from a right bronchial artery tributary. Phrenic nerve paresis, hepatomegaly, and marked abdominal distention caused persistent atelectasis and eventual right lower lobe collapse. Arteriovenous shunting and low oxygen saturation necessitated right lower lobectomy 15 days after transplantation, believed to be the first use of this procedure in a heart-lung graft recipient. Although oxygenation improved dramatically, continued ventilatory support led to tracheostomy. An intensive, psychologically oriented physical therapy program was initiated to access and retrain intercostal and accessory muscles. The tracheostomy cannula was removed after 43 days and gradual weaning from supplemental oxygen was accomplished. During this protracted recovery period, an episode of rejection was also encountered and successfully managed with steroid therapy. The patient continued to progress satisfactorily and was discharged 83 days after transplantation. She is well and active 20 months after discharge.

  13. Pilot study exploring lung allograft surfactant protein A (SP-A) expression in association with lung transplant outcome.

    PubMed

    D'Ovidio, F; Kaneda, H; Chaparro, C; Mura, M; Lederer, D; Di Angelo, S; Takahashi, H; Gutierrez, C; Hutcheon, M; Singer, L G; Waddell, T K; Floros, J; Liu, M; Keshavjee, S

    2013-10-01

    Primary graft failure and chronic lung allograft dysfunction (CLAD) limit lung transplant long-term outcomes. Various lung diseases have been correlated with surfactant protein (SP) expression and polymorphisms. We sought to investigate the role of SP expression in lung allografts prior to implantation, in relation to posttransplant outcomes. The expression of SP-(A, B, C, D) mRNA was assayed in 42 allografts. Posttransplant assessments include pulmonary function tests, bronchoscopy, broncho-alveolar lavage fluid (BALF) and biopsies to determine allograft rejection. BALF was assayed for SP-A, SP-D in addition to cytokines IL-8, IL-12 and IL-2. The diagnosis of CLAD was evaluated 6 months after transplantation. Lung allografts with low SP-A mRNA expression prior to implantation reduced survival (Log-rank p < 0.0001). No association was noted for the other SPs. Allografts with low SP-A mRNA had greater IL-2 (p = 0.03) and IL-12 (p < 0.0001) in the BALF and a greater incidence of rejection episodes (p = 0.003). Levels of SP-A mRNA expression were associated with the SP-A2 polymorphisms (p = 0.015). Specifically, genotype 1A1A(0) was associated with lower SP-A mRNA expression (p < 0.05). Lung allografts with low levels of SP-A mRNA expression are associated with reduced survival. Lung allograft SP-A mRNA expression appears to be associated with SP-A gene polymorphisms.

  14. Endogenous and exogenous stem cells: a role in lung repair and use in airway tissue engineering and transplantation

    PubMed Central

    2010-01-01

    Rapid repair of the denuded alveolar surface after injury is a key to survival. The respiratory tract contains several sources of endogenous adult stem cells residing within the basal layer of the upper airways, within or near pulmonary neuroendocrine cell rests, at the bronchoalveolar junction, and within the alveolar epithelial surface, which contribute to the repair of the airway wall. Bone marrow-derived adult mesenchymal stem cells circulating in blood are also involved in tracheal regeneration. However, an organism is frequently incapable of repairing serious damage and defects of the respiratory tract resulting from acute trauma, lung cancers, and chronic pulmonary and airway diseases. Therefore, replacement of the tracheal tissue should be urgently considered. The shortage of donor trachea remains a major obstacle in tracheal transplantation. However, implementation of tissue engineering and stem cell therapy-based approaches helps to successfully solve this problem. To date, huge progress has been achieved in tracheal bioengineering. Several sources of stem cells have been used for transplantation and airway reconstitution in animal models with experimentally induced tracheal defects. Most tracheal tissue engineering approaches use biodegradable three-dimensional scaffolds, which are important for neotracheal formation by promoting cell attachment, cell redifferentiation, and production of the extracellular matrix. The advances in tracheal bioengineering recently resulted in successful transplantation of the world's first bioengineered trachea. Current trends in tracheal transplantation include the use of autologous cells, development of bioactive cell-free scaffolds capable of supporting activation and differentiation of host stem cells on the site of injury, with a future perspective of using human native sites as micro-niche for potentiation of the human body's site-specific response by sequential adding, boosting, permissive, and recruitment impulses

  15. Lung Transplantation Is Increasingly Common Among Patients With Coal Workers’ Pneumoconiosis

    PubMed Central

    Blackley, David J.; Halldin, Cara N.; Cummings, Kristin J.; Laney, A. Scott

    2016-01-01

    Background The prevalence of coal workers’ pneumoconiosis (CWP) in U.S. coal miners has increased, and severe presentations are increasingly common. Methods We describe trends in lung transplantation during 1996–2014 for recipients with a primary diagnosis of CWP or pneumoconiosis unspecified, and we summarize recipient characteristics and estimate survival. Results A total of 47 transplants were included; nearly three-quarters were performed during 2008–2014. All recipients were male, 96% were white, and the mean age was 56 years. Mean FEV1% was 35%; mean FVC% was 53%. Mean time on a waitlist was 155 days, and 60% of transplants were bilateral. Median survival was 3.7 years. Conclusions These transplants reflect the use of a scarce resource for an entirely preventable disease, and highlight the need for enhanced efforts to reduce coal mine dust exposures. PMID:26725917

  16. Ex Vivo Lung Perfusion and Transplant: State of the Art and View to the Future.

    PubMed

    Mohamed, Mohamed S A

    2015-12-01

    After the first clinical application of ex vivo lung perfusion in 2001, the technique has been used in many lung transplant centers worldwide. In addition, many modifications have been tested, leading to the development of various ex vivo lung perfusion systems and application protocols. Currently, the Lund protocol, the Toronto protocol, and Organ Care System Lung protocol are the clinically applied ex vivo lung perfusion protocols, based on the favorable results of the safety studies. Accordingly, the comparison among these EVLP systems and protocols should be an important research target, in order to provide the evidence based medical data that would recommend one protocol over the others. In this manuscript, the current experience with EVLP is reviewed and some molecular and clinical targets, that could be used to compare the various protocols of the technique, are introduced.

  17. Adult to adult living related liver transplantation: where do we currently stand?

    PubMed

    Carlisle, Erica M; Testa, Giuliano

    2012-12-14

    Adult to adult living donor liver transplantation (AALDLT) was first preformed in the United States in 1997. The procedure was rapidly integrated into clinical practice, but in 2002, possibly due to the first widely publicized donor death, the number of living liver donors plummeted. The number of donors has since reached a steady plateau far below its initial peak. In this review we evaluate the current climate of AALDLT. Specifically, we focus on several issues key to the success of AALDLT: determining the optimal indications for AALDLT, balancing graft size and donor safety, assuring adequate outflow, minimizing biliary complications, and maintaining ethical practices. We conclude by offering suggestions for the future of AALDLT in United States transplantation centers. PMID:23239910

  18. Abnormal skeletal muscle oxidative capacity after lung transplantation by 31P-MRS.

    PubMed

    Evans, A B; Al-Himyary, A J; Hrovat, M I; Pappagianopoulos, P; Wain, J C; Ginns, L C; Systrom, D M

    1997-02-01

    Although lung transplantation improves exercise capacity by removal of a ventilatory limitation, recipients' postoperative maximum oxygen uptake (VO2max) remains markedly abnormal. To determine if abnormal skeletal muscle oxidative capacity contributes to this impaired aerobic capacity, nine lung transplant recipients and eight healthy volunteers performed incremental quadriceps exercise to exhaustion with simultaneous measurements of pulmonary gas exchange, minute ventilation, blood lactate, and quadriceps muscle pH and phosphorylation potential by 31P-magnetic resonance spectroscopy (31P-MRS). Five to 38 mo after lung transplantation, peak VO2 was decreased compared with that of normal control subjects (6.7 +/- 0.4 versus 12.3 +/- 1.0 ml/min/kg, p < 0.001), even after accounting for differences in age and lean body weight. Neither ventilation, arterial O2 saturation nor mild anemia could account for the decrease in aerobic capacity. Quadriceps muscle intracellular pH (pH(i)) was more acidic at rest (7.07 +/- 0.01 versus 7.12 +/- 0.01 units, p < 0.05) and fell during exercise from baseline values at a lower metabolic rate (282 +/- 21 versus 577 +/- 52 ml/min, p < 0.001). Regressions for pH(i) versus VO2, phosphocreatine/inorganic phosphate ratio (PCr/Pi) versus VO2, and blood lactate versus pH(i) were not different. Among transplant recipients, the metabolic rate at which pH(i) fell correlated closely with VO2max (r = 0.87, p < 0.01). The persistent decrease in VO2max after lung transplantation may be related to abnormalities of skeletal muscle oxidative capacity. PMID:9032203

  19. Adult allogeneic bone marrow transplantation: initial experience in the University Hospital, Kuala Lumpur.

    PubMed

    Teh, A; Bosco, J J; Leong, K W; Saw, M H; Menaka, N; Devashanti, P

    1997-03-01

    Prior to 1993, bone marrow transplantation for adult patients was not available in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia when the first transplant was conducted at the University Hospital, Kuala Lumpur on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been conducted at the University Hospital. Five patients had acute myeloid leukaemia in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic leukaemia in first partial remission. The age range of patients at the time of transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully and the survival for the first 100 days post-transplant is 90%. One patient demonstrated haematological relapse post-transplant but achieved remission with donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first 100 days. Locally available adult allogeneic bone marrow transplantation is safe, affordable and has comparable results with reputable overseas transplant centres.

  20. Local Origin of Mesenchymal Cells in a Murine Orthotopic Lung Transplantation Model of Bronchiolitis Obliterans

    PubMed Central

    Mimura, Takeshi; Walker, Natalie; Aoki, Yoshiro; Manning, Casey M.; Murdock, Benjamin J.; Myers, Jeffery L.; Lagstein, Amir; Osterholzer, John J.; Lama, Vibha N.

    2016-01-01

    Bronchiolitis obliterans is the leading cause of chronic graft failure and long-term mortality in lung transplant recipients. Here, we used a novel murine model to characterize allograft fibrogenesis within a whole-lung microenvironment. Unilateral left lung transplantation was performed in mice across varying degrees of major histocompatibility complex mismatch combinations. B6D2F1/J (a cross between C57BL/6J and DBA/2J) (Haplotype H2b/d) lungs transplanted into DBA/2J (H2d) recipients were identified to show histopathology for bronchiolitis obliterans in all allogeneic grafts. Time course analysis showed an evolution from immune cell infiltration of the bronchioles and vessels at day 14, consistent with acute rejection and lymphocytic bronchitis, to subepithelial and intraluminal fibrotic lesions of bronchiolitis obliterans by day 28. Allografts at day 28 showed a significantly higher hydroxyproline content than the isografts (33.21 ± 1.89 versus 22.36 ± 2.33 μg/mL). At day 40 the hydroxyproline content had increased further (48.91 ± 7.09 μg/mL). Flow cytometric analysis was used to investigate the origin of mesenchymal cells in fibrotic allografts. Collagen I–positive cells (89.43% ± 6.53%) in day 28 allografts were H2Db positive, showing their donor origin. This novel murine model shows consistent and reproducible allograft fibrogenesis in the context of single-lung transplantation and represents a major step forward in investigating mechanisms of chronic graft failure. PMID:25848843

  1. Video fluoroscopy swallow study and nutritional support during ambulatory venovenous extracorporeal membrane oxygenation as a bridge to lung transplantation.

    PubMed

    Hayes, Don; Tobias, Joseph D; Galantowicz, Mark; Preston, Thomas J; Tzemos, Kallirroe K; McConnell, Patrick I

    2014-01-01

    We present the successful completion of a video fluoroscopy swallow study and subsequent nutritional plan of a child bridged to lung transplantation with ambulatory venovenous (VV) extracorporeal membrane oxygenation (ECMO). With a limited number of programs bridging pediatric patients to lung transplantation with VV ECMO, a better understanding of nutritional support is needed to provide optimal care to this patient population awaiting organ donation. PMID:24403362

  2. Biopsy-verified bronchiolitis obliterans and other noninfectious lung pathologies after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle; Gormsen, Magdalena; Pedersen, Karen Damgaard; Buchvald, Frederik; Heilmann, Carsten; Nielsen, Kim Gjerum; Mortensen, Jann; Moser, Claus; Sengeløv, Henrik; Müller, Klaus Gottlob

    2015-03-01

    Bronchiolitis obliterans (BO) is a serious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Lung biopsy is the gold standard for diagnosis. This study describes the course of BO and assesses the congruity between biopsy-verified BO and a modified version of the National Institutes of Health's consensus criteria for BO syndrome (BOS) based exclusively on noninvasive measures. We included 44 patients transplanted between 2000 and 2010 who underwent lung biopsy for suspected BO. Of those, 23 were diagnosed with BO and 21 presented other noninfectious pulmonary pathologies, such as cryptogenic organizing pneumonia, diffuse alveolar damage, interstitial pneumonia, and nonspecific interstitial fibrosis. Compared with patients with other noninfectious pulmonary pathologies, BO patients had significantly lower values of forced expiratory volume in 1 second (FEV1), FEV1/forced vital capacity, and maximal mid-expiratory flow throughout follow-up, but there was no difference in the change in pulmonary function from the time of lung biopsy. The BO diagnosis was not associated with poorer overall survival. Fifty-two percent of patients with biopsy-verified BO and 24% of patients with other noninfectious pulmonary pathology fulfilled the BOS criteria. Pathological BO diagnosis was not superior to BOS criteria in predicting decrease in pulmonary function beyond the time of biopsy. A lung biopsy may provide a characterization of pathological patterns that can extend our knowledge on the pathophysiology of HSCT-related lung diseases. PMID:25498923

  3. [Extracorporeal membrane oxygenation in primary graft dysfunction in a paediatric double lung transplant: presentation of a case].

    PubMed

    López-Cantero, M; Grisolía, A L; Vicente, R; Moreno, I; Ramos, F; Porta, J; Torregrosa, S

    2014-04-01

    Primary graft dysfunction is a leading cause of morbimortality in the immediate postoperative period of patients undergoing lung transplantation. Among the treatment options are: lung protective ventilatory strategies, nitric oxide, lung surfactant therapy, and supportive treatment with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery of lung function or re-transplant. We report the case of a 9-year-old girl affected by cystic fibrosis who underwent double-lung transplantation complicated with a severe primary graft dysfunction in the immediate postoperative period and refractory to standard therapies. Due to development of multiple organ failure, it was decided to insert arteriovenous ECMO catheters (pulmonary artery-right atrium). The postoperative course was satisfactory, allowing withdrawal of ECMO on the 5th post-surgical day. Currently the patient survives free of rejection and with an excellent quality of life after 600 days of follow up. PMID:23731837

  4. Interdisciplinary collaboration applied to clinical research: an example of remote monitoring in lung transplantation.

    PubMed

    VanWormer, Arin; Lindquist, Ruth; Robiner, William; Finkelstein, Stanley

    2012-01-01

    Collaboration across disciplines is vital in clinical practice. It is also needed to generate high-quality actionable research, yet few frameworks for interdisciplinary collaboration exit to promote effective communications among researchers with common goals, but varied backgrounds. A review of what has been learned about collaboration was undertaken to determine attributes of effective interdisciplinary collaboration and barriers to its realization in patients undergoing lung transplantation. PMID:22475710

  5. Changes in the Lung Microbiome following Lung Transplantation Include the Emergence of Two Distinct Pseudomonas Species with Distinct Clinical Associations

    PubMed Central

    Dickson, Robert P.; Erb-Downward, John R.; Freeman, Christine M.; Walker, Natalie; Scales, Brittan S.; Beck, James M.; Martinez, Fernando J.; Curtis, Jeffrey L.; Lama, Vibha N.; Huffnagle, Gary B.

    2014-01-01

    Background Multiple independent culture-based studies have identified the presence of Pseudomonas aeruginosa in respiratory samples as a positive risk factor for bronchiolitis obliterans syndrome (BOS). Yet, culture-independent microbiological techniques have identified a negative association between Pseudomonas species and BOS. Our objective was to investigate whether there may be a unifying explanation for these apparently dichotomous results. Methods We performed bronchoscopies with bronchoalveolar lavage (BAL) on lung transplant recipients (46 procedures in 33 patients) and 26 non-transplant control subjects. We analyzed bacterial communities in the BAL fluid using qPCR and pyrosequencing of 16S rRNA gene amplicons and compared the culture-independent data with the clinical metadata and culture results from these subjects. Findings Route of bronchoscopy (via nose or via mouth) was not associated with changes in BAL microbiota (p = 0.90). Among the subjects with positive Pseudomonas bacterial culture, P. aeruginosa was also identified by culture-independent methods. In contrast, a distinct Pseudomonas species, P. fluorescens, was often identified in asymptomatic transplant subjects by pyrosequencing but not detected via standard bacterial culture. The subject populations harboring these two distinct pseudomonads differed significantly with respect to associated symptoms, BAL neutrophilia, bacterial DNA burden and microbial diversity. Despite notable differences in culturability, a global database search of UM Hospital Clinical Microbiology Laboratory records indicated that P. fluorescens is commonly isolated from respiratory specimens. Interpretation We have reported for the first time that two prominent and distinct Pseudomonas species (P. fluorescens and P. aeruginosa) exist within the post-transplant lung microbiome, each with unique genomic and microbiologic features and widely divergent clinical associations, including presence during acute infection

  6. National Healthcare Delivery Systems Influence Lung Transplant Outcomes for Cystic Fibrosis.

    PubMed

    Merlo, C A; Clark, S C; Arnaoutakis, G J; Yonan, N; Thomas, D; Simon, A; Thompson, R; Thomas, H; Orens, J; Shah, A S

    2015-07-01

    Successful lung transplantation (LTx) depends on multiple components of healthcare delivery and performance. Therefore, we conducted an international registry analysis to compare post-LTx outcomes for cystic fibrosis (CF) patients using the UNOS registry in the United States and the National Health Service (NHS) Transplant Registry in the United Kingdom. Patients with CF who underwent lung or heart-lung transplantation in the United States or United Kingdom between January 1, 2000 and December 31, 2011 were included. The primary outcome was all-cause mortality. Kaplan-Meier analysis and Cox proportional hazards regression evaluated the effect of healthcare system and insurance on mortality after LTx. 2,307 US LTx recipients and 451 individuals in the United Kingdom were included. 894 (38.8%) US LTx recipients had publically funded Medicare/Medicaid insurance. US private insurance and UK patients had improved median predicted survival compared with US Medicare/Medicaid recipients (p < 0.001). In multivariable Cox regression, US Medicare/Medicaid insurance was associated with worse survival after LTx (US private: HR0.78,0.68-0.90,p = 0.001 and UK: HR0.63,0.41-0.97, p = 0.03). This study in CF patients is the largest comparison of LTx in two unique health systems. Both the United States and United Kingdom have similar early survival outcomes, suggesting important dissemination of best practices internationally. However, the performance of US public insurance is significantly worse and may put patients at risk.

  7. Liver transplantation in adults: Choosing the appropriate timing

    PubMed Central

    Siciliano, Maria; Parlati, Lucia; Maldarelli, Federica; Rossi, Massimo; Ginanni Corradini, Stefano

    2012-01-01

    Liver transplantation is indicated in patients with acute liver failure, decompensated cirrhosis, hepatocellular carcinoma and rare liver-based genetic defects that trigger damage of other organs. Early referral to a transplant center is crucial in acute liver failure due to the high mortality with medical therapy and its unpredictable evolution. Referral to a transplant center should be considered when at least one complication of cirrhosis occurs during its natural history. However, because of the shortage of organ donors and the short-term mortality after liver transplantation on one hand and the possibility of managing the complications of cirrhosis with other treatments on the other, patients are carefully selected by the transplant center to ensure that transplantation is indicated and that there are no medical, surgical and psychological contraindications. Patients approved for transplantation are placed on the transplant waiting list and prioritized according to disease severity. Thus, the appropriate timing of transplantation depends on recipient disease severity and, although this is still a matter of debate, also on donor quality. These two variables are known to determine the “transplant benefit” (i.e., when the expected patient survival is better with, than without, transplantation) and should guide donor allocation. PMID:22966483

  8. A randomized trial of inhaled nitric oxide to prevent ischemia-reperfusion injury after lung transplantation.

    PubMed

    Meade, Maureen O; Granton, John T; Matte-Martyn, Andrea; McRae, Karen; Weaver, Bruce; Cripps, Paula; Keshavjee, Shaf H

    2003-06-01

    Inhalation of nitric oxide (NO) has been advocated as a method to prevent ischemia-reperfusion injury after lung transplantation. We enrolled 84 patients into a concealed, randomized, placebo-controlled trial to evaluate the effect of inhaled NO (20 ppm NO or nitrogen) initiated 10 minutes after reperfusion on outcomes after lung transplantation. The groups (n = 42) were balanced with respect to age, sex, lung disease, procedure, and total ischemic times. PaO2/FIO2 ratios were similar on admission to the intensive care unit (ICU) (NO 361 +/- 134; control patients 357 +/- 132), and over the duration of the study. There were no differences in hemodynamics between the two groups. Severe reperfusion injury (PaO2/FIO2 < 150) was present at the time of admission to the ICU in 14.6% NO patients versus 9.5% of control patients (p = 0.48). The groups had similar median times to first successful trial of unassisted breathing (25 vs. 27 hours; p = 0.76), successful extubation (32 vs. 34 hours; p = 0.65), ICU discharge (3.0 days for both groups), and hospital discharge (27 vs. 29 days; p = 0.563). Five NO versus six control patients died during their hospital stay. Adjusting for age, sex, lung disease etiology, presence of pulmonary hypertension, and total ischemic time did not alter these results. In conclusion, we did not detect a significant effect of inhaled NO administered 10 minutes after reperfusion on physiologic variables or outcomes in lung transplant patients.

  9. [Heart and combined heart-lung transplantation. Indications, chances and risks].

    PubMed

    Puehler, T; Ensminger, S; Schulz, U; Fuchs, U; Tigges-Limmer, K; Börgermann, J; Morshuis, M; Hakim, K; Oldenburg, O; Niedermeyer, J; Renner, A; Gummert, J

    2014-02-01

    Orthotopic heart transplantation (HTX) is nowadays the worldwide accepted gold standard for the treatment of terminal heart failure. The main indications for HTX are non-ischemic dilatative (54%) and ischemic (37%) heart failure. In the acute phase after HTX the survival rate is approximately 90%. Good short and long-term results with survival rates ranging from 81% after 1 year to more than 50% after 11 years demonstrate that there is currently no real treatment alternative to HTX for treatment of end-stage heart failure. In the case of irreversible pulmonary hypertension in combination with end-stage heart failure or complex congenital heart syndromes, a combined heart and lung transplantation (HLTX) is necessary. Compared with HTX the short-term survival of HLTX is reduced, mostly for technical reasons. Improved long-term results after HTX and HLTX are a result of highly specialized transplantation units and effective immunosuppression. However, a major problem is the shortage of organ donors in Germany and the resulting long waiting times for patients with frequently occurring blood groups of up to 10 months for transplantation. The consequence of the latter is the ever increasing number of implanted cardiac assist devices in patients not only as a bridge to transplant but also as destination therapy. PMID:24452762

  10. IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants.

    PubMed

    Burlingham, William J; Love, Robert B; Jankowska-Gan, Ewa; Haynes, Lynn D; Xu, Qingyong; Bobadilla, Joseph L; Meyer, Keith C; Hayney, Mary S; Braun, Ruedi K; Greenspan, Daniel S; Gopalakrishnan, Bagavathi; Cai, Junchao; Brand, David D; Yoshida, Shigetoshi; Cummings, Oscar W; Wilkes, David S

    2007-11-01

    Bronchiolitis obliterans syndrome (BOS), a process of fibro-obliterative occlusion of the small airways in the transplanted lung, is the most common cause of lung transplant failure. We tested the role of cell-mediated immunity to collagen type V [col(V)] in this process. PBMC responses to col(II) and col(V) were monitored prospectively over a 7-year period. PBMCs from lung transplant recipients, but not from healthy controls or col(IV)-reactive Goodpasture's syndrome patients after renal transplant, were frequently col(V) reactive. Col(V)-specific responses were dependent on both CD4+ T cells and monocytes and required both IL-17 and the monokines TNF-alpha and IL-1beta. Strong col(V)-specific responses were associated with substantially increased incidence and severity of BOS. Incidences of acute rejection, HLA-DR mismatched transplants, and induction of HLA-specific antibodies in the transplant recipient were not as strongly associated with a risk of BOS. These data suggest that while alloimmunity initiates lung transplant rejection, de novo autoimmunity mediated by col(V)-specific Th17 cells and monocyte/macrophage accessory cells ultimately causes progressive airway obliteration. PMID:17965778

  11. A Human-Mouse Chimeric Model of Obliterative Bronchiolitis after Lung Transplantation

    PubMed Central

    Xue, Jianmin; Zhu, Xuehai; George, M. Patricia; Myerburg, Michael M.; Stoner, Michael W.; Pilewski, Joseph W.; Duncan, Steven R.

    2011-01-01

    Obliterative bronchiolitis is a frequent, morbid, and usually refractory complication of lung transplantation. Mechanistic study of obliterative bronchiolitis would be aided by development of a relevant model that uses human immune effector cells and airway targets. Our objective was to develop a murine chimera model that mimics obliterative bronchiolitis of lung allograft recipients in human airways in vivo. Human peripheral blood mononuclear cells were adoptively transferred to immunodeficient mice lacking activity of T, B, and NK cells, with and without concurrent transplantations of human small airways dissected from allogeneic cadaveric lungs. Chimerism with human T cells occurred in the majority of recipient animals. The chimeric T cells became highly activated, rapidly infiltrated into the small human airway grafts, and caused obliterative bronchiolitis. In contrast, airways implanted into control mice that did not also receive human peripheral blood mononuclear cell transfers remained intact. In vitro proliferation assays indicated that the chimeric T cells had enhanced specific proliferative responses to donor airway alloantigens. This model confirms the critical role of T cells in development of obliterative bronchiolitis among human lung allograft recipients and provides a novel and easily implemented mechanism for detailed, reductionist in vivo studies of human T-cell responses to allogeneic human small airways. PMID:21801868

  12. Non-invasive ventilation in prone position for refractory hypoxemia after bilateral lung transplantation.

    PubMed

    Feltracco, Paolo; Serra, Eugenio; Barbieri, Stefania; Persona, Paolo; Rea, Federico; Loy, Monica; Ori, Carlo

    2009-01-01

    Temporary graft dysfunction with gas exchange abnormalities is a common finding during the postoperative course of a lung transplant and is often determined by the post-reimplantation syndrome. Supportive measures including oxygen by mask, inotropes, diuretics, and pulmonary vasodilators are usually effective in non-severe post-reimplantation syndromes. However, in less-responsive clinical pictures, tracheal intubation with positive pressure ventilation, or non-invasive positive pressure ventilation (NIV), is necessary. We report on the clinical course of two patients suffering from refractory hypoxemia due to post-reimplantation syndrome treated with NIV in the prone and Trendelenburg positions. NIV was well tolerated and led to resolution of atelectactic areas and dishomogeneous lung infiltrates. Repeated turning from supine to prone under non invasive ventilation determined a stable improvement of gas exchange and prevented a more invasive approach. Even though NIV in the prone position has not yet entered into clinical practice, it could be an interesting option to achieve a better match between ventilation and perfusion. This technique, which we successfully applied in lung transplantation, can be easily extended to other lung diseases with non-recruitable dorso-basal areas.

  13. Improved quality of life after lung transplantation in individuals with cystic fibrosis.

    PubMed

    Vermeulen, Karin M; van der Bij, Wim; Erasmus, Michiel E; Duiverman, Eric J; Koëter, Gerard H; TenVergert, Elisabeth M

    2004-05-01

    The aim of the present study was to assess the effect of lung transplantation (LgTX) on health-related quality of life (HRQL) in a group of patients with cystic fibrosis (CF), compared to patients with other diagnoses (non-CF). HRQL was assessed before transplantation in a group of 32 CF patients and 183 non-CF patients. After LgTX, we conducted a prospective longitudinal study among 10 CF patients and 35 non-CF patients who survived at least 31 months after LgTX. Measures were the Nottingham Health Profile (NHP), the State-Trait Anxiety Inventory (STAI), the Self-Rating Depression Scale (ZUNG), the Index of Well-Being (IWB), and the Karnofsky Performance Index. Patients in the CF group were younger, spent more days on the waiting list, and were more likely to be working or going to school than patients with other indications. Before transplantation, CF patients and non-CF patients experienced restrictions on almost all HRQL measures, compared to the general population. On the NHP dimensions of mobility and energy, CF patients had significantly better scores than non-CF patients. Between 1-4 months after transplantation, scores on the NHP, ZUNG, and Karnofsky performance indices improved, and STAI and IWB scores even occurred within the reference value in both groups. Significantly better scores in the CF group compared to the non-CF group were found on the NHP dimension of mobility 4 months after transplantation, and on the dimension of sleep 7 and 13 months after transplantation. Scores remained more or less stable over time in both groups. It may be concluded that patients in both groups experience major restrictions in HRQL before transplantation. However, pretransplant non-CF patients experience more restrictions than CF patients. After LgTX, both groups of patients showed substantial improvement in HRQL, and this improvement was maintained until 31 months after LgTX. PMID:15095325

  14. MSC from fetal and adult lungs possess lung-specific properties compared to bone marrow-derived MSC

    PubMed Central

    Rolandsson Enes, Sara; Andersson Sjöland, Annika; Skog, Ingrid; Hansson, Lennart; Larsson, Hillevi; Le Blanc, Katarina; Eriksson, Leif; Bjermer, Leif; Scheding, Stefan; Westergren-Thorsson, Gunilla

    2016-01-01

    Mesenchymal stromal cells (MSC) are multipotent cells with regenerative and immune-modulatory properties. Therefore, MSC have been proposed as a potential cell-therapy for bronchiolitis obliterans syndrome (BOS). On the other hand, there are publications demonstrating that MSC might be involved in the development of BOS. Despite limited knowledge regarding the functional role of tissue-resident lung-MSC, several clinical trials have been performed using MSC, particularly bone marrow (BM)-derived MSC, for various lung diseases. We aimed to compare lung-MSC with the well-characterized BM-MSC. Furthermore, MSC isolated from lung-transplanted patients with BOS were compared to patients without BOS. Our study show that lung-MSCs are smaller, possess a higher colony-forming capacity and have a different cytokine profile compared to BM-MSC. Utilizing gene expression profiling, 89 genes including lung-specific FOXF1 and HOXB5 were found to be significantly different between BM-MSC and lung-MSC. No significant differences in cytokine secretion or gene expression were found between MSC isolated from BOS patients compared recipients without BOS. These data demonstrate that lung-resident MSC possess lung-specific properties. Furthermore, these results show that MSC isolated from lung-transplanted patients with BOS do not have an altered phenotype compared to MSC isolated from good outcome recipients. PMID:27381039

  15. Orthotopic Heart Transplantation in an Adult Patient with Heterotaxy Syndrome: Surgical Implications.

    PubMed

    González-López, María-Teresa; Pérez-Caballero-Martínez, Ramón; Amoros-Rivera, Carlos; Zamorano-Serrano, José; Pita-Fernández, Ana-María; Gil-Jaurena, Juan-Miguel

    2015-12-01

    Modified techniques for orthotopic heart transplantation are mandatory when complex congenital anomalies are associated in adult patients. An unusual case of a heterotaxy syndrome and dilated cardiomyopathy following mitral ring annuloplasty is presented in a 62-year-old male. Orthotopic cardiac transplantation was performed by using a modified operative strategy: selective peripheral and central venous cannulation according to the thoraco-abdominal venous challenges, biatrial technique, and preservation of venous drainage via the native coronary sinus. We discuss the anatomical features of heterotaxy in adult patients and surgical approaches when heart transplantation is needed. PMID:26450654

  16. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy

    PubMed Central

    Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-01-01

    Abstract Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three‐dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity‐modulated radiotherapy appears to be the appropriate treatment in heart‐transplanted oncologic patients. PMID:27148425

  17. Mediastinal irradiation in a patient affected by lung carcinoma after heart transplantation: Helical tomotherapy versus three dimensional conformal radiotherapy.

    PubMed

    Giugliano, Francesca M; Iorio, Vincenzo; Cammarota, Fabrizio; Toledo, Diego; Senese, Rossana; Francomacaro, Ferdinando; Muto, Matteo; Muto, Paolo

    2016-04-26

    Patients who have undergone solid organ transplants are known to have an increased risk of neoplasia compared with the general population. We report our experience using mediastinal irradiation with helical tomotherapy versus three-dimensional conformal radiation therapy to treat a patient with lung carcinoma 15 years after heart transplantation. Our dosimetric evaluation showed no particular difference between the techniques, with the exception of some organs. Mediastinal irradiation after heart transplantation is feasible and should be considered after evaluation of the risk. Conformal radiotherapy or intensity-modulated radiotherapy appears to be the appropriate treatment in heart-transplanted oncologic patients.

  18. Integrative analysis correlates donor transcripts to recipient autoantibodies in primary graft dysfunction after lung transplantation

    PubMed Central

    Hagedorn, Peter H; Burton, Christopher M; Sahar, Eli; Domany, Eytan; Cohen, Irun R; Flyvbjerg, Henrik; Iversen, Martin

    2011-01-01

    Up to one in four lung-transplanted patients develop pulmonary infiltrates and impaired oxygenation within the first days after lung transplantation. Known as primary graft dysfunction (PGD), this condition increases mortality significantly. Complex interactions between donor lung and recipient immune system are the suspected cause. We took an integrative, systems-level approach by first exploring whether the recipient's immune response to PGD includes the development of long-lasting autoreactivity. We next explored whether proteins displaying such differential autoreactivity also display differential gene expression in donor lungs that later develop PGD compared with those that did not. We evaluated 39 patients from whom autoantibody profiles were already available for PGD based on chest radiographs and oxygenation data. An additional nine patients were evaluated for PGD based on their medical records and set aside for validation. From two recent donor lung gene expression studies, we reanalysed and paired gene profiles with autoantibody profiles. Primary graft dysfunction can be distinguished by a profile of differentially reactive autoantibodies binding to 17 proteins. Functional analysis showed that 12 of these proteins are part of a protein–protein interaction network (P=3 × 10−6) involved in proliferative processes. A nearest centroid classifier assigned correct PGD grades to eight out of the nine patients in the validation cohort (P=0·048). We observed significant positive correlation (r=0·63, P=0·011) between differences in IgM reactivity and differences in gene expression levels. This connection between donor lung gene expression and long-lasting recipient IgM autoantibodies towards a specific set of proteins suggests a mechanism for the development of autoimmunity in PGD. PMID:21070236

  19. Extracorporeal CO2 removal as bridge to lung transplantation in life-threatening hypercapnia.

    PubMed

    Schellongowski, Peter; Riss, Katharina; Staudinger, Thomas; Ullrich, Roman; Krenn, Claus G; Sitzwohl, Christian; Bojic, Andja; Wohlfarth, Philipp; Sperr, Wolfgang R; Rabitsch, Werner; Aigner, Clemens; Taghavi, Shahrokh; Jaksch, Peter; Klepetko, Walter; Lang, György

    2015-03-01

    In patients awaiting lung transplantation (LTX), adequate gas exchange may not be sufficiently achieved by mechanical ventilation alone if acute respiratory decompensation arises. We report on 20 patients with life-threatening hypercapnia who received extracorporeal CO2 removal (ECCO2-R) by means of the interventional lung assist (ILA®, Novalung) as bridge to LTX. The most common underlying diagnoses were bronchiolitis obliterans syndrome, cystic fibrosis, and idiopathic pulmonary fibrosis, respectively. The type of ILA was pumpless arteriovenous or pump-driven venovenous (ILA activve®, Novalung) in 10 patients each. ILA bridging was initiated in 15 invasively ventilated and five noninvasively ventilated patients, of whom one had to be intubated prior to LTX. Hypercapnia and acidosis were effectively corrected in all patients within the first 12 h of ILA therapy: PaCO2 declined from 109 (70-146) to 57 (45-64) mmHg, P < 0.0001; pH increased from 7.20 (7.06-7.28) to 7.39 (7.35-7.49), P < 0.0001. Four patients were switched to extracorporeal membrane oxygenation due to progressive hypoxia or circulatory failure. Nineteen patients (95%) were successfully transplanted. Hospital and 1-year survival was 75 and 72%, respectively. Bridging to LTX with ECCO2-R delivered by arteriovenous pumpless or venovenous pump-driven ILA is feasible and associated with high transplantation and survival rates.

  20. Reducing Stress and Anxiety in Caregivers of Lung Transplant Patients: Benefits of Mindfulness Meditation

    PubMed Central

    Haines, J.; Spadaro, K. C.; Choi, J.; Hoffman, L. A.; Blazeck, A. M.

    2014-01-01

    Background: Caregivers are a vital resource in the care of transplant candidates or recipients. However, few strategies have been tested that attempt to decrease the stress and anxiety they commonly encounter. Objective: To test the feasibility of using mindfulness-based stress reduction (MBSR) techniques to decrease stress and anxiety in caregivers of lung transplant candidates/recipients who required admission to an acute care facility. Methods: 30 caregivers of lung transplant candidates/recipients were recruited during hospitalization of their significant other. Each completed the perceived stress scale (PSS) and state trait anxiety inventory (STAI) before and 4 weeks after receiving a DVD that demonstrated MBSR techniques. Participants were asked to practice MBSR techniques for 5–15 min a day for 4 weeks. Results: The participants had a mean±SD age of 55.6±13.6 years; 77% of participants were female and 93% Caucasian. The mean PSS and STAI (trait and anxiety) scores of caregivers were higher than population norms pre- and post-intervention. Scores for caregivers who stated they watched the entire DVD and practiced MBSR techniques as requested (n=15) decreased significantly from pre- to post-testing for perceived stress (p=0.001), state anxiety (p=0.003) and trait anxiety (p=0.006). Scores for those who watched some or none of the DVD (n=15) did not change significantly. Conclusion: Caregivers can benefit from stress reduction techniques using MBSR. PMID:25013679

  1. Ochroconis gallopavum infection in a lung transplant recipient: report of a case.

    PubMed

    Brokalaki, E I; Sommerwerck, U; von Heinegg, E H; Hillen, U

    2012-11-01

    Disseminated phaeohyphomycoses are rare infections caused by dematiaceous fungi. Ochroconis gallopavum is a neurotropic dematiaceous mold responsible for life-threatening respiratory and central nervous system infections in domestic poultry and in immunologically compromised humans. The world literature describes only 13 previous O gallopavum infections in solid organ transplant recipients. We report herein an O gallopavum phaeohyphomycosis with involvement of skin in a transplant recipient. A 69-year-old white man with a history of bilateral lung transplantation 6 years ago presented with acute onset of severe respiratory distress. Chest X-ray showed no evidence of pneumonia. Lung function showed bronchiolitis obliterans syndrome. Excision biopsy was performed because of a suspected pigmented basal cell carcinoma. Histopathology revealed dermal granulomatous dermatitis, focally suppurative, dominated by epitheloid cells with brownish round fungi. Further microbiological work-up of the biopsy specimen subsequently revealed O gallopavum as the causative organism. No brain involvement was observed. Antimycotic therapy with voriconazole 200 mg twice a day was immediately initiated and the patient was treated for 3 months. Additional intravenous therapy with tobramycin and imipenem was started upon detection of Enterobacter clocae and Enterococci in the sputum. The patient recovered during the next few weeks and was discharged on day 26. PMID:23146522

  2. Primary human adult lung epithelial cells in vitro: response to interferon-gamma and cytomegalovirus.

    PubMed Central

    Ibrahim, L; Dominguez, M; Yacoub, M

    1993-01-01

    Primary human adult lung epithelial cells (ALEC) were established in culture using the most distal parts of the lung to avoid the airways. Immunocytochemical peroxidase staining and semiquantitative flow cytometry were used to characterize the cells in conjunction with a panel of monoclonal antibodies (mAb). The cells showed a constitutive expression of major histocompatibility complex (MHC) class I antigens, patchy expression of intercellular adhesion molecule-1 (ICAM-1) and a weak patchy expression of MHC class II antigens (detected using immunocytochemical staining). Incubation of the primary ALEC with interferon-gamma (IFN-gamma) (250 U/ml) stimulated an up-regulation of the expression of these three antigens to varying degrees; expression of MHC class I antigens and ICAM-1 molecules showed an up-regulation at 10 hr after the start of the treatment, reaching a peak at 48 hr, maintaining it for the next 24 hr and then, steadily and progressively, losing it towards the end of the experiment at 96 hr. Expression of HLA-DR showed an up-regulation at 17 hr after the start of the treatment, reaching a peak at 72 hr and maintaining it for the next 24 hr. Cytomegalovirus (CMV) infection of ALEC in culture caused an up-regulation of expression of class I antigens and ICAM-1, but not DR. However, when the infected cells were incubated with IFN-gamma, an up-regulation in the expression of DR took place. Therefore, within the micro-environment of the transplanted lung the presence of cytokines (IFN-gamma) produced by infiltrating activated mononuclear cells, may render the lung epithelial cells capable of acting as antigen-presenting cells, expressing high levels of class I antigens, ICAM-1 and class II antigens, activating CD8 and CD4 cells thus playing a major part in the process of rejection of the lung allograft; themselves becoming a primary target in the process. Images Figure 1 Figure 2 PMID:8099565

  3. Recurrence of pulmonary alveolar proteinosis after bilateral lung transplantation in a patient with a nonsense mutation in CSF2RB.

    PubMed

    Takaki, Masahiro; Tanaka, Takeshi; Komohara, Yoshihiro; Tsuchihashi, Yoshiko; Mori, Daisuke; Hayashi, Kentaro; Fukuoka, Junya; Yamasaki, Naoya; Nagayasu, Takeshi; Ariyoshi, Koya; Morimoto, Konosuke; Nakata, Koh

    2016-01-01

    Hereditary pulmonary alveolar proteinosis (PAP) caused by mutations in CSF2RA or CSF2RB, which encode GM-CSF receptor α and β respectively, is a rare disease. Although some experimental therapeutic strategies have been proposed, no clinical evidence has yet been reported. We herein describe the clinical course and recurrence of hereditary PAP after lung transplantation. A 36-year-old woman developed PAP of unknown etiology. She underwent bilateral lung transplantation from living donors at the age of 42 years because of severe respiratory failure complicated by pulmonary fibrosis. However, PAP recurred after 9 months, and we found that donor-origin alveolar macrophages had been almost completely replaced with recipient-origin macrophages. We performed a genetic analysis and identified a point deletion in the CSF2RB gene that caused a GM-CSF receptor-mediated signaling defect. PAP progressed with fibrosis in both transplanted lungs, and the patient died of respiratory failure 5 years after the lung transplantation. Distinct from recent reports on pulmonary macrophage transplantation in mice, this case suggests that human alveolar macrophages might not maintain their population only by self-renewal but may depend on a supply of precursor cells from the circulation. Bone marrow transplantation should be considered for treatment of severe PAP with GM-CSF receptor gene deficiency. PMID:27595063

  4. Predictors and influence of goal orientation on self-management and health-related quality of life after lung transplant.

    PubMed

    Zaldonis, Jenna; Alrawashdeh, Mohammad; Atman, Kathryn S; Fatigati, Angela; Dabbs, Annette DeVito; Bermudez, Christian A

    2015-09-01

    Context-Lung transplant recipients are encouraged to perform self-management behaviors to maximize health outcomes; however, performance is often less than ideal. Goal orientation is known to influence achievement of academic goals, but the influence of goal orientation on performance of self-management is unknown. Objectives-To identify characteristics at transplant that are predictive of higher goal orientation and examine relationships between Goal Orientation Index (GOI) subscores (Acting, Planning, Reflecting), self-management behaviors (adhering, self-monitoring, and communicating critical changes), and health-related quality of life (HRQOL) at 1 year after transplant. Design-A descriptive, secondary analysis of data from 33 lung transplant recipients who were assessed at transplant and followed for 1 year as part of a clinical trial. GOI subscores were dichotomized at the median to categorize recipients with high and low goal orientation. Logistic regression was used to identify predictors of higher GOI subscores. Correlations between higher GOI subscores, self-management, and HRQOL were examined. Results-Lung transplant recipients reported relatively high mean GOI subscores (Acting, Planning, and Reflecting) and the 3 subscores were correlated (r=0.31-0.86). Self-care agency was the only significant predictor (P=.04) of higher GOI (Reflecting). Lung transplant recipients with higher Planning and Reflecting subscores were more likely to adhere (r = 0.36 and 0.46, respectively). Recipients with higher GOI subscores reported significantly better mental HRQOL (r = 0.42-0.36). Recipients with higher GOI Planning or Acting subscores reported significantly less anxiety (r = -0.39-0.46) and fewer depressive symptoms (r = -0.40-0.43). Conclusion-Assessing goal orientation may offer a novel approach for promoting adherence and HRQOL after lung transplant. PMID:26308782

  5. Process of allogeneic hematopoietic cell transplantation decision making for older adults.

    PubMed

    Randall, J; Keven, K; Atli, T; Ustun, C

    2016-05-01

    Allogeneic hematopoietic cell transplantation (alloHCT) may be the only curative option for some older adults with hematologic malignancies, and its associated risks of significant morbidity and mortality warrant a clear, informed decision-making process. As older adults have not been transplanted routinely until recent years, younger people have been the prototypical group around whom the current process has developed. Yet, this process is applied to older adults who have different considerations than younger patients when making their transplant decision. Older adults do not have the open-ended lives of younger patients and are entitled to consider how to spend their remaining time. They also possess maturity and experience, and with proper knowledge, they can make informed choices rather than moving forward in the transplant process unaware. Notably, older patients face similar problems with the informed decision-making process in nephrology. Strategies such as providing education about alloHCT gradually and repeatedly during induction, presenting recent knowledge from the literature in plain language, and utilizing a team approach to patient education may help older adults make the best decision about transplant in light of their situation and values. Understanding when and how older adults decide on alloHCT is an important first step to further exploring this problem. PMID:26457910

  6. Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation

    PubMed Central

    Rivera-Lebron, Belinda N.; Kreider, Maryl; Lee, James; Kawut, Steven M.

    2016-01-01

    Abstract Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4–93.3) in 6-minute walk distance (P=0.02). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0–21.1; P<0.001). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1–29.5; P=0.006). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis. PMID:27076905

  7. Determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis undergoing lung transplant evaluation.

    PubMed

    Porteous, Mary K; Rivera-Lebron, Belinda N; Kreider, Maryl; Lee, James; Kawut, Steven M

    2016-03-01

    Little is known about the physiologic determinants of 6-minute walk distance in idiopathic pulmonary fibrosis. We investigated the demographic, pulmonary function, echocardiographic, and hemodynamic determinants of 6-minute walk distance in patients with idiopathic pulmonary fibrosis evaluated for lung transplantation. We performed a cross-sectional analysis of 130 patients with idiopathic pulmonary fibrosis who completed a lung transplantation evaluation at the Hospital of the University of Pennsylvania between 2005 and 2010. Multivariable linear regression analysis was used to generate an explanatory model for 6-minute walk distance. After adjustment for age, sex, race, height, and weight, the presence of right ventricular dilation was associated with a decrease of 50.9 m (95% confidence interval [CI], 8.4-93.3) in 6-minute walk distance ([Formula: see text]). For each 200-mL reduction in forced vital capacity, the walk distance decreased by 15.0 m (95% CI, 9.0-21.1; [Formula: see text]). For every increase of 1 Wood unit in pulmonary vascular resistance, the walk distance decreased by 17.3 m (95% CI, 5.1-29.5; [Formula: see text]). Six-minute walk distance in idiopathic pulmonary fibrosis depends in part on circulatory impairment and the degree of restrictive lung disease. Future trials that target right ventricular morphology, pulmonary vascular resistance, and forced vital capacity may potentially improve exercise capacity in patients with idiopathic pulmonary fibrosis.

  8. Fatal Scopulariopsis Infection in a Lung Transplant Recipient: Lessons of Organ Procurement

    PubMed Central

    Shaver, C. M.; Castilho, J. L.; Cohen, D. N.; Grogan, E. L.; Miller, G. G.; Dummer, J. S.; Gray, J.N.; Lambright, E. S.; Loyd, J.E.; Robbins, I. M.

    2014-01-01

    Seventeen days after double lung transplantation, a 56-year-old patient with idiopathic pulmonary fibrosis developed respiratory distress. Imaging revealed bilateral pulmonary infiltrates with pleural effusions and physical examination demonstrated sternal instability. Broad-spectrum antibacterial and antifungal therapy was initiated and bilateral thoracotomy tubes were placed. Both right and left pleural cultures grew a mold subsequently identified as Scopulariopsis brumptii. The patient underwent pleural irrigation and sternal debridement three times but pleural and wound cultures continued to grow S. brumptii. Despite treatment with five antifungal agents, the patient succumbed to his illness sixty-seven days after transplantation. Autopsy confirmed the presence of markedly invasive fungal disease and pleural rind formation. The patient’s organ donor had received bilateral thoracostomy tubes during resuscitation in a wilderness location. There were no visible pleural abnormalities at the time of transplantation. However, the patient’s clinical course and the location of the infection, in addition to the lack of similar infection in other organ recipients, strongly suggest that Scopulariopsis was introduced into the pleural space during pre-hospital placement of thoracostomy tubes. This case of lethal infection transmitted through transplantation highlights the unique risk of using organs from donors who are resuscitated in an outdoor location. PMID:25376207

  9. Lung and heart-lung transplantation for systemic sclerosis patients. A monocentric experience of 13 patients, review of the literature and position paper of a multidisciplinary Working Group.

    PubMed

    Launay, David; Savale, Laurent; Berezne, Alice; Le Pavec, Jérôme; Hachulla, Eric; Mouthon, Luc; Sitbon, Olivier; Lambert, Benoit; Gaudric, Marianne; Jais, Xavier; Stephan, Francois; Hatron, Pierre-Yves; Lamblin, Nicolas; Vignaux, Olivier; Cottin, Vincent; Farge, Dominique; Wallaert, Benoît; Guillevin, Loic; Simonneau, Gerald; Mercier, Olaf; Fadel, Elie; Dartevelle, Philippe; Humbert, Marc; Mussot, Sacha

    2014-10-01

    Systemic sclerosis per se should not be considered as an a priori contraindication for a pre-transplantation assessment in patients with advanced interstitial lung disease and/or pulmonary hypertension. For lung or heart-lung transplantation, a multidisciplinary approach, adapting the pre-transplant assessment to systemic sclerosis and optimizing systemic sclerosis patient management before, during and after surgery should improved the short- and long-term prognosis. Indications and contraindications for transplantation have to be adapted to the specificities of systemic sclerosis. A special focus on the digestive tract involvement and its thorough evaluation are mandatory before transplantation in systemic sclerosis. As the esophagus is almost always involved, isolated gastro-oesophageal reflux disease, pH metry and/or manometry abnormalities should not be a systematic per se contraindication for pre-transplantation assessment. Corticosteroids may be harmful in systemic sclerosis as they are associated with acute renal crisis. A low dose corticosteroids protocol for immunosuppression is therefore advisable in systemic sclerosis.

  10. Ex Vivo Adenoviral Vector Gene Delivery Results in Decreased Vector-associated Inflammation Pre- and Post–lung Transplantation in the Pig

    PubMed Central

    Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

    2012-01-01

    Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

  11. Ex vivo adenoviral vector gene delivery results in decreased vector-associated inflammation pre- and post-lung transplantation in the pig.

    PubMed

    Yeung, Jonathan C; Wagnetz, Dirk; Cypel, Marcelo; Rubacha, Matthew; Koike, Terumoto; Chun, Yi-Min; Hu, Jim; Waddell, Thomas K; Hwang, David M; Liu, Mingyao; Keshavjee, Shaf

    2012-06-01

    Acellular normothermic ex vivo lung perfusion (EVLP) is a novel method of donor lung preservation for transplantation. As cellular metabolism is preserved during perfusion, it represents a potential platform for effective gene transduction in donor lungs. We hypothesized that vector-associated inflammation would be reduced during ex vivo delivery due to isolation from the host immune system response. We compared ex vivo with in vivo intratracheal delivery of an E1-, E3-deleted adenoviral vector encoding either green fluorescent protein (GFP) or interleukin-10 (IL-10) to porcine lungs. Twelve hours after delivery, the lung was transplanted and the post-transplant function assessed. We identified significant transgene expression by 12 hours in both in vivo and ex vivo delivered groups. Lung function remained excellent in all ex vivo groups after viral vector delivery; however, as expected, lung function decreased in the in vivo delivered adenovirus vector encoding GFP (AdGFP) group with corresponding increases in IL-1β levels. Transplanted lung function was excellent in the ex vivo transduced lungs and inferior lung function was seen in the in vivo group after transplantation. In summary, ex vivo delivery of adenoviral gene therapy to the donor lung is superior to in vivo delivery in that it leads to less vector-associated inflammation and provides superior post-transplant lung function. PMID:22453765

  12. Kidney transplantation in HIV-positive adults: the UK experience.

    PubMed

    Gathogo, Esther N; Hamzah, Lisa; Hilton, Rachel; Marshall, Neal; Ashley, Caroline; Harber, Mark; Levy, Jeremy B; Jones, Rachael; Boffito, Marta; Khoo, Saye H; Drage, Martin; Bhagani, Sanjay; Post, Frank A

    2014-01-01

    HIV-positive patients are at increased risk of end-stage kidney disease (ESKD). Kidney transplantation (KT) is an established treatment modality for ESKD in the general population. Recent data have confirmed the feasibility of kidney transplantation in HIV-positive patients, and kidney transplantation is increasingly offered to ESKD patients with well-controlled HIV infection. We report clinical outcomes in a national cohort study of kidney transplantation in HIV-positive patients. In all, 35 HIV-positive KT recipients who had undergone KT up to December 2010 (66% male, 74% black ethnicity) were identified; the median CD4 cell count was 366, all had undetectable HIV RNA levels at kidney transplantation, and 44% received a kidney from a live donor. Patient survival at 1 and 3 years was 91.3%, and graft survival 91.3% and 84.7%, respectively. At one-year post-kidney transplantation, the cumulative incidence of acute rejection was 48%, and the median (IQR) eGFR was 64 (46, 78) mL/min/1.73 m(2). Although HIV viraemia and HIV disease progression were uncommon, renal complications were relatively frequent. Our study corroborates the feasibility of kidney transplantation in HIV-positive patients. The high rates of acute rejection suggest that the optimal immune suppression strategy in this population remains to be refined.

  13. The Association between Sarcopenia and the Risk of Serious Infection among Adults Undergoing Liver Transplantation

    PubMed Central

    Krell, Robert W.; Kaul, Daniel R.; Martin, Andrew R.; Englesbe, Michael J.; Sonnenday, Christopher J.; Cai, Shijie; Malani, Preeti N.

    2013-01-01

    Background While sarcopenia (muscle loss) is associated with increased mortality after liver transplant, its influence on other complications is less well understood. We examined the association between sarcopenia and the risk of severe post-transplant infections among adult liver transplant recipients. Methods We assessed sarcopenia among 207 liver transplant recipients by calculating total psoas area (TPA) on preoperative computed tomography scans. The presence or absence of severe post-transplant infection was determined by review of the medical chart. The influence of post-transplant infection on overall survival was also assessed. Results We identified 196 episodes of severe infections among 111 patients. Fifty-six patients had more than one infection. The median time to development of infection was 27 days (range 13–62). When grouped by tertiles, patients in the lowest tertile had a more than four-fold higher odds of developing severe infection compared to patients in the highest tertile; OR 4.6, CI 95 2.3–9.5). In multivariable analysis, recipient age (hazard ratio 1.04, p=0.02), pre-transplant TPA (hazard ratio 0.38, p<0.01) and pre-transplant total bilirubin level (hazard ratio 1.05, p=0.02) were independently associated with the risk of developing severe infections. Patients with severe post-transplant infections had worse 1-year survival compared to patients without infection (76% vs. 92%, p=0.003). Conclusions Among patients undergoing liver transplantation, lower TPA was associated with heightened risk for post-transplant infectious complications and mortality. Future efforts should focus on approaches to assess and mitigate vulnerability among patients undergoing transplantation. PMID:24151041

  14. [Kidney transplantation from paediatric cadaveric donors to adult recipients (review article)].

    PubMed

    Michalský, R

    2003-01-01

    The basic problem of all developed transplant programs is organs deficiency available for transplantation. There is an effort within last 10 years to get each organ for transplantation that it is supposed to be functional for several years. These problems also occur in the program of kidney transplantation. Apart from realizing of kidney transplantations from donors alive, which have an increasing tendency in Czech Republic (in 2001 more than 5%, in 2002 more than 10%), there is the only another possibility to get kidney grafts from non-ideal (suboptimal, marginal) donors. Both short-term and long-term results of kidney transplantation from non-ideal donors are comparable with the transplantation results from ideal donors. The kidneys from very young paediatric cadaveric donors, especially up to five years are the typical example of non-ideal graft. The article introduces the international position of the Czech Republic in organ procurement from cadaveric donors as well as in kidney transplantations. It shortly summarizes the history of kidney transplantations and at the same time it deals with realizing of kidney transplantation from paediatric cadaveric donors to adult recipients. The new division of kidney grafts from paediatric cadaveric donors into four groups according to their age is introduced. All at once the present surgical technique is described and the problems of some post-operative complications are discussed, especially the higher occurrence of primary graft non-function. The principle that kidneys from donor up to three years should be transplanted as a block to the single recipient is emphasized. In conclusion the author recommends, on the basis of his own experiences, the realizing of these transplantations.

  15. The potential role of activin and follistatin in lung transplant dysfunction.

    PubMed

    Snell, James N; Westall, Glen P; Snell, Gregory I

    2015-01-01

    Activin A, a member of the transforming growth factor β super-family, is a key regulator of multiple biological pathways including the physiological processes of organ development and homeostasis; as well as the pathological processes of inflammation, remodelling and fibrosis. Dysregulation of activin A and its naturally occurring antagonist follistatin, contribute to the development of disease in multiple organ systems. In this review, we summarize the regulation of activin A, its dysregulated expression in a number of respiratory diseases and postulate its potential role in contributing to allograft dysfunction following lung transplantation.

  16. Percutaneous dilatation of right inferior pulmonary vein stenosis following single-lung transplant

    PubMed Central

    Mohamed Mydin, Muhammad I.; Calvert, Patrick A.; Jenkins, David P.; Parmar, Jasvir

    2012-01-01

    We present a 62-year old male who underwent right single-lung transplantation. An autologous pericardial rim was constructed at implantation, as there was insufficient donor atrial cuff. The patient was discharged home but deteriorated over 12 months resulting in oxygen dependency. Computed tomography scan showed stenosis of the right inferior pulmonary vein. The patient underwent pulmonary vein angioplasty under general anaesthesia in September 2007, which was successful and resulted in significant improvement in clinical status. However, his symptoms recurred 2 months later and a second attempt at angioplasty failed. He died 6 weeks later. PMID:22611185

  17. Quality Improvement Targeting Adherence During the Transition from a Pediatric to Adult Liver Transplant Clinic.

    PubMed

    Fredericks, Emily M; Magee, John C; Eder, Sally J; Sevecke, Jessica R; Dore-Stites, Dawn; Shieck, Victoria; Lopez, M James

    2015-09-01

    The transition from pediatric to adult transplant care is a high risk period for non-adherence and poor health outcomes. This article describes a quality improvement initiative integrated into a pediatric liver transplant program that focused on improving outcomes following the transfer from pediatric to adult liver transplant care. Using improvement science methodology, we evaluated the impact of our center's transition readiness skills (TRS) program by conducting a chart review of 45 pediatric liver transplant recipients who transferred to adult transplant care. Medication adherence, clinic attendance, and health status variables were examined for the year pre-transfer and first year post-transfer. 19 recipients transferred without participating in the TRS program (control group) and 26 recipients participated in the program prior to transferring to the adult clinic (TRS group). The TRS group was significantly older at the time of transfer, more adherent with medications, and more likely to attend their first adult clinic visit compared to the control group. Among the TRS group, better adolescent and parent regimen knowledge were associated with greater adherence to post-transfer clinic appointments. Transition planning should focus on the gradual shift in responsibility for health management tasks, including clinic attendance, from parent to adolescent. There may be support for extending transition support for at least 1 year post-transfer to promote adherence.

  18. Surgical transplantation of adult Dirofilaria immitis to study heartworm infection and disease in dogs.

    PubMed

    Rawlings, C A; McCall, J W

    1985-01-01

    Heartworm infections were established in dogs by surgical transplantation of adult heartworms into the external jugular vein. The heartworms were obtained from donor dogs that had been infected with large numbers of infective larvae. This heartworm model standardized the infection with a known number of heartworms of a known age and sex. This paper presents the methods for obtaining heartworms from donor dogs, for selection of recipient dogs, and for transplantation of heartworms.

  19. Hydrogen Sulfide Decreases Reactive Oxygen in a Model of Lung Transplantation

    PubMed Central

    George, Timothy J.; Arnaoutakis, George J.; Beaty, Claude A.; Jandu, Simran K.; Santhanam, Lakshmi; Berkowitz, Dan E.; Shah, Ashish S.

    2012-01-01

    Objectives Ischemia-reperfusion injury(IRI) is a common complication following lung transplantation(LTx). IRI is thought to be mediated by reactive oxygen species(ROS). Hydrogen sulfide(H2S) is a novel agent that has been previously shown to scavenge ROS and slow metabolism. We evaluated the impact of infused H2S on the presence of ROS after reperfusion in an ex vivo model of LTx. Methods Heart-Lung blocks were recovered from New Zealand White rabbits(n=12) and cold stored in Perfadex solution for 18 hours. Following storage, the heart-lung blocks were reperfused ex vivo with donor rabbit blood. In the treatment group(n=7), a bolus of sodium hydrogen sulfide was added at the beginning of reperfusion(100ug/kg) and continuously infused throughout the two hour experiment(1mg/kg/hr). The vehicle group(n=5) received an equivalent volume of saline. Serial airway and pulmonary artery pressures were measured along with arterial and venous blood gases. Results Oxygenation and pulmonary artery pressures were similar between the two groups. However, treatment with H2S resulted in a dramatic reduction in the presence of ROS after 2 hours of reperfusion(4851 ± 2139 vs. 235 ± 462 RFU/mg protein, p=0.003). There was a trend toward increased levels of cGMP in the H2S treated group(3.08 ± 1.69 vs. 1.73 ± 1.41 fmol/mg tissue, p=0.23). Conclusions After prolonged ischemia, infusion of H2S during reperfusion is associated with a significant decrease in the presence of ROS, a suspected mediator of IRI. To our knowledge, this study represents the first reported therapeutic use of H2S in an experimental model of lung transplant. PMID:22464394

  20. Successful Lung Transplant After Prolonged Extracorporeal Membrane Oxygenation (ECMO) in a Child With Pulmonary Hypertension: A Case Report

    PubMed Central

    Tissot, Cecile; Habre, Walid; Soccal, Paola; Hug, Maja Isabel; Bettex, Dominique; Pellegrini, Michel; Aggoun, Yacine; Mornand, Anne; Kalangos, Afksendyios; Rimensberger, Peter; Beghetti, Maurice

    2016-01-01

    Introduction The use of extracorporeal membrane oxygenation (ECMO) is considered a risk factor for, or even a potential contraindication to, lung transplantation. However, only a few pediatric cases have been described thus far. Case Presentation A 9-year-old boy with idiopathic pulmonary arterial hypertension developed cardiac arrest after the insertion of a central catheter. ECMO was used as a bridge to lung transplantation. However, after prolonged resuscitation, he developed medullary ischemia and medullary syndrome. After 6 weeks of ECMO and triple combination therapy for pulmonary hypertension, including continuous intravenous prostacyclin, he was weaned off support, and after 2 weeks, bilateral lung transplantation was performed. At 4 years post-transplant, he has minimal problems. The medullary syndrome has also alleviated. He is now back to school and can walk with aids. Conclusions Increasing evidence supports the use of ECMO as a bridge to LT, reporting good outcomes. In the modern era of PAH therapy, it is feasible to use prolonged ECMO support as a bridge to lung transplant, with the aim of weaning off this support; however, its use requires more experience and knowledge of long-term outcomes. PMID:27800456

  1. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL). PMID:27000734

  2. Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.

    PubMed

    Claude Gorin, Norbert

    2016-04-01

    The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).

  3. Adult liver transplantation in the congenital absence of inferior vena cava.

    PubMed

    Angelico, R; Stonelake, S; Perera, D S; Mirza, D F; Russell, S; Muiesan, P; Perera, M T P R

    2015-10-01

    Whereas congenital absence of inferior vena cava observed in paediatric population more often than not, as an isolated or syndromic variety, this is seldom encountered in adult liver transplant recipients. There appear few sporadic reports in the literature on experience of such anomaly in adults. Given the rarity of situation, surprising encounters of such anomalies may pose challenge to the unprepared transplant surgeon and unfavourable outcomes may even have resulted in under-reportage of this condition. In this brief report we document our recent experience with two such cases and this is supplemented with extensive reference to the literature on classification of such anomalies with the endeavour to document implications of such in the adult liver transplant setting. PMID:26278662

  4. Early subclinical coronary artery calcification in young adults who were pediatric kidney transplant recipients.

    PubMed

    Ishitani, Michael B; Milliner, Dawn S; Kim, Dean Y; Bohorquez, Humberto E; Heimbach, Julie K; Sheedy, Patrick F; Morgenstern, Bruce Z; Gloor, James M; Murphy, Joseph G; McBane, Robert D; Bielak, Lawrence F; Peyser, Patricia A; Stegall, Mark D

    2005-07-01

    Coronary artery disease (CAD) is the leading cause of death in adults after successful kidney transplantation. Children who have undergone successful kidney transplantation are entering young adulthood; however, the prevalence and extent of CAD in this population is unknown. We conducted a pilot study in young adults with stable allograft function, who received kidney transplants as children to measure coronary artery calcification (CAC), a marker of coronary artery atherosclerosis and CAD. We evaluated 19 young adults after successful pediatric kidney transplantation for known CAD risk factors; these patients underwent noninvasive imaging with electron-beam computed tomography (EBCT) for measurement of CAC. Prevalence and quantity of CAC were then compared to asymptomatic individuals from the community. All patients had multiple risk factors for CAD. Mean age at evaluation was 32 years (range: 21-48 years). CAC is uncommon in individuals in the community in this age range; however, nearly half of our patients had CAC detected with the quantity of CAC comparable to asymptomatic individuals from the community 10-40 years older. These data suggest young adults who received pediatric kidney transplants are at increased risk for developing early CAC and need close monitoring to detect early CAD so as to prevent premature cardiac morbidity and mortality. PMID:15943627

  5. Bridge to thoracic organ transplantation in patients with pulmonary arterial hypertension using a pumpless lung assist device.

    PubMed

    Strueber, M; Hoeper, M M; Fischer, S; Cypel, M; Warnecke, G; Gottlieb, J; Pierre, A; Welte, T; Haverich, A; Simon, A R; Keshavjee, S

    2009-04-01

    We describe a novel technique of pumpless extracorporeal life support in four patients with cardiogenic shock due to end-stage pulmonary hypertension (PH) including patients with veno-occlusive disease (PVOD) using a pumpless lung assist device (LAD). The device was connected via the pulmonary arterial main trunk and the left atrium, thereby creating a septostomy-like shunt with the unique addition of gas exchange abilities in parallel to the lung. Using this approach, all four patients were successfully bridged to bilateral lung transplantation and combined heart-lung transplantation, respectively. Although all patients presented in cardiogenic shock, hemodynamic unloading of the right ventricle using the low-resistance LAD stabilized the hemodynamic situation immediately so that no pump support was subsequently required. PMID:19344471

  6. Utilization of the Organ Care System Lung for the assessment of lungs from a donor after cardiac death (DCD) before bilateral transplantation.

    PubMed

    Mohite, P N; Sabashnikov, A; García Sáez, D; Pates, B; Zeriouh, M; De Robertis, F; Simon, A R

    2015-07-01

    In this manuscript, we present the first experience of evaluating donation after circulatory death (DCD) lungs, using the normothermic preservation Organ Care System (OCS) and subsequent successful transplantation. The OCS could be a useful tool for the evaluation of marginal lungs from DCD donors as it allows a proper recruitment and bronchoscopy in such donations in addition to continuous ex-vivo perfusion and assessment and treatment during transport. The OCS could potentially be a standard of care in the evaluation of marginal lungs from DCD.

  7. Morbimortality in heart and lung transplantation in Cuba: a 20-year follow-up.

    PubMed

    Bazán Milián, M; Delgado Bereijo, L; González Jiménez, N

    2009-10-01

    The first orthotopic heart transplantation (OHT) was performed in 1967 by C.N. Barnard in Cape Town, South Africa. The first OHT in Cuba was performed in 1985. The main purpose of our study was to determine some of the aspects related to the short-, mid-, and long-term morbimortality rates of OHT patients in Cuba. We analyzed the first 120 OHTs (3 heart plus lung transplantations, 4 retransplantations, and 113 heart transplantations) which were performed in Cuba from December 1985 to December 2005. Based on the analysis, we performed a descriptive, retrospective research about morbimortality. There was a predominance of the masculine sex (5.31:1). The overall mean age was 45.13 +/- 11.58 years (range, 14-67 years). The most frequent pretransplant diagnosis was coronary artery disease (CAD; n = 69; 57.5%). Analyzing the Kaplan-Meier survival curve, we observed that the survival probability at 1 year was 83.3%; at 5 years, 45.7%; and at 10 years 19.2%. The complications by frequency were: sepsis (n = 41; 37%), acute rejection episodes (n = 42; 35.0%), and neoplasia (n = 4; 3.3%). Complications in frequency order were sepsis and acute rejection episodes among short term and chronic rejection and chronic renal failure among long-term survivors.

  8. Access to adult liver transplantation in Canada: a survey and ethical analysis.

    PubMed Central

    Mullen, M A; Kohut, N; Sam, M; Blendis, L; Singer, P A

    1996-01-01

    OBJECTIVES: To describe the substantive and procedural criteria used for placing patients on the waiting list for liver transplantation and for allocating available livers to patients on the waiting list; to identify principal decision-makers and the main factors limiting liver transplantation in Canada; and to examine how closely cadaveric liver allocation resembles theoretic models of source allocation. DESIGN: Mailed survey. PARTICIPANTS: Medical directors of all seven Canadian adult liver transplantation centres, or their designates. Six of the questionnaires were completed. OUTCOME MEASURES: Relative importance of substantive and procedural criteria used to place patients in the waiting list for liver transplantation and to allocate available livers. Identification of principal decision-makers and main limiting factors to adult liver transplantation. RESULTS: Alcoholism, drug addiction, HIV positivity, primary liver cancer, noncompliance and hepatitis B were the most important criteria that had a negative influence on decisions to place patients on the waiting list for liver transplantation. Severity of disease and urgency were the most important criteria used for selecting patients on the waiting list for transplantation. Criteria that were inconsistent across the centres included social support (for deciding who is placed on the waiting list) and length of time on the waiting list (for deciding who is selected from the list). Although a variety of people were reported as being involved in these decisions, virtually all were reported to be health to be health care professionals. Thirty-seven patients died while waiting for liver transplantation in 1991; the scarcity of cadaveric livers was the main limiting factor. CONCLUSIONS: Criteria for resource allocation decisions regarding liver transplantation are generally consistent among the centres across Canada, although some important inconsistencies remain. Because patients die while on the waiting list and

  9. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation.

    PubMed

    Budding, Kevin; van de Graaf, Eduard A; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M; Luijk, Bart D; Oudijk, Erik-Jan D; van Kessel, Diana A; Grutters, Jan C; Hack, C Erik; Otten, Henderikus G

    2016-05-24

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx.

  10. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation.

    PubMed

    Budding, Kevin; van de Graaf, Eduard A; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M; Luijk, Bart D; Oudijk, Erik-Jan D; van Kessel, Diana A; Grutters, Jan C; Hack, C Erik; Otten, Henderikus G

    2016-01-01

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx. PMID:27215188

  11. Soluble CD59 is a Novel Biomarker for the Prediction of Obstructive Chronic Lung Allograft Dysfunction After Lung Transplantation

    PubMed Central

    Budding, Kevin; van de Graaf, Eduard. A.; Kardol-Hoefnagel, Tineke; Kwakkel-van Erp, Johanna M.; Luijk, Bart D.; Oudijk, Erik-Jan D.; van Kessel, Diana A.; Grutters, Jan C.; Hack, C. Erik; Otten, Henderikus G.

    2016-01-01

    CD59 is a complement regulatory protein that inhibits membrane attack complex formation. A soluble form of CD59 (sCD59) is present in various body fluids and is associated with cellular damage after acute myocardial infarction. Lung transplantation (LTx) is the final treatment for end-stage lung diseases, however overall survival is hampered by chronic lung allograft dysfunction development, which presents itself obstructively as the bronchiolitis obliterans syndrome (BOS). We hypothesized that, due to cellular damage and activation during chronic inflammation, sCD59 serum levels can be used as biomarker preceding BOS development. We analyzed sCD59 serum concentrations in 90 LTx patients, of whom 20 developed BOS. We observed that BOS patients exhibited higher sCD59 serum concentrations at the time of diagnosis compared to clinically matched non-BOS patients (p = 0.018). Furthermore, sCD59 titers were elevated at 6 months post-LTx (p = 0.0020), when patients had no BOS-related symptoms. Survival-analysis showed that LTx patients with sCD59 titers ≥400 pg/ml 6 months post-LTx have a significant (p < 0.0001) lower chance of BOS-free survival than patients with titers ≤400 pg/ml, 32% vs. 80% respectively, which was confirmed by multivariate analysis (hazard ratio 6.2, p < 0.0001). We propose that circulating sCD59 levels constitute a novel biomarker to identify patients at risk for BOS following LTx. PMID:27215188

  12. Using the inherent chemistry of the endothelin-1 peptide to develop a rapid assay for pre-transplant donor lung assessment.

    PubMed

    Sage, Andrew T; Bai, Xiaohui; Cypel, Marcelo; Liu, Mingyao; Keshavjee, Shaf; Kelley, Shana O

    2015-12-21

    Endothelin-1 is a potent vasoconstrictive peptide that plays an important role in ex vivo lung perfusion. ET-1 expression levels are predictive of lung transplant outcomes and represent a valuable monitoring tool for surgeons; however, traditional techniques that measure [ET-1] are not suitable for the transplant setting. Herein, we demonstrate a new assay that rapidly measures ET-1 peptide levels in lung perfusate. PMID:26548776

  13. Using the inherent chemistry of the endothelin-1 peptide to develop a rapid assay for pre-transplant donor lung assessment.

    PubMed

    Sage, Andrew T; Bai, Xiaohui; Cypel, Marcelo; Liu, Mingyao; Keshavjee, Shaf; Kelley, Shana O

    2015-12-21

    Endothelin-1 is a potent vasoconstrictive peptide that plays an important role in ex vivo lung perfusion. ET-1 expression levels are predictive of lung transplant outcomes and represent a valuable monitoring tool for surgeons; however, traditional techniques that measure [ET-1] are not suitable for the transplant setting. Herein, we demonstrate a new assay that rapidly measures ET-1 peptide levels in lung perfusate.

  14. Comparison of an advanced minimally invasive cardiac output monitoring with a continuous invasive cardiac output monitoring during lung transplantation.

    PubMed

    Tomasi, Roland; Prueckner, Stephan; Czerner, Stephan; Schramm, Renè; Preissler, Gerhard; Zwißler, Bernhard; von Dossow-Hanfstingl, Vera

    2016-08-01

    The aim of this study was to compare a continuous non-calibrated left heart cardiac index (CI) measurement by arterial waveform analysis (FloTrac(®)/Vigileo(®)) with a continuous calibrated right heart CI measurement by pulmonary artery thermodilution (CCOmbo-PAC(®)/Vigilance II(®)) for hemodynamic monitoring during lung transplantation. CI was measured simultaneously by both techniques in 13 consecutive lung transplants (n = 4 single-lung transplants, n = 9 sequential double-lung transplants) at distinct time points perioperatively. Linear regression analysis and Bland-Altman analysis with percentage error calculation were used for statistical comparison of CI measurements by both techniques. In this study the FloTrac(®) system underestimated the CI in comparison with the continuous pulmonary arterial thermodilution (p < 0.000). For all measurement pairs we calculated a bias of -0.55 l/min/m(2) with limits of agreement between -2.31 and 1.21 l/min/m(2) and a percentage error of 55 %. The overall correlations before clamping a branch oft the pulmonary artery (percentage error 41 %) and during the clamping periods of a branch oft the pulmonary artery (percentage error 66 %) failed to reached the required percentage error of less than 30 %. We found good agreement of both CI measurements techniques only during the measurement point "15 min after starting the second one-lung ventilation period" (percentage error 30 %). No agreement was found during all other measurement points. This pilot study shows for the first time that the CI of the FloTrac(®) system is not comparable with the continuous pulmonary-artery thermodilution during lung transplantation including the time periods without clamping a branch of the pulmonary artery. Arterial waveform and continuous pulmonary artery thermodilution are, therefore, not interchangeable during these complex operations.

  15. Inhaled Hydrogen Sulfide Improves Graft Function in an Experimental Model of Lung Transplantation

    PubMed Central

    George, Timothy J.; Arnaoutakis, George J.; Beaty, Claude A.; Jandu, Simran K.; Santhanam, Lakshmi; Berkowitz, Dan E.; Shah, Ashish S.

    2014-01-01

    Objectives: Ischemia-reperfusion(IRI) is a common complication of lung transplantation(LTx). Hydrogen sulfide(H2S) is a novel agent previously shown to slow metabolism and scavenge reactive oxygen species, potentially mitigating IRI. We hypothesized that pre-treatment with inhaled H2S would improve graft function in an ex vivo model of LTx. Methods: Rabbits(n=10) were ventilated for 2 hours prior to heart-lung bloc procurement. The treatment group(n=5) inhaled room air(21% O2) supplemented with 150 ppm H2S while the control group(n=5) inhaled room air alone. Both groups were gradually cooled to 34 C. All heart-lung blocs were then recovered and cold-stored in low potassium dextran solution for 18 hours. Following storage, the blocs were reperfused with donor rabbit blood in an ex vivo apparatus. Serial clinical parameters were assessed and serial tissue biochemistry was examined. Results: Prior to heart-lung bloc procurement, rabbits pre-treated with H2S exhibited similar oxygenation(p=0.1), ventilation(p=0.7), and heart rate(p=0.5); however, treated rabbits exhibited consistently higher mean arterial blood pressures(p=0.01). During reperfusion, lungs pre-treated with H2S had better oxygenation(p<0.01) and ventilation(p=0.02) as well as lower pulmonary artery pressures(p<0.01). Reactive oxygen species levels were lower in treated lungs during reperfusion(p=0.01). Additionally, prior to reperfusion, treated lungs demonstrated more preserved mitochondrial cytochrome c oxidase activity(p=0.01). Conclusions: To our knowledge, this study represents the first reported therapeutic use of inhaled H2S in an experimental model of LTx. After prolonged ischemia, lungs pre-treated with inhaled H2S exhibited improved graft function during reperfusion. Donor pre-treatment with inhaled H2S represents a potentially novel adjunct to conventional preservation techniques and merits further exploration. PMID:22771242

  16. A Comparison of Outcomes for Cord Blood Transplantation and Unrelated Bone Marrow Transplantation in Adult Aplastic Anemia.

    PubMed

    Kuwatsuka, Yachiyo; Kanda, Junya; Yamazaki, Hirohito; Mori, Takehiko; Miyamura, Koichi; Kako, Shinichi; Uchida, Naoyuki; Ohashi, Kazuteru; Ozawa, Yukiyasu; Takahashi, Yoshiyuki; Kato, Chiaki; Iwato, Koji; Ishiyama, Ken; Kobayashi, Hikaru; Eto, Tetsuya; Kahata, Kaoru; Kato, Jun; Miyamoto, Toshihiro; Kato, Koji; Mori, Shinicihro; Atsuta, Yoshiko; Kimura, Fumihiko; Kanda, Yoshinobu

    2016-10-01

    Earlier reports suggested that umbilical cord blood transplantation (UCBT) for aplastic anemia (AA) was feasible in alternative transplantation. To identify differences in outcomes of UCBT and HLA-matched or mismatched unrelated bone marrow transplantation (UBMT) in adults with AA, we analyzed registry data of the Japan Society for Hematopoietic Cell Transplantation and compared results of UCBT (n = 69) to 8/8-matched (n = 101), 7/8-matched (n = 65), or 6/8-matched (n = 37) UBMT. The transplantation period was from 2002 to 2012, and patients 16 years or older with AA were eligible. Median ages were 49, 35, 28, and 30 years for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively. In multivariate analysis, risk of mortality was lower for 8/8-matched UBMT compared with that of UCBT (hazard ratio [HR], .55; 95% confidence interval [CI], .32 to .94; P = .029), adjusted for age and graft-versus-host disease (GVHD) prophylaxis, which were other associated factors. Mortality risks of 7/8-matched UBMT (HR, .55; 95% CI, .29 to 1.02) or 6/8-matched UBMT (HR, .67; 95% CI, .32 to 1.39) were not significantly different from those of UCBT. Risks of grade 3 or 4 acute and chronic GVHD were not different among the 4 groups. The most prevalent cause of death was graft failure in UCBT and 6/8-matched UBMT and infection in 8/8-matched and 7/8-matched UBMT. Under 40 years old,survival of UCBT was similar to that of UBMT (76%, 79%, 83%, and 83% for UCBT and 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years), adjusted for transplantation period, which was another associated factor; however, for ages over 40 years, that of UCBT tended to be lower (47%, 64%, 64%, and 75% for UCBT, 8/8-matched, 7/8-matched, and 6/8-matched UBMT, respectively, at 3 years). To conclude, these data suggest that UCBT could be an alternative treatment option for younger adults when matched sibling or adequate UBMT donors are not available. PMID:27401034

  17. The Impact of Alemtuzumab and Basiliximab Induction on Patient Survival and Time to Bronchiolitis Obliterans Syndrome in Double Lung Transplantation Recipients.

    PubMed

    Furuya, Y; Jayarajan, S N; Taghavi, S; Cordova, F C; Patel, N; Shiose, A; Leotta, E; Criner, G J; Guy, T S; Wheatley, G H; Kaiser, L R; Toyoda, Y

    2016-08-01

    We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk-adjusted all-cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no-induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67-0.95, p = 0.009) and basiliximab induction (0.88, 0.80-0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS. PMID:26833657

  18. The Impact of Alemtuzumab and Basiliximab Induction on Patient Survival and Time to Bronchiolitis Obliterans Syndrome in Double Lung Transplantation Recipients.

    PubMed

    Furuya, Y; Jayarajan, S N; Taghavi, S; Cordova, F C; Patel, N; Shiose, A; Leotta, E; Criner, G J; Guy, T S; Wheatley, G H; Kaiser, L R; Toyoda, Y

    2016-08-01

    We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk-adjusted all-cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no-induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67-0.95, p = 0.009) and basiliximab induction (0.88, 0.80-0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS.

  19. The Interplay of "Big Five" Personality Factors and Metaphorical Schemas: A Pilot Study with 20 Lung Transplant Recipients

    ERIC Educational Resources Information Center

    Goetzmann, Lutz; Moser, Karin S.; Vetsch, Esther; Grieder, Erhard; Klaghofer, Richard; Naef, Rahel; Russi, Erich W.; Boehler, Annette; Buddeberg, Claus

    2007-01-01

    The aim of the present study was to investigate the interplay between personality factors and metaphorical schemas. The "Big Five" personality factors of 20 patients after lung transplantation were examined with the NEO-FFI. Patients were questioned about their social network, and self- and body-image. The interviews were assessed with metaphor…

  20. Disseminated Trichosporon mycotoxinivorans, Aspergillus fumigatus, and Scedosporium apiospermum Coinfection after Lung and Liver Transplantation in a Cystic Fibrosis Patient

    PubMed Central

    Letscher-Bru, Valérie; Pottecher, Julien; Lannes, Béatrice; Jeung, Mi Young; Degot, Tristan; Santelmo, Nicola; Sabou, Alina Marcela; Herbrecht, Raoul; Kessler, Romain

    2012-01-01

    Trichosporon mycotoxinivorans is a novel pathogen recently found in cystic fibrosis patients. We report the first case of a disseminated fatal infection with T. mycotoxinivorans associated with invasive Aspergillus fumigatus and Scedosporium apiospermum infection after lung and liver transplantation in a cystic fibrosis patient. PMID:23035187

  1. Right lobe split liver transplantation versus whole liver transplantation in adult recipients: A systematic review and meta-analysis.

    PubMed

    Wan, Ping; Li, Qigen; Zhang, Jianjun; Xia, Qiang

    2015-07-01

    Split liver transplantation (SLT) has proven to be an effective technique to reduce the mortality of children on the waiting list, but whether creating 2 split grafts from 1 standard-criteria whole liver would compromise outcomes of adult recipients remains uncertain. We conducted this meta-analysis to compare outcomes of right lobe SLT and whole liver transplantation (WLT) in adult patients. PubMed, Embase, and the Cochrane Library were searched for relevant articles published before December 2014. Outcomes assessed were patient survival (PS), graft survival (GS), and major surgical complications after transplantation. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to synthesize the results. Seventeen studies with a total of 48,457 patients met the full inclusion criteria. PS and GS rates were all found to be equivalent between SLT and WLT recipients. However, SLT was associated with higher rates of overall biliary complications (OR = 1.66; 95% CI = 1.29-2.15; P < 0.001), bile leaks (OR = 4.30; 95% CI = 2.97-6.23; P < 0.001), overall vascular complications (OR = 1.81; 95% CI = 1.29-2.53; P < 0.001), hepatic artery thromboses (OR = 1.71; 95% CI = 1.17-2.50; P = 0.005), and outflow tract obstructions (OR = 4.17; 95% CI = 1.75-9.94; P = 0.001). No significant difference was observed in incidences of biliary stricture, portal vein complications, postoperative bleeding requiring surgical treatments, primary nonfunction, and retransplantations. In subgroup analyses, biliary and vascular complications only increased after ex vivo SLT rather than in situ SLT, and SLT recipients had more retransplantations if they matched with WLT recipients in terms of urgent status. In conclusion, adult right lobe SLT was associated with increased biliary and vascular complications compared with WLT, but it did not show significant inferiority in PSs and GSs. PMID:25832308

  2. Kidney transplantation in an adult patient with VACTERL association.

    PubMed

    Cimen, Sertac; Nantais, Jordan; Guler, Sanem; Lawen, Joseph

    2015-01-01

    The vertebral, anal, cardiac, tracheoesophageal, renal, and limb birth defects (VACTERL) association is a rare, non-random constellation of congenital abnormalities among which urinary tract anomalies can be included. In the presence of these anomalies, patients are suspected to have a higher rate of renal failure than average. We report a case of a 22-year-old woman with VACTERL association and consequent end stage renal failure. A live-related kidney transplant was carried out successfully and the postoperative course was uncomplicated. The patient had immediate graft function. Risk factors that may complicate kidney transplant surgery in this patient population as well as considerations relevant to peritransplant management are discussed. PMID:26106170

  3. Relationship between Fungal Colonisation of the Respiratory Tract in Lung Transplant Recipients and Fungal Contamination of the Hospital Environment

    PubMed Central

    Brugière, Olivier; Chochillon, Christian; Porcher, Raphael; Boelle, Pierre-Yves; Menotti, Jean; Houze, Sandrine; Lucet, Jean-Christophe

    2015-01-01

    Background Aspergillus colonisation is frequently reported after lung transplantation. The question of whether aspergillus colonisation is related to the hospital environment is crucial to prevention. Method To elucidate this question, a prospective study of aspergillus colonisation after lung transplantation, along with a mycological survey of the patient environment, was performed. Results Forty-four consecutive patients were included from the day of lung transplantation and then examined weekly for aspergillus colonisation until hospital discharge. Environmental fungal contamination of each patient was followed weekly via air and surface sampling. Twelve patients (27%) had transient aspergillus colonisation, occurring 1–13 weeks after lung transplantation, without associated manifestation of aspergillosis. Responsible Aspergillus species were A. fumigatus (6), A. niger (3), A. sydowii (1), A. calidoustus (1) and Aspergillus sp. (1). In the environment, contamination by Penicillium and Aspergillus was predominant. Multivariate analysis showed a significant association between occurrence of aspergillus colonisation and fungal contamination of the patient’s room, either by Aspergillus spp. in the air or by A.fumigatus on the floor. Related clinical and environmental isolates were genotyped in 9 cases of aspergillus colonisation. For A. fumigatus (4 cases), two identical microsatellite profiles were found between clinical and environmental isolates collected on distant dates or locations. For other Aspergillus species, isolates were different in 2 cases; in 3 cases of aspergillus colonisation by A. sydowii, A. niger and A. calidoustus, similarity between clinical and environmental internal transcribed spacer and tubulin sequences was >99%. Conclusion Taken together, these results support the hypothesis of environmental risk of hospital acquisition of aspergillus colonisation in lung transplant recipients. PMID:26629994

  4. Complications and mortality after adult to adult living donor liver transplantation: A retrospective cohort study

    PubMed Central

    Gad, Emad Hamdy; Alsebaey, Ayman; Lotfy, Maha; Eltabbakh, Mohamed; Sherif, Ahmed Alshawadfy

    2015-01-01

    Background and aims Living donor liver transplantation (LDLT) is widely performed for patients to resolve the critical shortage of organs from cadavers. Despite rapid implementation of the procedure, both complications and mortality of LDLT are annoying problems. The aim of this study was to analyze complications and mortality of patients after adult to adult LDLT (A-ALDLT) in a single center. Methods: Between April 2003 and November 2013, 167 (A-ALDLT) recipients in National Liver Institute, Egypt were included. We retrospectively analyzed complications and mortality in them. Results The overall incidence of complications was 86.2% (n = 144) and classified as biliary 43.7% (n = 73), vascular 21.6% (n = 36), Small for size syndrome (SFSS) 12.6% (n = 21), Gastrointestinal tract (GIT) 19.8% (n = 33), wound 12.6% (n = 21), chest 19.8% (n = 33), neurological 26.3% (n = 44), renal 21% (n = 35), intra abdominal collection 21.6% (n = 36), recurrent hepatitis C virus (HCV) 16.8% (n = 28), recurrent hepatocellular carcinoma (HCC) 2.4% (n = 4), acute rejection 19.2% (n = 32). 65 (45.1%) of 144 complicated patients died, while 10 (43.5%) of 23 non complicated died. The incidence of whole, in hospital and late mortalities were 44.9%, 28.7% and 16.2% respectively. Conclusions: Mortality was higher among complicated cases where vascular complications and SFSS had significant effect on it so prevention and treatment of them is required for improving outcome. PMID:26005570

  5. Outcomes of Adolescent and Adult Patients with Lung Metastatic Osteosarcoma and Comparison of Synchronous and Metachronous Lung Metastatic Groups.

    PubMed

    Gok Durnali, Ayse; Paksoy Turkoz, Fatma; Ardic Yukruk, Fisun; Tokluoglu, Saadet; Yazici, Omer Kamil; Demirci, Ayse; Bal, Oznur; Gundogdu Buyukbas, Selay; Esbah, Onur; Oksuzoglu, Berna; Alkis, Necati

    2016-01-01

    Osteosarcomas with lung metastases are rather heterogenous group. We aimed to evaluate the clinicopathological characteristics and outcomes of osteosarcoma patients with lung metastases and to compare the synchronous and metachronous lung metastatic groups. A total of 93 adolescent and adult patients with lung metastatic osteosarcoma, from March 1995 to July 2011, in a single center, were included. Sixty-five patients (69.9%) were male. The median age was 19 years (range, 14-74). Thirty-nine patients (41.9%) had synchronous lung metastases (Group A) and 54 patients (58.1%) had metachronous lung metastases (Group B). The 5-year and 10-year post-lung metastases overall survival (PLM-OS) was 17% and 15%, respectively. In multivariate analysis for PLM-OS, time to lung metastases (p = 0.010), number of metastatic pulmonary nodules (p = 0.020), presence of pulmonary metastasectomy (p = 0.007) and presence of chemotherapy for lung metastases (p< 0.001) were found to be independent prognostic factors. The median PLM-OS of Group A and Group B was 16 months and 9 months, respectively. In Group B, the median PLM-OS of the patients who developed lung metastases within 12 months was 6 months, whereas that of the patients who developed lung metastases later was 16 months. Time to lung metastases, number and laterality of metastatic pulmonary nodules, chemotherapy for lung metastatic disease and pulmonary metastasectomy were independent prognostic factors for patients with lung metastatic osteosarcoma. The best PLM-OS was in the subgroup of patients treated both surgery and chemotherapy. The prognosis of the patients who developed lung metastases within 12 months after diagnosis was worst.

  6. Outcomes of Adolescent and Adult Patients with Lung Metastatic Osteosarcoma and Comparison of Synchronous and Metachronous Lung Metastatic Groups

    PubMed Central

    Gok Durnali, Ayse; Paksoy Turkoz, Fatma; Ardic Yukruk, Fisun; Tokluoglu, Saadet; Yazici, Omer Kamil; Demirci, Ayse; Bal, Oznur; Gundogdu Buyukbas, Selay; Esbah, Onur; Oksuzoglu, Berna; Alkis, Necati

    2016-01-01

    Osteosarcomas with lung metastases are rather heterogenous group. We aimed to evaluate the clinicopathological characteristics and outcomes of osteosarcoma patients with lung metastases and to compare the synchronous and metachronous lung metastatic groups. A total of 93 adolescent and adult patients with lung metastatic osteosarcoma, from March 1995 to July 2011, in a single center, were included. Sixty-five patients (69.9%) were male. The median age was 19 years (range, 14–74). Thirty-nine patients (41.9%) had synchronous lung metastases (Group A) and 54 patients (58.1%) had metachronous lung metastases (Group B). The 5-year and 10-year post-lung metastases overall survival (PLM-OS) was 17% and 15%, respectively. In multivariate analysis for PLM-OS, time to lung metastases (p = 0.010), number of metastatic pulmonary nodules (p = 0.020), presence of pulmonary metastasectomy (p = 0.007) and presence of chemotherapy for lung metastases (p< 0.001) were found to be independent prognostic factors. The median PLM-OS of Group A and Group B was 16 months and 9 months, respectively. In Group B, the median PLM-OS of the patients who developed lung metastases within 12 months was 6 months, whereas that of the patients who developed lung metastases later was 16 months. Time to lung metastases, number and laterality of metastatic pulmonary nodules, chemotherapy for lung metastatic disease and pulmonary metastasectomy were independent prognostic factors for patients with lung metastatic osteosarcoma. The best PLM-OS was in the subgroup of patients treated both surgery and chemotherapy. The prognosis of the patients who developed lung metastases within 12 months after diagnosis was worst. PMID:27167624

  7. [Video-assisted thoracic surgery, lung transplantation and mediastinitis: major issues in thoracic surgery in 2010].

    PubMed

    Borro, José M; Moreno, Ramón; Gómez, Ana; Duque, José Luis

    2011-01-01

    We reviewed the major issues in thoracic surgery relating to the advances made in our specialty in 2010. To do this, the 43(rd) Congress of the Spanish Society of Pneumology and Thoracic Surgery held in La Coruña and the articles published in the Society's journal, Archivos de Bronconeumología, were reviewed. The main areas of interest were related to the development of video-assisted thoracic surgery, lung transplantation and descending mediastinitis. The new tumor-node-metastasis (TNM) classification (7(th) edition), presented last year, was still a topical issue this year. The First Forum of Thoracic Surgeons and the Update in Thoracic Surgery together with the Nurses' Area have constituted an excellent teaching program. PMID:21300211

  8. Conventional vs. Tablet Computer-Based Patient Education following Lung Transplantation – A Randomized Controlled Trial

    PubMed Central

    Suhling, Hendrik; Rademacher, Jessica; Zinowsky, Imke; Fuge, Jan; Greer, Mark; Warnecke, Gregor; Smits, Jacqueline M.; Bertram, Anna; Haverich, Axel; Welte, Tobias; Gottlieb, Jens

    2014-01-01

    Background Accurate immunosuppression is of critical importance in preventing rejection, while avoiding toxicity following lung transplantation. The mainstay immunosuppressants are calcineurin inhibitors, which require regular monitoring due to interactions with other medications and diet. Adherence to immunosuppression and patient knowledge is vital and can be improved through patient education. Education using tablet-computers was investigated. Objective To compare tablet-PC education and conventional education in improving immunosuppression trough levels in target range 6 months after a single education. Secondary parameters were ratio of immunosuppression level measurements divided by per protocol recommended measurements, time and patient satisfaction regarding education. Design Single-centre, open labelled randomised controlled trial. Participants Patients >6 months after lung-transplantation with <50% of calcineurin inhibitor trough levels in target range. Intervention Tablet-pc education versus personal, nurse-led education. Measurements Calcineurin inhibitor levels in target range 6 months after education, level variability, interval adherence, knowledge and adherence was studied. As outcome parameter, renal function was measured and adverse events registered. Results Sixty-four patients were 1:1 randomised for either intervention. Levels of immunosuppression 6 months after education were equal (tablet-PC 58% vs. conventional 48%, p = 0.27), both groups improved in achieving a CNI trough level within target range by either education method (delta tablet-PC 29% vs. conventional 20%). In all patients, level variability decreased (−20.4%), whereas interval adherence remained unchanged. Knowledge about immunosuppression improved by 7% and compliance tests demonstrated universal improvements with no significant difference between groups. Conclusion Education is a simple, effective tool in improving adherence to immunosuppression. Tablet-PC education was

  9. Propionibacterium acnes as a cause of lung abscess in a cardiac transplant recipient.

    PubMed

    Veitch, David; Abioye, Abu; Morris-Jones, Stephen; McGregor, Alastair

    2015-01-01

    A 29-year-old man was admitted with fevers, cough, left-sided chest pain and lethargy for 1 week. He had a cardiac transplant 10 years prior and was on immunosuppressive drugs. He was found to have a pulmonary lesion and went on to develop a lung abscess. Propionibacterium acnes was identified on matrix-assisted laser desorption ionisation mass spectrometry-time of flight and 16s rRNA gene sequencing after drainage. He was curatively treated with co-trimoxazole and co-amoxiclav. He divulged a longstanding history of seborrhoeic dermatitis with frequent flares leading to large volumes of squames collecting on his bed sheets. We hypothesise this was a possible route of entry: inhalation of the Propionibacterium. This case highlights how a common commensal bacterium, P. acnes, was able to cause pathology in an immunosuppressed patient. This is the only case of a patient with transplantation developing a P. acnes pulmonary infection and the only case of P. acnes causing these clinical features to be reported in the literature. PMID:26677153

  10. Propionibacterium acnes as a cause of lung abscess in a cardiac transplant recipient.

    PubMed

    Veitch, David; Abioye, Abu; Morris-Jones, Stephen; McGregor, Alastair

    2015-12-16

    A 29-year-old man was admitted with fevers, cough, left-sided chest pain and lethargy for 1 week. He had a cardiac transplant 10 years prior and was on immunosuppressive drugs. He was found to have a pulmonary lesion and went on to develop a lung abscess. Propionibacterium acnes was identified on matrix-assisted laser desorption ionisation mass spectrometry-time of flight and 16s rRNA gene sequencing after drainage. He was curatively treated with co-trimoxazole and co-amoxiclav. He divulged a longstanding history of seborrhoeic dermatitis with frequent flares leading to large volumes of squames collecting on his bed sheets. We hypothesise this was a possible route of entry: inhalation of the Propionibacterium. This case highlights how a common commensal bacterium, P. acnes, was able to cause pathology in an immunosuppressed patient. This is the only case of a patient with transplantation developing a P. acnes pulmonary infection and the only case of P. acnes causing these clinical features to be reported in the literature.

  11. Precursor frequency of donor-specific lymphocytes recovered from canine lung transplants.

    PubMed Central

    Kirby, J A; Pepper, J R; Reader, J A; Corbishley, C M; Hudson, L

    1986-01-01

    Dogs receiving left unilateral allo- or auto-grafts were treated with Cyclosporin A (Cy A) for 4 days. Thereafter allografted transplant recipients showed pulmonary pathology consistent with rejection. Blood and bronchoalveolar lavage (BAL)-derived lymphocytes were isolated from the recipient animals before and at various times after operation and the frequency of allospecific precursor cytolytic lymphocytes (pCTL) determined by limiting dilution analysis (LDA). Samples from the autografted control animal did not show any post-operative frequency changes; however, both blood and BAL-derived lymphocytes from allografted recipients showed a significant post-operative increase in the proportion of donor-specific pCTL. This increase was consistently greater in samples from the transplanted than the autochthonous lung. The frequency of pCTL determined using targets from an unrelated dog showed no post-operative increase. It is likely that the increase in frequency of donor-specific pCTL recorded during graft-rejection is a specific consequence of an interaction between the graft and recipient's immune system. Images Fig. 1 PMID:3516465

  12. The influence of clinical course after lung transplantation on rehabilitation success.

    PubMed

    Dierich, Martin; Tecklenburg, Andreas; Fuehner, Thomas; Tegtbur, Uwe; Welte, Tobias; Haverich, Axel; Warnecke, Gregor; Gottlieb, Jens

    2013-03-01

    Pulmonary rehabilitation (PR) is a cornerstone of treatment following lung transplantation (LTx). The aim of this study was to observe the influence of a prolonged postsurgical clinical course on success of a 3-week inpatient PR. LTx recipients were divided according to their clinical course defined by their individual length of stay (LOS) in the transplant center (cohort 1: LOS >; cohort 2: ≤42 days). Peak work rate (PWR), maximum oxygen uptake (VO(2max) ), 6-min walk distance (6-MWD), vital capacity (VC), forced expiratory volume in one second (FEV1), physical activity of daily life (ADL), and health-related quality of life (HRQoL) measured using Short Form 36 questionnaire (SF36) were assessed at beginning and completion of PR. A total of 138 patients were included (LOS >42 days: 30; LOS ≤42 days: 108). At completion, physical functioning (VC, FEV1, PWR, VO(2max) , 6-MWD, ADL), and HRQoL (all SF36 domains) improved in each cohort (P < 0.05). No differences were found in between both cohorts in VC, FEV1, and ADL (n.s.), but in PWR, 6-MWD, and the SF36 domain 'physical functioning' (P < 0.05). A 3-week inpatient PR improves physical functioning despite prolonged hospitalization. HRQoL is close to normal. (ClinicalTrials.gov. identifier: NCT00759538).

  13. Effects of Allogeneic Hematopoietic Stem Cell Transplantation Plus Thymus Transplantation on Malignant Tumors: Comparison Between Fetal, Newborn, and Adult Mice

    PubMed Central

    Zhang, Yuming; Hosaka, Naoki; Cui, Yunze; Shi, Ming

    2011-01-01

    We have recently shown that allogeneic intrabone marrow–bone marrow transplantation + adult thymus transplantation (TT) is effective for hosts with malignant tumors. However, since thymic and hematopoietic cell functions differ with age, the most effective age for such intervention needed to be determined. We performed hematopoietic stem cell transplantation (HSCT) using the intrabone marrow method with or without TT from fetal, newborn, and adult B6 mice (H-2b) into BALB/c mice (H-2d) bearing Meth-A sarcoma (H-2d). The mice treated with all types of HSCT + TT showed more pronounced regression and longer survival than those treated with HSCT alone in all age groups. Those treated with HSCT + TT showed increased numbers of CD4+ and CD8+ T cells but decreased numbers of Gr-1/Mac-1 myeloid suppressor cells and decreased percentages of FoxP3 cells in CD4+ T cells, compared with those treated with HSCT alone. In all mice, those treated with fetal liver cell (as fetal HSCs) transplantation + fetal TT or with newborn liver cell (as newborn HSCs) transplantation (NLT) + newborn TT (NTT) showed the most regression, and the latter showed the longest survival. The number of Gr-1/Mac-1 cells was the lowest, whereas the percentage of CD62L−CD44+ effector memory T cells and the production of interferon γ (IFN-γ) were highest in the mice treated with NLT + NTT. These findings indicate that, at any age, HSCT + TT is more effective against cancer than HSCT alone and that NLT + NTT is most effective. PMID:20672991

  14. EBV-associated post-transplant lymphoproliferative disorder after umbilical cord blood transplantation in adults with hematological diseases.

    PubMed

    Sanz, J; Arango, M; Senent, L; Jarque, I; Montesinos, P; Sempere, A; Lorenzo, I; Martín, G; Moscardó, F; Mayordomo, E; Salavert, M; Cañigral, C; Boluda, B; Salazar, C; López-Hontangas, J L; Sanz, M A; Sanz, G F

    2014-03-01

    We analyzed the incidence, clinicopathological features, risk factors and prognosis of patients with EBV-associated post-transplant lymphoproliferative disorder (EBV-PTLD) in 288 adults undergoing umbilical cord blood transplantation (UCBT) at a single institution. Twelve patients developed proven EBV-PTLD at a median time of 73 days (range, 36-812). Three-year cumulative incidence (CI) of EBV-PTLD was 4.3% (95% CI: 1.9-6.7). All patients presented with extranodal involvement. Most frequently affected sites were the liver, spleen, central nervous system (CNS), Waldeyer's ring and BM in 7, 6, 4, 3 and 3 patients, respectively. One patient had polymorphic and 11 had monomorphic EBV-PTLD (7 diffuse large B-cell lymphomas not otherwise specified, 4 plasmablastic lymphomas). We confirmed donor origin and EBV infection in all histological samples. EBV-PTLD was the cause of death in 11 patients at a median time of 23 days (range, 1-84). The 3-year CI of EBV-PTLD was 12.9% (95% CI: 3.2-22.5) and 2.6% (95% CI: 0.5-4.7) for patients receiving reduced-intensity conditioning (RIC) and myeloablative conditioning, respectively (P<0.0001). In conclusion, adults with EBV-PTLD after UCBT showed frequent visceral and CNS involvement. The prognosis was poor despite routine viral monitoring and early intervention. An increased risk of EBV-PTLD was noted among recipients of RIC regimens.

  15. Evaluation of Initial Telomere Length and Changes after Transplantation in Adult Double-Unit Cord Blood Transplant Recipients.

    PubMed

    Ashbridge, Beth; Zehir, Ahmet; Lubin, Marissa; Barker, Juliet N; Moore, Malcolm A S

    2015-07-01

    Cord blood (CB) leukocytes have inherent telomere length (TL) variation, and CB hematopoietic stem cells (HSC) can maintain high telomerase levels preventing telomere attrition in vitro. We evaluated TL changes in 13 adult double-unit CB transplant (CBT) recipients. In the 26 units, we observed a marked variation in CB TL at thaw (median, 9.99 kilobases [kb]; range, 6.85 to 13.5). All 13 patients engrafted. Of 11 engrafting with 1 unit, there was no correlation between unit dominance and TL (mean dominant unit TL, 8.84 kb ± 1.76; mean nonengrafting unit TL, 10.3 kb ± 1.81; P = .77). Serial measurements of TL up to 1 year after CBT demonstrated an overall mean 3.04 kb ± .16 TL decrease with only 1 patient exhibiting telomere maintenance. In summary, initial TL does not predict CB unit dominance. Moreover, our analysis suggests neonatal hematopoiesis makes a transition to an HSC characterized by changes in average TL and potentially low telomerase asymmetric cell division in adult CBT recipients. Further investigation of alterations in telomere length and its clinical implications after transplantation of this observation are indicated.

  16. 'Double or quits': perceptions and management of organ transplantation by adults with cystic fibrosis.

    PubMed

    Lowton, Karen

    2003-03-01

    Medical sociologists have often considered lay perceptions of the risks of medical interventions, yet in many empirical studies respondents are people who are not likely to be exposed to a particular intervention. Furthermore, it has been well documented that risk perceptions may change over time and with diminishing health state. This paper explores perceptions and management of the risks of organ transplantation amongst adults with cystic fibrosis (CF), the most common autosomal recessive genetic disease in the UK. Although the focus of medical research is now on providing gene replacement therapy to this group, transplantation is currently the last treatment that an adult with CF can be offered when all other treatment has failed to maintain their health. Thirty-one respondents with varying degrees of health state from a specialist CF centre were interviewed as part of a larger study concerning perceptions of health and risks of treatment. Interviews were audiotaped, transcribed and analysed using ATLAS-ti. During analysis respondents' transcripts were divided into two groups: firstly those who did not anticipate needing a transplant in the near future (if at all) and secondly those who were currently being considered for transplantation, on the transplant list, or who had already received donor organs. The paper focuses on themes arising from interview transcripts and finds that although the focus of risk differs between the two groups, the influence of luck is perceived as strong for both groups and emotion work features heavily in those undergoing the transplant process. Contrary to previous research, fears of inheriting donor characteristics are not found amongst adults with CF, but rather body components are commodified when talking of both giving and receiving organs. PMID:12600371

  17. Survival improvements in adolescents and young adults after myeloablative allogeneic transplantation for acute lymphoblastic leukemia.

    PubMed

    Wood, William A; Lee, Stephanie J; Brazauskas, Ruta; Wang, Zhiwei; Aljurf, Mahmoud D; Ballen, Karen K; Buchbinder, David K; Dehn, Jason; Freytes, Cesar O; Lazarus, Hillard M; Lemaistre, Charles F; Mehta, Paulette; Szwajcer, David; Joffe, Steven; Majhail, Navneet S

    2014-06-01

    Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children. PMID:24607554

  18. Liver repopulation and correction of metabolic liver disease by transplanted adult mouse pancreatic cells.

    PubMed

    Wang, X; Al-Dhalimy, M; Lagasse, E; Finegold, M; Grompe, M

    2001-02-01

    The emergence of cells with hepatocellular properties in the adult pancreas has been described in several experimental models. To determine whether adult pancreas contains cells that can give rise to therapeutically useful and biochemically normal hepatocytes, we transplanted suspensions of wild-type mouse pancreatic cells into syngeneic recipients deficient in fumarylacetoacetate hydrolase and manifesting tyrosinemia. Four of 34 (12%) mutant mice analyzed were fully rescued by donor-derived cells and had normal liver function. Ten additional mice (29%) showed histological evidence of donor-derived hepatocytes in the liver. Previous work has suggested that pancreatic liver precursors reside within or close to pancreatic ducts. We therefore performed additional transplantations using either primary cell suspensions enriched for ducts or cultured ducts. Forty-four mutant mice were transplanted with cells enriched for pancreatic duct cells, but only three of the 34 (9%) recipients analyzed displayed donor-derived hepatocytes. In addition, 28 of the fumarylacetoacetate hydrolase-deficient mice were transplanted with cultured pancreatic duct cells, but no donor-derived hepatocytes were observed. Our results demonstrate for the first time that adult mouse pancreas contains hepatocyte progenitor cells capable of significant therapeutic liver reconstitution. However, contrary to previous reports, we were unable to detect these cells within the duct compartment. PMID:11159194

  19. Evaluation of a hand-held, computer-based intervention to promote early self-care behaviors after lung transplant

    PubMed Central

    Dabbs, Annette DeVito; Dew, Mary Amanda; Myers, Brad; Begey, Alex; Hawkins, Robert; Ren, Dianxu; Dunbar-Jacob, Jacqueline; Oconnell, Erin; McCurry, Kenneth R.

    2011-01-01

    Background Lung transplant recipients are expected to perform self-care behaviors to maximize transplant-related health outcomes. Despite high non-adherence rates in performing these self-care behaviors, and the dire clinical consequences of such non-adherence, interventions are lacking. Pocket Personal Assistant for Tracking Health (Pocket PATH) is a hand-held device developed for patients to record health data, review data trends, and report condition changes to the transplant team. Methods A pilot trial was conducted to compare self-care agency, self-care behaviors, and health-related quality of life (HRQOL) between recipients randomized to use Pocket PATH (n = 15) vs. standard care (n = 15) for the first two months following hospital discharge after lung transplantation. Results Baseline characteristics were equivalent across groups. Patients in the Pocket PATH group showed significantly higher ratings of self-care agency, performed self-care behaviors at significantly higher rates, and reported significantly better HRQOL than standard care controls. Conclusion Pocket PATH is more efficacious than standard care in promoting early self-care agency, self-care behaviors, and HRQOL in lung recipients. A large-scale randomized controlled trial is needed to test the impact of Pocket PATH on long-term self-care behaviors. PMID:19473201

  20. Hepatitis B Vaccination in End-Stage Pulmonary Disease Patients Evaluated for Lung Transplantation: A Retrospective Single-Center Evaluation.

    PubMed

    Wald, Alexandra; Deterding, Lea; Maier, Melanie; Liebert, Uwe G; Berg, Thomas; Wirtz, Hubert; Wiegand, Johannes

    2016-06-14

    BACKGROUND In times of limited organs for transplantation, anti-HBc-positive organs can be accepted for lung transplantation to increase the number of donors. Transplant recipients should be vaccinated against hepatitis B to prevent HBV infection. However, response after HBV vaccination has only been poorly evaluated in patients with end-stage pulmonary disease. MATERIAL AND METHODS Anti-HBs titers of 40 anti-HBc negative patients with end-stage pulmonary disease evaluated for lung transplantation were analyzed with the Architect® system (Abbott, Germany). Responders, partial responders, or non-responders after HBV vaccination were defined by anti-HBs titers >100 IU/L, 10-100 IU/L, and <10 IU/L, respectively. RESULTS There were 34/40 individuals (85%) vaccinated against hepatitis B, and 6 were not vaccinated. Response, partial response, and non-response after vaccination were observed in 10/34 (29.4%), 11/34 (32.4%), and 13/34 (38.2%) of patients, respectively. Response to vaccination did not correlate with sex, pulmonary disease, comorbidities, immunosuppressive therapy, or smoking status. CONCLUSIONS Although 85% of patients evaluated for lung transplantation were vaccinated against hepatitis B, 38.2% did not show an anti-HBs titer >10 IU/L. Thus, anti-HBs titers should be regularly monitored. Nonresponders should be considered for booster vaccinations, alternative vaccination schedules, or prophylactic treatment with a nucleos(t)ide analogue in case of transplantation of an anti-HBc-positive organ.

  1. Chronic rejection of a lung transplant is characterized by a profile of specific autoantibodies

    PubMed Central

    Hagedorn, Peter H; Burton, Christopher M; Carlsen, Jørn; Steinbrüchel, Daniel; Andersen, Claus B; Sahar, Eli; Domany, Eytan; Cohen, Irun R; Flyvbjerg, Henrik; Iversen, Martin

    2010-01-01

    Obliterative bronchiolitis (OB) continues to be the major limitation to long-term survival after lung transplantation. The specific aetiology and pathogenesis of OB are not well understood. To explore the role of autoreactivity in OB, we spotted 751 different self molecules onto glass slides, and used these antigen microarrays to profile 48 human serum samples for immunoglobulin G (IgG) and IgM autoantibodies; 27 patients showed no or mild bronchiolitis obliterans syndrome (BOS; a clinical correlate of OB) and 15 patients showed medium to severe BOS. We now report that these BOS grades could be differentiated by a profile of autoantibodies binding to 28 proteins or their peptides. The informative autoantibody profile included down-regulation as well as up-regulation of both IgM and IgG specific reactivities. This profile was evaluated for robustness using a panel of six independent test patients. Analysis of the functions of the 28 informative self antigens showed that eight of them are connected in an interaction network involved in apoptosis and protein metabolism. Thus, a profile of autoantibodies may reflect pathological processes in the lung allograft, suggesting a role for autoimmunity in chronic rejection leading to OB. PMID:20201985

  2. A Comparative Analysis of Bronchial Stricture Following Lung Transplantation in Recipients With and Without Early Acute Rejection

    PubMed Central

    Castleberry, Anthony W.; Worni, Mathias; Kuchibhatla, Maragatha; Lin, Shu S.; Snyder, Laurie D.; Shofer, Scott L.; Palmer, Scott M.; Pietrobon, Ricardo S.; Davis, R. Duane; Hartwig, Matthew G.

    2014-01-01

    Background Risk factors and outcomes of bronchial stricture following lung transplantation are not well defined. An association between acute rejection and development of stricture has been suggested in small case series. We evaluated this relationship using a large, national registry. Methods All lung transplants between 04/1994 and 12/2008 per the United Network for Organ Sharing database were analyzed. Generalized linear models were used to determine the association between early rejection and development of stricture after adjusting for potential confounders. The association of stricture with postoperative lung function and overall survival was also evaluated. Results 9,335 patients were included for analysis. The incidence of stricture was 11.5% (=1,077/9,335) with no significant change in incidence during the study period (p=0.13). Early rejection was associated with a significantly greater incidence of stricture [adjusted odds ratio (AOR) 1.40, 95% confidence interval (CI) 1.22 - 1.61; p<0.0001]. Male gender, restrictive lung disease, and pre-transplant requirement for hospitalization were also associated with stricture. Those who developed stricture had and a lower postoperative peak percent predicted forced expiratory volume at one second (median 74% vs. 86% for bilateral transplants only, p<0.0001), shorter unadjusted survival (median 6.09 vs. 6.82 years, p<0.001) and increased risk of death after adjusting for potential confounders (adjusted hazard ratio 1.13, CI 1.03 - 1.23, p=0.007). Conclusions Early rejection is associated with an increased incidence of stricture. Recipients with stricture demonstrate worse postoperative lung function and survival. Prospective studies may be warranted to further assess causality and the potential for coordinated rejection and stricture surveillance strategies to improve postoperative outcomes. PMID:23870829

  3. Organ transplantation in the Madrid Autonomous Region.

    PubMed

    Chamorro, C; Aparicio, M; Marmisa, G; Martinez-Urrialde, J L

    2009-01-01

    The Madrid Autonomous Region, a Spanish area with 6,200,000 inhabitants, has 7 hospitals authorized for organ transplantation, with 25 active programs for carrying out various transplantations: 18 for adults and 7 for children. Most of these hospitals are reference transplant centers for other Spanish regions. Between 715 and 760 transplantations are performed annually, which represents between 19% and 22% of Spanish activity. During 2007, 395 kidney, 220 liver, 55 heart, and 35 lung transplantations were performed, as well as 23 isolated or combination transplantations of other abdominal organs (pancreatic, intestinal, or multivisceral). Kidney, liver, heart, and children's intestinal transplant activity in 2007 represented 37%, 63%, 80%, and 100%, respectively, of all pediatric national activity. The Madrid Autonomous Region has a donation rate of 34.2 donors per million inhabitants. Of these, 30% are from non-heart-beating donors (NHBD), Maastrich criteria category 1 or 2. Various hospitals perform kidney, liver, and lung transplantations with these organs, representing 11% of the lung transplantations carried out in recent years, with this being a pioneer procedure worldwide. Despite the important transplant activity, we are working to increase donations, to improve organ donor detection and management protocols, as well as to reach a consensus on criteria to decrease the nonviability rates of potential transplant organs.

  4. Cost-effectiveness and clinical outcomes of double versus single cord blood transplantation in adults with acute leukemia in France

    PubMed Central

    Labopin, Myriam; Ruggeri, Annalisa; Gorin, Norbert Claude; Gluckman, Eliane; Blaise, Didier; Mannone, Lionel; Milpied, Noel; Yakoub-Agha, Ibrahim; Deconinck, Eric; Michallet, Mauricette; Fegueux, Nathalie; Socié, Gerard; Nguyen, Stephanie; Cahn, Jean Yves; de Revel, Thierry; Garnier, Federico; Faucher, Catherine; Taright, Namik; Kenzey, Chantal; Volt, Fernanda; Bertrand, Dominique; Mohty, Mohamad; Rocha, Vanderson

    2014-01-01

    Double cord blood transplantation extends the use of cord blood to adults for whom a single unit is not available, but the procedure is limited by its cost. To evaluate outcomes and cost-effectiveness of double compared to single cord blood transplantation, we analyzed 134 transplants in adults with acute leukemia in first remission. Transplants were performed in France with reduced intensity or myeloablative conditioning regimens. Costs were estimated from donor search to 1 year after transplantation. A Markov decision analysis model was used to calculate quality-adjusted life-years and cost-effectiveness ratio within 4 years. The overall survival at 2 years after single and double cord blood transplants was 42% versus 62%, respectively (P=0.03), while the leukemia-free-survival was 33% versus 53%, respectively (P=0.03). The relapse rate was 21% after double transplants and 42% after a single transplant (P=0.006). No difference was observed for non-relapse mortality or chronic graft-versus-host-disease. The estimated costs up to 1 year after reduced intensity conditioning for single and double cord blood transplantation were € 165,253 and €191,827, respectively. The corresponding costs after myeloablative conditioning were € 192,566 and € 213,050, respectively. Compared to single transplants, double cord blood transplantation was associated with supplementary costs of € 21,302 and € 32,420 up to 4 years, but with increases in quality-adjusted life-years of 0.616 and 0.484, respectively, and incremental cost-effectiveness ratios of € 34,581 and €66,983 in the myeloablative and reduced intensity conditioning settings, respectively. Our results showed that for adults with acute leukemia in first complete remission in France, double cord transplantation is more cost-effective than single cord blood transplantation, with better outcomes, including quality-adjusted life-years. PMID:24143000

  5. Quantification of Pathologic Air Trapping in Lung Transplant Patients Using CT Density Mapping: Comparison with Other CT Air Trapping Measures.

    PubMed

    Solyanik, Olga; Hollmann, Patrick; Dettmer, Sabine; Kaireit, Till; Schaefer-Prokop, Cornelia; Wacker, Frank; Vogel-Claussen, Jens; Shin, Hoen-oh

    2015-01-01

    To determine whether density mapping (DM) is more accurate for detection and quantification of pathologic air trapping (pAT) in patients after lung transplantation compared to other CT air trapping measures. One-hundred forty-seven lung and heart-lung transplant recipients underwent CT-examinations at functional residual capacity (FRC) and total lung capacity (TLC) and PFT six months after lung transplantation. Quantification of air trapping was performed with the threshold-based method in expiration (EXP), density mapping (DM) and the expiratory to inspiratory ratio of the mean lung density (E/I-ratio MLD). A non-rigid registration of inspiration-expiration CT-data with a following voxel-to-voxel mapping was carried out for DM. Systematic variation of attenuation ranges was performed for EXP and DM and correlated with the ratio of residual volume to total lung capacity (RV/TLC) by Spearman rank correlation test. AT was considered pathologic if RV/TLC was above the 95th percentile of the predicted upper limit of normal values. Receiver operating characteristic (ROC) analysis was performed. The optimal attenuation range for the EXP method was from -790 HU to -950 HU (EXP(-790 to -950HU)) (r = 0.524, p<0.001) to detect air trapping. Within the segmented lung parenchyma, AT was best defined as voxel difference less than 80 HU between expiration and registered inspiration using the DM method. DM correlated best with RV/TLC (r = 0.663, p<0.001). DM and E/I-ratio MLD showed a larger AUC (0.78; 95% CI 0.69-0.86; 0.76, 95% CI 0.67-0.85) than EXP(-790 HU to -950 HU) (0.71, 95% CI 0.63-0.78). DM and E/I-ratio MLD showed better correlation with RV/TLC and are more suited quantitative CT-methods to detect pAT in lung transplant patients than the EXP(-790HU to -950HU).

  6. Fibrosing cholestatic hepatitis C in post-transplant adult recipients of liver transplantation

    PubMed Central

    Hori, Tomohide; Onishi, Yasuharu; Kamei, Hideya; Kurata, Nobuhiko; Ishigami, Masatoshi; Ishizu, Yoji; Ogura, Yasuhiro

    2016-01-01

    Hepatitis C recurrence continues to present a major challenge in liver transplantation (LT). Approximately 10% of hepatitis C virus (HCV)-positive recipients will develop fibrosing cholestatic hepatitis (FCH) after LT. FCH is clinically characterized as marked jaundice with cholestatic hepatic dysfunction and high titers of viremia. Pathologically, FCH manifests as marked hepatocyte swelling, cholestasis, periportal peritrabecular fibrosis and only mild inflammation. This progressive form usually involves acute liver failure, and rapidly results in graft loss. A real-time and precise diagnosis based on histopathological examination and viral measurement is indispensable for the adequate treatment of FCH. Typical pathological findings of FCH are shown. Currently, carefully selected combinations of direct-acting antivirals (DAAs) offer the potential for highly effective and safe regimens for hepatitis C, both in the pre- and post-transplant settings. Here, we review FCH caused by HCV in LT recipients, and current strategies for sustained virological responses after LT. Only a few cases of successfully treated FCH C after LT by DAAs have been reported. The diagnostic findings and therapeutic dilemma are discussed based on a literature review. PMID:27708510

  7. Living donor liver transplantation in an adult patient with situs inversus totalis

    PubMed Central

    Yankol, Yücel; Mecit, Nesimi; Kanmaz, Turan; Acarlı, Koray; Kalayoğlu, Münci

    2015-01-01

    Situs inversus totalis (SIT) is a rare congenital anomaly, and liver transplantation (LT) in an adult SIT patient is extremely rare. Liver transplantation in a SIT patient is also technically challenging due to reversed anatomical structures. Here we present the case of an 18-year-old female with SIT in whom left lobe living donor LT was performed. The patient suffered from cirrhosis due to autoimmune hepatitis. The recipient and donor are doing well without complications 20 months after LT. Situs inversus totalis should not be considered a contraindication for LT. If possible, use of a living donor left lobe graft for LT is more feasible than a living donor right lobe graft. It is also technically easier than using deceased donor full-size liver graft in SIT patients who require liver transplantation. PMID:26668533

  8. The Impact of the Lung Allocation Score on Resource Utilization After Lung Transplantation in the United States

    PubMed Central

    Arnaoutakis, George J.; Allen, Jeremiah G.; Merlo, Christian A.; Reeb, Brigitte E.; Baumgartner, William A.; Conte, John V.; Shah, Ashish S.

    2011-01-01

    Background The United States lung allocation score (LAS) allows rapid organ allocation to higher acuity patients. Although, waitlist time and waitlist mortality have improved, the costs of lung transplantation (LTx) in these higher acuity patients are largely unknown. We hypothesize that LTx in high LAS recipients is associated with increased charges and resource utilization. Methods and Materials Clinical and financial data for LTx patients at our institution in the post-LAS era (5/2005–2009) were reviewed with follow-up through 12/2009. Patients were stratified by LAS quartiles (Q). Total hospital charges for index admission and all admissions within 1yr of LTx were compared between Q4 versus the Q1–3 using Rank-Sum and Kruskal-Wallis tests, as charge data were not normally distributed. Results 84 LTx’s were performed during the study period. 63 (75%) survived 1yr; 10 (11.9%) died during the index admission. Median LAS was 37.5 (interquartile range (IQR) 34.3–44.8). LAS quartiles were: Q1,30.1–34.3, n=21; Q2,34.4–37.5, n=21; Q3,37.6–44.8, n=21; Q4,44.9–94.3, n=21. Charges for index admission were: Q4,$276,668 (IQR191,301–300,156) vs. Q1–3, $153,995(IQR 129,796–176,849), P<0.001. Index admission median length of stay was greater in Q4 (Q4:35d IQR 23–46 vs Q1–3:15d IQR11–22, P=0.003). For 1yr charges: Q4, $292,247 (IQR 229,192–421,597) vs. Q1–3, $188,342 (IQR 153,455–252,045), P=0.002. Index admission and 1yr charges in Q4 were higher than other quartiles when examined individually. Conclusions This is the first study to show increased charges in high LAS patients. Charges for the index admission and hospital care in the year post-LTx were higher in the highest LAS quartile compared to patients in the lowest 75% of LAS. PMID:20869886

  9. Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes.

    PubMed

    Lee, Joon; Stagg, Mark A; Fukushima, Satsuki; Soppa, Gopal K R; Siedlecka, Urszula; Youssef, Samuel J; Suzuki, Ken; Yacoub, Magdi H; Terracciano, Cesare M N

    2009-04-01

    Adult progenitor cell transplantation has been proposed for the treatment of heart failure, but the mechanisms effecting functional improvements remain unknown. The aim of this study was to test the hypothesis that, in failing hearts treated with cell transplantation, the mechanical properties and excitation-contraction coupling of recipient cardiomyocytes are altered. Adult rats underwent coronary artery ligation, leading to myocardial infarction and chronic heart failure. After 3 wk, they received intramyocardial injections of either 10(7) green fluorescence protein (GFP)-positive bone marrow mononuclear cells or 5 x 10(6) GFP-positive skeletal myoblasts. Four weeks after injection, both cell types increased ejection fraction and reduced cardiomyocyte size. The contractility of isolated GFP-negative cardiomyocytes was monitored by sarcomere shortening assessment, Ca(2+) handling by indo-1 and fluo-4 fluorescence, and electrophysiology by patch-clamping techniques. Injection of either bone marrow cells or skeletal myoblasts normalized the impaired contractile performance and the prolonged time to peak of the Ca(2+) transient observed in failing cardiomyocytes. The smaller and slower L-type Ca(2+) current observed in heart failure normalized after skeletal myoblast, but not bone marrow cell, transplantation. Measurement of Ca(2+) sparks suggested a normalization of sarcoplasmic reticulum Ca(2+) leak after skeletal myoblast transplantation. The increased Ca(2+) wave frequency observed in failing myocytes was reduced by either bone marrow cells or skeletal myoblasts. In conclusion, the morphology, contractile performance, and excitation-contraction coupling of individual recipient cardiomyocytes are altered in failing hearts treated with adult progenitor cell transplantation. PMID:19181964

  10. Altered differentiation of CNS neural progenitor cells after transplantation into the injured adult rat spinal cord.

    PubMed

    Onifer, S M; Cannon, A B; Whittemore, S R

    1997-01-01

    Denervation of CNS neurons and peripheral organs is a consequence of traumatic SCI. Intraspinal transplantation of embryonic CNS neurons is a potential strategy for reinnervating these targets. Neural progenitor cell lines are being investigated as alternates to embryonic CNS neurons. RN33B is an immortalized neural progenitor cell line derived from embryonic rat raphe nuclei following infection with a retrovirus encoding the temperature-sensitive mutant of SV40 large T-antigen. Transplantation studies have shown that local epigenetic signals in intact or partially neuron-depleted adult rat hippocampal formation or striatum direct RN33B cell differentiation to complex multipolar morphologies resembling endogenous neurons. After transplantation into neuron-depleted regions of the hippocampal formation or striatum, RN33B cells were relatively undifferentiated or differentiated with bipolar morphologies. The present study examines RN33B cell differentiation after transplantation into normal spinal cord and under different lesion conditions. Adult rats underwent either unilateral lesion of lumbar spinal neurons by intraspinal injection of kainic acid or complete transection at the T10 spinal segment. Neonatal rats underwent either unilateral lesion of lumbar motoneurons by sciatic nerve crush or complete transection at the T10 segment. At 2 or 6-7 wk postinjury, lacZ-labeled RN33B cells were transplanted into the lumbar enlargement of injured and age-matched normal rats. At 2 wk posttransplantation, bipolar and some multipolar RN33B cells were found throughout normal rat gray matter. In contrast, only bipolar RN33B cells were seen in gray matter of kainic acid lesioned, sciatic nerve crush, or transection rats. These observations suggest that RN33B cell multipolar morphological differentiation in normal adult spinal cord is mediated by direct cell-cell interaction through surface molecules on endogenous neurons and may be suppressed by molecules released after SCI

  11. Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo

    PubMed Central

    Zhang, Kuan; Chen, Chunhai; Yang, Zhiqi; He, Wenjing; Liao, Xiang; Ma, Qinlong; Deng, Ping; Lu, Jian; Li, Jingcheng; Wang, Meng; Li, Mingli; Zheng, Lianghong; Zhou, Zhuan; Sun, Wei; Wang, Liting; Jia, Hongbo; Yu, Zhengping; Zhou, Zhou; Chen, Xiaowei

    2016-01-01

    Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca2+ imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca2+ signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID:27405333

  12. Comparable outcomes between autologous and allogeneic transplant for adult acute myeloid leukemia in first CR.

    PubMed

    Mizutani, M; Hara, M; Fujita, H; Aoki, J; Kanamori, H; Ohashi, K; Usuki, K; Fukuda, T; Chou, T; Tanaka, J; Atsuta, Y; Takami, A

    2016-05-01

    Although allogeneic hematopoietic stem cell transplantation from an HLA-matched sibling donor (MSD) is a potentially curative post-remission treatment for adults with acute myeloid leukemia (AML) in their first CR, transplant-related morbidity and mortality remains a major drawback. We retrospectively compared the outcomes of patients who underwent autologous peripheral blood stem cell transplantation (auto-PBSCT; n=375) with those who underwent allogeneic bone marrow transplantation (allo-BMT; n=521) and allo-PBSCT (n=380) from MSDs for adults with AML/CR1, in which propensity score models were used to adjust selection biases among patients, primary physicians and institutions to overcome ambiguity in the patients' background information. Both the multivariate analysis and propensity score models indicated that the leukemia-free survival rate of auto-PBSCT was not significantly different from that of allo-BMT (hazard ratio (HR), 1.23; 95% confidence interval (CI), 0.92 to 1.66; P=0.16) and allo-PBSCT (HR, 1.13; 95% CI, 0.85-1.51; P=0.40). The current results suggest that auto-PBSCT remains a promising alternative treatment for patients with AML/CR1 in the absence of an available MSD. PMID:26808566

  13. Sensory Response of Transplanted Astrocytes in Adult Mammalian Cortex In Vivo.

    PubMed

    Zhang, Kuan; Chen, Chunhai; Yang, Zhiqi; He, Wenjing; Liao, Xiang; Ma, Qinlong; Deng, Ping; Lu, Jian; Li, Jingcheng; Wang, Meng; Li, Mingli; Zheng, Lianghong; Zhou, Zhuan; Sun, Wei; Wang, Liting; Jia, Hongbo; Yu, Zhengping; Zhou, Zhou; Chen, Xiaowei

    2016-09-01

    Glial precursor transplantation provides a potential therapy for brain disorders. Before its clinical application, experimental evidence needs to indicate that engrafted glial cells are functionally incorporated into the existing circuits and become essential partners of neurons for executing fundamental brain functions. While previous experiments supporting for their functional integration have been obtained under in vitro conditions using slice preparations, in vivo evidence for such integration is still lacking. Here, we utilized in vivo two-photon Ca(2+) imaging along with immunohistochemistry, fluorescent indicator labeling-based axon tracing and correlated light/electron microscopy to analyze the profiles and the functional status of glial precursor cell-derived astrocytes in adult mouse neocortex. We show that after being transplanted into somatosensory cortex, precursor-derived astrocytes are able to survive for more than a year and respond with Ca(2+) signals to sensory stimulation. These sensory-evoked responses are mediated by functionally-expressed nicotinic receptors and newly-established synaptic contacts with the host cholinergic afferents. Our results provide in vivo evidence for a functional integration of transplanted astrocytes into adult mammalian neocortex, representing a proof-of-principle for sensory cortex remodeling through addition of essential neural elements. Moreover, we provide strong support for the use of glial precursor transplantation to understand glia-related neural development in vivo. PMID:27405333

  14. Long-Term Extracorporeal Membrane Oxygenation as Bridging Strategies to Lung Transplantation in Rapidly Devastating Isolated Langerhans Cell Histiocytosis.

    PubMed

    Sacco, Oliviero; Moscatelli, Andrea; Conte, Massimo; Grasso, Chiara; Magnano, Gian Michele; Sementa, Angela Rita; Martelli, Alberto; Rossi, Giovanni A

    2016-05-01

    Isolated pulmonary involvement in pediatric Langerhans cell histiocytosis (LCH) is extremely rare. While the multisystem-LCH course varies from spontaneous remission to rapid deterioration with lethal outcome, single system involvement is generally associated with favorable prognosis. A child with isolated pulmonary LCH had an extremely rapid progression leading to respiratory failure, despite treatment with prednisone and vinblastine. Since lung hyperinflation and cystic degeneration contraindicated conventional mechanical ventilation, extracorporeal membrane oxygenation (ECMO) was chosen for 50 days as a bridge to lung transplantation. The mechanisms involved in disease progression and the usefulness of long-term ECMO are discussed. PMID:26840616

  15. A Promoter Polymorphism in the CD59 Complement Regulatory Protein Gene in Donor Lungs Correlates With a Higher Risk for Chronic Rejection After Lung Transplantation.

    PubMed

    Budding, K; van de Graaf, E A; Kardol-Hoefnagel, T; Broen, J C A; Kwakkel-van Erp, J M; Oudijk, E-J D; van Kessel, D A; Hack, C E; Otten, H G

    2016-03-01

    Complement activation leads primarily to membrane attack complex formation and subsequent target cell lysis. Protection against self-damage is regulated by complement regulatory proteins, including CD46, CD55, and CD59. Within their promoter regions, single-nucleotide polymorphisms (SNPs) are present that could influence transcription. We analyzed these SNPs and investigated their influence on protein expression levels. A single SNP configuration in the promoter region of CD59 was found correlating with lower CD59 expression on lung endothelial cells (p = 0.016) and monocytes (p = 0.013). Lung endothelial cells with this SNP configuration secreted more profibrotic cytokine IL-6 (p = 0.047) and fibroblast growth factor β (p = 0.036) on exposure to sublytic complement activation than cells with the opposing configuration, whereas monocytes were more susceptible to antibody-mediated complement lysis (p < 0.0001). Analysis of 137 lung transplant donors indicated that this CD59 SNP configuration correlates with impaired long-term survival (p = 0.094) and a significantly higher incidence of bronchiolitis obliterans syndrome (p = 0.046) in the recipient. These findings support a role for complement in the pathogenesis of this posttransplant complication and are the first to show a deleterious association of a donor CD59 promoter polymorphism in lung transplantation.

  16. A Promoter Polymorphism in the CD59 Complement Regulatory Protein Gene in Donor Lungs Correlates With a Higher Risk for Chronic Rejection After Lung Transplantation.

    PubMed

    Budding, K; van de Graaf, E A; Kardol-Hoefnagel, T; Broen, J C A; Kwakkel-van Erp, J M; Oudijk, E-J D; van Kessel, D A; Hack, C E; Otten, H G

    2016-03-01

    Complement activation leads primarily to membrane attack complex formation and subsequent target cell lysis. Protection against self-damage is regulated by complement regulatory proteins, including CD46, CD55, and CD59. Within their promoter regions, single-nucleotide polymorphisms (SNPs) are present that could influence transcription. We analyzed these SNPs and investigated their influence on protein expression levels. A single SNP configuration in the promoter region of CD59 was found correlating with lower CD59 expression on lung endothelial cells (p = 0.016) and monocytes (p = 0.013). Lung endothelial cells with this SNP configuration secreted more profibrotic cytokine IL-6 (p = 0.047) and fibroblast growth factor β (p = 0.036) on exposure to sublytic complement activation than cells with the opposing configuration, whereas monocytes were more susceptible to antibody-mediated complement lysis (p < 0.0001). Analysis of 137 lung transplant donors indicated that this CD59 SNP configuration correlates with impaired long-term survival (p = 0.094) and a significantly higher incidence of bronchiolitis obliterans syndrome (p = 0.046) in the recipient. These findings support a role for complement in the pathogenesis of this posttransplant complication and are the first to show a deleterious association of a donor CD59 promoter polymorphism in lung transplantation. PMID:26517734

  17. Beyond cancer treatment – a review of total lymphoid irradiation for heart and lung transplant recipients

    PubMed Central

    McKay, Clare; Knight, Kellie A; Wright, Caroline

    2014-01-01

    Immunosuppressive drugs used in the management of heart and lung transplants have a large monetary and quality of life cost due to their side effects. Total lymphoid irradiation (TLI) is one method of minimising the need for or replacing post-operative immunosuppressive drugs. A literature review was conducted on electronic databases using defined search terms. The aim was to establish the indications for the use of TLI, its advantages and disadvantages and the weaknesses associated with the methods used in related research. Eight articles were located that focused on TLI usage in combating organ rejection. These studies identified that the use of TLI resulted in a reduction in early rejection. One study reported a drop in rejection episodes from 0.46 to 0.14 episodes per patient per month once the TLI was complete. While the short-term prognosis is excellent, the long-term outlook is less positive with an increased risk of organ rejection and myelodysplasia 3.5 years post-TLI. This review reminds us that radiation therapy (RT) is not exclusively indicated for cancer treatment. While TLI cannot replace immunosuppressive drug therapy, it can offer a treatment option for people that cannot tolerate immunosuppressive drugs, or when conventional anti-rejection treatment is no longer viable. Reported long-term complications suggest that TLI should be used with caution. However, this modality should not be overlooked in cases of chronic rejection. Further research is required to establish the efficacy of RT in the treatment of transplant patients who are unsuitable for drug-based anti-rejection therapies. PMID:26229656

  18. Beyond cancer treatment – a review of total lymphoid irradiation for heart and lung transplant recipients

    SciTech Connect

    McKay, Clare Knight, Kellie A; Wright, Caroline

    2014-09-15

    Immunosuppressive drugs used in the management of heart and lung transplants have a large monetary and quality of life cost due to their side effects. Total lymphoid irradiation (TLI) is one method of minimising the need for or replacing post-operative immunosuppressive drugs. A literature review was conducted on electronic databases using defined search terms. The aim was to establish the indications for the use of TLI, its advantages and disadvantages and the weaknesses associated with the methods used in related research. Eight articles were located that focused on TLI usage in combating organ rejection. These studies identified that the use of TLI resulted in a reduction in early rejection. One study reported a drop in rejection episodes from 0.46 to 0.14 episodes per patient per month once the TLI was complete. While the short-term prognosis is excellent, the long-term outlook is less positive with an increased risk of organ rejection and myelodysplasia 3.5 years post-TLI. This review reminds us that radiation therapy (RT) is not exclusively indicated for cancer treatment. While TLI cannot replace immunosuppressive drug therapy, it can offer a treatment option for people that cannot tolerate immunosuppressive drugs, or when conventional anti-rejection treatment is no longer viable. Reported long-term complications suggest that TLI should be used with caution. However, this modality should not be overlooked in cases of chronic rejection. Further research is required to establish the efficacy of RT in the treatment of transplant patients who are unsuitable for drug-based anti-rejection therapies.

  19. Looking Beyond Respiratory Cultures: Microbiome-Cytokine Signatures of Bacterial Pneumonia and Tracheobronchitis in Lung Transplant Recipients.

    PubMed

    Shankar, J; Nguyen, M H; Crespo, M M; Kwak, E J; Lucas, S K; McHugh, K J; Mounaud, S; Alcorn, J F; Pilewski, J M; Shigemura, N; Kolls, J K; Nierman, W C; Clancy, C J

    2016-06-01

    Bacterial pneumonia and tracheobronchitis are diagnosed frequently following lung transplantation. The diseases share clinical signs of inflammation and are often difficult to differentiate based on culture results. Microbiome and host immune-response signatures that distinguish between pneumonia and tracheobronchitis are undefined. Using a retrospective study design, we selected 49 bronchoalveolar lavage fluid samples from 16 lung transplant recipients associated with pneumonia (n = 8), tracheobronchitis (n = 12) or colonization without respiratory infection (n = 29). We ensured an even distribution of Pseudomonas aeruginosa or Staphylococcus aureus culture-positive samples across the groups. Bayesian regression analysis identified non-culture-based signatures comprising 16S ribosomal RNA microbiome profiles, cytokine levels and clinical variables that characterized the three diagnoses. Relative to samples associated with colonization, those from pneumonia had significantly lower microbial diversity, decreased levels of several bacterial genera and prominent multifunctional cytokine responses. In contrast, tracheobronchitis was characterized by high microbial diversity and multifunctional cytokine responses that differed from those of pneumonia-colonization comparisons. The dissimilar microbiomes and cytokine responses underlying bacterial pneumonia and tracheobronchitis following lung transplantation suggest that the diseases result from different pathogenic processes. Microbiomes and cytokine responses had complementary features, suggesting that they are closely interconnected in the pathogenesis of both diseases. PMID:26693965

  20. Isolation and clonal assay of adult lung epithelial stem/progenitor cells.

    PubMed

    Bertoncello, Ivan; McQualter, Jonathan

    2011-01-01

    Adult mouse lung epithelial stem/progenitor cells (EpiSPC) can be defined in vitro as epithelial colony-forming units that are capable of self-renewal, and which when co-cultured with lung mesenchymal stromal cells (MSC) are able to give rise to differentiated progeny comprising mature lung epithelial cells. This unit describes a protocol for the prospective isolation and in vitro propagation and differentiation of adult mouse lung EpiSPC. The strategy used for selection of EpiSPC and MSC from adult mouse lung by enzymatic digestion and flow cytometry is based on the differential expression of CD45, CD31, Sca-1, EpCAM, and CD24. The culture conditions required for the differentiation (co-culture with MSC) and expansion (stromal-free culture with FGF-10 and HGF) of EpiSPC are described.

  1. Transition to routine use of venoarterial extracorporeal oxygenation during lung transplantation could improve early outcomes

    PubMed Central

    Yu, Woo Sik; Paik, Hyo Chae; Haam, Seok Jin; Lee, Chang Young; Nam, Kyung Sik; Jung, Hee Suk; Do, Young Woo; Shu, Jee Won

    2016-01-01

    Background The study objective was to compare the outcomes of intraoperative routine use of venoarterial (VA) extracorporeal membrane oxygenation (ECMO) versus selective use of cardiopulmonary bypass (CPB). Methods Between January 2010 and February 2013, 41 lung transplantations (LTx) were performed, and CPB was used as a primary cardiopulmonary support modality by selective basis (group A). Between March 2013 and December 2014, 41 LTx were performed, and ECMO was used routinely (group B). The two groups were compared retrospectively. Results The operative time was significantly longer in group A (group A, 458 min; group B, 420 min; P=0.041). Postoperatively, patients in group B had less fresh frozen plasma (FFP) transfusion (P=0.030). Complications were not different between the two groups. The 30- and 90-day survival rates were better in group B (30-day survival: group A, 75.6%; group B, 95.1%, P=0.012; 90-day survival: group A, 68.3%; group B, 87.8%, P=0.033). The 1-year survival showed better trends in group B, but it was not significant. Forced vital capacity (FVC) at 1, 3, and 6 months after LTx was better in group B than in group A (1 month: group A, 43.8%; group B, 52.9%, P=0.043; 3 months: group A, 45.5%; group B, 59.0%, P=0.005; 6 months: group A, 51.5%; group B, 65.2%, P=0.020). Forced expiratory volume in 1 second (FEV1) at 3 months after LTx was better in patients in group B than that in patient in group A (group A, 53.3%; group B, 67.5%, P=0.017). Conclusions Routine use of ECMO during LTx could improve early outcome and postoperative lung function without increased extracorporeal-related complication such as vascular and neurologic complications. PMID:27499961

  2. Adult Intestinal and Multivisceral Transplantation: Experience From a Single Center in the United Kingdom.

    PubMed

    Rutter, C S; Amin, I; Russell, N K; Sharkey, L M; Butler, A J; Middleton, S J

    2016-03-01

    Cambridge is one of two designated adult intestinal transplant centers in the United Kingdom and has performed 60 transplants on 54 patients since 2007; 52% of these were undertaken in the last 3 years. This increasing trend is in contrast with that reported worldwide; 27% were small bowel grafts (SBT), 15% modified multivisceral (MMVT), and 58% multivisceral (MVT). Median recipient age was 47 years; the female-to-male ratio was 27/33. Primary diseases included visceral arterial thromboses (17%), Crohn's disease (17%), motility disorders (12%), visceral venous thromboses (12%), familial adenomatous polyposis (FAP)/desmoids (8%), alcoholic cirrhosis (3%), nonalcoholic fatty liver disease (3%), ulcerative colitis (2%), and other (15%). Indications for transplant included intestinal failure-associated liver disease (IFALD) (27%), loss of central venous access (17%), FAP/desmoid disease (5%), extensive portomesenteric venous thrombosis (PMVT) (20%), widespread mesenteric arterial ischemia (WMAI) (13%), re-transplant (8%), and other (10%). Overall 1-year/5-year patient survival rates were 77%/62%. One-year/5-year patient survival rates were 92%/83%, 85%/65%, and 71%/33% for SBT, MMVT, and MVT. One-year/5-year survival rates for patients with IFALD, PMVT, and other indications who underwent MVT were 80%/20%, 65%/55%, and 55%/35%. The greatest proportion of patient deaths occurred during the first year after transplant (50% in year 1, 23% in year 2, 9% in year 3, 5% in year 4, and 14% in year 5), particularly in the MVT group. Referrals to our United Kingdom center are increasing, and the indications for transplant are becoming more diverse. Our patient survival rates remain comparable with figures reported worldwide.

  3. Lung Volume during Swallowing: Single Bolus Swallows in Healthy Young Adults

    ERIC Educational Resources Information Center

    Hegland, Karen M. Wheeler; Huber, Jessica E.; Pitts, Teresa; Sapienza, Christine M.

    2009-01-01

    Purpose: This study examined the relationship between swallowing and lung volume initiation in healthy adults during single swallows of boluses differing in volume and consistency. Differences in lung volume according to respiratory phase surrounding the swallow were also assessed. Method: Nine men and 11 women between the ages of 19 and 28 years…

  4. Mean lung pressure during adult high-frequency oscillatory ventilation: an experimental study using a lung model.

    PubMed

    Hirayama, Takahiro; Nagano, Osamu; Shiba, Naoki; Yumoto, Tetsuya; Sato, Keiji; Terado, Michihisa; Ugawa, Toyomu; Ichiba, Shingo; Ujike, Yoshihito

    2014-12-01

    In adult high-frequency oscillatory ventilation (HFOV), stroke volume (SV) and mean lung pressure (PLung) are important for lung protection. We measured the airway pressure at the Y-piece and the lung pressure during HFOV using a lung model and HFOV ventilators for adults (R100 and 3100B). The lung model was made of a 20-liter, airtight rigid plastic container (adiabatic compliance: 19.3 ml/cmH2O) with or without a resistor (20 cmH2O/l/sec). The ventilator settings were as follows: mean airway pressure (MAP), 30 cmH2O; frequency, 5-15 Hz (every 1 Hz); airway pressure amplitude (AMP), maximum;and % of inspiratory time (IT), 50% for R100, 33% or 50% for 3100B. The measurements were also performed with an AMP of 2/3 or 1/3 maximum at 5, 10 and 15 Hz. The PLung and the measured MAP were not consistently identical to the setting MAP in either ventilator, and decreasing IT decreased the PLung in 3100B. In conclusion, we must pay attention to the possible discrepancy between the PLung and the setting MAP during adult HFOV. PMID:25519026

  5. Successful Kidney and Lung Transplantation From a Deceased Donor With Blunt Abdominal Trauma and Intestinal Perforation.

    PubMed

    van Smaalen, Tim C; Krikke, Christina; Haveman, Jan Willem; van Heurn, L W Ernest

    2016-01-01

    The number of organ donors is limited by many contraindications for donation and poor quality of potential organ donors. Abdominal infection is a generally accepted contraindication for donation of abdominal organs. We present a 43-year-old man with lethal brain injury, blunt abdominal trauma, and intestinal perforation. After withdrawal of life-sustaining treatment and circulatory arrest, a minilaparotomy confirmed abdominal contamination with intestinal content. After closure of the abdomen, organs were preserved with in situ preservation with an aortic cannula inserted via the femoral artery. Thereafter, the kidneys were procured via bilateral lumbotomy to reduce the risk of direct bacterial contamination; lungs were retrieved following a standard practice. There was no bacterial or fungal growth in the machine preservation fluid of both kidneys. All organs were successfully transplanted, without postoperative infection, and functioned well after 6 months. We hereby show that direct contamination of organs can be avoided with the use of in situ preservation and retroperitoneal procurement. Intestinal perforation is not an absolute contraindication for donation, although the risk of bacterial or fungal transmission has to be evaluated per case. PMID:27500248

  6. Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors: Three Case Reports.

    PubMed

    Hu, Liangshuo; Liu, Xuemin; Zhang, Xiaogang; Yu, Liang; Sha, Huanchen; Zhou, Ying; Tian, Min; Shi, Jianhua; Wang, Wanli; Liu, Chang; Guo, Kun; Lv, Yi; Wang, Bo

    2016-02-01

    Development of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately. Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation. Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well. DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed.

  7. Child-to-Adult Liver Transplantation With Donation After Cardiac Death Donors

    PubMed Central

    Hu, Liangshuo; Liu, Xuemin; Zhang, Xiaogang; Yu, Liang; Sha, Huanchen; Zhou, Ying; Tian, Min; Shi, Jianhua; Wang, Wanli; Liu, Chang; Guo, Kun; Lv, Yi; Wang, Bo

    2016-01-01

    Abstract Development of organ transplantation is restricted by the discrepancy between the lack of donors and increasing number of patients. The outcome of pediatric donors transplanted into adult recipients especially with donation after circulatory death (DCD) pattern has not been well studied. The aim of this paper is to describe our experience of 3 successful DCD donor child-to-adult liver transplantations lately. Three DCD donors were separately 7, 5, and 8 years old. The ratio between donor graft weight and recipient body weight was 1.42%, 1.00%, and 1.33%, respectively. Ratio between the volume of donor liver and the expected liver volume was 0.65, 0.46, and 0.60. Splenectomy was undertaken for the second recipient according to the portal vein pressure (PVP) which was observed during the operation. Two out of 3 of the recipients suffered with acute kidney injury and got recovered after renal replacement therapy. The first recipient also went through early allograft dysfunction and upper gastrointestinal bleeding. The hospital course of the third recipient was uneventful. After 1 year of follow-up visit, the first and second recipients maintain good quality of life and liver function. The third patient was followed up for 5 months until now and recovered well. DCD child-to-adult liver transplantation should only be used for comparatively matched donor and recipient. PVP should be monitored during the operation. The short-term efficacy is good, but long-term follow-up and clinical study with large sample evaluation are still needed. PMID:26886643

  8. Neurologic complications in adult living donor liver transplant patients: an underestimated factor?

    PubMed

    Saner, Fuat Hakan; Gensicke, Julia; Olde Damink, Steven W M; Pavlaković, Goran; Treckmann, Juergen; Dammann, Marc; Kaiser, Gernot M; Sotiropoulos, Georgios C; Radtke, Arnold; Koeppen, Susanne; Beckebaum, Susanne; Cicinnati, Vito; Nadalin, Silvio; Malagó, Massimo; Paul, Andreas; Broelsch, Christoph E

    2010-02-01

    Liver transplantation is the only curative treatment in patients with end-stage liver disease. Neurological complications (NC) are increasingly reported to occur in patients after cadaveric liver transplantation. This retrospective cohort study aims to evaluate the incidence and causes of NC in living donor liver transplant (LDLT) patients in our transplant center. Between August 1998 and December 2005, 121 adult LDLT patients were recruited into our study. 17% of patients experienced NC, and it occurred significantly more frequently in patients with alcoholic cirrhosis (42%) and autoimmune hepatitis (43%) as compared with patients with hepatitis B or C (9/10%, P = 0.013). The most common NC was encephalopathy (47.6%) followed by seizures (9.5%). The choice of immunosuppression by calcineurin inhibitor (Tacrolimus or Cyclosporin A) showed no significant difference in the incidence of NC (19 vs. 17%). The occurrence of NC did not influence the clinical outcome, since mortality rate, median ICU stay and length of hospital stay were similar between the two groups. Most patients who survived showed a nearly complete recovery of their NC. NCs occur in approximately 1 in 6 patients after LDLT and seem to be predominantly transient in nature, without major impact on clinical outcome. PMID:19727899

  9. Mycophenolic acid formulations in adult renal transplantation – update on efficacy and tolerability

    PubMed Central

    Golshayan, Déla; Pascual, M; Vogt, Bruno

    2009-01-01

    The description more than 30 years ago of the role of de novo purine synthesis in T and B lymphocytes clonal proliferation opened the possibility for selective immunosuppression by targeting specific enzymatic pathways. Mycophenolic acid (MPA) blocks the key enzyme inosine monophosphate dehydrogenase and the production of guanosine nucleotides required for DNA synthesis. Two MPA formulations are currently used in clinical transplantation as part of the maintenance immunosuppressive regimen. Mycophenolate mofetil (MMF) was the first MPA agent to be approved for the prevention of acute rejection following renal transplantation, in combination with cyclosporine and steroids. Enteric-coated mycophenolate sodium (EC-MPS) is an alternative MPA formulation available in clinical transplantation. In this review, we will discuss the clinical trials that have evaluated the efficacy and safety of MPA in adult kidney transplantation for the prevention of acute rejection and their use in new combination regimens aiming at minimizing calcineurin inhibitor toxicity and chronic allograft nephropathy. We will also discuss MPA pharmacokinetics and the rationale for therapeutic drug monitoring in optimizing the balance between efficacy and safety in individual patients. PMID:19753127

  10. Orthotopic liver transplantation in an adult with cholesterol ester storage disease.

    PubMed

    Ambler, Graeme K; Hoare, Matthew; Brais, Rebecca; Shaw, Ashley; Butler, Andrew; Flynn, Paul; Deegan, Patrick; Griffiths, William J H

    2013-01-01

    Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit. PMID:23430518

  11. Voriconazole Exposure and Risk of Cutaneous Squamous Cell Carcinoma, Aspergillus Colonization, Invasive Aspergillosis and Death in Lung Transplant Recipients.

    PubMed

    Mansh, M; Binstock, M; Williams, K; Hafeez, F; Kim, J; Glidden, D; Boettger, R; Hays, S; Kukreja, J; Golden, J; Asgari, M M; Chin-Hong, P; Singer, J P; Arron, S T

    2016-01-01

    Voriconazole is a triazole antifungal used to prevent and treat invasive fungal infections after lung transplantation, but it has been associated with an increased risk of developing cutaneous squamous cell carcinoma (SCC). Despite widespread use, there are no clear guidelines for optimal prophylactic regimens that balance the competing risks and benefits. We conducted a retrospective cohort study of all lung transplant recipients at the University of California, San Francisco, who were transplanted between October 1991 and December 2012 (n = 455) to investigate whether voriconazole exposure affected development of SCC, Aspergillus colonization, invasive aspergillosis and all-cause mortality. Voriconazole exposure was associated with a 73% increased risk of developing SCC (hazard ratio [HR] 1.73; 95% confidence interval [CI]: 1.04-2.88; p = 0.03), with each additional 30-day exposure at the standard dose increasing the risk by 3.0% (HR 1.03; 95% CI: 1.02-1.04; p < 0.001). Voriconazole exposure reduced risk of Aspergillus colonization by 50% (HR 0.50; 95% CI: 0.34-0.72; p < 0.001), but we were underpowered to detect risk reduction for invasive aspergillosis. Voriconazole exposure significantly reduced all-cause mortality among subjects who developed Aspergillus colonization (HR 0.34; 95% CI: 0.13-0.91; p = 0.03) but had no significant impact on those without colonization. Physicians should consider patient-specific factors that modify the potential risks and benefits of voriconazole for the care of lung transplant recipients. PMID:26372838

  12. A model utilizing adult murine stem cells for creation of personalized islets for transplantation.

    PubMed

    Wang, J; Song, L J; Gerber, D A; Fair, J H; Rice, L; LaPaglia, M; Andreoni, K A

    2004-05-01

    Clinical islet cell transplantation has demonstrated great promise for diabetes treatment. Two major obstacles are the organ donor shortage and the immunoresponse. The purpose of this study was to create a model using the patient's own adult stem cell sources, possibly in combination with non-self cells, such as pancreatic, hepatic, or embryonic stem cells, to create "personalized" islets. We hypothesize that the reconstructed islets have the normal capability to produce insulin and glucagon with reduced immunoresponses after transplantation. Stem cells are a proliferating population of master cells that have the ability for self-renewal and multilineage differentiation. The recently developed photolithograph-based, biologic, microelectromechanic system (BioMEMS) technique supplies a useful tool for biomedical applications. Our lab has developed a novel method that integrates the adult stem cell and BioMEMS to reconstruct personalized islets. We selected islet-derived progenitor cells (IPC) for repairing and reconstructing STZ-diabetic islets. A6(+)/PYY(+) or A6(+)/ngn3(+) cells were selected to manipulate the neoislets. After 3 to 4 weeks in culture, the reconstructed cells formed islet-like clusters containing insulin or glucagon producing cells. The pilot results showed the ability of these reconstructed islets to correct hyperglycemia when transplanted into a STZ-diabetic isograft mouse model. Although several technical problems remain with the mouse model, namely, the difficulty to collect enough islets from a single mouse because of animal size, the mouse isograft model is suitable for personalized islet development.

  13. Successful xenogeneic germ cell transplantation from Jundia catfish (Rhamdia quelen) into adult Nile tilapia (Oreochromis niloticus) testes.

    PubMed

    Silva, M A; Costa, G M J; Lacerda, S M S N; Brandão-Dias, P F P; Kalapothakis, E; Silva Júnior, A F; Alvarenga, E R; França, L R

    2016-05-01

    Fish germ cell transplantation presents several important potential applications for aquaculture, including the preservation of germplasm from endangered fish species with high genetic and commercial values. Using this technique in studies developed in our laboratory with adult male Nile tilapias (Oreochromis niloticus), all the necessary procedures were successfully established, allowing the production of functional sperm and healthy progeny approximately 2months after allogeneic transplantation. In the present study, we evaluated the viability of the adult Nile tilapia testis to generate sperm after xenogeneic transplant of germ cells from sexually mature Jundia catfish (Rhamdia quelen) that belong to a different taxonomic order. Therefore, in order to investigate at different time-periods post-transplantation, the presence and development of donor PKH26 labeled catfish germ cells were followed in the tilapia seminiferous tubules. From 7 to 20days post-transplantation, only PKH26 labeled spermatogonia were observed, whereas spermatocytes at different stages of development were found at 70days. Germ cell transplantation success and progression of spermatogenesis were indicated by the presence of labeled PKH26 spermatids and sperm on days 90 and 120 post-transplantation, respectively. Confirming the presence of the catfish genetic material in the tilapia testis, all recipient tilapias evaluated (n=8) showed the genetic markers evaluated. Therefore, we demonstrated for the first time that the adult Nile tilapia testis offers the functional conditions for development of spermatogenesis with sperm production from a fish species belonging to a different order, which provides an important new venue for aquaculture advancement.

  14. Successful xenogeneic germ cell transplantation from Jundia catfish (Rhamdia quelen) into adult Nile tilapia (Oreochromis niloticus) testes.

    PubMed

    Silva, M A; Costa, G M J; Lacerda, S M S N; Brandão-Dias, P F P; Kalapothakis, E; Silva Júnior, A F; Alvarenga, E R; França, L R

    2016-05-01

    Fish germ cell transplantation presents several important potential applications for aquaculture, including the preservation of germplasm from endangered fish species with high genetic and commercial values. Using this technique in studies developed in our laboratory with adult male Nile tilapias (Oreochromis niloticus), all the necessary procedures were successfully established, allowing the production of functional sperm and healthy progeny approximately 2months after allogeneic transplantation. In the present study, we evaluated the viability of the adult Nile tilapia testis to generate sperm after xenogeneic transplant of germ cells from sexually mature Jundia catfish (Rhamdia quelen) that belong to a different taxonomic order. Therefore, in order to investigate at different time-periods post-transplantation, the presence and development of donor PKH26 labeled catfish germ cells were followed in the tilapia seminiferous tubules. From 7 to 20days post-transplantation, only PKH26 labeled spermatogonia were observed, whereas spermatocytes at different stages of development were found at 70days. Germ cell transplantation success and progression of spermatogenesis were indicated by the presence of labeled PKH26 spermatids and sperm on days 90 and 120 post-transplantation, respectively. Confirming the presence of the catfish genetic material in the tilapia testis, all recipient tilapias evaluated (n=8) showed the genetic markers evaluated. Therefore, we demonstrated for the first time that the adult Nile tilapia testis offers the functional conditions for development of spermatogenesis with sperm production from a fish species belonging to a different order, which provides an important new venue for aquaculture advancement. PMID:26972155

  15. Ventilation-perfusion scintigraphy in an adult with congenital unilateral hyperlucent lung

    SciTech Connect

    Wegener, W.A.; Velchik, M.G. )

    1990-10-01

    A variety of congenital and acquired etiologies can give rise to the radiographic finding of a unilateral hyperlucent lung. An unusual case of congenital lobar emphysema diagnosed in a young adult following the initial discovery of a hyperexpanded, hyperlucent lung is reported. Although subsequent bronchoscopy and radiologic studies detailed extensive anatomic abnormalities, functional imaging also played an important role in arriving at this rare diagnosis. In particular, ventilation-perfusion scintigraphy identified the small contralateral lung as the functional lung and helped narrow the differential diagnosis to etiologies involving obstructive airway disorders.

  16. A new type of Schwann cell graft transplantation to promote optic nerve regeneration in adult rats.

    PubMed

    Fang, Yuan; Mo, Xiaofen; Guo, Wenyi; Zhang, Meng; Zhang, Peihua; Wang, Yan; Rong, Xianfang; Tian, Jie; Sun, Xinghuai

    2010-12-01

    Like other parts of the central nervous system, the adult mammalian optic nerve is difficult to regenerate after injury. Transplantation of the peripheral nerve or a Schwann cell (SC) graft can promote injured axonal regrowth. We tried to develop a new type of tissue-engineered SC graft that consisted of SCs seeded onto a poly(lactic-co-glycolic acid)/chitosan conduit. Meanwhile, SCs were transfected along the ciliary neurotrophic factor (CNTF) gene in vitro by electroporation to increase their neurotrophic effect. Four weeks after transplantation, GAP-43 labelled regenerating axons were found in the SC grafts, and axons in the CNTF-SC graft were longer than those in the SC graft. Tissue-engineered SC grafts can provide a feasible environment for optic nerve regeneration and may become an alternative for bridging damaged nerves and repairing nerve defects in the future.

  17. First-in-Human Case Study: Multipotent Adult Progenitor Cells for Immunomodulation After Liver Transplantation.

    PubMed

    Soeder, Yorick; Loss, Martin; Johnson, Christian L; Hutchinson, James A; Haarer, Jan; Ahrens, Norbert; Offner, Robert; Deans, Robert J; Van Bokkelen, Gil; Geissler, Edward K; Schlitt, Hans J; Dahlke, Marc H

    2015-08-01

    Mesenchymal stem cells and multipotent adult progenitor cells (MAPCs) have been proposed as novel therapeutics for solid organ transplant recipients with the aim of reducing exposure to pharmacological immunosuppression and its side effects. In the present study, we describe the clinical course of the first patient of the phase I, dose-escalation safety and feasibility study, MiSOT-I (Mesenchymal Stem Cells in Solid Organ Transplantation Phase I). After receiving a living-related liver graft, the patient was given one intraportal injection and one intravenous infusion of third-party MAPC in a low-dose pharmacological immunosuppressive background. Cell administration was found to be technically feasible; importantly, we found no evidence of acute toxicity associated with MAPC infusions.

  18. Twenty years of evolving trends in racial disparities for adult kidney transplant recipients.

    PubMed

    Taber, David J; Gebregziabher, Mulugeta; Hunt, Kelly J; Srinivas, Titte; Chavin, Kenneth D; Baliga, Prabhakar K; Egede, Leonard E

    2016-10-01

    Disparities in outcomes for African American (AA) kidney transplant recipients have persisted for 40 years without a comprehensive analysis of evolving trends in the risks associated with this disparity. Here we analyzed U.S. transplant registry data, which included adult Caucasian or AA solitary kidney recipients undergoing transplantation between 1990 and 2009 comprising 202,085 transplantations. During this 20-year period, the estimated rate of 5-year graft loss decreased from 27.6% to 12.8%. Notable trends in baseline characteristics that significantly differed by race over time included the following: increased prevalence of diabetes from 2001 to 2009 in AAs (5-year slope difference: 3.4%), longer time on the waiting list (76.5 more days per 5 years in AAs), fewer living donors in AAs from 2003 to 2009 (5-year slope difference: -3.36%), more circulatory death donors in AAs from 2000-09 (5-year slope difference: 1.78%), and a slower decline in delayed graft function in AAs (5-year slope difference: 0.85%). The absolute risk difference between AAs and Caucasians for 5-year graft loss significantly declined over time (-0.92% decrease per 5 years), whereas the relative risk difference actually significantly increased (3.4% increase per 5 years). These results provide a mixed picture of both promising and concerning trends in disparities for AA kidney transplant recipients. Thus, although the disparity for graft loss has significantly improved, equity is still far off, and other disparities, including living donation rates and delayed graft function rates, have widened during this time.

  19. Social barriers to listing for adult liver transplantation: their prevalence and association with program characteristics.

    PubMed

    Flattau, Anna; Olaywi, Manhal; Gaglio, Paul J; Marcus, Paula; Meissner, Paul; L Dorfman, Emily B; Reinus, John F

    2011-10-01

    Social barriers to effective medical care are mandated to be routinely assessed as part of an evaluation for liver transplantation. This study explores how frequently liver transplant programs encounter these barriers in patients undergoing an evaluation and whether programs with higher proportions of Medicaid patients, historically disadvantaged minority patients, and rural patients encounter social barriers more frequently. A survey for assessing patient demographics and social barriers was electronically completed by representatives of 61 of 104 eligible US adult liver transplant programs (59%). Fifty-eight of the 61 programs identified themselves, and their characteristics were similar to those of all 104 US programs according to publicly available data from the Organ Procurement and Transplantation Network. Social barriers were reported to be encountered sometimes (10%-30%) or frequently (>30%) by the 61 programs as follows: inadequate or unstable health insurance (68.9% of the programs), a chaotic social environment (63.9%), a lack of a care partner (60.7%), an inability to obtain transportation (49.2%), a low educational level (36.1%), inadequate housing (23.0%), a language barrier (19.7%), no reliable way of contacting the patient (16.4%), difficulty in obtaining child care (11.5%), and food insecurity (8.2%). The frequencies of perceived social barriers did not differ significantly between programs reporting higher or lower proportions of Medicaid, minority, or rural patients. Our analysis suggests that program-level operational planning for addressing social barriers to transplant listing should be considered regardless of the proportions of Medicaid-insured, racial or ethnic minority, and rural patients in the population.

  20. Liver graft regeneration in right lobe adult living donor liver transplantation.

    PubMed

    Cheng, Y-F; Huang, T-L; Chen, T-Y; Tsang, L L-C; Ou, H-Y; Yu, C-Y; Concejero, A; Wang, C-C; Wang, S-H; Lin, T-S; Liu, Y-W; Yang, C-H; Yong, C-C; Chiu, K-W; Jawan, B; Eng, H-L; Chen, C-L

    2009-06-01

    Optimal portal flow is one of the essentials in adequate liver function, graft regeneration and outcome of the graft after right lobe adult living donor liver transplantation (ALDLT). The relations among factors that cause sufficient liver graft regeneration are still unclear. The aim of this study is to evaluate the potential predisposing factors that encourage liver graft regeneration after ALDLT. The study population consisted of right lobe ALDLT recipients from Chang Gung Memorial Hospital-Kaohsiung Medical Center, Taiwan. The records, preoperative images, postoperative Doppler ultrasound evaluation and computed tomography studies performed 6 months after transplant were reviewed. The volume of the graft 6 months after transplant divided by the standard liver volume was calculated as the regeneration ratio. The predisposing risk factors were compiled from statistical analyses and included age, recipient body weight, native liver disease, spleen size before transplant, patency of the hepatic venous graft, graft weight-to-recipient weight ratio (GRWR), posttransplant portal flow, vascular and biliary complications and rejection. One hundred forty-five recipients were enrolled in this study. The liver graft regeneration ratio was 91.2 +/- 12.6% (range, 58-151). The size of the spleen (p = 0.00015), total portal flow and GRWR (p = 0.005) were linearly correlated with the regeneration rate. Patency of the hepatic venous tributary reconstructed was positively correlated to graft regeneration and was statistically significant (p = 0.017). Splenic artery ligation was advantageous to promote liver regeneration in specific cases but splenectomy did not show any positive advantage. Spleen size is a major factor contributing to portal flow and may directly trigger regeneration after transplant. Control of sufficient portal flow and adequate hepatic outflow are important factors in graft regeneration.

  1. Twenty years of evolving trends in racial disparities for adult kidney transplant recipients.

    PubMed

    Taber, David J; Gebregziabher, Mulugeta; Hunt, Kelly J; Srinivas, Titte; Chavin, Kenneth D; Baliga, Prabhakar K; Egede, Leonard E

    2016-10-01

    Disparities in outcomes for African American (AA) kidney transplant recipients have persisted for 40 years without a comprehensive analysis of evolving trends in the risks associated with this disparity. Here we analyzed U.S. transplant registry data, which included adult Caucasian or AA solitary kidney recipients undergoing transplantation between 1990 and 2009 comprising 202,085 transplantations. During this 20-year period, the estimated rate of 5-year graft loss decreased from 27.6% to 12.8%. Notable trends in baseline characteristics that significantly differed by race over time included the following: increased prevalence of diabetes from 2001 to 2009 in AAs (5-year slope difference: 3.4%), longer time on the waiting list (76.5 more days per 5 years in AAs), fewer living donors in AAs from 2003 to 2009 (5-year slope difference: -3.36%), more circulatory death donors in AAs from 2000-09 (5-year slope difference: 1.78%), and a slower decline in delayed graft function in AAs (5-year slope difference: 0.85%). The absolute risk difference between AAs and Caucasians for 5-year graft loss significantly declined over time (-0.92% decrease per 5 years), whereas the relative risk difference actually significantly increased (3.4% increase per 5 years). These results provide a mixed picture of both promising and concerning trends in disparities for AA kidney transplant recipients. Thus, although the disparity for graft loss has significantly improved, equity is still far off, and other disparities, including living donation rates and delayed graft function rates, have widened during this time. PMID:27555121

  2. Type II (adult onset) citrullinaemia: clinical pictures and the therapeutic effect of liver transplantation

    PubMed Central

    Ikeda, S; Yazaki, M; Takei, Y; Ikegami, T; Hashikura, Y; Kawasaki, S; Iwai, M; Kobayashi, K; Saheki, T

    2001-01-01

    OBJECTIVE—Adult onset type II citrullinemia is an inherited disorder of amino acid metabolism caused by a deficiency of liver specific argininosuccinate synthetase activity. Most of the patients with this disease were reported in Japan and therefore, this disease has not been well recognised outside this country. The detailed clinical pictures of the patients with type II citrullinaemia are reported and their outcomes after liver transplantation referred to.
METHODS—Ten patients with this disease were evaluated. Seven of them underwent liver transplants using a graft obtained from a healthy family member.
RESULTS—There were six men and four women; the age of onset of encephalopathy ranged from 17 to 51 years. The initial symptom in nine patients was sudden onset disturbance of consciousness, and one patient had long been regarded as having a chronic progressive psychotic illness. High concentrations of plasma citrulline and ammonia were commonly seen on admission. Although brain CT or MRI lacked any consistent findings, the EEG was abnormal in all patients, showing diffuse slow waves. Additionally, in five patients chronic pancreatitis preceded the onset of encephalopathy. After liver transplantation the metabolic abnormalities, including abnormal plasma concentrations of citrulline and ammonia, were immediately corrected and all neuropsychic symptoms soon disappeared, except for impaired cognitive function in one patient. Six out of these seven patients returned to their previous social lives, including work.
CONCLUSIONS—The clinical concept of adult onset type II citrullinaemia coincides well with the range of hepatic encephalopathy, and liver transplantation is a very promising therapeutic approach.

 PMID:11606680

  3. Lung vital capacity and oxygen saturation in adults with cerebral palsy

    PubMed Central

    Lampe, Renée; Blumenstein, Tobias; Turova, Varvara; Alves-Pinto, Ana

    2014-01-01

    Background Individuals with infantile cerebral palsy have multiple disabilities. The most conspicuous syndrome being investigated from many aspects is motor movement disorder with a spastic gait pattern. The lung function of adults with spasticity attracts less attention in the literature. This is surprising because decreased thoracic mobility and longstanding scoliosis should have an impact on lung function. With increasing age and the level of disability, individuals become susceptible to lung infections and reflux illness, and these are accompanied by increased aspiration risk. This study examined, with different methods, to what extent adults with congenital cerebral palsy and acquired spastic paresis – following traumatic brain injury – showed restriction of lung function. It also assessed the contribution of disability level on this restriction. Methods The oxygen saturation of 46 adults with a diagnosis of cerebral palsy was measured with an oximeter. Lung vital capacity was measured with a mobile spirometer and excursion of the thorax was clinically registered. The gross motor function levels and the presence or absence of scoliosis were determined. Results A significantly positive correlation between lung vital capacity and chest expansion was established. Both the lung vital capacity and the thorax excursion decreased with increases in gross motor function level. Oxygen saturation remained within the normal range in all persons, in spite of reduced values of the measured lung parameters. No statistically significant dependency between lung vital capacity and oxygen saturation, and between chest expansion and oxygen saturation was found. The scoliotic deformities of the spine were associated with an additional decrease in the vital capacity, but this did not affect blood oxygen supply. Conclusion Despite the decreased chest expansion and the significantly reduced lung volume in adults with cerebral palsy, sufficient oxygen supply was registered. PMID

  4. Lung Volume Measured during Sequential Swallowing in Healthy Young Adults

    ERIC Educational Resources Information Center

    Hegland, Karen Wheeler; Huber, Jessica E.; Pitts, Teresa; Davenport, Paul W.; Sapienza, Christine M.

    2011-01-01

    Purpose: Outcomes from studying the coordinative relationship between respiratory and swallow subsystems are inconsistent for sequential swallows, and the lung volume at the initiation of sequential swallowing remains undefined. The first goal of this study was to quantify the lung volume at initiation of sequential swallowing ingestion cycles and…

  5. Longitudinal dose and type of immunosuppression in a national cohort of Australian liver, heart, and lung transplant recipients, 1984-2006.

    PubMed

    Na, Renhua; Laaksonen, Maarit A; Grulich, Andrew E; Webster, Angela C; Meagher, Nicola S; McCaughan, Geoffrey W; Keogh, Anne M; Vajdic, Claire M

    2015-11-01

    Unconfounded comparative data on the type and dose of immunosuppressive agents among solid organ transplant recipients are sparse, as are data on longitudinal immunosuppressive therapy since transplantation. We addressed this issue in a population-based cohort of Australian liver (n = 1895), heart (n = 1220), and lung (n = 1059) transplant recipients, 1984-2006. Data on immunosuppressive therapy were retrospectively collected at discharge, three months, and one, five, 10, and 15 yr after first transplant. We computed unadjusted and adjusted estimates for the association between the type and dose of immunosuppressive therapy and organ type. After adjustment for confounders, use of induction antibody and maintenance corticosteroids was more common in heart and lung compared to liver recipients (p < 0.001), and antibody therapy for rejection more common in liver recipients (p < 0.001). Liver recipients were more likely to receive calcineurin inhibitor monotherapy, with or without corticosteroids, compared to heart and lung recipients (p < 0.001). Liver recipients consistently received lower doses of azathioprine than heart and lung recipients (p < 0.001). These differences in immunosuppression may partly explain variations in immunosuppression-related morbidity by transplanted organ, for example, malignancy risk. Longitudinal changes in the type and the dose of immunosuppressive therapy over time since transplantation also demonstrate the need for time-dependent data in observational research.

  6. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

    PubMed

    Dhédin, Nathalie; Huynh, Anne; Maury, Sébastien; Tabrizi, Reza; Beldjord, Kheira; Asnafi, Vahid; Thomas, Xavier; Chevallier, Patrice; Nguyen, Stéphanie; Coiteux, Valérie; Bourhis, Jean-Henri; Hichri, Yosr; Escoffre-Barbe, Martine; Reman, Oumedaly; Graux, Carlos; Chalandon, Yves; Blaise, Didier; Schanz, Urs; Lhéritier, Véronique; Cahn, Jean-Yves; Dombret, Hervé; Ifrah, Norbert

    2015-04-16

    Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678. PMID:25587040

  7. Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia.

    PubMed

    Dhédin, Nathalie; Huynh, Anne; Maury, Sébastien; Tabrizi, Reza; Beldjord, Kheira; Asnafi, Vahid; Thomas, Xavier; Chevallier, Patrice; Nguyen, Stéphanie; Coiteux, Valérie; Bourhis, Jean-Henri; Hichri, Yosr; Escoffre-Barbe, Martine; Reman, Oumedaly; Graux, Carlos; Chalandon, Yves; Blaise, Didier; Schanz, Urs; Lhéritier, Véronique; Cahn, Jean-Yves; Dombret, Hervé; Ifrah, Norbert

    2015-04-16

    Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678.

  8. Prolonged Mechanical Ventilation After Lung Transplantation-A Single-Center Study.

    PubMed

    Hadem, J; Gottlieb, J; Seifert, D; Fegbeutel, C; Sommer, W; Greer, M; Wiesner, O; Kielstein, J T; Schneider, A S; Ius, F; Fuge, J; Kühn, C; Tudorache, I; Haverich, A; Welte, T; Warnecke, G; Hoeper, M M

    2016-05-01

    This single-center study examines the incidence, etiology, and outcomes associated with prolonged mechanical ventilation (PMV), defined as time to definite spontaneous ventilation >21 days after double lung transplantation (LTx). A total of 690 LTx recipients between January 2005 and December 2012 were analyzed. PMV was necessary in 95 (13.8%) patients with decreasing incidence during the observation period (p < 0.001). Independent predictors of PMV were renal replacement therapy (odds ratio [OR] 11.13 [95% CI, 5.82-21.29], p < 0.001), anastomotic dehiscence (OR 8.74 [95% CI 2.42-31.58], p = 0.001), autoimmune comorbidity (OR 5.52 [95% CI 1.86-16.41], p = 0.002), and postoperative neurologic complications (OR 5.03 [95% CI 1.98-12.81], p = 0.001), among others. Overall 1-year survival was 86.0% (90.4% for LTx between 2010 and 2012); it was 60.7% after PMV and 90.0% in controls (p < 0.001). Conditional long-term outcome among hospital survivors, however, did not differ between the groups (p = 0.78). Multivariate analysis identified renal replacement therapy (hazard ratio [HR] 3.55 [95% CI 2.40-5.25], p < 0.001), post-LTx extracorporeal membrane oxygenation (HR 3.47 [95% CI 2.06-5.83], p < 0.001), and prolonged inotropic support (HR 1.95 [95% CI 1.39-2.75], p < 0.001), among others, as independent predictors of mortality. In conclusion, PMV complicated 14% of LTx procedures and, although associated with increased in-hospital mortality, outcomes among patients surviving to hospital discharge were unaffected. PMID:26607844

  9. Prostacyclin (epoprostenol) and heart-lung transplantation as treatments for severe pulmonary hypertension.

    PubMed Central

    Higenbottam, T W; Spiegelhalter, D; Scott, J P; Fuster, V; Dinh-Xuan, A T; Caine, N; Wallwork, J

    1993-01-01

    OBJECTIVE--To determine whether epoprostenol (prostacyclin, PGI2) or heart-lung transplantation (HLT), or both improves survival of patients with severe pulmonary hypertension. DESIGN--This was a prospective study where the effects of epoprostenol were compared with conventional treatment. Also, the benefits of epoprostenol and HLT were assessed by comparing survival in this group with that of 120 patients at the Mayo Clinic before HLT and epoprostenol treatment became available. PATIENTS AND INTERVENTIONS--Forty four patients were studied; 25 received continuous epoprostenol over a four year period (mean (SD) cardiac index 1.8 (0.4) 1 min-1 m-2 and mean (SD) pulmonary artery pressure (PAP) 70 (16) mm Hg) and 19 did not (cardiac index 2.1 (0.6) 1 min-1 m-2 and PAP 64 (13) mm Hg). Ten patients underwent HLT: seven had received epoprostenol, and three had not. RESULTS--The therapeutic intervention with epoprostenol, or HLT, or both improved survival compared with the Mayo clinic patients (p = 0.05). Most of the benefit was conferred by epoprostenol, which prolonged survival twofold from a median time of eight to 17 months and doubled the changes of successful HLT. The improved survival with epoprostenol was not related to its immediate capacity to cause pulmonary vasodilation. Those patients who had limited acute pulmonary vasodilation when treated with epoprostenol showed the greatest improvement in survival. CONCLUSIONS--These preliminary results indicate that those pulmonary hypertensive patients with the poorest chance of survival can be helped by epoprostenol and by HLT. PMID:8217447

  10. Periostitis secondary to prolonged voriconazole therapy in a lung transplant recipient.

    PubMed

    Lustenberger, David P; Granata, Jaymes D; Scharschmidt, Thomas J

    2011-11-09

    This article reports a case of perostitis deformans in a lung transplantation patient taking the fluoride-containing medication voriconazole, a relatively new and potent anti-fungal. The patient had a normal range of motion in all joints and a normal gait. On radiographs at presentation, multifocal areas of periostitis were visualized involving the left-hand first, second, and third proximal phalanx shafts. Similar periostitis was present on the left-hand third, fourth, and fifth middle phalanx shafts. Plain radiographs of the right hand also demonstrated multifocal periostitis of the third and fourth proximal and middle phalanges. Aggressive periostitis at the level of the right fourth proximal and middle phalanges was also present. Given her long-term treatment with voriconazole and a presentation consistent with periostitis deformans, voriconazole was presumed to be the offending agent and was replaced with itraconazole. The patient's symptoms resolved shortly after withdrawal of voriconazole.Voriconazole-associated periostitis has only recently been reported in the literature. Food and Drug Administration-approved in 2002, voriconazole is efficacious in treating serious, invasive fungal infections that are generally seen in immunocompromised patients. Due to the novel nature of voriconazole and the uncommon indications for its long-term use, the periostitis deformans described in this article may be unfamiliar to the orthopedic surgeon. Consequently, a patient presenting with bone pain and periosteal involvement on plain radiographs may provoke a broad, expensive, and ultimately unnecessary diagnostic evaluation. The clinical case and imaging findings presented here can help to promote understanding of this benign condition and its simple cure: voriconazole discontinuation.

  11. Preoperative Thromboelastometry as a Predictor of Transfusion Requirements during Adult Living Donor Liver Transplantation

    PubMed Central

    Fayed, Nirmeen; Mourad, Wessam; Yassen, Khaled; Görlinger, Klaus

    2015-01-01

    Background The ability to predict transfusion requirements may improve perioperative bleeding management as an integral part of a patient blood management program. Therefore, the aim of our study was to evaluate preoperative thromboelastometry as a predictor of transfusion requirements for adult living donor liver transplant recipients. Methods The correlation between preoperative thromboelastometry variables in 100 adult living donor liver transplant recipients and intraoperative blood transfusion requirements was examined by univariate and multivariate linear regression analysis. Thresholds of thromboelastometric parameters for prediction of packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelets, and cryoprecipitate transfusion requirements were determined with receiver operating characteristics analysis. The attending anesthetists were blinded to the preoperative thromboelastometric analysis. However, a thromboelastometry-guided transfusion algorithm with predefined trigger values was used intraoperatively. The transfusion triggers in this algorithm did not change during the study period. Results Univariate analysis confirmed significant correlations between PRBCs, FFP, platelets or cryoprecipitate transfusion requirements and most thromboelastometric variables. Backward stepwise logistic regression indicated that EXTEM coagulation time (CT), maximum clot firmness (MCF) and INTEM CT, clot formation time (CFT) and MCF are independent predictors for PRBC transfusion. EXTEM CT, CFT and FIBTEM MCF are independent predictors for FFP transfusion. Only EXTEM and INTEM MCF were independent predictors of platelet transfusion. EXTEM CFT and MCF, INTEM CT, CFT and MCF as well as FIBTEM MCF are independent predictors for cryoprecipitate transfusion. Thromboelastometry-based regression equation accounted for 63% of PRBC, 83% of FFP, 61% of cryoprecipitate, and 44% of platelet transfusion requirements. Conclusion Preoperative thromboelastometric analysis is

  12. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

    PubMed

    Mehra, Mandeep R; Crespo-Leiro, Maria G; Dipchand, Anne; Ensminger, Stephan M; Hiemann, Nicola E; Kobashigawa, Jon A; Madsen, Joren; Parameshwar, Jayan; Starling, Randall C; Uber, Patricia A

    2010-07-01

    The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology.

  13. International Society for Heart and Lung Transplantation working formulation of a standardized nomenclature for cardiac allograft vasculopathy-2010.

    PubMed

    Mehra, Mandeep R; Crespo-Leiro, Maria G; Dipchand, Anne; Ensminger, Stephan M; Hiemann, Nicola E; Kobashigawa, Jon A; Madsen, Joren; Parameshwar, Jayan; Starling, Randall C; Uber, Patricia A

    2010-07-01

    The development of cardiac allograft vasculopathy remains the Achilles heel of cardiac transplantation. Unfortunately, the definitions of cardiac allograft vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, cardiac allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of cardiac allograft vasculopathy, similar to the development of the system for adjudication of cardiac allograft rejection by histology. PMID:20620917

  14. Cord Blood Transplantation Following Reduced-intensity Conditioning for Adult-onset Inherited Hemophagocytic Lymphohistiocytosis.

    PubMed

    Kuriyama, Takuro; Kato, Koji; Sakamoto, Keiji; Hayashi, Masayasu; Takashima, Shuichiro; Mori, Yasuo; Takenaka, Katsuto; Iwasaki, Hiromi; Teshima, Takanori; Harada, Naoki; Nagafuji, Koji; Miyamoto, Toshihiro; Akashi, Koichi

    2016-01-01

    Inherited hemophagocytic lymphohistiocytosis (HLH) is a genetic anomaly disorder in which abnormally activated cytotoxic T lymphocytes cannot induce the apoptosis of target cells and antigen-presenting cells, leading to hemophagocytosis, pancytopenia, and a variety of symptoms such as a high fever. The present patient with adult-onset HLH developed refractory disease despite receiving immunosuppressive treatments. He underwent a reduced-intensity conditioning (RIC) regimen that comprised antithymocyte globulin (ATG) followed by cord blood transplantation (RIC-CBT). He achieved and maintained a complete donor type. The incorporation of ATG into RIC-CBT may prevent graft failure and control hemophagocytosis, however, further efforts are necessary to reduce infectious complications. PMID:26984088

  15. Combined Detection of Serum IL-10, IL-17, and CXCL10 Predicts Acute Rejection Following Adult Liver Transplantation

    PubMed Central

    Kim, Nayoung; Yoon, Young-In; Yoo, Hyun Ju; Tak, Eunyoung; Ahn, Chul-Soo; Song, Gi-Won; Lee, Sung-Gyu; Hwang, Shin

    2016-01-01

    Discovery of non-invasive diagnostic and predictive biomarkers for acute rejection in liver transplant patients would help to ensure the preservation of liver function in the graft, eventually contributing to improved graft and patient survival. We evaluated selected cytokines and chemokines in the sera from liver transplant patients as potential biomarkers for acute rejection, and found that the combined detection of IL-10, IL-17, and CXCL10 at 1-2 weeks post-operation could predict acute rejection following adult liver transplantation with 97% specificity and 94% sensitivity. PMID:27498551

  16. The Role of Donor Chronic Alcohol Abuse in the Development of Primary Graft Dysfunction in Lung Transplant Recipients

    PubMed Central

    Mitchell, Patrick O.; Shah, Nimesh S.; Force, Seth D.; Elon, Lisa; Brown, Lou Ann S.; Guidot, David M.

    2015-01-01

    Abstract: Primary graft dysfunction (PGD) following lung transplantation is clinically similar to the acute respiratory distress syndrome. Because alcohol abuse independently increases the incidence of acute respiratory distress syndrome in at-risk individuals, we hypothesized that donor alcohol use is correlated with an increased risk of PGD. As a pilot study, we collected alcohol use histories using a validated instrument, the Alcohol Use Disorder Identification Test questionnaire, from 74 donors and correlated these with the development of PGD in corresponding recipients. Nineteen percent (14/74) of donors were classified as heavy alcohol users, as defined by the Alcohol Use Disorder Identification Test scores ≥8. In the 1st 4 days post-transplantation, similar percentages of recipients developed grade 3 PGD on at least 1 day (heavy alcohol user = 29% [4/14] versus lighter alcohol user = 27% [16/60]); however, recipients receiving a lung from a heavy alcohol user were more likely to have multiple and consecutive days of grade 3 PGD, especially in the 1st 48 hours post-transplant. Both median length of stay in the intensive care unit and hospital were somewhat longer in the heavy alcohol user group (9 versus 7 days and 19.5 versus 17.5 days, respectively). If these preliminary findings are validated in a multi-center study, they would have important implications not only for our understanding of the pathophysiology of PGD but also for the development of novel treatments based on the evolving evidence from experimental and clinical studies on how alcohol abuse renders the lung susceptible to acute edematous injury. PMID:25310510

  17. The role of donor chronic alcohol abuse in the development of primary graft dysfunction in lung transplant recipients.

    PubMed

    Pelaez, Andres; Mitchell, Patrick O; Shah, Nimesh S; Force, Seth D; Elon, Lisa; Brown, Lou Ann S; Guidot, David M

    2015-02-01

    Primary graft dysfunction (PGD) following lung transplantation is clinically similar to the acute respiratory distress syndrome. Because alcohol abuse independently increases the incidence of acute respiratory distress syndrome in at-risk individuals, we hypothesized that donor alcohol use is correlated with an increased risk of PGD. As a pilot study, we collected alcohol use histories using a validated instrument, the Alcohol Use Disorder Identification Test questionnaire, from 74 donors and correlated these with the development of PGD in corresponding recipients. Nineteen percent (14/74) of donors were classified as heavy alcohol users, as defined by the Alcohol Use Disorder Identification Test scores≥8. In the 1st 4 days post-transplantation, similar percentages of recipients developed grade 3 PGD on at least 1 day (heavy alcohol user=29% [4/14] versus lighter alcohol user=27% [16/60]); however, recipients receiving a lung from a heavy alcohol user were more likely to have multiple and consecutive days of grade 3 PGD, especially in the 1st 48 hours post-transplant. Both median length of stay in the intensive care unit and hospital were somewhat longer in the heavy alcohol user group (9 versus 7 days and 19.5 versus 17.5 days, respectively). If these preliminary findings are validated in a multi-center study, they would have important implications not only for our understanding of the pathophysiology of PGD but also for the development of novel treatments based on the evolving evidence from experimental and clinical studies on how alcohol abuse renders the lung susceptible to acute edematous injury.

  18. Successful cord blood transplantation in an adult acute lymphoblastic leukemia patient with congenital heart disease.

    PubMed

    Kowata, Shugo; Fujishima, Yukiteru; Suzuki, Yuzo; Tsukushi, Yasuhiko; Oyake, Tatsuo; Togawa, Ryou; Oyama, Kotaro; Ikai, Akio; Ito, Shigeki; Ishida, Yoji

    2016-08-01

    Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation. PMID:27599417

  19. [Role of biomarkers in the differential diagnosis of acute respiratory failure in the immediate postoperative period of lung transplantation].

    PubMed

    Ruano, L; Sacanell, J; Roman, A; Rello, J

    2013-01-01

    Lung transplant recipients are at high risk of suffering many complications during the immediate postoperative period, such as primary graft dysfunction, acute graft rejection or infection. The most common symptom is the presence of acute respiratory failure, and the use of biomarkers could be useful for establishing an early diagnosis of these conditions. Different biomarkers have been studied, but none have proven to be the gold standard in the differential diagnosis of acute respiratory failure. This paper offers a review of the different biomarkers that have been studied in this field.

  20. [Role of biomarkers in the differential diagnosis of acute respiratory failure in the immediate postoperative period of lung transplantation].

    PubMed

    Ruano, L; Sacanell, J; Roman, A; Rello, J

    2013-01-01

    Lung transplant recipients are at high risk of suffering many complications during the immediate postoperative period, such as primary graft dysfunction, acute graft rejection or infection. The most common symptom is the presence of acute respiratory failure, and the use of biomarkers could be useful for establishing an early diagnosis of these conditions. Different biomarkers have been studied, but none have proven to be the gold standard in the differential diagnosis of acute respiratory failure. This paper offers a review of the different biomarkers that have been studied in this field. PMID:23462428

  1. Effect of chronic hyperoxic exposure on duroquinone reduction in adult rat lungs.

    PubMed

    Audi, Said H; Bongard, Robert D; Krenz, Gary S; Rickaby, David A; Haworth, Steven T; Eisenhauer, Jessica; Roerig, David L; Merker, Marilyn P

    2005-11-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) plays a dominant role in the reduction of the quinone compound 2,3,5,6-tetramethyl-1,4-benzoquinone (duroquinone, DQ) to durohydroquinone (DQH2) on passage through the rat lung. Exposure of adult rats to 85% O2 for > or =7 days stimulates adaptation to the otherwise lethal effects of >95% O2. The objective of this study was to examine whether exposure of adult rats to hyperoxia affected lung NQO1 activity as measured by the rate of DQ reduction on passage through the lung. We measured DQH2 appearance in the venous effluent during DQ infusion at different concentrations into the pulmonary artery of isolated perfused lungs from rats exposed to room air or to 85% O2. We also evaluated the effect of hyperoxia on vascular transit time distribution and measured NQO1 activity and protein in lung homogenate. The results demonstrate that exposure to 85% O2 for 21 days increases lung capacity to reduce DQ to DQH2 and that NQO1 is the dominant DQ reductase in normoxic and hyperoxic lungs. Kinetic analysis revealed that 21-day hyperoxia exposure increased the maximum rate of pulmonary DQ reduction, Vmax, and the apparent Michaelis-Menten constant for DQ reduction, Kma. The increase in Vmax suggests a hyperoxia-induced increase in NQO1 activity of lung cells accessible to DQ from the vascular region, consistent qualitatively but not quantitatively with an increase in lung homogenate NQO1 activity in 21-day hyperoxic lungs. The increase in Kma could be accounted for by approximately 40% increase in vascular transit time heterogeneity in 21-day hyperoxic lungs.

  2. Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies.

    PubMed

    Shah, Gunjan L; Shune, Leyla; Purtill, Duncan; Devlin, Sean; Lauer, Emily; Lubin, Marissa; Bhatt, Valkal; McElrath, Courtney; Kernan, Nancy A; Scaradavou, Andromachi; Giralt, Sergio; Perales, Miguel A; Ponce, Doris M; Young, James W; Shah, Monica; Papanicolaou, Genovefa; Barker, Juliet N

    2015-12-01

    Because cord blood (CB) lacks memory T and B cells and recent decreases in herd immunity to vaccine-preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine-eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five patients (63%; engrafting units median HLA-allele match 5/8; range, 2 to 7/8) received protein conjugated vaccines, and 63 patients (median age, 34 years; range, .9 to 64) were evaluated for responses. Median vaccination time was 17 months (range, 7 to 45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19F, 23F) were seen in children and adults (60% versus 49%, P = .555). Responses to tetanus, diphtheria, pertussis, Haemophilus influenzae, and polio were observed in children (86% to 100%) and adults (53% to 89%) even if patients had prior GVHD or rituximab. CD4(+)CD45RA(+) and CD19(+) cell recovery significantly influenced tetanus and polio responses. In a smaller cohort responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side effects were identified, and all vaccinated patients survived (median follow-up, 57 months). Although GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients. PMID:26271191

  3. Cardiac transplantation.

    PubMed

    Shanewise, Jack

    2004-12-01

    Cardiac transplantation is a proven, accepted mode of therapy for selected patients with end-stage heart failure, but the inadequate number of suitable donor hearts available ultimately limits its application. This chapter reviews adult cardiac transplantation, with an emphasis on the anesthetic considerations of the heart transplant operation itself.

  4. Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success

    PubMed Central

    Lin, Xue; Li, Wenjun; Lai, Jiaming; Okazaki, Mikio; Sugimoto, Seiichiro; Yamamoto, Sumiharu; Wang, Xingan; Gelman, Andrew E.; Kreisel, Daniel

    2012-01-01

    It has been 5 years since our team reported the first successful model of orthotopic single lung transplantation in the mouse. There has been great demand for this technique due to the obvious experimental advantages the mouse offers over other large and small animal models of lung transplantation. These include the availability of mouse-specific reagents as well as knockout and transgenic technology. Our laboratory has utilized this mouse model to study both immunological and non-immunological mechanisms of lung transplant physiology while others have focused on models of chronic rejection. It is surprising that despite our initial publication in 2007 only few other laboratories have published data using this model. This is likely due to the technical complexity of the surgical technique and perioperative complications, which can limit recipient survival. As two of the authors (XL and WL) have a combined experience of over 2500 left and right single lung transplants, this review will summarize their experience and delineate tips and tricks necessary for successful transplantation. We will also describe technical advances made since the original description of the model. PMID:22754663

  5. [Annual review of Archivos de Neumología in interventional pneumology, interstitial diseases and lung transplantation].

    PubMed

    Disdier, Carlos; Bollo, Elena; Morales, Pilar; Montero, Carmen

    2009-01-01

    A review has been made of original articles on invasive pneumology techniques, interstitial diseases and lung transplantation, published in the Archivos de Bronconeumología during the year 2008. We have selected the publication by Martínez-Olondrins et al on the mediastinal staging of bronchogenic carcinoma by transbronchial needle aspiration to highlight the role of this simple, safe and cost-effective technique at a time when aspiration by ultrasound-guided bronchoscopy is profiled as an alternative to staging by mediastinoscopy. Besides its usefulness in the study of lymph nodes, transbronchial needle aspiration increases the overall performance of bronchoscopy by 20%, which means that it should be considered as a basic tool in the study of lung cancer. We also comment on the work by Galvis-Caravajal et al, who describe percutaneous radiofrequency as an alternative to radiotherapy in small lung or metastasic tumours. In diffuse interstitial disease, Morell et al analysed the diagnostic methods in 500 patients with this clinical-radiological presentation in which a definitive diagnosis was achieved in 85%, with 25% of them being obtained by non-invasively. Baloira et al analysed the characteristics of 19 patients with desquamative interstitial pneumonia and respiratory bronchiolitis associated-interstitial lung disease obtained from the National register of Interstitial Diseases.

  6. [Annual review of Archivos de Neumología in interventional pneumology, interstitial diseases and lung transplantation].

    PubMed

    Disdier, Carlos; Bollo, Elena; Morales, Pilar; Montero, Carmen

    2009-01-01

    A review has been made of original articles on invasive pneumology techniques, interstitial diseases and lung transplantation, published in the Archivos de Bronconeumología during the year 2008. We have selected the publication by Martínez-Olondrins et al on the mediastinal staging of bronchogenic carcinoma by transbronchial needle aspiration to highlight the role of this simple, safe and cost-effective technique at a time when aspiration by ultrasound-guided bronchoscopy is profiled as an alternative to staging by mediastinoscopy. Besides its usefulness in the study of lymph nodes, transbronchial needle aspiration increases the overall performance of bronchoscopy by 20%, which means that it should be considered as a basic tool in the study of lung cancer. We also comment on the work by Galvis-Caravajal et al, who describe percutaneous radiofrequency as an alternative to radiotherapy in small lung or metastasic tumours. In diffuse interstitial disease, Morell et al analysed the diagnostic methods in 500 patients with this clinical-radiological presentation in which a definitive diagnosis was achieved in 85%, with 25% of them being obtained by non-invasively. Baloira et al analysed the characteristics of 19 patients with desquamative interstitial pneumonia and respiratory bronchiolitis associated-interstitial lung disease obtained from the National register of Interstitial Diseases. PMID:19303530

  7. Intestinal type of lung adenocarcinoma in younger adults.

    PubMed

    Stojsic, Jelena; Kontic, Milica; Subotic, Dragan; Popovic, Marko; Tomasevic, Dragana; Lukic, Jelena

    2014-01-01

    Intestinal type of lung adenocarcinoma (ILADC) was initially described by Tsao and Fraser in 1991. Morphology and immunophenotype of ILADC are the same as in colorectal adenocarcinoma. Rectocolonoscopy must be performed to exclude colorectal origin of adenocarcinoma. Colorectal adenocarcinoma claimed to be genetically similar to an ILADC. Patients. We describe 24- and 26-year-old patients of both genders who went under surgery because of a lung tumor mass detected on CT scan. ILADC was diagnosed on resected lung specimens. According to positivity of Cytokeratin20, CDX-2, and Villin, respectively, and negativity of Cytokeratin7, TTF-1, Napsin-A, SurfactantB, MUC-1, and MUC-2, respectively, ILADC was diagnosed. KRAS mutation was detected in tumor tissue of the male patient. Conclusion. Rectocolonoscopy is the only relevant method for distinguishing the intestinal type of lung adenocarcinoma from metastatic colorectal carcinoma because immunohistochemistry and detection of mutation status are frequently the same in both types of adenocarcinoma. More investigations are needed for further understanding of ILADC in purpose of personalized lung carcinoma therapy particularly introducing detection of mutation status, especially in younger patients. PMID:24782938

  8. Sarcopenia of thoracic muscle mass is not a risk factor for survival in lung transplant recipients

    PubMed Central

    Lee, Seokkee; Paik, Hyo Chae; Haam, Seok Jin; Lee, Chang Young; Nam, Kyung Sik; Jung, Hee Suk; Do, Young Woo; Shu, Jee Won

    2016-01-01

    Background In lung transplantation (LTx), patients with thoracic muscle sarcopenia may have to require longer to recovery. We measured thoracic muscle volume by using the cross sectional area (CSA) and assessed its effect on early outcomes after LTx. Methods A retrospective analysis was conducted to evaluate the effect of thoracic sarcopenia in patients undergoing LTx between January 2010 and July 2015. The lowest CSA quartile (Q1) was defined as sarcopenia. Results In total, 109 patients were enrolled. The mean CSA was 58.24±15.82 cm2. Patients in the highest CSA quartile were more likely to be male (92.6% vs. 17.9%, P<0.001), older (55.2±10.1 vs. 43.2±14.9 years, P=0.001), to have a higher body mass index (BMI) (22.3±4.0 vs. 19.4±3.7 kg/m2, P=0.007), and to have pulmonary fibrosis (85.2% vs. 35.7%, P=0.003) compared with the lowest CSA quartile. Early outcomes including ventilator support duration [32.9±49.2 vs. 24.5±39.9 days, P= not significant (ns)], intensive care unit (ICU) stay duration (28.4±43.7 vs. 24.4±35.9 days, P= ns) and hospital stay duration (61.4±48.2 vs. 50.8±37.2 days, P= ns) tended to be longer in Q1 than Q4, but the difference was not significant. However, the 1-year survival rate was better in Q1 compared with Q4 (66.6% vs. 46.0%, P=0.04). Conclusions Although patients with thoracic sarcopenia seem to require a longer post-operative recovery time after LTx, this does not compromise their early outcomes. By contrast, patients with larger thoracic muscle volume (Q4) showed poorer survival times. PMID:27621854

  9. Bilateral Lung Transplantation in a Patient with Humoral Immune Deficiency: A Case Report with Review of the Literature

    PubMed Central

    Farmer, Jocelyn R.; Sokol, Caroline L.; Bonilla, Francisco A.; Murali, Mandakolathur R.; Kradin, Richard L.; Astor, Todd L.; Walter, Jolan E.

    2014-01-01

    Humoral immune deficiencies have been associated with noninfectious disease complications including autoimmune cytopenias and pulmonary disease. Herein we present a patient who underwent splenectomy for autoimmune cytopenias and subsequently was diagnosed with humoral immune deficiency in the context of recurrent infections. Immunoglobulin analysis prior to initiation of intravenous immunoglobulin (IVIG) therapy was notable for low age-matched serum levels of IgA (11 mg/dL), IgG2 (14 mg/L), and IgG4 (5 mg/L) with a preserved total level of IgG. Flow cytometry was remarkable for B cell maturation arrest at the IgM+/IgD+ stage. Selective screening for known primary immune deficiency-causing genetic defects was negative. The disease course was uniquely complicated by the development of pulmonary arteriovenous malformations (AVMs), ultimately requiring bilateral lung transplantation in 2012. This is a patient with humoral immune deficiency that became apparent only after splenectomy, which argues for routine immunologic evaluation prior to vaccination and splenectomy. Lung transplantation is a rare therapeutic endpoint and to our knowledge has never before been described in a patient with humoral immune deficiency for the indication of pulmonary AVMs. PMID:25379312

  10. Quality of Recipient-Caregiver Relationship and Psychological Distress are Correlates of Self-Care Agency after Lung Transplantation

    PubMed Central

    Dabbs, Annette DeVito; Terhorst, Lauren; Song, Mi-Kyung; Shellmer, Diana A.; Aubrecht, Jill; Connolly, Mary; Dew, Mary Amanda

    2012-01-01

    Self-care behaviors are crucial for following the complex regimen after lung transplantation, yet little is known about recipients’ levels of self-care agency (the capability and willingness to engage in self-care behaviors) and its correlates. We examined levels of self-care agency and recipient characteristics (socio-demographics, psychological distress, quality of relationship with primary lay caregiver, and health locus of control) in 111 recipients. Based on Perceived Self-Care Agency scores, recipients were assigned to either the low or high self-care agency comparison group. Characteristics were compared between groups to identify characteristics likely to be associated with lower self-care agency. Mean (S.D.) score for self-care agency (scale range 53–265) was 223.02 (22.46). Recipients with lowest self-care agency scores reported significantly poorer quality of caregiver relationships (p < .001) and greater psychological distress (p < .001). After controlling for psychological distress, the quality of the recipient-caregiver relationship remained significantly associated with self-care agency. Every one-point decrease in the quality of caregiver relationship increased the risk of low self-care agency by 12%. Recipients with poorer caregiver relationships and greater psychological distress may need additional support to perform the self-care behaviors expected after lung transplantation. PMID:23004565

  11. Human herpesvirus 6 in bronchalveolar lavage fluid after lung transplantation: a risk factor for bronchiolitis obliterans syndrome?

    PubMed

    Neurohr, C; Huppmann, P; Leuchte, H; Schwaiblmair, M; Bittmann, I; Jaeger, G; Hatz, R; Frey, L; Uberfuhr, P; Reichart, B; Behr, J

    2005-12-01

    Bronchiolitis obliterans syndrome (BOS) is the limiting factor to long-term survival after lung transplantation. Previous studies suggested respiratory viral tract infections are associated with the development of BOS. To identify the impact of virus detection in bronchoalveolar lavage (BAL) fluid, we analyzed BAL samples from 87 consecutive lung transplant recipients for human herpesvirus (HHV)-6, Epstein-Barr virus, Herpes simplex virus 1/2, Cytomegalovirus, respiratory syncytical virus and adenovirus by PCR. Acute rejection, BOS and death were recorded for a mean follow-up time of 3.27 +/- 0.47 years. Results of PCR analysis and other potential risk factors were entered into a Cox regression analysis of BOS predictors and death. Only acute rejection was a distinct risk factor for BOS of all stages, death and death from BOS. HHV-6 was detected in 20 patients. Univariate and multivariate analysis revealed that HHV-6 was associated with an increased risk to develop BOS > orb = stage 1 and death, separate from the risk attributable to acute rejection. Identification of HHV-6 DNA in BAL fluid is a potential risk factor for BOS. Our results warrant further studies to elucidate a possible causal link between HHV-6 and BOS. PMID:16303014

  12. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

    PubMed

    Zhou, Y; Othus, M; Araki, D; Wood, B L; Radich, J P; Halpern, A B; Mielcarek, M; Estey, E H; Appelbaum, F R; Walter, R B

    2016-07-01

    Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies.

  13. Pre- and post-transplant quantification of measurable ('minimal') residual disease via multiparameter flow cytometry in adult acute myeloid leukemia.

    PubMed

    Zhou, Y; Othus, M; Araki, D; Wood, B L; Radich, J P; Halpern, A B; Mielcarek, M; Estey, E H; Appelbaum, F R; Walter, R B

    2016-07-01

    Measurable ('minimal') residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas two patients developed new evidence of disease. The 214 MRD(neg)/MRD(neg) patients had excellent outcomes, whereas both MRD(neg)/MRD(pos) patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was only observed among the 58 patients with decreasing but not the seven patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with overall survival and risk of relapse. These data indicate that MRD(pos) patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies. PMID:27012865

  14. Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

    PubMed Central

    Gugliotta, Marinella; Rolfe, Andrew; Reid, Wendy; McQuiston, A. Rory; Hu, Wenhui; Young, Harold

    2011-01-01

    Abstract Multipotent neural stem/progenitor cells (NS/NPCs) that are capable of generating neurons and glia offer enormous potential for treating neurological diseases. Adult NS/NPCs that reside in the mature mammalian brain can be isolated and expanded in vitro, and could be a potential source for autologous transplantation to replace cells lost to brain injury or disease. When these cells are transplanted into the normal brain, they can survive and become region-specific cells. However, it has not been reported whether these cells can survive for an extended period and become functional cells in an injured heterotypic environment. In this study, we tested survival, maturation fate, and electrophysiological properties of adult NS/NPCs after transplantation into the injured rat brain. NS/NPCs were isolated from the subventricular zone of adult Fisher 344 rats and cultured as a monolayer. Recipient adult Fisher 344 rats were first subjected to a moderate fluid percussive injury. Two days later, cultured NS/NPCs were injected into the injured brain in an area between the white matter tracts and peri-cortical region directly underneath the injury impact. The animals were sacrificed 2 or 4 weeks after transplantation for immunohistochemical staining or patch-clamp recording. We found that transplanted cells survived well at 2 and 4 weeks. Many cells migrated out of the injection site into surrounding areas expressing astrocyte or oligodendrocyte markers. Whole cell patch-clamp recording at 4 weeks showed that transplanted cells possessed typical mature glial cell properties. These data demonstrate that adult NS/NPCs can survive in an injured heterotypic environment for an extended period and become functional cells. PMID:21332258

  15. Heart transplant

    MedlinePlus

    ... PA: Elsevier Saunders; 2014:chap 28. Bernstein D. Pediatric heart and heart-lung transplantation. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics . 19th ed. Philadelphia, PA: Elsevier Saunders; 2011:chap ...

  16. Can Particulate Pollution Affect Lung Function in Healthy Adults?

    EPA Science Inventory

    Accompanying editorial to paper from Harvard by Rice et al. entitled "Long-Term Exposure to Traffic Emissions and Fine Particulate Matter and Lung Function Decline in the Framingham Heart StudyBy almost any measure the Clean Air Act and its amendments has to be considered as one...

  17. [Prophylaxis against Toxoplasma gondii disease in pediatric and adult patients undergoing solid organ and hematopoietic stem cells transplantation].

    PubMed

    Payá, Ernesto; Noemí, Isabel; Tassara, Renzo; Catalán, Paula; Avilés, Carmen L

    2012-09-01

    Toxoplasmosis is a widely distributed zoonosis produced by the parasite T. gondii. In Chile the seroprevalence has been estimated between 20-37% in general population. Defined risk groups acquire or reactivate the infection by T. gondii in patients undergoing SOT and HSCT are: heart transplant or heart-lung with D (+) and R (-), allogeneic HSCT with R (+), HSCT with cord cells, GVHD, history of previous clinical toxoplasmosis and use of corticosteroids for prolonged periods or in high doses. Hand washing, hygiene in food handling and weekly post-transplant surveillance since day 15 post transplant for six months, are universally recommended. All patients with SOT and HSCT, regardless of risk, should receive prophylaxis with cotrimoxazole and require no another specific prophylaxis against T. gondii (A2). It is particularly important in high-risk patients who cannot receive cotrimoxazole prophylaxis establish specific alternative against T. gondii (B3). PMID:23282555

  18. Intravenous Transplantation of Mesenchymal Progenitors Distribute Solely to the Lungs and Improve Outcomes in Cervical Spinal Cord Injury.

    PubMed

    White, Seok Voon; Czisch, Chris E; Han, May H; Plant, Christine D; Harvey, Alan R; Plant, Giles W

    2016-07-01

    Cellular transplantation strategies utilizing intraspinal injection of mesenchymal progenitor cells (MPCs) have been reported as beneficial for spinal cord injuries. However, intraspinal injection is not only technically challenging, but requires invasive surgical procedures for patients. Therefore, we investigated the feasibility and potential benefits of noninvasive intravenous injection of MPCs in two models of cervical spinal cord injury, unilateral C5 contusion and complete unilateral C5 hemisection. MPCs isolated from green fluorescence protein (GFP)-luciferase transgenic mice compact bone (1 × 10(6) cells), or vehicle Hank's Buffered Saline Solution (HBSS), were intravenously injected via the tail vein at D1, D3, D7, D10, or D14. Transplanted MPCs were tracked via bioluminescence imaging. Live in vivo imaging data showed that intravenously injected MPCs accumulate in the lungs, confirmed by postmortem bioluminescence signal-irrespective of the time of injection or injury model. The results showed a rapid, positive modulation of the inflammatory response providing protection to the injured spinal cord tissue. Histological processing of the lungs showed GFP(+) cells evenly distributed around the alveoli. We propose that injected cells can act as cellular target decoys to an immune system primed by injury, thereby lessening the inflammatory response at the injury site. We also propose that intravenous injected MPCs modulate the immune system via the lungs through secreted immune mediators or contact interaction with peripheral organs. In conclusion, the timing of intravenous injection of MPCs is key to the success for improving function and tissue preservation following cervical spinal cord injury. Stem Cells 2016;34:1812-1825.

  19. Intravenous Transplantation of Mesenchymal Progenitors Distribute Solely to the Lungs and Improve Outcomes in Cervical Spinal Cord Injury.

    PubMed

    White, Seok Voon; Czisch, Chris E; Han, May H; Plant, Christine D; Harvey, Alan R; Plant, Giles W

    2016-07-01

    Cellular transplantation strategies utilizing intraspinal injection of mesenchymal progenitor cells (MPCs) have been reported as beneficial for spinal cord injuries. However, intraspinal injection is not only technically challenging, but requires invasive surgical procedures for patients. Therefore, we investigated the feasibility and potential benefits of noninvasive intravenous injection of MPCs in two models of cervical spinal cord injury, unilateral C5 contusion and complete unilateral C5 hemisection. MPCs isolated from green fluorescence protein (GFP)-luciferase transgenic mice compact bone (1 × 10(6) cells), or vehicle Hank's Buffered Saline Solution (HBSS), were intravenously injected via the tail vein at D1, D3, D7, D10, or D14. Transplanted MPCs were tracked via bioluminescence imaging. Live in vivo imaging data showed that intravenously injected MPCs accumulate in the lungs, confirmed by postmortem bioluminescence signal-irrespective of the time of injection or injury model. The results showed a rapid, positive modulation of the inflammatory response providing protection to the injured spinal cord tissue. Histological processing of the lungs showed GFP(+) cells evenly distributed around the alveoli. We propose that injected cells can act as cellular target decoys to an immune system primed by injury, thereby lessening the inflammatory response at the injury site. We also propose that intravenous injected MPCs modulate the immune system via the lungs through secreted immune mediators or contact interaction with peripheral organs. In conclusion, the timing of intravenous injection of MPCs is key to the success for improving function and tissue preservation following cervical spinal cord injury. Stem Cells 2016;34:1812-1825. PMID:26989838

  20. Regulation of transplanted mesenchymal stem cells by the lung progenitor niche in rats with chronic obstructive pulmonary disease

    PubMed Central

    2014-01-01

    Background Stem cell transplantation is a promising method for the treatment of chronic obstructive pulmonary disease (COPD), and mesenchymal stem cells (MSCs) have clinical potential for lung repair/regeneration. However, the rates of engraftment and differentiation are generally low following MSC therapy for lung injury. In previous studies, we constructed a pulmonary surfactant-associated protein A (SPA) suicide gene system, rAAV-SPA-TK, which induced apoptosis in alveolar epithelial type II (AT II) cells and vacated the AT II cell niche. We hypothesized that this system would increase the rates of MSC engraftment and repair in COPD rats. Methods The MSC engraftment rate and morphometric changes in lung tissue in vivo were investigated by in situ hybridization, hematoxylin and eosin staining, Masson’s trichrome staining, immunohistochemistry, and real-time PCR. The expression of hypoxia inducible factor (HIF-1α) and stromal cell-derived factor-1 (SDF-1), and relationship between HIF-1α and SDF-1 in a hypoxic cell model were analyzed by real-time PCR, western blotting, and enzyme-linked immunosorbent assay. Results rAAV-SPA-TK transfection increased the recruitment of MSCs but induced pulmonary fibrosis in COPD rats. HIF-1α and SDF-1 expression were enhanced after rAAV-SPA-TK transfection. Hypoxia increased the expression of HIF-1α and SDF-1 in the hypoxic cell model, and SDF-1 expression was augmented by HIF-1α under hypoxic conditions. Conclusions Vacant AT II cell niches increase the homing and recruitment of MSCs to the lung in COPD rats. MSCs play an important role in lung repair and promote collagen fiber deposition after induction of secondary damage in AT II cells by rAAV-SPA-TK, which involves HIF-1α and SDF-1 signaling. PMID:24661402

  1. Mortality and functional performance in severe emphysema after lung volume reduction or transplant.

    PubMed

    Weinstein, Michael S; Martin, Ubaldo J; Crookshank, Aaron D; Chatila, Wissam; Vance, Gwendolyn B; Gaughan, John P; Furukawa, Satoshi; Criner, Gerard J

    2007-03-01

    The purpose of this endeavor is to compare the morbidity, mortality and costs of LVRS versus transplantation in severe emphysema. This was a retrospective review of severe emphysema patients who received LVRS (n = 70) from 1994-1999, or transplant (n = 87) from 1994-2004. Change in functional status was calculated by the change in modified BODE (mBODE) score. Financial data included physician, hospital and medication costs. Preoperatively, there was no significant difference between the transplant and LVRS groups (mean +/- SD) in age (57.7 +/- 5.7 vs. 59.1 +/- 8.3 years), BMI, Borg dyspnea score, 6-minute walk distance or mBODE (10.4 +/- 2.6 vs. 9.6 +/- 2.7, p = 0.4). Preoperatively, FEV1% (23.6 +/- 8.5 vs. 31.9 +/- 17.7, p = 0.008) was significantly lower in the transplant group. One year post-operatively, transplantation patients had a significantly greater improvement in mBODE (-5.7 vs. -2.0, p = 0.0004), FEV1% (43.4 vs. 2.2%, p = 0.0004) and Borg score (-3.0 vs. -1.4, p = 0.04). Transplantation patients had lower long-term survival compared to LVRS patients (p = 0.01). The only variable that affected survival was type of surgery favoring LVRS (hazard ratio 1.7, 95% confidence limits 1.05-2.77). During a mean follow-up of 2.4 +/- 2.5 years after transplant and 5.0 +/- 3.1 years after LVRS, transplantation mean total costs were greater ($381,732 vs. $140,637, p < 0.0001). Transplantation patients spent more time in the hospital (74.3 +/- 81.3 vs. 39.5 +/- 66.7 days, p = 0.009) and had more outpatient visits (29.9 +/- 28.8 vs. 12.3 +/- 12.6 visits, p < 0.0001). In patients who survive over 1 year, transplantation provides a higher level of functional status and a greater improvement in airflow obstruction, dyspnea, exercise tolerance, and mBODE score, but costs more and carries greater mortality.

  2. Vascular complications after adult living donor liver transplantation: Evaluation with ultrasonography

    PubMed Central

    Ma, Lin; Lu, Qiang; Luo, Yan

    2016-01-01

    Living donor liver transplantation (LDLT) has been widely used to treat end-stage liver disease with improvement in surgical technology and the application of new immunosuppressants. Vascular complications after liver transplantation remain a major threat to the survival of recipients. LDLT recipients are more likely to develop vascular complications because of their complex vascular reconstruction and the slender vessels. Early diagnosis and treatment are critical for the survival of graft and recipients. As a non-invasive, cost-effective and non-radioactive method with bedside availability, conventional gray-scale and Doppler ultrasonography play important roles in identifying vascular complications in the early postoperative period and during the follow-up. Recently, with the detailed vascular tracing and perfusion visualization, contrast-enhanced ultrasound (CEUS) has significantly improved the diagnosis of postoperative vascular complications. This review focuses on the role of conventional gray-scale ultrasound, Doppler ultrasound and CEUS for early diagnosis of vascular complications after adult LDLT. PMID:26819527

  3. A Prognostic Model Predicting Autologous Transplantation Outcomes in Children, Adolescents and Young Adults with Hodgkin Lymphoma

    PubMed Central

    Satwani, Prakash; Ahn, Kwang Woo; Carreras, Jeanette; Abdel-Azim, Hisham; Cairo, Mitchell S.; Cashen, Amanda; Chen, Andy I.; Cohen, Jonathon B.; Costa, Luciano J.; Dandoy, Christopher; Fenske, Timothy S.; Freytes, César O.; Ganguly, Siddhartha; Gale, Robert Peter; Ghosh, Nilanjan; Hertzberg, Mark S.; Hayashi, Robert J.; Kamble, Rummurti T.; Kanate, Abraham S.; Keating, Armand; Kharfan-Dabaja, Mohamed A.; Lazarus, Hillard M.; Marks, David I.; Nishihori, Taiga; Olsson, Richard F.; Prestidge, Tim D.; Rolon, Juliana Martinez; Savani, Bipin N.; Vose, Julie M.; Wood, William A.; Inwards, David J.; Bachanova, Veronika; Smith, Sonali M.; Maloney, David G.; Sureda, Anna; Hamadani, Mehdi

    2015-01-01

    Autologous hematopoietic cell transplantation (AutoHCT) is a potentially curative treatment modality for relapsed/refractory Hodgkin lymphoma (HL). However, no large studies have evaluated pre-transplant factors predictive of outcomes of AutoHCT in children, adolescents and young adults (CAYA, age <30 years). In a retrospective study, we analyzed 606 CAYA patients (median age 23 years) with relapsed/refractory HL who underwent AutoHCT between 1995–2010. The probabilities of progression free survival (PFS) at 1, 5 and 10 years were 66% (95% CI: 62–70), 52% (95% CI: 48–57) and 47% (95% CI: 42–51), respectively. Multivariate analysis for PFS demonstrated that at the time of AutoHCT patients with Karnofsky/Lansky score ≥90, no extranodal involvement and chemosensitive disease had significantly improved PFS. Patients with time from diagnosis to first relapse of <1 year had a significantly inferior PFS. A prognostic model for PFS was developed that stratified patients into low, intermediate and high-risk groups, predicting for 5-year PFS probabilities of 72% (95% CI: 64–80), 53% (95% CI: 47–59) and 23% (95% CI: 9–36), respectively. This large study identifies a group of CAYA patients with relapsed/refractory HL who are at high risk for progression after AutoHCT. Such patients should be targeted for novel therapeutic and/or maintenance approaches post-AutoHCT. PMID:26237164

  4. The Neuropsychological Course of Acute Delirium in Adult Hematopoietic Stem Cell Transplantation Patients

    PubMed Central

    Beglinger, Leigh J.; Mills, James A.; Vik, Stacie M.; Duff, Kevin; Denburg, Natalie L.; Weckmann, Michelle T.; Paulsen, Jane S.; Gingrich, Roger

    2011-01-01

    Although delirium is a common medical comorbidity with altered cognition as its defining feature, few publications have addressed the neuropsychological prodrome, profile, and recovery of patients tested during delirium. We characterize neuropsychological performance in 54 hemapoietic stem cell/bone marrow transplantation (BMT) patients shortly before, during, and after delirium and in BMT patients without delirium and 10 healthy adults. Patients were assessed prospectively before and after transplantation using a brief battery. BMT patients with delirium performed more poorly than comparisons and those without delirium on cross-sectional and trend analyses. Deficits were in expected areas of attention and memory, but also in psychomotor speed and learning. The patients with delirium did not return to normative “average” on any test during observation. Most tests showed a mild decline in the visit before delirium, a sharp decline with delirium onset, and variable performance in the following days. This study adds to the few investigations of neuropsychological performance surrounding delirium and provides targets for monitoring and early detection; Trails A and B, RBANS Coding, and List Recall may be useful for delirium assessment. PMID:21183605

  5. Role of Allogeneic Hematopoietic Stem Cell Transplantation in Adult Patients with Acute Lymphoblastic Leukemia

    PubMed Central

    Lussana, Federico; Rambaldi, Alessandro

    2014-01-01

    Adult acute lymphoblastic leukemia (ALL) is a heterogeneous disease, due to the expression of different biological and clinical risk factors, for which allogeneic stem cell transplantation (alloHSCT) is an effective consolidation therapy. The non-relapse mortality of alloHSCT remains significantly higher compared with that of conventional chemotherapy. Therefore, one of the main challenges in the care of ALL is to establish a more precise prognostic definition to select patients who could take advantage from an alloHSCT. Currently, the use of minimal residual disease following induction and early consolidation therapy has improved the prognostic accuracy in defining ALL risk class. In Philadelphia-positive ALL, the introduction of tyrosine kinase inhibitors pre and post alloHSCT appears to improve outcomes significantly and, in the absence of specially designed clinical trials, alloHSCT remains the most effective post-remission therapy. Nowadays, alloHSCT can be performed according to various modalities encompassing the use of different conditioning regimens, as well as distinct donors and stem cell source, with a significant accessibility to transplant. PMID:25408851

  6. Radiological patterns of primary graft dysfunction after lung transplantation evaluated by 64-multi-slice computed tomography: a descriptive study.

    PubMed

    Belmaati, Esther Okeke; Steffensen, Ida; Jensen, Claus; Kofoed, Klaus F; Mortensen, Jann; Nielsen, Michael B; Iversen, Martin

    2012-06-01

    We evaluated the diagnostic value of high-resolution computed tomography (HRCT) images generated from 64 detector multi-slice CT scanners (HRCT(64-MSCT) imaging) in relation to primary graft dysfunction (PGD) after lung-transplantation (LUTX) in a pilot study. PGD has mortality rates ranging from 17 to 50% over a 90-day period. Detailed HRCT lung images, reconstructed using 64-MSCT, may aid diagnostic and therapeutic efforts in PGD. Thirty-two patients were scanned four times within a year post-LUTX, in a single-centre prospective study. HRCT lung images were reviewed, evaluated and scored by two observers, for ground-glass (GG) opacities, consolidation, septal thickening (ST) and pulmonary embolism. Image and PGD scores were compared in each patient. GG and consolidation changes were largely present up until 2 weeks post-LUTX, and markedly reduced by the 12th week. ST was predominantly found in patients with PGD. There were no vascular changes found at CT angiographies. The most severe cases of GG opacities and consolidation were found in patients with PGD. ST seems to be an important indicator of PGD. HRCT(64-MSCT) imaging may be a useful tool for the identification of pathological features of PGD not detected by classical evaluation in patients undergoing LUTX. PMID:22378316

  7. First Case of Lung Abscess due to Salmonella enterica Serovar Abony in an Immunocompetent Adult Patient

    PubMed Central

    Dendrinos, John; Nikitiadis, Emanuel; Vrioni, Georgia; Tsakris, Athanassios

    2016-01-01

    In healthy individuals, nontyphoidal Salmonella species predominantly cause a self-limited form of gastroenteritis, while they infrequently invade or cause fatal disease. Extraintestinal manifestations of nontyphoidal Salmonella infections are not common and mainly occur among individuals with specific risk factors; among them, focal lung infection is a rare complication caused by nontyphoidal Salmonella strains typically occurring in immunocompromised patients with prior lung disease. We describe the first case of a localized lung abscess formation in an immunocompetent healthy female adult due to Salmonella enterica serovar Abony. The patient underwent lobectomy and was discharged after full clinical recovery. This case report highlights nontyphoidal Salmonellae infections as a potential causative agent of pleuropulmonary infections even in immunocompetent healthy adults. PMID:27429814

  8. First Case of Lung Abscess due to Salmonella enterica Serovar Abony in an Immunocompetent Adult Patient.

    PubMed

    Pitiriga, Vassiliki; Dendrinos, John; Nikitiadis, Emanuel; Vrioni, Georgia; Tsakris, Athanassios

    2016-01-01

    In healthy individuals, nontyphoidal Salmonella species predominantly cause a self-limited form of gastroenteritis, while they infrequently invade or cause fatal disease. Extraintestinal manifestations of nontyphoidal Salmonella infections are not common and mainly occur among individuals with specific risk factors; among them, focal lung infection is a rare complication caused by nontyphoidal Salmonella strains typically occurring in immunocompromised patients with prior lung disease. We describe the first case of a localized lung abscess formation in an immunocompetent healthy female adult due to Salmonella enterica serovar Abony. The patient underwent lobectomy and was discharged after full clinical recovery. This case report highlights nontyphoidal Salmonellae infections as a potential causative agent of pleuropulmonary infections even in immunocompetent healthy adults. PMID:27429814

  9. How Is Childhood Interstitial Lung Disease Treated?

    MedlinePlus

    ... the NHLBI on Twitter. How Is Childhood Interstitial Lung Disease Treated? Childhood interstitial lung disease (chILD) is ... prevent acid reflux, which can lead to aspiration. Lung Transplant A lung transplant may be an option ...

  10. Retinal Afferent Ingrowth to Neocortical Transplants in the Adult Rat Superior Colliculus is due to the Regeneration of Damaged Axons

    PubMed Central

    Ross, D. T.; Das, G. D.

    1994-01-01

    Retinal afferent ingrowth to embryonic neural transplants in the adult rat superior colliculus may represent either sprouting of intact axons or the regeneration of transected axons. If ingrowth represents regeneration of damaged retinofugai axons, then lesions that axotomize more retinofugal axons at the transplantation site should induce greater retinal afferent ingrowth. Alternately, if ingrowth represents terminal or collateral sprouting of intact retinofugal axons at or near the transplant/host optic layer interface, then the magnitude of retinal afferent ingrowth should be directly related to the total area of this interface. To test between these two hypotheses surgical knife wounds were made either parallel (in the sagittal plane) or perpendicular (in the transverse plane) to the course of axons in the stratum opticum, embryonic neocortical tissue was transplanted at the coordinates of these tectal slits, and retinal afferent ingrowth visualized 1-90 days after surgery using anterogradely transported HRP. A zone of traumatic reaction (ztr) in the optic layers was seen in every case, characterized by hypertrophied axons and swollen terminal clubs at 1 day. Between 30 and 90 days the damaged retinofugal axons in the zone formed dense fascicles and neuroma-like tangles. Retinal afferent ingrowth occurred only across transplant interface regions with the ztr. The magnitude of ingrowth was directly related to the area of the ztr interface and not the total optic layer interface area. Retinal afferent ingrowth appears to reflect the intrinsic regenerative capacity of adult mammalian retinal ganglion cells and not sprouting of undamaged axons. PMID:7703292

  11. Bone marrow transplantation alters lung antigen-presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection.

    PubMed

    Zhou, X; Loomis-King, H; Gurczynski, S J; Wilke, C A; Konopka, K E; Ptaschinski, C; Coomes, S M; Iwakura, Y; van Dyk, L F; Lukacs, N W; Moore, B B

    2016-05-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplantion (BMT) followed by infection with murine gamma herpesvirus-68 that results in pneumonitis and fibrosis and mimics human "noninfectious" HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection. CD4 T cells in BMT mice are skewed toward interleukin (IL)-17A rather than interferon (IFN)-γ production. Transplantation of bone marrow from Il-17a(-/-) donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more transforming growth factor beta-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest that "noninfectious" HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  12. Use of a novel virus detection assay to identify coronavirus HKU1 in the lungs of a hematopoietic stem cell transplant recipient with fatal pneumonia

    PubMed Central

    Uhlenhaut, Christine; Cohen, Jeffrey I.; Pavletic, Steven; Illei, Gabor; Gea-Banacloche, Juan Carlos; Abu-Asab, Mones; Krogmann, Tammy; Gubareva, Larisa; McClenahan, Shasta; Krause, Philip R.

    2012-01-01

    A 38-year-old patient with systemic lupus erythematosus presented with pulmonary infiltrates and hypoxemia for several months following immunodepleting autologous hematopoietic stem cell transplantation. She was treated for influenza, which was isolated repeatedly from ororpharynx and bronchoalveolar lavage fluids, and later empirically for lupus pneumonitis, but expired 6 months after transplant. Autopsy findings failed to show influenza in the lungs or lupus pneumonitis. A novel generic PCR-based assay using degenerate primers identified human coronavirus HKU1 RNA in bronchoalveolar lavage fluid at autopsy. Coronavirus was confirmed by virus-specific PCRs of lung tissue at autopsy. Electron microscopy showed viral particles consistent with coronavirus HKU1 in lung tissue both at autopsy and from a previous biopsy. While human coronavirus HKU1 infection is not usually severe, in highly immunocompromised patients, it can be associated with fatal pneumonia. PMID:21749586

  13. Autologous Transplantation of Bone Marrow Adult Stem Cells for the Treatment of Idiopathic Dilated Cardiomyopathy

    PubMed Central

    Westphal, Ricardo João; Bueno, Ronaldo Rocha Loures; Galvão, Paulo Bezerra de Araújo; Zanis Neto, José; Souza, Juliano Mendes; Guérios, Ênio Eduardo; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto; Pasquini, Ricardo; da Cunha, Claudio Leinig Pereira

    2014-01-01

    Background Morbimortality in patients with dilated idiopathic cardiomyopathy is high, even under optimal medical treatment. Autologous infusion of bone marrow adult stem cells has shown promising preliminary results in these patients. Objective Determine the effectiveness of autologous transplantation of bone marrow adult stem cells on systolic and diastolic left ventricular function, and on the degree of mitral regurgitation in patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Methods We administered 4,54 x 108 ± 0,89 x 108 bone marrow adult stem cells into the coronary arteries of 24 patients with dilated idiopathic cardiomyopathy in functional classes NYHA II and III. Changes in functional class, systolic and diastolic left ventricular function and degree of mitral regurgitation were assessed after 3 months, 6 months and 1 year. Results During follow-up, six patients (25%) improved functional class and eight (33.3%) kept stable. Left ventricular ejection fraction improved 8.9%, 9.7% e 13.6%, after 3, 6 and 12 months (p = 0.024; 0.017 and 0.018), respectively. There were no significant changes neither in diastolic left ventricular function nor in mitral regurgitation degree. A combined cardiac resynchronization and implantable cardioversion defibrillation was implanted in two patients (8.3%). Four patients (16.6%) had sudden death and four patients died due to terminal cardiac failure. Average survival of these eight patients was 2.6 years. Conclusion Intracoronary infusion of bone marrow adult stem cells was associated with an improvement or stabilization of functional class and an improvement in left ventricular ejection fraction, suggesting the efficacy of this intervention. There were no significant changes neither in left ventricular diastolic function nor in the degree of mitral regurgitation. PMID:25590932

  14. Long-term outcomes of children after solid organ transplantation

    PubMed Central

    Kim, Jon Jin; Marks, Stephen D.

    2014-01-01

    Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation. PMID:24860856

  15. Long-term outcomes of children after solid organ transplantation.

    PubMed

    Kim, Jon Jin; Marks, Stephen D

    2014-01-01

    Solid organ transplantation has transformed the lives of many children and adults by providing treatment for patients with organ failure who would have otherwise succumbed to their disease. The first successful transplant in 1954 was a kidney transplant between identical twins, which circumvented the problem of rejection from MHC incompatibility. Further progress in solid organ transplantation was enabled by the discovery of immunosuppressive agents such as corticosteroids and azathioprine in the 1950s and ciclosporin in 1970. Today, solid organ transplantation is a conventional treatment with improved patient and allograft survival rates. However, the challenge that lies ahead is to extend allograft survival time while simultaneously reducing the side effects of immunosuppression. This is particularly important for children who have irreversible organ failure and may require multiple transplants. Pediatric transplant teams also need to improve patient quality of life at a time of physical, emotional and psychosocial development. This review will elaborate on the long-term outcomes of children after kidney, liver, heart, lung and intestinal transplantation. As mortality rates after transplantation have declined, there has emerged an increased focus on reducing longer-term morbidity with improved outcomes in optimizing cardiovascular risk, renal impairment, growth and quality of life. Data were obtained from a review of the literature and particularly from national registries and databases such as the North American Pediatric Renal Trials and Collaborative Studies for the kidney, SPLIT for liver, International Society for Heart and Lung Transplantation and UNOS for intestinal transplantation. PMID:24860856

  16. Lung ultrasound in adult and paediatric cardiac surgery: is it time for routine use?

    PubMed

    Cantinotti, Massimiliano; Giordano, Raffaele; Volpicelli, Giovanni; Kutty, Shelby; Murzi, Bruno; Assanta, Nadia; Gargani, Luna

    2016-02-01

    Respiratory complications are common causes of morbidity and the need of repeated X-ray examinations after cardiac surgery. Ultrasound of the chest, including the lung parenchyma, has been recently introduced as a new tool to detect many pulmonary abnormalities. Despite this, the use of lung ultrasound (LUS) in adult and congenital cardiac surgery remains limited. In particular, lung ultrasound has been mainly used in the evaluation of pleural effusion (PLE), but no consensus exists on methods to quantify the volume of the effusion. Usefulness of LUS for the assessment of diaphragmatic motion in children has also been highlighted, but no clear recommendation exists regarding its routine use. Accuracy of LUS in detecting pulmonary congestion after adult cardiac surgery has been demonstrated, whereas studies in children are still scarce, and data on pneumothorax and lung consolidations are limited in the paediatric population. There are methodological and practicality issues regarding diagnostic protocols (i.e. image views and their sequential order) and instrumentation (transducers and their setting) used in different studies. It also remains unclear which practitioner-the cardiologist, intensivist, pulmonologist or the radiologist, should perform the examination. Cost analysis pertaining to extensive clinical application of lung ultrasound in cardiac surgery has never been performed. Guidelines and recommendations are warranted for a systematic and extensive use of this technique in cardiac surgery at different ages, as it could serve as a useful, versatile tool that could potentially decrease time, radiation exposure and costs. PMID:26586677

  17. Differential effect of plasma and red blood cell transfusion on acute lung injury and infection risk following liver transplantation

    PubMed Central

    Benson, Alexander B.; Burton, James R.; Austin, Gregory L.; Biggins, Scott W.; Zimmerman, Michael A.; Kam, Igal; Mandell, Susan; Silliman, Christopher C.; Rosen, Hugo; Moss, Marc

    2010-01-01

    Rationale Patients with chronic liver disease are at an increased risk of developing transfusion-associated acute lung injury (TRALI) from plasma containing blood products. Similarly, red blood cell transfusions have been associated with post-operative and nosocomial infections in surgical and critical care populations. Patients undergoing liver transplantation receive a large amount of cellular and plasma containing blood products, but it is presently unclear which blood components are associated with these post-operative complications. Results A retrospective cohort study of 525 consecutive liver transplant patients revealed a peri-operative TRALI incidence of 1.3% (7/525), 95%CI [0.6%–2.7%], associated with an increased hospital mortality (28.6% (2/7) vs. 2.9% (15/518), p=0.02) and intensive care unit (ICU) length of stay (2 days, [1–11] vs. 0 days [0–2], 0.03). Only high plasma containing blood products (plasma and platelets) were associated with the development of TRALI. A total of 14.3% (74/525) of patients developed a post-operative infection which was also associated with an increased in-hospital mortality (10.8% (8/74) vs. 2.0% (9/451), p < 0.01) and prolonged length of stay. Multivariate logistic regression identified the number of red blood cell units transfused (adj OR 1.08 95%CI [1.02–1.14], p<0.01), the presence of peri-operative renal dysfunction and re-operation to be significantly associated with post-operative infection. Conclusions Patients undergoing liver transplantation are at high risk of developing post-operative complications from blood transfusion. Plasma containing blood products were associated with the development of TRALI while red blood cells were associated with the development of post-operative infection in a dose dependent manner. PMID:21280188

  18. Quantitative survival model for short-term survival after adult-to-adult living donor liver transplantation.

    PubMed

    Tsunematsu, Ichiro; Ogura, Yasuhiro; Inoue, Kayoko; Koizumi, Akio; Tanigawa, Nobuhiko; Tanaka, Koichi

    2006-06-01

    Adult-to-adult living donor liver transplantation (ALDLT) has been accepted as an important option for end-stage liver disease, but information regarding the risk factors remains fragmentary. We aimed to establish a predictive model for 90-day survival. In the first step, a total of 286 cases who had received primary ALDLT using a right lobe graft between 1998 and 2004 were randomly divided into 2 cohorts at a ratio of 2:1 (191 vs. 95 recipients). The larger cohort of patients was used to develop a model. The outcome was defined as 90-day survival, and a total of 39 preoperative and operative variables, including the period of surgery (1998-2001 vs. 2002-2004), were included using Cox's proportional hazard regression model. Two mismatches of human leukocyte antigen (HLA) type DR (hazard ratio [HR] = 4.45; confidence interval [CI] = 1.96-10.1), log(e)[blood loss volume] (HR = 2.43; CI = 1.64-3.60), period of surgery (1998-2001 vs. 2002-2004) (HR = 2.41; CI = 1.04-5.57), and log(e)[serum C-reactive protein or CRP] (HR = 1.64; CI = 1.13-2.38) were found to be independent risk factors. In the second step, we tried to establish a realistic survival model. In this step, we created 2 models, 1 that used all 4 variables (model 1) and 1 (model 2) in which blood loss volume was replaced with the past history of upper abdominal surgery and Model for End-Stage Liver Disease (MELD) score (> or =25), both of which showed associations with blood loss volume. These models were applied to the smaller cohort of 95 patients. Receiver operating characteristic analyses demonstrated that both models showed similar significant c-statistics (0.63 and 0.62, respectively). In conclusion, model 2 can provide a rough estimation of the 90-day survival after ALDLT.

  19. Donor Safety in Adult-Adult Living Donor Liver Transplantation: A Single-Center Experience of 356 Cases

    PubMed Central

    Meng, Haipeng; Yang, Jiayin; Yan, Lunan

    2016-01-01

    Background As an important means to tackle the worldwide shortage of liver grafts, adult-adult living donor liver transplantation (A-ALDLT) is the most massive operation a healthy person could undergo, so donor safety is of prime importance. However, most previous research focused on recipients, while complications in donors have not been fully described or investigated. Material/Methods To investigate donor safety in terms of postoperative complications, the clinical data of 356 A-ALDLT donors in our center from January 2002 to September 2015 were retrospectively analyzed. These patients were divided into a pre-2008 group (before January 2008) and a post-2008 group (after January 2008). Donor safety was evaluated with regard to the type, frequency, and severity of postoperative complications. Results There were no donor deaths in our center during this period. The overall complication rate was 23.0% (82/356). The proportion of Clavien I, II, III, and IV complications was 51.2% (42/82), 25.6% (21/82), 22.0% (18/82), and 1.2% (1/82), respectively. In all the donors, the incidence of Clavien I, II, III, and IV complications was 11.8% (42/356), 5.9% (21/356), 5.1% (18/356), and 0.3% (1/356), respectively. The overall complication rate in the post-2008 group was significantly lower than that in the pre-2008 group (18.1% (41/227) vs. 32.6% (42/129), P<0.01). Biliary complications were the most common, with an incidence of 8.4% (30/356). Conclusions The risk to A-ALDLT donors is controllable and acceptable with improvement in preoperative assessment and liver surgery. PMID:27178367

  20. Serum Methylarginines and Spirometry-Measured Lung Function in Older Adults

    PubMed Central

    McEvoy, Mark A.; Schofield, Peter W.; Smith, Wayne T.; Agho, Kingsley; Mangoni, Arduino A.; Soiza, Roy L.; Peel, Roseanne; Hancock, Stephen J.; Carru, Ciriaco; Zinellu, Angelo; Attia, John R.

    2013-01-01

    Rationale Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in animal models of lung disease but have not previously been examined for their association with spirometric measures of lung function in humans. Objectives This study measured serum concentrations of asymmetric and symmetric dimethylarginine in a representative sample of older community-dwelling adults and determined their association with spirometric lung function measures. Methods Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and L-arginine (measured using LC-MS/MS) were collected from a population-based sample of older Australian adults from the Hunter Community Study. The five key lung function measures included as outcomes were Forced Expiratory Volume in 1 second, Forced Vital Capacity, Forced Expiratory Volume in 1 second to Forced Vital Capacity ratio, Percent Predicted Forced Expiratory Volume in 1 second, and Percent Predicted Forced Vital Capacity. Measurements and Main Results In adjusted analyses there were statistically significant independent associations between a) higher asymmetric dimethylarginine, lower Forced Expiratory Volume in 1 second and lower Forced Vital Capacity; and b) lower L-arginine/asymmetric dimethylarginine ratio, lower Forced Expiratory Volume in 1 second, lower Percent Predicted Forced Expiratory Volume in 1 second and lower Percent Predicted Forced Vital Capacity. By contrast, no significant associations were observed between symmetric dimethylarginine and lung function. Conclusions After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum asymmetric dimethylarginine was independently associated with a reduction in key measures of lung function. Further research is needed to determine if methylarginines predict the decline in lung function. PMID:23690915

  1. Long-Term Outcomes of Cultivated Limbal Epithelial Transplantation: Evaluation and Comparison of Results in Children and Adults

    PubMed Central

    Ganger, Anita; Vanathi, M.; Mohanty, Sujata; Tandon, Radhika

    2015-01-01

    Purpose. To compare the long-term clinical outcomes of cultivated limbal epithelial transplantation (CLET) in children and adults with limbal stem cell deficiency. Design. Retrospective case series. Methods. Case records of patients with limbal stem cell deficiency (LSCD) who underwent CLET from April 2004 to December 2014 were studied. Outcome measures were compared in terms of anatomical success and visual improvement. Parameters for total anatomical success were avascular, epithelized, and clinically stable corneal surface without conjunctivalization, whereas partial anatomical success was considered when mild vascularization (sparing centre of cornea) and mild conjunctivalization were noted along with complete epithelization. Results. A total of 62 cases underwent the CLET procedure: 38 (61.3%) were children and 24 (38.7%) were adults. Patients with unilateral LSCD (33 children and 21 adults) had autografts and those with bilateral LSCD (5 children and 3 adults) had allografts. Amongst the 54 autografts partial and total anatomical success were noted in 21.2% and 66.6% children, respectively, and 19.0% and 80.9% in adults, respectively (p value 0.23). Visual improvement of 1 line and ≥2 lines was seen in 57.5% and 21.2% children, respectively, and 38% and 38% in adults, respectively (p value 0.31). Conclusion. Cultivated limbal epithelial transplantation gives good long-term results in patients with LSCD and the outcomes are comparable in children and adults. PMID:26770973

  2. Graft downsizing during ex vivo lung perfusion: case report and technical notes.

    PubMed

    Nosotti, M; Rosso, L; Mendogni, P; Tosi, D; Palleschi, A; Righi, I; Froio, S; Valenza, F; Santambrogio, L

    2014-09-01

    Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, ex vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during ex vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during ex vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation.

  3. Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation

    PubMed Central

    Pawlick, Rena L.; Kahana, Meygal; Pepper, Andrew R.; Bruni, Antonio; Gala-Lopez, Boris; Kin, Tatsuya; Mitrani, Eduardo; Shapiro, A. M. James

    2016-01-01

    There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs) made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group). Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ), 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group). Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ. PMID:27227978

  4. Population pharmacokinetics of sirolimus in de novo Chinese adult renal transplant patients

    PubMed Central

    Jiao, Zheng; Shi, Xiao-jin; Li, Zhong-dong; Zhong, Ming-kang

    2009-01-01

    AIMS This study was aimed at determining the population pharmacokinetics of sirolimus and identifying factors that explain pharmacokinetic variability in de novo Chinese adult renal transplant patients. METHODS Data were retrospectively extracted from a formal multicentre clinical trial, which was originally designed to evaluate the safety and efficacy of ciclosporin dose reduction and ciclosporin elimination in patients receiving sirolimus. All patients received 12-month treatment, i.e. induction therapy with ciclosporin, sirolimus and corticosteroids during the first 3 months followed by either ciclosporin dose reduction or ciclosporin discontinuation thereafter. Eight-hundred and four sirolimus trough blood concentrations (C0) from 112 patients were used to develop a population pharmacokinetic model using the nonmem program. A one-compartment model with first-order absorption and elimination was selected as the base model. The influence of demographic characteristics, biochemical and haematological indices, ciclosporin daily dose, ciclosporin C0 as well as other commonly used co-medications were explored. RESULTS The typical values with interindividual variability for apparent clearance (CL/F) and apparent volume of distribution (V/F) were 10.1 l h−1 (23.8%) and 3670 l (56.7%), respectively. The residual variability was 29.9%. CL/F decreased significantly with silymarin or glycyrrhizin co-therapy in hepatically impaired patients, and with increasing total cholesterol levels or ciclosporin C0. Moreover, CL/F increased nonlinearly with increasing sirolimus daily dose. The median parameter estimates from a nonparametric bootstrap procedure were comparable and within 5% of the estimates from nonmem. CONCLUSIONS These results provide important information for clinicians to optimize sirolimus regimens in Chinese renal transplant patients. PMID:19660003

  5. Vasculobiliary complications following adult right lobe split liver transplantation from the perspective of reconstruction techniques.

    PubMed

    Mabrouk Mourad, Moustafa; Liossis, Christos; Kumar, Senthil; Gunson, Bridget K; Mergental, Hynek; Isaac, John; Bramhall, Simon R; Muiesan, Paolo; Mirza, Darius F; Thamara P R Perera, M

    2015-01-01

    Split liver transplantation (SLT) compensates for the organ shortage and provides an alternative solution for recipients disadvantaged by a smaller body size. Variations in the hepatic arterial anatomy and reconstructive techniques may lead to more technical complications, and we sought to analyze the incidence and risk factors of vasculobiliary complications with respect to reconstructive techniques. We identified 171 adult right lobe SLT procedures and 1412 whole liver transplantation (WLT) procedures between January 2000 and June 2012 and compared the results of these 2 groups. In the SLT group, arterial reconstruction techniques were classified into 4 subgroups (I-IV), and biliary reconstruction was classified into 2 groups [duct-to-duct (DD) anastomosis and Roux-en-Y hepaticojejunostomy (RH)]. Specific surgical complications were analyzed against reconstruction techniques. The overall incidence of vascular and biliary complications in the SLT group was greater than that in the WLT group (P = 0.009 and P = 0.001, respectively). There was no difference in hepatic artery thrombosis (HAT), but we saw a tendency toward early HAT in the presence of multiple hepatic arteries supplying the right lobe graft (group IV; 20%) in comparison with the other arterial reconstruction groups (P = 0.052). No difference was noticed in the overall incidence of biliary complications in either DD or RH recipients across 4 arterial reconstruction groups. When the arterial reconstruction involved a right hepatic artery (groups II and III) combined with a DD biliary anastomosis, there was a significant preponderance of biliary complications (P = 0.04 and P = 0.01, respectively). There was no survival difference between SLT and WLT grafts. In conclusion, the complications of SLT are directly related to arterial and biliary reconstruction techniques, and this classification helps to identify high-risk reconstructive techniques. PMID:25302412

  6. Percutaneous Endovascular Treatment of Hepatic Artery Stenosis in Adult and Pediatric Patients After Liver Transplantation

    SciTech Connect

    Maruzzelli, Luigi; Miraglia, Roberto Caruso, Settimo; Milazzo, Mariapina; Mamone, Giuseppe; Gruttadauria, Salvatore; Spada, Marco; Luca, Angelo; Gridelli, Bruno

    2010-12-15

    The purpose of this study was to evaluate the efficacy of percutaneous endovascular techniques for the treatment of hepatic artery stenosis (HAS) occurring after liver transplantation (LT) in adult and pediatrics patients. From February 2003 to March 2009, 25 patients (15 adults and 10 children) whose developed HAS after LT were referred to our interventional radiology unit. Technical success was achieved in 96% (24 of 25) of patients. Percutaneous transluminal angioplasty (PTA) was performed in 13 patients (7 children), and stenting was performed in 11 patients (2 children). After the procedure, all patients were followed-up with liver function tests, Doppler ultrasound, and/or computed tomography. Mean follow-up was 15.8 months (range 5 days to 58 months). Acute hepatic artery thrombosis occurred immediately after stent deployment in 2 patients and was successfully treated with local thrombolysis. One patient developed severe HA spasm, which reverted after 24 h. After the procedure, mean trans-stenotic pressure gradient decreased from 30.5 to 6.2 mmHg. Kaplan-Meyer curve of HA primary patency was 77% at 1 and 2 years. During the follow-up period, 5 patients (20%) had recurrent stenosis, and 2 patients (8.3%) had late thrombosis. Two of 7 patients with stenosis/thrombosis underwent surgical revascularization (n = 1) and liver retransplantation (n = 1). Six (25%) patients died during follow-up, but overall mortality was not significantly different when comparing patients having patent hepatic arteries with those having recurrent stenosis/thrombosis. There were no significant differences in recurrent stenosis/thrombosis and mortality comparing patients treated by PTA versus stenting and comparing adult versus pediatric status. Percutaneous interventional treatment of HAS in LT recipients is safe and effective and decreases the need for surgical revascularization and liver retransplantation. However, the beneficial effects for survival are not clear, probably because

  7. The impact of recurrent acute chest syndrome on the lung function of young adults with sickle cell disease.

    PubMed

    Knight-Madden, Jennifer M; Forrester, Terrence S; Lewis, Norma A; Greenough, Anne

    2010-12-01

    The aim of this study was to assess the impact of recurrent acute chest syndrome (ACS) episodes on the lung function of young adults with sickle cell disease (SCD). Our prospective study included 80 SCD adults [26 with recurrent acute chest syndrome (ACS)] and 80 ethnically matched controls aged between 18 and 28 years. Lung function (spirometry and lung volumes) was measured and the results were expressed as the percentage predicted for height. Bronchial hyperresponsiveness (BHR) was assessed by the response to either a bronchodilator or an exercise challenge. The adults with recurrent ACS (two or more ACS episodes) had lower median forced vital capacity (74 vs. 83%, p = 0.03), forced expiratory volume in 1 s (79 vs. 90%, p < 0.03), and total lung capacity (69 vs. 81%, p = 0.04) than SCD adults who had one or no ACS episodes. The greater the number of ACS episodes, the greater the reduction in lung function (p = 0.001). The adults with SCD had lower median forced vital capacity (81 vs. 106%), forced expiratory volume in 1 s (85 vs. 107%), and total lung capacity (80 vs. 87%) than the controls (p < 0.001). Similar numbers in each group had BHR (p = 0.2). The prevalence of restrictive ventilatory defect in the patients with SCD was almost double that of the controls (p = 0.004). Young adults with SCD have worse lung function than ethnically matched controls, particularly if they have suffered recurrent ACS episodes.

  8. Limited sampling strategy of mycophenolic acid in adult kidney transplant recipients: influence of the post-transplant period and the pharmacokinetic profile.

    PubMed

    Chaabane, Amel; Aouam, Karim; Ben Fredj, Nadia; Hammouda, Mouna; Chadly, Zohra; El May, Mezri; Boughattas, Naceur; Skhiri, Habib

    2013-09-01

    We aimed to develop an accurate and convenient LSS for predicting MPA-AUC(0-12 hours) in Tunisian adult kidney transplant recipients whose immunosuppressive regimen consisted of MMF and tacrolimus combination with regards to the post-transplant period and the pharmacokinetic profile. Each pharmacokinetic profile consisted of eight blood samples collected during the 12-hour dosing interval. The AUC(0-12 hours) was calculated according to the linear trapezoidal rule. The MPA concentrations at each sampling time were correlated by a linear regression analysis with the measured AUC(0-12). We analyzed all the developed models for their ability to estimate the MPA-AUC(0-12 hours). The best multilinear regression model for predicting the full MPA-AUC(0-12 hours) was found to be the combination of C1, C4, and C6. All the best correlated models and the most convenient ones were verified to be also applicable before 5 months after transplantation and thereafter. These models were also verified to be applicable for patients having or not the second peak in their pharmacokinetic profiles. For practical reasons we recommend a LSS using C0, C1, and C4 that provides a reasonable MPA-AUC(0-12 hours) estimation. PMID:23813362

  9. Preventive azithromycin treatment reduces noninfectious lung injury and acute graft-versus-host disease in a murine model of allogeneic hematopoietic cell transplantation.

    PubMed

    Radhakrishnan, Sabarinath Venniyil; Palaniyandi, Senthilnathan; Mueller, Gunnar; Miklos, Sandra; Hager, Max; Spacenko, Elena; Karlsson, Fridrik J; Huber, Elisabeth; Kittan, Nicolai A; Hildebrandt, Gerhard C

    2015-01-01

    Noninfectious lung injury and acute graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT) are associated with significant morbidity and mortality. Azithromycin is widely used in allogeneic HCT recipients for pulmonary chronic GVHD, although current data appear controversial. We induced GVHD and noninfectious lung injury in lethally irradiated B6D2F1 mice by transplanting bone marrow and splenic T cells from allogeneic C57BL/6 mice. Experimental groups were treated with oral azithromycin starting on day 14 until the end of week 6 or week 14 after transplantation. Azithromycin treatment resulted in improved survival and decreased lung injury; the latter characterized by improved pulmonary function, reduced peribronchial and perivascular inflammatory cell infiltrates along with diminished collagen deposition, and a decrease in lung cytokine and chemokine expression. Azithromycin also improved intestinal GVHD but did not affect liver GVHD at week 6 early after transplantation. At week 14, azithromycin decreased liver GVHD but had no effect on intestinal GVHD. In vitro, allogeneic antigen-presenting cell (APC)- dependent T cell proliferation and cytokine production were suppressed by azithromycin and inversely correlated with relative regulatory T cell (Treg) expansion, whereas no effect was seen when T cell proliferation occurred APC independently through CD3/CD28-stimulation. Further, azithromycin reduced alloreactive T cell expansion but increased Treg expansion in vivo with corresponding downregulation of MHC II on CD11c(+) dendritic cells. These results demonstrate that preventive administration of azithromycin can reduce the severity of acute GVHD and noninfectious lung injury after allo-HCT, supporting further investigation in clinical trials.

  10. Rare Case of Unilateral Hypoplasia of Lung with Associated Ventricular Mass in an Adult

    PubMed Central

    Alam, Azad; Iyer, Aparna; Kutty, Jayalakshmi Thelapurath

    2016-01-01

    Hypoplasia of the lung is a rare congenital condition which can be: a) primary i.e. no apparent cause is found; or b) secondary i.e. associated with other congenital anomalies that are implicated in its pathogenesis. These anomalies may involve the diaphragm, cardiovascular, central nervous, urogenital and musculoskeletal system. Patients usually present in neonatal, infancy or childhood period and very rarely in adulthood. Our patient was an adult having a unilateral hypoplastic lung associated with a ventricular mass and to our knowledge this rare combination has never been reported in the English literature; though there are reports of prenatal or newborns with hypoplastic lung and rhabdomyoma of ventricle who did not survive. PMID:27630888

  11. Rare Case of Unilateral Hypoplasia of Lung with Associated Ventricular Mass in an Adult.

    PubMed

    Mirchandani, Lavina Vishnu; Alam, Azad; Iyer, Aparna; Kutty, Jayalakshmi Thelapurath

    2016-07-01

    Hypoplasia of the lung is a rare congenital condition which can be: a) primary i.e. no apparent cause is found; or b) secondary i.e. associated with other congenital anomalies that are implicated in its pathogenesis. These anomalies may involve the diaphragm, cardiovascular, central nervous, urogenital and musculoskeletal system. Patients usually present in neonatal, infancy or childhood period and very rarely in adulthood. Our patient was an adult having a unilateral hypoplastic lung associated with a ventricular mass and to our knowledge this rare combination has never been reported in the English literature; though there are reports of prenatal or newborns with hypoplastic lung and rhabdomyoma of ventricle who did not survive. PMID:27630888

  12. Transplantation of Adult Monkey Neural Stem Cells into A Contusion Spinal Cord Injury Model in Rhesus Macaque Monkeys

    PubMed Central

    Hajinasrollah, Mostafa; Zare Mehrjerdi, Nargess; Azizi, Hossein; Hemmesi, Katayoun; Moghiminasr, Reza; Azhdari, Zahra; Talebi, Ardeshir; Mohitmafi, Soroush; Vosough Taqi Dizaj, Ahmad; Sharifi, Giuve; Baharvand, Hossein; Rezaee, Omidvar; Kiani, Sahar

    2014-01-01

    Objective Currently, cellular transplantation for spinal cord injuries (SCI) is the subject of numerous preclinical studies. Among the many cell types in the adult brain, there is a unique subpopulation of neural stem cells (NSC) that can self-renew and differentiate into neurons. The study aims, therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. Materials and Methods In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model was confirmed by magnetic resonance imaging (MRI) and histological analysis. Animals were clinically observed for 6 months. Results Analysis confirmed homing of mNSCs into the injury site. Transplanted cells expressed neuronal markers (TubIII). Hind limb performance improved in trans- planted animals based on Tarlov’s scale and our established behavioral tests for monkeys. Conclusion Our findings have indicated that mNSCs can facilitate recovery in contusion SCI models in rhesus macaque monkeys. Additional studies are necessary to determine the im- provement mechanisms after cell transplantation. PMID:24567941

  13. Outcomes of Chinese Patients with End-stage Pulmonary Disease while Awaiting Lung Transplantation: A Single-center Study

    PubMed Central

    He, Wen-Xin; Yang, Yu-Ling; Xia, Yan; Song, Nan; Liu, Ming; Zhang, Peng; Fan, Jiang; Jiang, Ge-Ning

    2016-01-01

    Background: The factors affecting the outcome of patients referred for lung transplantation (LTx) still have not been investigated extensively. The aim of this study was to characterize the patient outcomes and identify the prognostic factors for death while awaiting the LTx. Methods: From January 2003 to November 2013, the clinical data of 103 patients with end-stage lung disease that had been referred for LTx to Department of Thoracic Surgery, Shanghai Pulmonary Hospital were analyzed retrospectively. The relationship between predictors and survival was evaluated using the Kaplan–Meier method and the Cox proportional hazards model. Results: Twenty-five patients (24.3%) died while awaiting the LTx. Fifty patients (48.5%) underwent LTx, and 28 patients (27.2%) were still on the waitlist. Compared to the candidates with chronic obstructive pulmonary disease (COPD), patients with idiopathic pulmonary fibrosis (IPF) had a higher mortality while awaiting the LTx (40.0% vs. 12.3%, P = 0.003). Patients requiring mechanical ventilation (MV) had a higher mortality while waiting than others (50.0% vs. 20.2%, P = 0.038). Two variables, using MV and IPF but not COPD as primary disease, emerged as significant independent risk factors for death on the waitlist (hazard ratio [HR] = 56.048, 95% confidence interval [CI]: 3.935–798.263, P = 0.003 and HR = 14.859, 95% CI: 2.695–81.932, P = 0.002, respectively). Conclusion: The type of end-stage lung disease, pulmonary hypertension, and MV may be distinctive prognostic factors for death while awaiting the LTx. PMID:26712425

  14. A model of donors' decision-making in adult-to-adult living donor liver transplantation in Japan: having no choice.

    PubMed

    Fujita, Misao; Akabayashi, Akira; Slingsby, Brian Taylor; Kosugi, Shinji; Fujimoto, Yasuhiro; Tanaka, Koichi

    2006-05-01

    This study examined the decision-making processes of donors in adult-to-adult living donor liver transplantation. Twenty-two donors were interviewed using a semi-structured format. Interview contents were transcribed verbatim and analyzed qualitatively using grounded theory. A decision-making model was developed consisting of 5 stages: (1) recognition, (2) digestion, (3) decision-making, (4) reinforcement, and (5) resolution. The second and the third stages described donors' experiences of "reaching a decision"; the fourth and fifth stages described those of "facing transplantation." The central theme of this model was "having no choice," which consisted of 4 codes: (1) priority of life, (2) only LDLT, (3) for family, and (4) only me. In conclusion, this model can help health care professionals to understand the donor experience and, based on that understanding, to provide sufficient support to the donor.

  15. Genome-wide association study of lung function decline in adults with and without asthma

    PubMed Central

    Imboden, Medea; Bouzigon, Emmanuelle; Curjuric, Ivan; Ramasamy, Adaikalavan; Kumar, Ashish; Hancock, Dana B; Wilk, Jemma B; Vonk, Judith M; Thun, Gian A; Siroux, Valerie; Nadif, Rachel; Monier, Florent; Gonzalez, Juan R; Wjst, Matthias; Heinrich, Joachim; Loehr, Laura R; Franceschini, Nora; North, Kari E; Altmüller, Janine; Koppelman, Gerard H.; Guerra, Stefano; Kronenberg, Florian; Lathrop, Mark; Moffatt, Miriam F; O’Connor, George T; Strachan, David P; Postma, Dirkje S; London, Stephanie J; Schindler, Christian; Kogevinas, Manolis; Kauffmann, Francine; Jarvis, Debbie L; Demenais, Florence; Probst-Hensch, Nicole M

    2012-01-01

    Background Genome-wide association studies (GWAS) have identified determinants of chronic obstructive pulmonary disease, asthma and lung function level, however none addressed decline in lung function. Aim We conducted the first GWAS on age-related decline in forced expiratory volume in the first second (FEV1) and in its ratio to forced vital capacity (FVC) stratified a priori by asthma status. Methods Discovery cohorts included adults of European ancestry (1441 asthmatics, 2677 non-asthmatics; Epidemiological Study on the Genetics and Environment of Asthma (EGEA); Swiss Cohort Study on Air Pollution And Lung And Heart Disease In Adults (SAPALDIA); European Community Respiratory Health Survey (ECRHS)). The associations of FEV1 and FEV1/FVC decline with 2.5 million single nucleotide polymorphisms (SNPs) were estimated. Thirty loci were followed-up by in silico replication (1160 asthmatics, 10858 non-asthmatics: Atherosclerosis Risk in Communities (ARIC); Framingham Heart Study (FHS); British 1958 Birth Cohort (B58C); Dutch asthma study). Results Main signals identified differed between asthmatics and non-asthmatics. None of the SNPs reached genome-wide significance. The association between the height related gene DLEU7 and FEV1 decline suggested for non-asthmatics in the discovery phase was replicated (discovery P=4.8×10−6; replication P=0.03) and additional sensitivity analyses point to a relation to growth. The top ranking signal, TUSC3, associated with FEV1/FVC decline in asthmatics (P=5.3×10−8) did not replicate. SNPs previously associated with cross-sectional lung function were not prominently associated with decline. Conclusions Genetic heterogeneity of lung function may be extensive. Our results suggest that genetic determinants of longitudinal and cross-sectional lung function differ and vary by asthma status. PMID:22424883

  16. Regulation of proto-oncogene expression in adult and developing lungs.

    PubMed Central

    Molinar-Rode, R; Smeyne, R J; Curran, T; Morgan, J I

    1993-01-01

    Activation of immediate-early gene expression has been associated with mitogenesis, differentiation, nerve cell depolarization, and recently, terminal differentiation processes and programmed cell death. Previous evidence also suggested that immediate-early genes play a role in the physiology of the lungs (J. I. Morgan, D. R. Cohen, J. L. Hempstead, and T. Curran, Science 237:192-197, 1987). Therefore, we analyzed c-fos expression in adult and developing lung tissues. Seizures elicited by chemoconvulsants induced expression of mRNA for c-fos, c-jun, and junB and Fos-like immunoreactivity in lung tissue. The use of pharmacological antagonists and adrenalectomy indicated that this increased expression was neurogenic. Interestingly, by using a fos-lacZ transgenic mouse, it was shown that Fos-LacZ expression in response to seizure occurred preferentially in clusters of epithelial cells at the poles of the bronchioles. This was the same location of Fos-LacZ expression detected during early lung development. These data imply that pharmacological induction of immediate-early gene expression in adult mice recapitulates an embryological program of gene expression. Images PMID:8497249

  17. Sexuality, Lung Cancer, and the Older Adult: An Unlikely Trio?

    PubMed Central

    Williams, Anna Cathy; Reckamp, Karen; Freeman, Bonnie; Sidhu, Rupinder; Grant, Marcia

    2013-01-01

    Case Study  Mrs. L. is a 60-year-old retired female teacher with stage IIIA squamous cell carcinoma of the lung, status postchemoradiation. She recently developed radiation pneumonitis, which was managed conservatively, and she did not require steroids. Mrs. L. has noted some progression of her underlying dyspnea. She is monitoring her oxygen saturation at home, and most of the time it is in the range of 94% to 96%. On one occasion only, her oxygen dropped to 88% and rapidly improved to the mid-90s. Her cough has improved for the past 4 to 6 weeks. She denies sputum production, congestion, or fever. Mrs. L. does not require a walker and uses a wheelchair only for long distances. She has occasional, slight dysphagia. A recent CT scan shows stable disease, and she is to return to the clinic in 2 months for restaging and possible further chemotherapy. Mrs. L. and her husband have been married for 33 years, and they have been very close. Until recently, they have continued to be sexually active and very intimate with each other. Since Mrs. L.’s diagnosis, and during treatment, the couple have become extremely stressed and psychologically spent. The act of sexual intercourse has ceased, yet they have attempted to remain close and maintain open communication. In addition to Mrs. L.’s increasing dyspnea, she has also suffered a great deal of fatigue and depression, along with alopecia and vaginal atrophy, due to the chemotherapy and radiation treatments. Both Mr. and Mrs. L. are very distressed over the change in their sexual lives. Mr. L. has mentioned that he now feels more like a "nursemaid" than a husband or lover. Mrs. L. has made concerted efforts to maintain intimacy with her husband, but her fatigue is profound. She has taken to sleeping in the living room, sitting up on the couch, as it relieves her dyspnea to some degree. PMID:25032012

  18. Predictions of ozone absorption in human lungs from newborn to adult

    SciTech Connect

    Overton, J.H.; Graham, R.C.

    1989-01-01

    Dosimetry models for gases mainly have been used to predict absorption in adult humans and laboratory animals. The lack of lower respiratory tract (LRT) lung models for children has discouraged the application of theoretical gaseous dosimetry to this important sub-population. To fill this gap the authors have used several sources of data on age dependent LRT volumes, age dependent airway dimensions, a model of an adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adult. An ozone (O{sub 3}) dosimetry model was then used to estimate the regional and local uptake of O{sub 3} in the (theoretical) LRTs of children and adults. For sedentary breathing, the LRT distribution of absorbed O{sub 3}, the percent uptake (76 to 85%), and the centriacinar O{sub 3} tissue dose are not very sensitive to age. For maximal work during exercise, predicted uptakes range from 83 to 91%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, total O{sub 3} absorption per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O{sub 3} is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage due to O{sub 3}.

  19. Retinyl ester synthesis by isolated adult rabbit lung type II cells.

    PubMed

    Zachman, R D; Tsao, F H

    1988-01-01

    Type II alveolar cells were isolated from adult rabbit lungs and then cultured on monolayers for 16 hours. These cells were then covered with buffered medium containing [3H]-retinol. After 30-120 minutes incubation, the cells were extracted with Hexane: Ethanol and the hexane extract analyzed by HPLC. A linear synthesis of [3H]-retinyl palmitate with time of incubation was demonstrated. PMID:3170088

  20. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

    PubMed

    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

  1. Prolonged varicella-zoster virus reinfection in an adult after unrelated cord blood transplantation.

    PubMed

    Oka, Masahiro; Kunisada, Makoto; Oba, Yuichiro; Okamura, Atsuo; Nishigori, Chikako

    2012-09-01

    Most varicella-zoster virus (VZV) infections after cord blood transplantation (CBT) present as localized herpes zoster. Here, we report a case of VZV reinfection in an adult patient after CBT that appeared clinically to be varicella. A 50-year-old Japanese man underwent CBT for the management of acute lymphoblastic leukemia. Seventeen months later, he developed a small number of vesicles with umbilicated centers. A skin biopsy showed an intraepidermal blister containing degenerated balloon cells. Subsequently, the skin eruption developed over his entire body. The patient was treated with intravenous acyclovir for 5 days, followed by oral valacyclovir for 9 days. It took more than 3 weeks for most of the skin lesions to scab. Serum levels of anti-VZV IgG on days 3 and 33 after the onset of the skin eruption were negative and 260 mIU/ml, respectively. Serum anti-VZV IgM on days 3 and 33 was not detected. Our patient was diagnosed with VZV reinfection.

  2. Liver transplantation versus conservative treatment for adult-onset type II citrullinemia: our experience and a review of the literature.

    PubMed

    Kimura, N; Kubo, N; Narumi, S; Toyoki, Y; Ishido, K; Kudo, D; Umehara, M; Yakoshi, Y; Hakamada, K

    2013-11-01

    Adult-onset type II citrullinemia (CTLN2), an autosomal recessive disorder caused by a mutation in the SLC25A13 gene, is characterized by increased serum citrulline and ammonia levels. Patients with CTLN2 also display various neuropsychiatric symptoms. Many individuals with CTLN2 are fond of protein-rich and/or lipid-rich foods with an aversion to carbohydrate-rich foods. We herein report two cases of CTLN2 treated with living donor liver transplantation (LDLT) and provide a review of the pertinent literature. Case 1 was a 43-year-old man admitted to our hospital for repetitive episodes of consciousness disturbance. Case 2 was a 37-year-old man admitted to our hospital because of abnormal behavior associated with hyperammonemia. A definitive diagnosis of CTLN2 was accomplished by DNA analysis in both patients, who successfully underwent LDLT using liver segments from donor siblings with confirmed heterozygous gene expression. Case 2 also underwent conservative therapy with arginine and a high-fat, carbohydrate-restricted diet prior to LDLT. Postoperative recovery was uneventful and food was unrestricted in both patients. We also identified 77 cases of CTLN2 in the literature and reviewed them in terms of outcome of both liver transplantation and conservative therapy. The survival rate in patients treated by liver transplantation was 100%, whereas that in patients treated by conservative treatment showed improvement from 39.5% to 76.5% over the years. Liver transplantation is a practical treatment that fundamentally improves patient quality of life after transplantation. However, recent studies have suggested that arginine and sodium pyruvate administration combined with intensive nutritional support is also an effective therapy for CTLN2. Further development of conservative therapy may provide a safer, more affordable alternative to liver transplantation in the near future.

  3. Combinations of differentiation markers distinguish subpopulations of alveolar epithelial cells in adult lung.

    PubMed

    Liebler, Janice M; Marconett, Crystal N; Juul, Nicholas; Wang, Hongjun; Liu, Yixin; Flodby, Per; Laird-Offringa, Ite A; Minoo, Parviz; Zhou, Beiyun

    2016-01-15

    Distal lung epithelium is maintained by proliferation of alveolar type II (AT2) cells and, for some daughter AT2 cells, transdifferentiation into alveolar type I (AT1) cells. We investigated if subpopulations of alveolar epithelial cells (AEC) exist that represent various stages in transdifferentiation from AT2 to AT1 cell phenotypes in normal adult lung and if they can be identified using combinations of cell-specific markers. Immunofluorescence microscopy showed that, in distal rat and mouse lungs, ∼ 20-30% of NKX2.1(+) (or thyroid transcription factor 1(+)) cells did not colocalize with pro-surfactant protein C (pro-SP-C), a highly specific AT2 cell marker. In distal rat lung, NKX2.1(+) cells coexpressed either pro-SP-C or the AT1 cell marker homeodomain only protein x (HOPX). Not all HOPX(+) cells colocalize with the AT1 cell marker aquaporin 5 (AQP5), and some AQP5(+) cells were NKX2.1(+). HOPX was expressed earlier than AQP5 during transdifferentiation in rat AEC primary culture, with robust expression of both by day 7. We speculate that NKX2.1 and pro-SP-C colocalize in AT2 cells, NKX2.1 and HOPX or AQP5 colocalize in intermediate or transitional cells, and HOPX and AQP5 are expressed without NKX2.1 in AT1 cells. These findings suggest marked heterogeneity among cells previously identified as exclusively AT1 or AT2 cells, implying the presence of subpopulations of intermediate or transitional AEC in normal adult lung. PMID:26545903

  4. TXA127 in Enhancement of Engraftment in Adult Double Cord Blood Transplantation

    ClinicalTrials.gov

    2016-08-29

    Double Cord Blood Transplant; Acute Myelogenous Leukemia; Myelodysplastic Syndrome; Myelofibrosis; Acute Lymphoblastic Leukemia; Chronic Myelocytic Leukemia; Non Hodgkins Lymphoma; Hodgkins Lymphoma; Chronic Lymphocytic Leukemia

  5. Neonatal hyperoxic lung injury favorably alters adult right ventricular remodeling response to chronic hypoxia exposure

    PubMed Central

    Goss, Kara N.; Cucci, Anthony R.; Fisher, Amanda J.; Albrecht, Marjorie; Frump, Andrea; Tursunova, Roziya; Gao, Yong; Brown, Mary Beth; Petrache, Irina; Tepper, Robert S.; Ahlfeld, Shawn K.

    2015-01-01

    The development of pulmonary hypertension (PH) requires multiple pulmonary vascular insults, yet the role of early oxygen therapy as an initial pulmonary vascular insult remains poorly defined. Here, we employ a two-hit model of PH, utilizing postnatal hyperoxia followed by adult hypoxia exposure, to evaluate the role of early hyperoxic lung injury in the development of later PH. Sprague-Dawley pups were exposed to 90% oxygen during postnatal days 0–4 or 0–10 or to room air. All pups were then allowed to mature in room air. At 10 wk of age, a subset of rats from each group was exposed to 2 wk of hypoxia (Patm = 362 mmHg). Physiological, structural, and biochemical endpoints were assessed at 12 wk. Prolonged (10 days) postnatal hyperoxia was independently associated with elevated right ventricular (RV) systolic pressure, which worsened after hypoxia exposure later in life. These findings were only partially explained by decreases in lung microvascular density. Surprisingly, postnatal hyperoxia resulted in robust RV hypertrophy and more preserved RV function and exercise capacity following adult hypoxia compared with nonhyperoxic rats. Biochemically, RVs from animals exposed to postnatal hyperoxia and adult hypoxia demonstrated increased capillarization and a switch to a fetal gene pattern, suggesting an RV more adept to handle adult hypoxia following postnatal hyperoxia exposure. We concluded that, despite negative impacts on pulmonary artery pressures, postnatal hyperoxia exposure may render a more adaptive RV phenotype to tolerate late pulmonary vascular insults. PMID:25659904

  6. Allogeneic hematopoietic stem cell transplantation in adult acute lymphoblastic leukemia: potential benefit of medium-dose etoposide conditioning.

    PubMed

    Imamura, Masahiro; Shigematsu, Akio

    2015-01-01

    The outcomes of adult acute lymphoblastic leukemia (ALL) patients with chemotherapy or autologous hematopoietic stem cell transplantation (HSCT) are unsatisfactory. Therefore, allogeneic (allo) HSCT has been applied to those patients in first complete remission (CR1), and has shown a long-term survival rate of approximately 50 %. In terms of myeloablative conditioning (MAC) regimen, higher dose of cyclophosphamide (CY) and total body irradiation (TBI) (the standard CY + TBI) has been generally applied to allo HSCT. Other MAC regimens such as busulfan-based or etoposide-based regimens have also been used. Among those, medium-dose etoposide (ETP) in addition to the standard CY + TBI conditioning regimen appears to be promising for allo HSCT in adult ALL when transplanted in ALL patients aged under 50 years in CR1 and also in CR2, showing an excellent outcome without increasing relapse or transplant-related mortality (TRM) rates. By contrast, reduced-intensity conditioning (RIC) regimens have also been applied to adult ALL patients and favorable outcomes have been obtained; however, relapse and TRM rates remain high. Therefore, an allo HSCT conditioning regimen which deserves further study for adult ALL patients aged under 50 years in CR1 and CR2 appears to be medium-dose ETP + CY + TBI and RIC is suitable for patients aged over 50 years or for younger patients with comorbid conditions. On the contrary, new therapeutic strategies for adult ALL patients are increasingly utilized with better outcomes; namely, various tyrosine kinase inhibitors for Philadelphia chromosome (Ph)-positive ALL, human leukocyte antigen-haploidentical HSCT, and pediatric-inspired regimens for Ph-negative ALL. Therefore, the optimal treatment modality should be selected considering patient's age, Ph-positivity, donor availability, risk classification, efficacy, and safety. PMID:26322249

  7. Development and Preclinical Application of an Immunocompetent Transplant Model of Basal Breast Cancer with Lung, Liver and Brain Metastases

    PubMed Central

    Hoenerhoff, Mark; Hixon, Julie A.; Durum, Scott K.; Qiu, Ting-hu; He, Siping; Burkett, Sandra; Liu, Zi-Yao; Swanson, Steven M.; Green, Jeffrey E.

    2016-01-01

    Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is associated with a poor prognosis and for which no targeted therapies currently exist. In order to improve preclinical testing for TNBC that relies primarily on using human xenografts in immunodeficient mice, we have developed a novel immunocompetent syngeneic murine tumor transplant model for basal-like triple-negative breast cancer. The C3(1)/SV40-T/t-antigen (C3(1)/Tag) mouse mammary tumor model in the FVB/N background shares important similarities with human basal-like TNBC. However, these tumors or derived cell lines are rejected when transplanted into wt FVB/N mice, likely due to the expression of SV40 T-antigen. We have developed a sub-line of mice (designated REAR mice) that carry only one copy of the C3(1)/Tag-antigen transgene resulting from a spontaneous transgene rearrangement in the original founder line. Unlike the original C3(1)/Tag mice, REAR mice do not develop mammary tumors or other phenotypes observed in the original C3(1)/Tag transgenic mice. REAR mice are more immunologically tolerant to SV40 T-antigen driven tumors and cell lines in an FVB/N background (including prostate tumors from TRAMP mice), but are otherwise immunologically intact. This transplant model system offers the ability to synchronously implant the C3(1)/Tag tumor-derived M6 cell line or individual C3(1)/Tag tumors from various stages of tumor development into the mammary fat pads or tail veins of REAR mice. C3(1)/Tag tumors or M6 cells implanted into the mammary fat pads spontaneously metastasize at a high frequency to the lung and liver. M6 cells injected by tail vein can form brain metastases. We demonstrate that irradiated M6 tumor cells or the same cells expressing GM-CSF can act as a vaccine to retard tumor growth of implanted tumor cells in the REAR model. Preclinical studies performed in animals with an intact immune system should more authentically replicate treatment responses in

  8. Autologous transplantation of adipose-derived stromal cells ameliorates ventilator-induced lung injury in rats

    PubMed Central

    2013-01-01

    Background Adipose-derived stromal cells (ADSCs) are a good alternative to multipotent stem cells for regenerative medicine. Low tidal volume (LVT) has proved to be an effective ventilation strategy. However, it is not known if ADSCs and LVT can protect against ventilator-induced lung injury (VILI). This study was aimed to determine the potential of ADSCs and LVT to repair following VILI and to elucidate the mechanisms responsible for this section. Methods A total of 72 rats were randomly assigned into group I (sham group, n = 18), group II (1 h of high tidal volume-ventilated (HVT) 40 mL/kg to peak airway pressures of approximately 35 cm H2O and 100% oxygen, n = 18), group III (1 h of HVT followed by 6 h LVT 6 mL/kg to peak airway pressures of approximately 6 cm H2O and 100% oxygen, n = 18) and group IV (1 h of HVT followed by intravenous injection of 5 × 106 ADSCs, n = 18). All animals were sacrificed 7 after the experiments lasted for 7 hours. Bronchoalveolar lavage fluid (BALF) was collected and lungs were harvested for analysis. Results High tidal volume-ventilated (HVT) rats exhibited typical VILI features compared with sham rats. Lung edema, histological lung injury index, concentrations of total protein, total cell counts, number of neutrophils in bronchoalveolar lavage fluid (BALF), tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-10 and transforming growth factor-β1 in BALF were significantly increased in HVT rats. Additionally, gene and protein levels of Na+ channel subunits, Na-K-ATPase pump activity and alveolar fluid clearance were significantly decreased in HVT rats. All these indices of VILI were significantly improved in rats treated with ADSCs. However, compared with ADSCs treatment, LVT strategy had little therapeutic effect in the present study. Conclusion These results may provide valuable insights into the effects of ADSCs in acute lung injury. PMID:23890086

  9. 10 years of prophylaxis with nebulized liposomal amphotericin B and the changing epidemiology of Aspergillus spp. infection in lung transplantation.

    PubMed

    Peghin, Maddalena; Monforte, Victor; Martin-Gomez, Maria-Teresa; Ruiz-Camps, Isabel; Berastegui, Cristina; Saez, Berta; Riera, Jordi; Ussetti, Piedad; Solé, Juan; Gavaldá, Joan; Roman, Antonio

    2016-01-01

    The aim of this study was to assess the outcome and tolerability of prophylactic nebulized liposomal amphotericin B (n-LAB) in lung transplant recipients (LTR) and the changing epidemiology of Aspergillus spp. infection and colonization. We performed an observational study including consecutive LTR recipients (2003-2013) undergoing n-LAB prophylaxis lifetime. A total of 412 patients were included (mean postoperative follow-up 2.56 years; IQR 1.01-4.65). Fifty-three (12.8%) patients developed 59 Aspergillus spp. infections, and 22 invasive aspergillosis (overall incidence 5.3%). Since 2009, person-time incidence rates of Aspergillus spp. colonization and infection decreased (2003-2008, 0.19; 2009-2014, 0.09; P = 0.0007), but species with reduced susceptibility or resistance to amphotericin significantly increased (2003-2008, 38.1% vs 2009-2014, 58.1%; P = 0.039). Chronic lung allograft dysfunction (CLAD) was associated with Aspergillus spp. colonization and infection (HR 24.4, 95% CI 14.28-41.97; P = 0.00). Only 2.9% of patients presented adverse effects, and 1.7% required discontinuation. Long-term administration of prophylaxis with n-LAB has proved to be tolerable and can be used for preventing Aspergillus spp. infection in LTR. Over the last years, the incidence of Aspergillus spp. colonization and infection has decreased, but species with reduced amphotericin susceptibility or resistance are emerging. CLAD is associated with Aspergillus spp. colonization and infection.

  10. Bone marrow transplantation alters lung antigen presenting cells to promote TH17 response and the development of pneumonitis and fibrosis following gammaherpesvirus infection

    PubMed Central

    Zhou, Xiaofeng; Loomis-King, Hillary; Gurczynski, Stephen J.; Wilke, Carol A.; Konopka, Kristine E.; Ptaschinski, Catherine; Coomes, Stephanie M; Iwakura, Yoichiro; van Dyk, Linda F.; Lukacs, Nicholas W.; Moore, Bethany B.

    2015-01-01

    Hematopoietic stem cell transplantation (HSCT) efficacy is limited by numerous pulmonary complications. We developed a model of syngeneic bone marrow transplant (BMT) followed by infection with murine gamma herpesvirus (γHV-68) that results in pneumonitis and fibrosis and mimics human “non-infectious” HSCT complications. BMT mice experience increased early lytic replication, but establish viral latency by 21 days post infection (dpi). CD4 T cells in BMT mice are skewed towards IL-17A rather than IFN-γ production. Transplantation of bone marrow from Il-17a−/− donors or treatment with anti-IL-17A neutralization antibodies at late stages attenuates pneumonitis and fibrosis in infected BMT mice, suggesting that hematopoietic-derived IL-17A is essential for development of pathology. IL-17A directly influences activation and extracellular matrix production by lung mesenchymal cells. Lung CD11c+ cells of BMT mice secrete more TGF-β1, and pro-TH17 mRNAs for IL-23 and IL-6, and less TH1-promoting cytokine mRNA for IFN-γ but slightly more IL-12 mRNA in response to viral infection. Adoptive transfer of non-BMT lung CD11c-enriched cells restores robust TH1 response and suppresses aberrant TH17 response in BMT mice to improve lung pathology. Our data suggest “non-infectious” HSCT lung complications may reflect preceding viral infections and demonstrate that IL-17A neutralization may offer therapeutic advantage even after disease onset. PMID:26376362

  11. The effect of music therapy on relaxation, anxiety, pain perception, and nausea in adult solid organ transplant patients.

    PubMed

    Madson, Amy T; Silverman, Michael J

    2010-01-01

    Organ transplant recipients characteristically experience low levels of relaxation and high levels of anxiety, pain, and nausea. Although music therapy has demonstrated effectiveness in ameliorating these types of conditions with patients in other areas of medical hospitals, no studies have evaluated the effects of music therapy on solid organ transplant patients. The purpose of this study was to assess the impact of music therapy on anxiety, relaxation, pain, and nausea levels in recovering patients on the adult transplant unit of the hospital utilizing a pre-posttest design. Participants (N = 58) received an individual 15-35 minute music therapy session consisting of live patient-preferred music and therapeutic social interaction. To remain consistent with the hospital's evaluative instruments during this pilot study, participants' self-reported levels of anxiety, relaxation, pain, and nausea, were based on separate 10-point Likert-type scales. The principal investigator observed affect and verbalizations at pre and posttest. Results indicated there were significant improvements in self-reported levels of relaxation, anxiety (both p < .001), pain (p < .01), and nausea (p < .05). Although there was no reliability measure, there were significant increases in positive verbalizations and positive affect (p < .001). All participants reported that they would desire music therapy again during a future long-term hospital stay. From the results of this exploratory study, it seems that music therapy can be a viable psychosocial intervention for hospitalized postoperative solid transplant patients. Implications for clinical practice and suggestions for future research are provided.

  12. Decision-making in adult thalassemia patients undergoing unrelated bone marrow transplantation: quality of life, communication and ethical issues.

    PubMed

    Caocci, G; Pisu, S; Argiolu, F; Giardini, C; Locatelli, F; Vacca, A; Orofino, M G; Piras, E; De Stefano, P; Addari, M C; Ledda, A; La Nasa, G

    2006-01-01

    Bone marrow transplantation (BMT) represents a potentially curative treatment of thalassemia. For patients without an HLA-identical sibling donor, recourse to an unrelated donor is a practicable option but the candidates and their families are faced with a difficult decision. They can either choose to continue the supportive therapy, with no chance of definitive cure, or they accept the mortality risk of BMT in the hope of obtaining a definitive resolution of the disease. We investigated the communication strategies and the post transplantation quality of life (QoL) in 19 adult thalassemia patients surviving after an unrelated donor BMT. The patients were given two questionnaires: a questionnaire to evaluate pre-transplantation communication factors and the EORTC QLQ-C30 questionnaire to assess global QoL. All patients were satisfied with the communication modalities employed by the physicians. The global post transplantation QoL in our patient cohort was found to be good. The approach used in this study may offer a contribution to understanding the decision-making process leading to the choice of a treatment with a high mortality risk for a chronic, non-malignant disease. Finally, some ethical issues of this therapeutic approach are briefly addressed. PMID:16299541

  13. Reduced intensity conditioning followed by peripheral blood stem cell transplantation for adult patients with high-risk acute lymphoblastic leukemia

    PubMed Central

    Stein, Anthony S.; Palmer, Joycelynne M.; O'Donnell, Margaret R.; Kogut, Neil M.; Spielberger, Ricardo T.; Slovak, Marilyn L.; Tsai, Ni-Chun; Senitzer, David; Snyder, David S.; Thomas, Sandra H.; J.Forman, Stephen

    2009-01-01

    Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT), however it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine/melphalan prior to allogeneic peripheral blood stem cell transplant between 6/14/02 and 6/15/07 at City of Hope. Indications for the RIC regimen were: 1) age 50 or older (42%), 2) compromised organ function (54%), or 3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 months for living patients. Both overall survival and disease-free survival at two years was 61.5%. Relapse incidence was 21.1% and non-relapse mortality was 21.5% at two years. cGVHD developed in 86% of evaluable patients. In this series, no significant correlations were made between outcomes and patient age, presence of Philadelphia chromosome, relatedness of donor source or prior HCT. These high survival rates for high-risk ALL patients following RIC HCT may offer a promising option for patients not eligible for a standard myeloablative transplant. PMID:19822300

  14. Restoration of portal flow using a pericholedochal varix in adult living donor liver transplantation for patients with total portosplenomesenteric thrombosis.

    PubMed

    Moon, Deok-Bog; Lee, Sung-Gyu; Ahn, Chul-Soo; Hwang, Shin; Kim, Ki-Hun; Ha, Tae-Yong; Song, Gi-Won; Park, Gil-Chun; Jung, Dong-Hwan; Namkoong, Jung-Man; Park, Hyung-Woo; Park, Yo-Han

    2014-05-01

    In total portosplenomesenteric thrombosis patients, cavoportal hemitransposition (CPHT) is indicated but rarely applicable for adult-to-adult (A-to-A) living donor liver transplantation (LDLT) because partial liver graft requires splanchno-portal inflow for liver graft regeneration. If intra- & peri-pancreatic collaterals draining into pericholedochal varix were present, pericholedochal varix may provide splanchnic blood flow to the transplanted liver and also relieve recipient's portal hypertension. To date, however, there is no successful report using pericholedochal varix in liver transplantation (LT). We successfully performed A-to-A LDLTs using pericholedochal varix for those 2 patients. The surgical strategies are followings: (a) dissection of hepatic hilum to isolate left hepatic artery using for arterial reconstruction of implanted right lobe graft, (b) en-mass clamping of the undissected remaining hilum if we can leave adequate length of stump from the clamping site, and then hilum is divided, (c) delay the donor hepatectomy until the feasibility of the recipient operation is confirmed. Portal flow was established between the sizable pericholedochal varix (caliber > 1cm) and graft portal vein, but the individually designed approaches were used for each patients. Currently, they have been enjoying normal life on posttransplant 92 and 44 months respectively. In conclusion, enlarged pericholedochal varix in patients with totally obliterated splanchnic veins might be an useful inflow to restore portal flow and secure good outcome in A-to-A LDLT. AASLD.

  15. Relationship between birth weight and adult lung function: controlling for maternal factors

    PubMed Central

    Edwards, C; Osman, L; Godden, D; Campbell, D; Douglas, J

    2003-01-01

    Methods: In 2001 the cohort was assessed for current lung function, smoking status, and respiratory symptoms. Birth details obtained from the Aberdeen Maternity and Neonatal Databank recorded birth weight, gestation, parity, and mother's age and height. Results: 381 subjects aged 45–50 years were traced and tested for lung function; 323 (85%) had birth details available. A significant linear trend (p<0.01) was observed between birth weight and current forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) values (adjusted for height, age, sex, weight, deprivation category (Depcat), childhood group, and smoking status). This trend remained significant after adjusting birth weight for gestation, parity, sex, mother's height and weight (p = 0.01). The relationship between birth weight and FEV1 and FVC remained significant when adjusted for smoking history. There was no association between birth weight and current wheezing symptoms. Conclusion: There is a positive linear trend between birth weight, adjusted for maternal factors, and lung function in adulthood. The strength of this association supports the "fetal origins hypothesis" that impairment of fetal growth is a significant influence on adult lung function. PMID:14645976

  16. Fat quantification and analysis of lung transplant patients on unenhanced chest CT images based on standardized anatomic space

    NASA Astrophysics Data System (ADS)

    Tong, Yubing; Udupa, Jayaram K.; Torigian, Drew A.; Wu, Caiyun; Christie, Jason; Lederer, David J.

    2016-03-01

    Chest fat estimation is important for identifying high-risk lung transplant candidates. In this paper, an approach to chest fat quantification based on a recently formulated concept of standardized anatomic space (SAS) is presented. The goal of this paper is to seek answers to the following questions related to chest fat quantification on single slice versus whole volume CT, which have not been addressed in the literature. What level of correlation exists between total chest fat volume and fat areas measured on single abdominal and thigh slices? What is the anatomic location in the chest where maximal correlation of fat area with fat volume can be expected? Do the components of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have the same area-to-volume correlative behavior or do they differ? The SAS approach includes two steps: calibration followed by transformation which will map the patient slice locations non-linearly to SAS. The optimal slice locations found for SAT and VAT based on SAS are different and at the mid-level of the T8 vertebral body for SAT and mid-level of the T7 vertebral body for VAT. Fat volume and area on optimal slices for SAT and VAT are correlated with Pearson correlation coefficients of 0.97 and 0.86, respectively. The correlation of chest fat volume with abdominal and thigh fat areas is weak to modest.

  17. Considerations for anesthetic management during veno-venous bypass in adult hepatic transplantation.

    PubMed

    Paulsen, A W; Whitten, C W; Ramsay, M A; Klintmalm, G B

    1989-04-01

    Intraoperative data from 42 adult orthotopic hepatic transplant recipients were analyzed retrospectively to assess the hemodynamic, coagulation, and thermal effects of heparinless veno-venous bypass using a constrained vortex pump. Transient hemodynamic changes occurring at the onset of bypass included decreases in temperature (-10.7%), heart rate (-18.7%) and arterial pressure (-15.1%); and increases in central venous pressure (27.6%) and ECG T wave amplitude (231.6%). Abrupt decreases in cardiac output and pump flow occurred with termination of the portal limb of bypass, which is required to allow completion of the portal vein anastomosis. However, significant continuous decreases were observed in bypass flow and cardiac output during the entire bypass period. The blood volume became concentrated as indicated by increases in hematocrit, colloid osmotic pressure, serum osmolality and serum sodium. Changes in colloid osmotic pressure were inversely related to bypass flow. These data, along with an accumulating base deficit, suggest that veno-venous bypass is associated with less than optimal perfusion of the abdomen and lower extremities. Flow dependent third space fluid accumulation is most likely responsible for decreasing cardiac output and pump flow during the bypass period. No clinically significant coagulopathy could be attributed to the use of veno-venous bypass. There were no significant changes in platelet counts, fibrinogen levels or prothrombin times. The activated partial thromboplastin time decreased from 60.5 to 50.2 seconds. Patient core temperature decreased three times more rapidly (0.9 degrees C/hr) during bypass than at any other time during the procedure.

  18. Birth weight, childhood lower respiratory tract infection, and adult lung function

    PubMed Central

    Shaheen, S; Sterne, J; Tucker, J; Florey, C

    1998-01-01

    BACKGROUND—Historical cohort studies in England have found that impaired fetal growth and lower respiratory tract infections in early childhood are associated with lower levels of lung function in late adult life. These relations are investigated in a similar study in Scotland.
METHODS—In 1985-86 a follow up study was carried out of 1070 children who had been born in St Andrew's from 1921 to 1935 and followed from birth to 14 years of age by the Mackenzie Institute for Medical Research. Recorded information included birth weight and respiratory illnesses. The lung function of 239 of these individuals was measured.
RESULTS—There was no association between birth weight and lung function. Pneumonia before two years of age was associated with a difference in mean forced expiratory volume in one second (FEV1) of −0.39 litres (95% confidence interval (CI) −0.67, −0.11; p = 0.007) and in mean forced vital capacity (FVC) of −0.60 litres (95% CI −0.92, −0.28; p<0.001), after controlling for age, sex, height, smoking, type of spirometer, and other illnesses before two years. Similar reductions were seen in men and women. Bronchitis before two years was associated with smaller deficits in FEV1 and FVC. Asthma or wheeze at two years and older and cough after five years were also associated with a reduction in FEV1.
CONCLUSIONS—The relation between impaired fetal growth and lower lung function in late adult life seen in previous studies was not confirmed in this cohort. The deficits in FEV1 and FVC associated with pneumonia and bronchitis in the first two years of life are consistent with a causal relation.

 PMID:9797752

  19. Pilates Method for Lung Function and Functional Capacity in Obese Adults.

    PubMed

    Niehues, Janaina Rocha; Gonzáles, Inês; Lemos, Robson Rodrigues; Haas, Patrícia

    2015-01-01

    Obesity is defined as the condition in which the body mass index (BMI) is ≥ 30 kg/m2 and is responsible for decreased quality of life and functional limitations. The harmful effects on ventilatory function include reduced lung capacity and volume; diaphragmatic muscle weakness; decreased lung compliance and stiffness; and weakness of the abdominal muscles, among others. Pilates is a method of resistance training that works with low-impact muscle exercises and is based on isometric exercises. The current article is a review of the literature that aims to investigate the hypothesis that the Pilates method, as a complementary method of training, might be beneficial to pulmonary function and functional capacity in obese adults. The intent of the review was to evaluate the use of Pilates as an innovative intervention in the respiratory dysfunctions of obese adults. In studies with other populations, it has been observed that Pilates can be effective in improving chest capacity and expansion and lung volume. That finding is due to the fact that Pilates works through the center of force, made ​​up of the abdominal muscles and gluteus muscles lumbar, which are responsible for the stabilization of the static and dynamic body that is associated with breath control. It has been observed that different Pilates exercises increase the activation and recruitment of the abdominal muscles. Those muscles are important in respiration, both in expiration and inspiration, through the facilitation of diaphragmatic action. In that way, strengthening the abdominal muscles can help improve respiratory function, leading to improvements in lung volume and capacity. The results found in the current literature review support the authors' observations that Pilates promotes the strengthening of the abdominal muscles and that improvements in diaphragmatic function may result in positive outcomes in respiratory function, thereby improving functional capacity. However, the authors did not

  20. Impact and mechanism of non-steroidal anti-inflammatory drugs combined with chemotherapeutic drugs on human lung cancer-nude mouse transplanted tumors

    PubMed Central

    SUN, WEIYI; CHEN, GANG

    2016-01-01

    The present study aimed to investigate the impact of indomethacin treatment combined with oxaliplatin treatment on the expression of cluster of differentiation 44 variant 6 (CD44v6), matrix metalloproteinase-2 (MMP-2) and survivin in human lung cancer-nude mouse transplanted tumors. The human lung adenocarcinoma (A549)-nude mouse transplanted tumor model was established, and the mice were divided into a control group, an indomethacin treatment group, an oxaliplatin treatment group and an indomethacin-oxaliplatin combination treatment group. The tumor inhibition rate was calculated following sacrificing of the mice. Immunohistochemical staining and fluorescence reverse transcription-quantitative polymerase chain reaction were utilized to detect the protein and messenger (m)RNA expression of CD44v6, MMP-2 and survivin. The tumor inhibition rates of the indomethacin group, the oxaliplatin group and the combination group were 26.67, 47.70 and 68.88%, respectively. The protein and mRNA expression levels of CD44v6, MMP-2 and survivin in the transplanted tumors of each treatment group were reduced compared with the control group (P<0.05), and those of the combination group were lower compared with the single-drug treatment groups (P<0.05). Survivin and MMP-2, MMP-2 and CD44v6, and MMP-2 and CD44v6 all exhibited linear positive correlation. The present study provides evidence that the administration of indomethacin alone, or in combination with oxaliplatin, may significantly inhibit the growth of lung cancer-nude mouse transplanted tumors and the expression of CD44v6, MMP-2 and survivin inside the tumor. The combination of non-steroidal anti-inflammatory drugs with chemotherapeutic drugs may improve the antitumor effects. PMID:27313765

  1. Liver transplantation for a giant mesenchymal hamartoma of the liver in an adult: Case report and review of the literature.

    PubMed

    Li, Jiang; Cai, Jin-Zhen; Guo, Qing-Jun; Li, Jun-Jie; Sun, Xiao-Ye; Hu, Zhan-Dong; Cooper, David K C; Shen, Zhong-Yang

    2015-05-28

    Mesenchymal hamartomas of the liver (MHLs) in adults are rare and potentially premalignant lesions, which present as solid/cystic neoplasms. We report a rare case of orthotopic liver transplantation in a patient with a giant MHL. In 2013, a 34-year-old female sought medical advice after a 2-year history of progressive abdominal distention and respiratory distress. Physical examination revealed an extensive mass in the abdomen. Computed tomography (CT) of her abdomen revealed multiple liver cysts, with the diameter of largest cyst being 16 cm × 14 cm. The liver hilar structures were not clearly displayed. The adjacent organs were compressed and displaced. Initial laboratory tests, including biochemical investigations and coagulation profile, were unremarkable. Tumor markers, including levels of AFP, CEA and CA19-9, were within the normal ranges. The patient underwent orthotopic liver transplantation in November 2013, the liver being procured from a 40-year-old man after cardiac death following traumatic brain injury. Warm ischemic time was 7.5 min and cold ischemic time was 3 h. The recipient underwent classical orthotopic liver transplantation. The recipient operative procedure took 8.5 h, the anhepatic phase lasting for 1 h without the use of venovenous bypass. The immunosuppressive regimen included intraoperative induction with basiliximab and high-dose methylprednisolone, and postoperative maintenance with tacrolimus, mycophenolate mofetil, and prednisone. The recipient's diseased liver weighed 21 kg (dry weight) and measured 41 cm × 32 cm × 31 cm. Histopathological examination confirmed the diagnosis of an MHL. The patient did not experience any acute rejection episode or other complication. All the laboratory tests returned to normal within one month after surgery. Three months after transplantation, the immunosuppressive therapy was reduced to tacrolimus monotherapy, and the T-tube was removed after cholangiography showed no abnormalities. Twelve months

  2. Whole Lung Irradiation for Adults With Pulmonary Metastases From Ewing Sarcoma

    SciTech Connect

    Casey, Dana L.; Alektiar, Kaled M.; Gerber, Naamit K.; Wolden, Suzanne L.

    2014-08-01

    Purpose: To evaluate feasibility and patterns of failure in adult patients with Ewing sarcoma (ES) treated with whole lung irradiation (WLI) for pulmonary metastases. Methods and Materials: Retrospective review of all ES patients treated at age 18 or older with 12-15 Gy WLI for pulmonary metastases at a single institution between 1990 and 2014. Twenty-six patients met the study criteria. Results: The median age at WLI was 23 years (range, 18-40). The median follow-up time of the surviving patients was 3.8 years (range, 1.0-9.6). The 3-year cumulative incidence of pulmonary relapse (PR) was 55%, with a 3-year cumulative incidence of PR as the site of first relapse of 42%. The 3-year event-free survival (EFS) and overall survival (OS) were 38 and 45%, respectively. Patients with exclusively pulmonary metastases had better outcomes than did those with extrapulmonary metastases: the 3-year PR was 45% in those with exclusively lung metastases versus 76% in those with extrapulmonary metastases (P=.01); the 3-year EFS was 49% versus 14% (P=.003); and the 3-year OS was 61% versus 13% (P=.009). Smoking status was a significant prognostic factor for EFS: the 3-year EFS was 61% in nonsmokers versus 11% in smokers (P=.04). Two patients experienced herpes zoster in the radiation field 6 and 12 weeks after radiation. No patients experienced pneumonitis or cardiac toxicity, and no significant acute or late sequelae were observed among the survivors. Conclusion: WLI in adult patients with ES and lung metastases is well tolerated and is associated with freedom from PR of 45% at 3 years. Given its acceptable toxicity and potential therapeutic effect, WLI for pulmonary metastases in ES should be considered for adults, as it is in pediatric patients. All patients should be advised to quit smoking before receiving WLI.

  3. Effects of an acute, outpatient physiotherapy exercise program following pediatric heart or lung transplantation.

    PubMed

    Deliva, R D; Hassall, A; Manlhiot, C; Solomon, M; McCrindle, B W; Dipchand, A I

    2012-12-01

    This prospective interventional study investigated the impact of a three-month, ambulatory HA or HB, semi-individualized, PT-prescribed exercise program following pediatric HTx or LTx. SMW distance, strength, and flexibility were assessed at start and completion of the program and one yr after enrollment. Subjects received either an HB or HA exercise program three times per week. The cohort demonstrated clinically and statistically significant improvements in SMW distances at three months (425.7 ± 109.4-500.6 ± 93.6 m, p < 0.001) and at one yr (528.5 ± 66.6 m, p = 0.001), although there was no difference between the two groups at any time. Similar improvements were also observed in strength and flexibility measures. Correlates with higher SMW distance at three months and one yr included older age, male gender, and underlying diagnosis other than CHD. Male gender and diagnosis other than CHD were associated with a slower improvement in the SMW distance. This is the first report of institutionally based, outpatient exercise rehabilitation in the recovery following pediatric thoracic transplantation. We found similar improvements to HB interventions up to one yr after surgery. Further study of the role of exercise rehabilitation and long-term fitness outcomes is needed.

  4. Indoor nitrous acid and respiratory symptoms and lung function in adults

    PubMed Central

    Jarvis, D; Leaderer, B; Chinn, S; Burney, P

    2005-01-01

    Background: Nitrogen dioxide (NO2) is an important pollutant of indoor and outdoor air, but epidemiological studies show inconsistent health effects. These inconsistencies may be due to failure to account for the health effects of nitrous acid (HONO) which is generated directly from gas combustion and indirectly from NO2. Methods: Two hundred and seventy six adults provided information on respiratory symptoms and lung function and had home levels of NO2 and HONO measured as well as outdoor levels of NO2. The association of indoor HONO levels with symptoms and lung function was examined. Results: The median indoor HONO level was 3.10 ppb (IQR 2.05–5.09), with higher levels in homes with gas hobs, gas ovens, and in those measured during the winter months. Non-significant increases in respiratory symptoms were observed in those living in homes with higher HONO levels. An increase of 1 ppb in indoor HONO was associated with a decrease in forced expiratory volume in 1 second (FEV1) percentage predicted (–0.96%; 95% CI –0.09 to –1.82) and a decrease in percentage FEV1/forced vital capacity (FVC) (–0.45%; 95% CI –0.06 to –0.83) after adjustment for relevant confounders. Measures of indoor NO2 were correlated with HONO (r = 0.77), but no significant association of indoor NO2 with symptoms or lung function was observed. After adjustment for NO2 measures, the association of HONO with low lung function persisted. Conclusion: Indoor HONO levels are associated with decrements in lung function and possibly with more respiratory symptoms. Inconsistencies between studies examining health effects of NO2 and use of gas appliances may be related to failure to account for this association. PMID:15923247

  5. KLF4 regulates adult lung tumor-initiating cells and represses K-Ras-mediated lung cancer.

    PubMed

    Yu, T; Chen, X; Zhang, W; Liu, J; Avdiushko, R; Napier, D L; Liu, A X; Neltner, J M; Wang, C; Cohen, D; Liu, C

    2016-02-01

    Lung cancer is the leading cause of cancer-related mortality in both men and women worldwide. To identify novel factors that contribute to lung cancer pathogenesis, we analyzed a lung cancer database from The Cancer Genome Atlas and found that Krüppel-like Factor 4 (KLF4) expression is significantly lower in patients' lung cancer tissue than in normal lung tissue. In addition, we identified seven missense mutations in the KLF4 gene. KLF4 is a transcription factor that regulates cell proliferation and differentiation as well as the self-renewal of stem cells. To understand the role of KLF4 in the lung, we generated a tamoxifen-induced Klf4 knockout mouse model. We found that KLF4 inhibits lung cancer cell growth and that depletion of Klf4 altered the differentiation pattern in the developing lung. To understand how KLF4 functions during lung tumorigenesis, we generated the K-ras(LSL-G12D/+);Klf4(fl/fl) mouse model, and we used adenovirus-expressed Cre to induce K-ras activation and Klf4 depletion in the lung. Although Klf4 deletion alone or K-ras mutation alone can trigger lung tumor formation, Klf4 deletion combined with K-ras mutation significantly enhanced lung tumor formation. We also found that Klf4 deletion in conjunction with K-ras activation caused lung inflammation. To understand the mechanism whereby KLF4 is regulated during lung tumorigenesis, we analyzed KLF4 promoter methylation and the profiles of epigenetic factors. We found that Class I histone deacetylases (HDACs) are overexpressed in lung cancer and that HDAC inhibitors induced expression of KLF4 and inhibited proliferation of lung cancer cells, suggesting that KLF4 is probably repressed by histone acetylation and that HDACs are valuable drug targets for lung cancer treatment.

  6. Report of the Psychosocial Outcomes Workgroup of the Nursing and Social Sciences Council of the International Society for Heart and Lung Transplantation: present status of research on psychosocial outcomes in cardiothoracic transplantation: review and recommendations for the field.

    PubMed

    Cupples, Sandra; Dew, Mary Amanda; Grady, Kathleen L; De Geest, Sabina; Dobbels, Fabienne; Lanuza, Dorothy; Paris, Wayne

    2006-06-01

    Cardiothoracic transplantation's success at prolonging life--and its economic costs--must be considered relative to its psychosocial benefits and costs. Moreover, psychosocial outcomes themselves influence long-term post-transplant morbidity and mortality rates. Although psychosocial outcomes--encompassing patients' physical, psychologic and social functioning, their management of their medical regimen and global quality of life--are the focus of many recent studies, these investigations have yet to yield many evidence-based interventions that are routinely applied to improve patient outcomes. Our goals were to summarize existing work on psychosocial outcomes, delineate areas requiring attention, offer recommendations for steps to advance the field, and thereby provide an impetus for the conduct of clinical trials of interventions to improve these outcomes. We concluded that research must generally shift away from descriptive studies and toward prospective and clinical trial designs to: (a) examine a full range of risk factors and clinical sequelae of patients' psychosocial status; and (b) evaluate the effectiveness of psychosocial interventions. In addition, these issues must be considered across all cardiothoracic recipients, including not only heart recipients but the less-studied populations of lung and heart-lung recipients, and must include longer-term (5+ years) outcomes than is typical in most work. The importance of adequately sized samples to ensure statistical power, and the need to construct study samples representative of the larger cardiothoracic transplant population, cannot be overestimated. Implementing these changes in research design and substantive focus will ensure that psychosocial outcomes research will have maximum impact on transplant recipients' clinical care. PMID:16730578

  7. Post-transplant lymphoproliferative disorder after autologous peripheral stem cell transplantation in a pediatric patient.

    PubMed

    Lones, M A; Kirov, I; Said, J W; Shintaku, I P; Neudorf, S

    2000-11-01

    Post-transplant lymphoproliferative disorder (PTLD) is a complication of allogeneic bone marrow transplantation (BMT). Rare cases of PTLD after autologous BMT have been reported only in adults. This case report is the first to describe PTLD in a pediatric patient after autologous peripheral stem cell transplantation (PSCT). This 2-year-old male with stage IV neuroblastoma underwent autologous PSCT. The post-PSCT course was complicated by fever with hematochezia and a lung mass. On day 94 post PSCT, colonoscopy revealed an ulcer due to a PTLD, monomorphic type, B cell phenotype, associated with Epstein-Barr virus. Fine needle aspiration identified the lung mass as neuroblastoma. PTLD can occur in pediatric autologous PSCT recipients, and may occur more frequently in autologous grafts manipulated by T cell depletion or CD34+ cell selection.

  8. Efficient estimation of the total number of acini in adult rat lung

    PubMed Central

    Barré, Sébastien F.; Haberthür, David; Stampanoni, Marco; Schittny, Johannes C.

    2014-01-01

    Abstract Pulmonary airways are subdivided into conducting and gas‐exchanging airways. An acinus is defined as the small tree of gas‐exchanging airways, which is fed by the most distal purely conducting airway. Until now a dissector of five consecutive sections or airway casts were used to count acini. We developed a faster method to estimate the number of acini in young adult rats. Right middle lung lobes were critical point dried or paraffin embedded after heavy metal staining and imaged by X‐ray micro‐CT or synchrotron radiation‐based X‐rays tomographic microscopy. The entrances of the acini were counted in three‐dimensional (3D) stacks of images by scrolling through them and using morphological criteria (airway wall thickness and appearance of alveoli). Segmentation stopper were placed at the acinar entrances for 3D visualizations of the conducting airways. We observed that acinar airways start at various generations and that one transitional bronchiole may serve more than one acinus. A mean of 5612 (±547) acini per lung and a mean airspace volume of 0.907 (±0.108) μL per acinus were estimated. In 60‐day‐old rats neither the number of acini nor the mean acinar volume did correlate with the body weight or the lung volume. PMID:24997068

  9. About the Operation: Liver Transplant

    MedlinePlus

    ... Heart/Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Liver Transplant There are two very different surgical approaches to liver transplantation: the orthotopic and the heterotopic approach, both ...

  10. The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion?

    PubMed

    Satyanarayana, G; Marty, F M; Tan, C S

    2014-08-01

    BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft-versus-host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin-G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV-specific cytotoxic T cells in healthy adults as well as in post-HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.

  11. Haploidentical hematopoietic stem cell transplantation to adults with hematologic malignancies: analysis of 66 cases at a single Japanese center.

    PubMed

    Kurokawa, Toshiro; Ishiyama, Ken; Ozaki, Jun; Yamashita, Yumiko; Iwaki, Noriko; Saito, Chizuru; Arahata, Masahisa; Kaya, Hiroyasu; Yoshida, Takashi

    2010-05-01

    Sixty-six adult patients with hematologic malignancies underwent haploidentical hematopoietic stem cell transplantation (haplo-HSCT) without T cell depletion. The patients were preconditioned with a reduced intensity regimen, and tacrolimus was used for graft-versus-host disease (GVHD) prophylaxis. Successful engraftment occurred in 60 patients (90.1%) and graft rejection in only 4 patients (6.1%). Among the 60 engrafted patients, only 5 developed severe (grade III or IV) acute GVHD. Twenty patients, including 19 relapse-free patients were alive at a median follow-up of 48 months (range 6-77 months). The overall survival (OS) at 6 years was 29.3%. The OS of 45 patients < 60 years of age was 43.6%, which was superior to that of 21 patients who were 60 years of age and older (9.5%) (P < 0.01). The OS of 11 patients from human leukocyte antigen (HLA) 1 locus-mismatched donors (63.6%) was higher than that of 28 patients from HLA 3 loci-mismatched donors (12.5%) (P < 0.01). Organ injury and infection were the main causes of mortality. Notably, immunosuppressive therapy could be successfully stopped in 9 patients transplanted from HLA 2 or 3 loci-mismatched donors with a median duration of 45 months (range 5-71 months). These data suggest that haplo-HSCT is a promising treatment for patients who need urgent allogeneic transplantation but lack HLA-identical family donors.

  12. Predictions of ozone absorption in human lungs from newborn to adult

    SciTech Connect

    Overton, J.H.; Graham, R.C. )

    1989-01-01

    Although children are an important human population, dosimetry models for gases have been used to predict absorption mainly in laboratory animals and adult humans. To correct this omission, we have used several sources of data on age-dependent lower respiratory tract (LRT) volumes, age-dependent airway dimensions, a model of the adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adulthood. An ozone (O3) dosimetry model was then used to estimate the regional and local uptake of O3 in the (theoretical) LRT of children and adults. For sedentary or quiet breathing, the LRT distribution of absorbed O3, the percent uptake (84 to 88%) and the centriacinar O3 tissue dose are not very sensitive to age. For maximal work during exercise, predicted LRT uptakes range from 87 to 93%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, the total quantity of O3 absorbed per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O3 is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage from O3.

  13. Immunosuppressive therapy for kidney transplantation in adults: a systematic review and economic model.

    PubMed Central

    Jones-Hughes, Tracey; Snowsill, Tristan; Haasova, Marcela; Coelho, Helen; Crathorne, Louise; Cooper, Chris; Mujica-Mota, Ruben; Peters, Jaime; Varley-Campbell, Jo; Huxley, Nicola; Moore, Jason; Allwood, Matt; Lowe, Jenny; Hyde, Chris; Hoyle, Martin; Bond, Mary; Anderson, Rob

    2016-01-01

    BACKGROUND End-stage renal disease is a long-term irreversible decline in kidney function requiring renal replacement therapy: kidney transplantation, haemodialysis or peritoneal dialysis. The preferred option is kidney transplantation, followed by immunosuppressive therapy (induction and maintenance therapy) to reduce the risk of kidney rejection and prolong graft survival. OBJECTIVES To review and update the evidence for the clinical effectiveness and cost-effectiveness of basiliximab (BAS) (Simulect(®), Novartis Pharmaceuticals UK Ltd) and rabbit anti-human thymocyte immunoglobulin (rATG) (Thymoglobulin(®), Sanofi) as induction therapy, and immediate-release tacrolimus (TAC) (Adoport(®), Sandoz; Capexion(®), Mylan; Modigraf(®), Astellas Pharma; Perixis(®), Accord Healthcare; Prograf(®), Astellas Pharma; Tacni(®), Teva; Vivadex(®), Dexcel Pharma), prolonged-release tacrolimus (Advagraf(®) Astellas Pharma), belatacept (BEL) (Nulojix(®), Bristol-Myers Squibb), mycophenolate mofetil (MMF) (Arzip(®), Zentiva; CellCept(®), Roche Products; Myfenax(®), Teva), mycophenolate sodium (MPS) (Myfortic(®), Novartis Pharmaceuticals UK Ltd), sirolimus (SRL) (Rapamune(®), Pfizer) and everolimus (EVL) (Certican(®), Novartis) as maintenance therapy in adult renal transplantation. METHODS Clinical effectiveness searches were conducted until 18 November 2014 in MEDLINE (via Ovid), EMBASE (via Ovid), Cochrane Central Register of Controlled Trials (via Wiley Online Library) and Web of Science (via ISI), Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects and Health Technology Assessment (The Cochrane Library via Wiley Online Library) and Health Management Information Consortium (via Ovid). Cost-effectiveness searches were conducted until 18 November 2014 using a costs or economic literature search filter in MEDLINE (via Ovid), EMBASE (via Ovid), NHS Economic Evaluation Database (via Wiley Online Library), Web of Science (via ISI

  14. Definition of three somatic adult cell nuclear transplant methods in zebrafish (Danio rerio): before, during and after egg activation by sperm fertilization.

    PubMed

    Pérez-Camps, M; Cardona-Costa, J; Francisco-Simao, M; García-Ximénez, F

    2010-02-01

    Zebrafish somatic nuclear transplant has only been attempted using preactivated eggs. In this work, three methods to carry out the nuclear transplant using adult cells before, during and after the egg activation/fertilization were developed in zebrafish with the aim to be used in reprogramming studies. The donor nucleus from somatic adult cells was inserted: (method A) in the central region of the egg and subsequently fertilized; (method B) in the incipient animal pole at the same time that the egg was fertilized; and (method C) in the completely defined animal pole after fertilization. Larval and adult specimens were obtained using the three methods. Technical aspects related to temperature conditions, media required, egg activation/fertilization, post-ovulatory time of the transplant, egg aging, place of the donor nucleus injection in each methodology are presented. In conclusion, the technical approach developed in this work can be used in reprogramming studies.

  15. B-cell surface marker analysis for improvement of rituximab prophylaxis in ABO-incompatible adult living donor liver transplantation.

    PubMed

    Egawa, Hiroto; Ohmori, Katsuyuki; Haga, Hironori; Tsuji, Hiroaki; Yurugi, Kimiko; Miyagawa-Hayashino, Aya; Oike, Fumitaka; Fukuda, Akinari; Yoshizawa, Jun; Takada, Yasutsugu; Tanaka, Koichi; Maekawa, Taira; Ozawa, Kazue; Uemoto, Shinji

    2007-04-01

    Although the effectiveness of rituximab has been reported in ABO blood group (ABO)-incompatible (ABO-I) organ transplantation, the protocol is not yet established. We studied the impact of the timing of rituximab prophylaxis and the humoral immune response of patients undergoing ABO-I living donor liver transplantation (LDLT), focusing on clinicopathological findings and the B-cell subset. From July 2003 to December 2005, 30 adult patients were treated with hepatic artery infusion (HAI) protocol without splenectomy for ABO-I LDLT. A total of 17 patients were treated only with HAI (no prophylaxis), and the other 13 were treated with rituximab prophylaxis at various times prior to transplantation. For B-cell study of the spleen, another 4 patients undergoing ABO-I LDLT both with HAI after prophylaxis and eventual splenectomy, and 3 patients with ABO-compatible LDLT with splenectomy were enrolled. The mortality of the 30 patients with HAI, without splenectomy, and with/without rituximab prophylaxis was 33% and the main cause of death was sepsis. Peripheral blood B cells were completely depleted, anti-donor blood-type antibody titer was lower, and clinical and pathological antibody-mediated rejection was not observed in patients with prophylaxis earlier than 7 days before transplantation (early prophylaxis). Early rituximab prophylaxis significantly depleted B cells and memory B cells in the spleen but not in lymph nodes. On the other hand, B cells and memory B cells increased and memory B cells became dominant during antibody-mediated rejection. In conclusion, early prophylaxis with rituximab depletes B cells, including memory B cells, in the spleen and is associated with a trend toward lower humoral rejection rates and lower peak immunoglobulin (Ig)G titers in ABO-I LDLT patients.

  16. Anesthetic considerations for an adult heart transplant recipient undergoing noncardiac surgery: a case report.

    PubMed

    Valerio, Regalado; Durra, Omar; Gold, Michele E

    2014-08-01

    Approximately 3,500 Americans undergo heart transplantation each year. A portion of this patient population will possibly present later for an elective noncardiac surgery. Anesthesia professionals can be tasked to assess and provide the anesthesia management for heart transplant recipients undergoing a noncardiac surgical procedure. A 57-year-old man with a complicated cardiac history before undergoing heart transplantation was scheduled to undergo a right inguinal hernia repair. The patient underwent general anesthesia and had an uneventful course of surgery and recovery. Management of the patient with a heart transplant includes consideration of the altered physiology of a denervated heart; the perioperative anesthetic considerations specific to this patient population; and the risks of rejection, infection, and pharmacologic interactions brought about by immunosuppression. The purposes of this case report were to discuss the indications for the perioperative care of heart transplant recipients undergoing noncardiac procedures, and to discuss the evidence-based literature to provide delivery of safe and effective patient care. PMID:25167609

  17. A population-based cohort study of late mortality in adult autologous hematopoietic stem cell transplant recipients in Australia.

    PubMed

    Ashton, Lesley J; Le Marsney, Renate E; Dodds, Anthony J; Nivison-Smith, Ian; Wilcox, Leonie; O'Brien, Tracey A; Vajdic, Claire M

    2014-07-01

    We assessed overall and cause-specific mortality and risk factors for late mortality in a nation-wide population-based cohort of 4547 adult cancer patients who survived 2 or more years after receiving an autologous hematopoietic stem cell transplantation (HSCT) in Australia between 1992 and 2005. Deaths after HSCT were identified from the Australasian Bone Marrow Transplant Recipient Registry and through data linkage with the National Death Index. Overall, the survival probability was 56% at 10 years from HSCT, ranging from 34% for patients with multiple myeloma to 90% for patients with testicular cancer. Mortality rates moved closer to rates observed in the age- and sex-matched Australian general population over time but remained significantly increased 11 or more years from HSCT (standardized mortality ratio, 5.9). Although the proportion of deaths from nonrelapse causes increased over time, relapse remained the most frequent cause of death for all diagnoses, 10 or more years after autologous HSCT. Our findings show that prevention of disease recurrence remains 1 of the greatest challenges for autologous HSCT recipients, while the increasing rates of nonrelapse deaths due to the emergence of second cancers, circulatory diseases, and respiratory diseases highlight the long-term health issues faced by adult survivors of autologous HSCT. PMID:24631736

  18. Susceptibility to Inhaled Flame-Generated Ultrafine Soot in Neonatal and Adult Rat Lungs

    PubMed Central

    Chan, Jackie K. W.; Fanucchi, Michelle V.; Anderson, Donald S.; Abid, Aamir D.; Wallis, Christopher D.; Dickinson, Dale A.; Kumfer, Benjamin M.; Kennedy, Ian M.; Wexler, Anthony S.; Van Winkle, Laura S.

    2011-01-01

    Over a quarter of the U.S. population is exposed to harmful levels of airborne particulate matter (PM) pollution, which has been linked to development and exacerbation of respiratory diseases leading to morbidity and mortality, especially in susceptible populations. Young children are especially susceptible to PM and can experience altered anatomic, physiologic, and biological responses. Current studies of ambient PM are confounded by the complex mixture of soot, metals, allergens, and organics present in the complex mixture as well as seasonal and temporal variance. We have developed a laboratory-based PM devoid of metals and allergens that can be replicated to study health effects of specific PM components in animal models. We exposed 7-day-old postnatal and adult rats to a single 6-h exposure of fuel-rich ultrafine premixed flame particles (PFPs) or filtered air. These particles are high in polycyclic aromatic hydrocarbons content. Pulmonary cytotoxicity, gene, and protein expression were evaluated at 2 and 24 h postexposure. Neonates were more susceptible to PFP, exhibiting increased lactate dehydrogenase activity in bronchoalveolar lavage fluid and ethidium homodimer-1 cellular staining in the lung in situ as an index of cytotoxicity. Basal gene expression between neonates and adults differed for a significant number of antioxidant, oxidative stress, and proliferation genes and was further altered by PFP exposure. PFP diminishes proliferation marker PCNA gene and protein expression in neonates but not adults. We conclude that neonates have an impaired ability to respond to environmental exposures that increases lung cytotoxicity and results in enhanced susceptibility to PFP, which may lead to abnormal airway growth. PMID:21914721

  19. Airborne particles of the california central valley alter the lungs of healthy adult rats.

    PubMed Central

    Smith, Kevin R; Kim, Seongheon; Recendez, Julian J; Teague, Stephen V; Ménache, Margaret G; Grubbs, David E; Sioutas, Constantinos; Pinkerton, Kent E

    2003-01-01

    Epidemiologic studies have shown that airborne particulate matter (PM) with a mass median aerodynamic diameter < 10 microm (PM10) is associated with an increase in respiratory-related disease. However, there is a growing consensus that particles < 2.5 microm (PM2.5), including many in the ultrafine (< 0.1 microm) size range, may elicit greater adverse effects. PM is a complex mixture of organic and inorganic compounds; however, those components or properties responsible for biologic effects on the respiratory system have yet to be determined. During the fall and winter of 2000-2001, healthy adult Sprague-Dawley rats were exposed in six separate experiments to filtered air or combined fine (PM2.5) and ultrafine portions of ambient PM in Fresno, California, enhanced approximately 20-fold above outdoor levels. The intent of these studies was to determine if concentrated fine/ultrafine fractions of PM are cytotoxic and/or proinflammatory in the lungs of healthy adult rats. Exposures were for 4 hr/day for 3 consecutive days. The mean mass concentration of particles ranged from 190 to 847 microg/m3. PM was enriched primarily with ammonium nitrate, organic and elemental carbon, and metals. Viability of cells recovered by bronchoalveolar lavage (BAL) from rats exposed to concentrated PM was significantly decreased during 4 of 6 weeks, compared with rats exposed to filtered air (p< 0.05). Total numbers of BAL cells were increased during 1 week, and neutrophil numbers were increased during 2 weeks. These observations strongly suggest exposure to enhanced concentrations of ambient fine/ultrafine particles in Fresno is associated with mild, but significant, cellular effects in the lungs of healthy adult rats. PMID:12782490

  20. Health status in young adults two decades after pediatric liver transplantation.

    PubMed

    Mohammad, S; Hormaza, L; Neighbors, K; Boone, P; Tierney, M; Azzam, R K; Butt, Z; Alonso, E M

    2012-06-01

    We conducted a cross-sectional study of patients who underwent pediatric liver transplant (LT) between 1988 and 1992 to evaluate long-term health status. Survivors completed socio-demographic, medical and Health-Related Quality of Life (HRQOL) surveys by mail including the SF-36v2, PedsQL™4.0 Generic Core Scale, PedsQL™ Cognitive Functioning Scale and PedsQL™3.0 Transplant Module. SF-36 scores were converted to SF6D-based utilities and risk factors for lower outcomes were assessed. Eighty-five of 171 patients had survived. Fifty-six were contacted with a response rate of 66%. Median age at LT was 0.86 years (IQR 0.58-3.0) and 64.3% had biliary atresia. Mean age at survey was 23.0 ± 4.4 years: 62% attended college, 68% lived with parents and 80% of those over 23 were employed. Patient health utilities were lower than norms (0.75 ± 0.12 vs. 0.82 ± 0.18, p < 0.01) and correlated with unemployment (p < 0.042), hospitalizations (p < 0.005) and lower education level (p < 0.016). Lower PedsQL™3.0 Transplant Module and PedsQL™ 4.0 Generic Core Scale scores correlated with unemployment (p = 0.006, p = 0.009) and hospitalizations (p = 0.006, p = 0.02). Pediatric transplant recipients who survive to adulthood have lower physical HRQOL, measurable transplant-related disability and lower health utility. Transplantation is life saving; however, physical and psychological sequelae continue to affect health status up to two decades later.

  1. Molecular Characterization of a Voriconazole-Resistant, Posaconazole-Susceptible Aspergillus fumigatus Isolate in a Lung Transplant Recipient in the United States

    PubMed Central

    Vazquez, Jose A.

    2015-01-01

    Molecular characterization of cyp51A from the azole-resistant Aspergillus fumigatus isolate 50593 from a lung transplant patient showed Y121F/T289A changes coupled with a 46-bp tandem repeat (TR46) on the promoter, whereas cyp51A from the pretherapy isolate, A. fumigatus 47381, showed no changes. This is the first reported case of A. fumigatus azole resistance due to Y121F/T289A/TR46 in the United States, suggesting that multiple mutational alterations of cyp51A resulting in high-level azole resistance could occur during prolonged antifungal therapy. PMID:26574014

  2. Chronic obstructive pulmonary disease - adults - discharge

    MedlinePlus

    ... adults - discharge; Chronic obstructive airways disease - adults - discharge; Chronic obstructive lung disease - adults - discharge; Chronic bronchitis - adults - discharge; Emphysema - adults - ...

  3. ARSENIC AND SKIN LESION STATUS IN RELATION TO MALIGNANT AND NON-MALIGNANT LUNG DISEASE MORTALITY IN BANGLADESHI ADULTS

    PubMed Central

    Argos, Maria; Parvez, Faruque; Rahman, Mahfuzar; Rakibuz-Zaman, Muhammad; Ahmed, Alauddin; Hore, Samar Kumar; Islam, Tariqul; Chen, Yu; Pierce, Brandon L.; Slavkovich, Vesna; Olopade, Christopher; Yunus, Muhammad; Baron, John A.; Graziano, Joseph H.; Ahsan, Habibul

    2015-01-01

    Background Chronic arsenic exposure through drinking water is a public health problem affecting millions of people worldwide, including at least 30 million in Bangladesh. We prospectively investigated the associations of arsenic exposure and arsenical skin lesion status with lung disease mortality in Bangladeshi adults. Methods Data are from a population-based sample of 26,043 adults, with an average of 8.5 years of follow-up (220,157 total person-years). There were 156 non-malignant lung disease deaths and 90 lung cancer deaths ascertained through October 2013. We used Cox proportional hazards models to estimate adjusted hazard ratios and 95% confidence intervals (CIs) for lung disease mortality. Results Creatinine-adjusted urinary total arsenic was associated with non-malignant lung disease mortality, with persons in the highest tertile of exposure having a 75% increased risk for mortality (95% CI=1.15–2.66) compared with those in the lowest tertile of exposure. Persons with arsenical skin lesions were at increased risk of lung cancer mortality (hazard ratio=4.53 [95% CI=2.82–7.29]) compared with those without skin lesions. Conclusions This prospective investigation of lung disease mortality, utilizing individual-level arsenic measures and skin lesion status, confirms a deleterious effect of ingested arsenic on mortality from lung disease. Further investigations should evaluate effects on the incidence of specific lung diseases, more fully characterize dose-response, and evaluate screening and biomedical interventions to prevent premature death among arsenic-exposed populations, particularly among those who may be most susceptible to arsenic toxicity. PMID:24802365

  4. CRISPLD2 (LGL1) inhibits proinflammatory mediators in human fetal, adult, and COPD lung fibroblasts and epithelial cells.

    PubMed

    Zhang, Hui; Kho, Alvin T; Wu, Qing; Halayko, Andrew J; Limbert Rempel, Karen; Chase, Robert P; Sweezey, Neil B; Weiss, Scott T; Kaplan, Feige

    2016-09-01

    Chronic lung disease of prematurity/bronchopulmonary dysplasia (BPD) is the leading cause of perinatal morbidity in developed countries. Inflammation is a prominent finding. Currently available interventions have associated toxicities and limited efficacy. While BPD often resolves in childhood, survivors of preterm birth are at risk for acquired respiratory disease in early life and are more likely to develop chronic obstructive pulmonary disease (COPD) in adulthood. We previously cloned Crispld2 (Lgl1), a glucocorticoid-regulated mesenchymal secretory protein that modulates lung branching and alveogenesis through mesenchymal-epithelial interactions. Absence of Crispld2 is embryonic lethal. Heterozygous Crispld2+/- mice display features of BPD, including distal airspace enlargement, disruption of elastin, and neonatal lung inflammation. CRISPLD2 also plays a role in human fetal lung fibroblast cell expansion, migration, and mesenchymal-epithelial signaling. This study assessed the effects of endogenous and exogenous CRISPLD2 on expression of proinflammatory mediators in human fetal and adult (normal and COPD) lung fibroblasts and epithelial cells. CRISPLD2 expression was upregulated in a lipopolysaccharide (LPS)-induced human fetal lung fibroblast line (MRC5). LPS-induced upregulation of the proinflammatory cytokines IL-8 and CCL2 was exacerbated in MRC5-CRISPLD2(knockdown) cells. siRNA suppression of endogenous CRISPLD2 in adult lung fibroblasts (HLFs) led to augmented expression of IL-8, IL-6, CCL2. LPS-stimulated expression of proinflammatory mediators by human lung epithelial HAEo- cells was attenuated by purified secretory CRISPLD2. RNA sequencing results from HLF-CRISPLD2(knockdown) suggest roles for CRISPLD2 in extracellular matrix and in inflammation. Our data suggest that suppression of CRISPLD2 increases the risk of lung inflammation in early life and adulthood. PMID:27597766

  5. Pre- and Post-Transplant Quantification of Measurable (“Minimal”) Residual Disease via Multiparameter Flow Cytometry in Adult Acute Myeloid Leukemia

    PubMed Central

    Zhou, Yi; Othus, Megan; Araki, Daisuke; Wood, Brent L.; Radich, Jerald P.; Halpern, Anna B.; Mielcarek, Marco; Estey, Elihu H.; Appelbaum, Frederick R.; Walter, Roland B.

    2016-01-01

    Measurable (“minimal”) residual disease (MRD) before or after hematopoietic cell transplantation (HCT) identifies adults with AML at risk of poor outcomes. Here, we studied whether peri-transplant MRD dynamics can refine risk assessment. We analyzed 279 adults receiving myeloablative allogeneic HCT in first or second remission who survived at least 35 days and underwent 10-color multiparametric flow cytometry (MFC) analyses of marrow aspirates before and 28±7 days after transplantation. MFC-detectable MRD before (n=63) or after (n=16) transplantation identified patients with high relapse risk and poor survival. Forty-nine patients cleared MRD with HCT conditioning, whereas 2 patients developed new evidence of disease. The 214 MRDneg/MRDneg patients had excellent outcomes, whereas both MRDneg/MRDpos patients died within 100 days following transplantation. For patients with pre-HCT MRD, outcomes were poor regardless of post-HCT MRD status, although survival beyond 3 years was observed among the 58 patients with decreasing but not the 7 patients with increasing peri-HCT MRD levels. In multivariable models, pre-HCT but not post-HCT MRD was independently associated with OS and RR. These data indicate that MRDpos patients before transplantation have a high relapse risk regardless of whether or not they clear MFC-detectable disease with conditioning and should be considered for pre-emptive therapeutic strategies. PMID:27012865

  6. Pneumonia in Childhood and Impaired Lung Function in Adults: A Longitudinal Study

    PubMed Central

    Chan, Johnny Y.C.; Stern, Debra A.; Guerra, Stefano; Wright, Anne L.; Morgan, Wayne J.

    2015-01-01

    BACKGROUND: Diminished lung function and increased prevalence of asthma have been reported in children with a history of early lower respiratory illnesses (LRIs), including pneumonia. Whether these associations persist up to adulthood has not been established. METHODS: As part of the prospective Tucson Children's Respiratory Study, LRIs during the first 3 years of life were ascertained by pediatricians. Spirometry was performed at ages 11, 16, 22, and 26 years. The occurrence of asthma/wheeze during the previous year was ascertained at ages 11, 13, 16, 18, 22, 24, 26, and 29 years. Longitudinal random effects models and generalized estimating equations were used to assess the relation of LRIs to lung function and asthma. RESULTS: Compared with participants without early-life LRIs, those with pneumonia had the most severe subsequent lung function impairment, with mean ± SE deficits of −3.9% ± 0.9% (P < .001) and −2.5% ± 0.8% (P = .001) for pre- and post-bronchodilator FEV1:FVC ratio from age 11 to 26 years, respectively. Pneumonia was associated with increased risk for asthma (odds ratio [OR]: 1.95; 95% confidence interval [CI]: 1.11–3.44) and wheeze (OR: 1.94; 95% CI: 1.28–2.95) over the same age range. Early non-pneumonia LRIs were associated with mildly impaired pre-bronchodilator FEV1 (−62.8 ± 27.9mL, P = .024) and FEV1:FVC ratio (−1.1 ± 0.5%, P = .018), and wheeze (OR: 1.37; 95% CI: 1.09–1.72). CONCLUSIONS: Early pneumonia is associated with asthma and impaired airway function, which is partially reversible with bronchodilators and persists into adulthood. Early pneumonia may be a major risk factor for adult chronic obstructive pulmonary disease. PMID:25733757

  7. [Ultrastructural changes in the lung in acute adult respiratory distress syndrome].

    PubMed

    Szemenyei, K; Széll, K; Kádas, L

    1980-04-01

    Morphological alterations of the lung in respiratory distress syndrome of adults (ARDS) were analyzed in 10 cases with traumatic-and septic shock, laryngitis subglottica descendens and bronchopneumonia. For the better understanding of the pathomechanism of the disease in addition to the standard methods, first of all ultrastructural alterations were studied. Two phases of the morphologic alterations could be distinguished, the phase of the destruction and the phase of the repair. These two processes are not sharply distinguishable. Genesis of the characteristic histological alterations (damage to the epithelial and endothelial cells, formation of hyaline membranes, microcoagulation, proliferation of the type II pneumocytes and fibroblasts, fibrosis) is discussed, with regard to the data of the literature.

  8. Neonatal pneumococcal colonisation caused by Influenza A infection alters lung function in adult mice

    PubMed Central

    FitzPatrick, Meaghan; Royce, Simon G.; Langenbach, Shenna; McQualter, Jonathan; Reading, Patrick C.; Wijburg, Odilia; Anderson, Gary P.; Stewart, Alastair; Bourke, Jane; Bozinovski, Steven

    2016-01-01

    There is emerging epidemiological data to suggest that upper respiratory tract bacterial colonisation in infancy may increase the risk of developing respiratory dysfunction later in life, and respiratory viruses are known to precipitate persistent colonisation. This study utilized a neonatal mouse model of Streptococcus pneumonia (SP) and influenza A virus (IAV) co-infection, where bronchoalveolar leukocyte infiltration had resolved by adulthood. Only co-infection resulted in persistent nasopharyngeal colonisation over 40 days and a significant increase in airway resistance in response to in vivo methacholine challenge. A significant increase in hysteresivity was also observed in IAV and co-infected mice, consistent with ventilatory heterogeneity and structural changes in the adult lung. Airway hyper-responsiveness was not associated with a detectable increase in goblet cell transdifferentiation, peribronchial smooth muscle bulk or collagen deposition in regions surrounding the airways. Increased reactivity was not observed in precision cut lung slices challenged with methacholine in vitro. Histologically, the airway epithelium appeared normal and expression of epithelial integrity markers (ZO-1, occludin-1 and E-cadherin) were not altered. In summary, neonatal co-infection led to persistent nasopharyngeal colonisation and increased airway responsiveness that was not associated with detectable smooth muscle or mucosal epithelial abnormalities, however increased hysteresivity may reflect ventilation heterogeneity. PMID:26940954

  9. Equal overall rejection rate in pre-transplant flow-cytometric cross-match negative and positive adult recipients in liver transplantation.

    PubMed

    Matinlauri, Irma H; Höckerstedt, Krister A; Isoniemi, Helena M

    2005-10-01

    T cell IgG flow-cytometric cross-matches (FCXM) using 48 stored pre-transplant patient serum samples and 40 stored serum samples collected 3 wk after liver transplantation and frozen spleen cells of cadaveric donors in 48 consecutive liver transplantations were performed retrospectively. T cell IgG FCXM using pre-transplant serum samples was compared with 46 complement-dependent lymphocytotoxic cross-matches (CDCXM) performed at the time of transplantation. Clinical relevance of these tests was evaluated in relation to acute rejection, 1-, 3- and 5-yr graft and patient survival. The incidence of positive FCXM was 33% (16 of 48) and 13% (six of 46) by CDCXM. The median time of acute rejection was 29 d after transplantation in FCXM positive group (range 13-101 d) and 22 d in FCXM negative group (range 7-157 d, NS). Rejection rate was similar in 16 pre-transplant FCXM positive patients (eight of 16, 50%) compared with six pre-transplant CDCXM positive patients (three of six, 50%; NS). Recipients having graft rejection tended to be more often pre-transplant FCXM positive (eight of 21, 38%) than CDCXM positive (three of 21, 14%), but the difference was not significant (p > 0.1). No difference was found in the positive predictive value in relation to acute rejection between positive FCXM and CDCXM (69% vs. 50%; NS). Furthermore there was no correlation between post-transplant positive FCXM and acute rejection. No difference was found between pre-transplant T cell IgG FCXM positive and negative recipients in relation to graft or patient survival. Our findings are supportive for little risk associated with preformed donor-specific antibodies in liver transplantation.

  10. Double lumen bi-cava cannula for veno-venous extracorporeal membrane oxygenation as bridge to lung transplantation in non-intubated patient.

    PubMed

    Reeb, Jérémie; Falcoz, Pierre-Emmanuel; Santelmo, Nicola; Massard, Gilbert

    2012-01-01

    Extracorporeal membrane oxygenation (ECMO) is used for refractory respiratory failure. Normally, ECMO is implanted in intubated patients as a last resort. We report the case of a non-intubated patient who benefited from veno-venous (VV) ECMO. A 35-year old cystic fibrosis man presented a severe respiratory decompensation with refractory hypercapnia. We opted for an ECMO instead of mechanical ventilation (MV). We implanted a double lumen bi-cava cannula (DLC) (Avalon Elite(TM)) in the right jugular vein. Before ECMO implantation, the patient presented refractory respiratory failure (pH = 7.1, PaO(2) = 83 mmHg, PaCO(2 )= 103 mmHg). We proposed that the patient be placed on the high emergency lung transplantation waiting list after failure to wean him from ECMO. This registration was effective 10 days after ECMO implantation. The patient was grafted the next day. Under ECMO, mean PaO(2), PaCO(2) and TCA were 80.6 ± 14.2, 53.8 ± 6.4 mmHg and 56.2 ± 9.7 s, respectively. The patient could eat, drink, talk and practice chest physiotherapy. The evolution was uneventful under ECMO. Weaning from ECMO was done in the operating theatre after transplantation. VV ECMO with DLC is safe and feasible in non-intubated patients. It avoids potential complications of MV, and allows respiratory assistance as bridge to transplantation. PMID:22108944

  11. Intrahepatic transplantation of CD34+ cord blood stem cells into newborn and adult NOD/SCID mice induce differential organ engraftment.

    PubMed

    Wulf-Goldenberg, Annika; Keil, Marlen; Fichtner, Iduna; Eckert, Klaus

    2012-04-01

    In vivo studies concerning the function of human hematopoietic stem cells (HSC) are limited by relatively low levels of engraftment and the failure of the engrafted HSC preparations to differentiate into functional immune cells after systemic application. In the present paper we describe the effect of intrahepatically transplanted CD34(+) cells from cord blood into the liver of newborn or adult NOD/SCID mice on organ engraftment and differentiation. Analyzing the short and long term time dependency of human cell recruitment into mouse organs after cell transplantation in the liver of newborn and adult NOD/SCID mice by RT-PCR and FACS analysis, a significantly high engraftment was found after transplantation into liver of newborn NOD/SCID mice compared to adult mice, with the highest level of 35% human cells in bone marrow and 4.9% human cells in spleen at day 70. These human cells showed CD19 B-cell, CD34 and CD38 hematopoietic and CD33 myeloid cell differentiation, but lacked any T-cell differentiation. HSC transplantation into liver of adult NOD/SCID mice resulted in minor recruitment of human cells from mouse liver to other mouse organs. The results indicate the usefulness of the intrahepatic application route into the liver of newborn NOD/SCID mice for the investigation of hematopoietic differentiation potential of CD34(+) cord blood stem cell preparations.

  12. Informed consent and decision-making about adult-to-adult living donor liver transplantation: a systematic review of empirical research.

    PubMed

    Gordon, Elisa J; Daud, Amna; Caicedo, Juan Carlos; Cameron, Kenzie A; Jay, Colleen; Fryer, Jonathan; Beauvais, Nicole; Skaro, Anton; Baker, Talia

    2011-12-27

    Adult-to-adult living donor liver transplantation (LDLT) is a complex procedure that poses serious health risks to and provides no direct health benefit for the donor. Because of this uneven risk-benefit ratio, ensuring donor autonomy through informed consent is critical. To assess the current knowledge pertaining to informed consent for LDLT, we conducted a systematic review of the empirical literature on donors' decision-making process, comprehension about risks and outcomes, and information needs for LDLT. Of the 1423 identified articles, 24 met final review criteria, representing the perspective of approximately 2789 potential and actual donors. As donors' decisions to donate often occur before evaluation, they often make uninformed decisions. The review found that 88% to 95% of donors reported understanding information clinicians disclosed about risks and benefits. However, donors reported unmet information needs, knowledge gaps regarding risks, and unanticipated complications. Few donors reported feeling pressure to donate. Most studies were limited by cultural differences, small sample sizes, inconsistent measures, and poor methodological approaches. This systematic review suggests that informed consent for LDLT is sub-optimal as donors do not adequately appreciate disclosed information during the informed consent process, despite United Network for Organ Sharing/CMS regulations requiring formal psychological evaluation of donor candidates. Interventions are needed to improve donor-clinician communication during the LDLT informed consent process such as through the use of comprehension assessment tools and e-health educational tools that leverage adult learning theory to effectively convey LDLT outcome data. PMID:22143436

  13. Developmental changes of cytochrome P450 dependent monooxygenase functions after transplantation of fetal liver tissue suspension into spleens of adult syngenic rats.

    PubMed

    Lupp, A; Trautmann, A K; Krausse, T; Klinger, W

    1998-06-01

    Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic Fisher 344 inbred rats. Animals were sacrificed at 3 days, 1, 2, 4 weeks, and 2, 4 and 6 months after transplantation and cytochrome P450 (P450) dependent monooxygenase functions in spleen and liver 9000 g supernatants were assessed by measuring three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; mainly 1A), ethoxycoumarin O-deethylation (ECOD; predominantly 1A, 2A, 2B) and ethylmorphine N-demethylation (END; mainly 3A). Values of transplant recipients were compared to those of sham operated and age matched control rats. Spleen weights were significantly higher in transplanted rats, compared to controls or sham operated animals, but there was no influence of the transplants within the spleens on liver weights. With fetal livers at the 21st day of gestation, the day of transplantation, a weak EROD and ECOD, but no END activity was seen. Spleens of controls or sham operated animals displayed nearly no P450 mediated monooxygenase functions. In the explant containing spleens a significant and increasing EROD activity was found from 4 weeks after surgery on and an ECOD activity already 2 weeks after transplantation. END was only slightly enhanced at 6 months after surgery. The livers of all three groups of rats displayed normal EROD, ECOD and END activities. Transplantation of fetal liver tissue suspensions into the spleens did not influence the P450 dependent monooxygenase functions within the livers of the animals. From these results it can be concluded that intrasplenically transplanted liver cells originating from syngenic fetal liver tissue suspensions proliferate and differentiate within the host organs. They display P450 dependent monooxygenase functions with some developmental changes during the observed time period of 6 months.

  14. Significant Improvements in the Practice Patterns of Adult Related Donor Care in US Transplantation Centers.

    PubMed

    Anthias, Chloe; Shaw, Bronwen E; Kiefer, Deidre M; Liesveld, Jane L; Yared, Jean; Kamble, Rammurti T; D'Souza, Anita; Hematti, Peiman; Seftel, Matthew D; Norkin, Maxim; DeFilipp, Zachariah; Kasow, Kimberly A; Abidi, Muneer H; Savani, Bipin N; Shah, Nirali N; Anderlini, Paolo; Diaz, Miguel A; Malone, Adriana K; Halter, Joerg P; Lazarus, Hillard M; Logan, Brent R; Switzer, Galen E; Pulsipher, Michael A; Confer, Dennis L; O'Donnell, Paul V

    2016-03-01

    Recent investigations have found a higher incidence of adverse events associated with hematopoietic cell donation in related donors (RDs) who have morbidities that if present in an unrelated donor (UD) would preclude donation. In the UD setting, regulatory standards ensure independent assessment of donors, one of several crucial measures to safeguard donor health and safety. A survey conducted by the Center for International Blood and Marrow Transplant Research (CIBMTR) Donor Health and Safety Working Committee in 2007 reported a potential conflict of interest in >70% of US centers, where physicians had simultaneous responsibility for RDs and their recipients. Consequently, several international organizations have endeavored to improve practice through regulations and consensus recommendations. We hypothesized that the changes in the 2012 Foundation for the Accreditation of Cellular Therapy and the Joint Accreditation Committee-International Society for Cellular Therapy and European Society for Blood and Marrow Transplantation standards resulting from the CIBMTR study would have significantly impacted practice. Accordingly, we conducted a follow-up survey of US transplantation centers to assess practice changes since 2007, and to investigate additional areas where RD care was predicted to differ from UD care. A total of 73 centers (53%), performing 79% of RD transplantations in the United States, responded. Significant improvements were observed since the earlier survey; 62% centers now ensure separation of RD and recipient care (P < .0001). This study identifies several areas where RD management does not meet international donor care standards, however. Particular concerns include counseling and assessment of donors before HLA typing, with 61% centers first disclosing donor HLA results to an individual other than the donor, the use of unlicensed mobilization agents, and the absence of long-term donor follow-up. Recommendations for improvement are made.

  15. Transplantation of fetal liver tissue suspension into the spleens of adult syngenic rats: inducibility of cytochrome P450 dependent monooxygenase functions by beta-naphthoflavone, phenobarbital and dexamethasone.

    PubMed

    Lupp, A; Lau, K; Trautmann, A K; Krausse, T; Klinger, W

    1999-01-01

    In the present study the effects of beta-naphthoflavone (BNF), phenobarbital (PB) and dexamethasone (DEX) on cytochrome P450 (P450) dependent monooxygenase functions were investigated in intrasplenic liver cell explants in comparison to adult liver. Fetal liver tissue suspensions were transplanted into the spleens of 60-90 days old adult male syngenic Fisher 344 inbred rats. 2, 4 or 6 months after surgery, transplant recipients and age matched controls were orally treated with BNF (1x50 mg/kg body weight (b.wt.)), PB (1x50 mg/kg b.wt.), DEX (for 3 days 4 mg/kg b.wt. per day), or the respective solvents (dimethylsulfoxide or 0.9% NaCl). The animals were sacrificed 24 (BNF, DEX) or 48 (PB) hours after the last treatment. P450 mediated monooxygenase functions were measured in spleen and liver 9000 g supernatants by three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; 1A), ethoxycoumarin O-deethylation (ECOD; 1A, 2A, 2B), and ethylmorphine N-demethylation (END; 3A). Spleen weights were significantly higher in transplanted rats, compared to controls, at all three time points after surgery. Induction with PB or DEX, and in some cases also with BNF, lead to a significant increase in liver weights of transplant recipients and control rats independent of the time after transplantation. In contrast, there was no influence on spleen weights due to BNF or PB. At all time points after surgery, with DEX a marked decrease in body weights, weights of adrenal glands and of lymphatic organs like thymus glands and spleens was observed, with the weights of the transplant containing spleens being still higher in comparison to control organs. Spleens of control animals displayed nearly no P450 mediated monooxygenase functions neither without nor with induction. After transplantation, however, significant EROD and ECOD, but hardly any END activities were seen in the host organs at all three time points after surgery. In transplant containing spleens

  16. Advances in conditioning regimens for older adults undergoing allogeneic stem cell transplantation to treat hematologic malignancies.

    PubMed

    William, Basem M; de Lima, Marcos

    2013-06-01

    Allogeneic stem cell transplantation (SCT) is a potentially curative treatment for patients with hematological malignancies. These diseases, however, have their peak incidence in the sixth to eighth decades of life. Historically, elderly patients have been considered unsuitable candidates for SCT because of high treatment-related mortality (TRM). Over the past 15 years, the use of reduced-intensity conditioning (RIC) regimens before SCT has allowed patients in the sixth and seventh decades of life to be routinely transplanted. Despite major differences among transplant centers in the intensity and composition of the conditioning regimen and immunosuppression, choice of graft source, postgraft immunomodulation, and supportive care, there has been a dramatic decrease in TRM, allowing safer delivery of SCT. Major obstacles to SCT in elderly patients include donor availability, graft-versus-host disease, delayed immune recovery, multiple comorbidities, and chemo refractoriness. Here we review the current results of SCT in elderly patients, focusing on the role of RIC, and using myeloid diseases as the model for discussion.

  17. Effects of the CYP3A4*1B Genetic Polymorphism on the Pharmacokinetics of Tacrolimus in Adult Renal Transplant Recipients: A Meta-Analysis

    PubMed Central

    Shi, Wei-Long; Tang, Hui-Lin; Zhai, Suo-Di

    2015-01-01

    Background and Objective The association between the CYP3A4*1B single nucleotide polymorphism (SNP) and tacrolimus pharmacokinetics in different studies is controversial. Therefore, a meta-analysis was employed to evaluate the correlation between the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics at different post-transplantation times in adult renal transplant recipients. Methods Studies evaluating the CYP3A4*1B genetic polymorphism and tacrolimus pharmacokinetics were retrieved through a systematical search of Embase, PubMed, the Cochrane Library, ClinicalTrials.gov and three Chinese literature databases (up to Sept. 2014). The pharmacokinetic parameters (weight-adjusted tacrolimus daily dose and tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio) were extracted, and the meta-analysis was performed using Stata 12.1. Results Seven studies (involving 1182 adult renal transplant recipients) were included in this meta-analysis. For the weight-adjusted tacrolimus daily dose, in all included renal transplant recipients (European & Indian populations), CYP3A4*1/*1 recipients required a significantly lower weight-adjusted tacrolimus daily dose than did CYP3A4*1B carriers at 7 days (WMD -0.048; 95% CI -0.083 ~ -0.014), 6 months (WMD -0.058; 95% CI -0.081 ~ -0.036) and 12 months (WMD - 0.061; 95% CI -0.096 ~ -0.027) post-transplantation. In light of the heterogeneity, the analysis was repeated after removing the only study in an Indian population, and CYP3A4*1/*1 European recipients (mostly Caucasian) required a lower weight-adjusted tacrolimus daily dose within the first year post-transplantation. The tacrolimus trough concentration/weight-adjusted tacrolimus daily dose ratio (C0/Dose ratio) was significantly higher in CYP3A4*1/*1 recipients than in CYP3A4*1B carriers at 6 months (WMD 52.588; 95% CI 22.387 ~ 82.789) and 12 months (WMD 62.219; 95% CI 14.218 ~ 110.221) post-transplantation. When the only study in an Indian population

  18. Urinary Dialkyl Phosphate Concentrations and Lung Function Parameters in Adolescents and Adults: Results from the Canadian Health Measures Survey

    PubMed Central

    Ye, Ming; Beach, Jeremy; Martin, Jonathan W.; Senthilselvan, Ambikaipakan

    2015-01-01

    Background: Epidemiological studies have reported associations between lung function parameters and organophosphate (OP) pesticide exposures in agricultural occupations, but to our knowledge associations have not been evaluated in general populations. Objectives: We examined associations between OP metabolite dialkyl phosphates (DAPs) and lung function using data from the Canadian Health Measures Survey (CHMS) Cycle 1. Methods: Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEV1/FVC ratio, and forced expiratory flow between 25% and 75% of FVC (FEF25%–75%) were measured for 4,446 CHMS participants. Urinary concentrations of six DAP metabolites (DMP, DMTP, DMDTP, DEP, DETP, and DEDTP), smoking status, and other predictors of lung function were also measured in the CHMS-Cycle 1. Multiple linear regression analyses were used to examine the relationship between total DAP concentrations (ΣDAPs) and lung function in adolescents (12–19 years) and adults (20–79 years). Results: In adults, estimates from multiple regression analyses suggested that a 1-unit increase on natural logarithmic scale (171% increase on the original scale) in the creatinine-corrected urinary concentration (nanomoles per gram creatinine) of ΣDAP was associated with a 32.6-mL (95% CI: –57.2, –8.1) reduction in FVC, 32.6-mL (95% CI: –59.0, –6.3) reduction in FEV1, 0.2% (95% CI: –0.6, 0.2) reduction in FEV1/FVC ratio, and 53.1-mL/sec (95% CI: –113.9, 7.7) reduction in FEF25%–75%. In adolescents, associations between ΣDAP and FEV1 were closer to the null and positive for FVC, whereas associations with FEV1/FVC and FEF25%–75% were negative, as in adults. However, none of the associations were significant in adolescents. Conclusions: The negative association between ΣDAP and lung function in adult participants suggests a detrimental effect of OP pesticides on lung function in the adult general population. Further studies using prospective designs are

  19. Second Cancer Risk and Late Mortality in Adult Australians Receiving Allogeneic Hematopoietic Stem Cell Transplantation: A Population-Based Cohort Study.

    PubMed

    Vajdic, Claire M; Mayson, Eleni; Dodds, Anthony J; O'Brien, Tracey; Wilcox, Leonie; Nivison-Smith, Ian; Le Marsney, Renate; Daniels, Benjamin; Ashton, Lesley J

    2016-05-01

    We quantified the risk of second cancer and late mortality in a population-based Australian cohort of 3273 adult (≥15 years) allogeneic hematopoietic stem cell transplant recipients (1992 to 2007). Most recipients received nonradiation-based conditioning and a peripheral blood graft from a matched related donor. Using record linkage with death and cancer registries, 79 second cancers were identified a median of 3.5 years after transplantation. The competing-risk adjusted cumulative incidence of second cancers was 3.35% (95% CI, 2.59 to 4.24) at 10 years, and the cancer risk relative to the matched general population was 2.10 (95% CI, 1.65 to 2.56). We observed an excess risk of melanoma and lip, tongue, esophagus, and soft tissue cancers. Cancer risk relative to the general population was elevated for those transplanted for lymphoma, some leukemia subtypes, and severe aplastic anemia, recipients who developed chronic graft-versus-host disease (cGVHD) and irrespective of radiation-based conditioning or stem cell source. In those alive 2 years after transplantation (n = 1463), the cumulative incidence of late mortality was 22.2% (95% CI, 19.7 to 24.9) at 10 years, and the risk of death relative to the matched general population was 13.8 (95% CI, 12.2 to 15.6). In multivariable modeling, risk of late death was reduced for females compared with males and those transplanted for chronic myeloid leukemia compared with acute myeloid leukemia; risk was increased for recipients with discordant sex donors, cGVHD, those undergoing second transplants, and disease relapse. Adults undergoing allogeneic transplantation have unique cancer and mortality risk profiles that continue to warrant prevention and surveillance activities targeted at high-risk subgroups.

  20. Antibiotic Treatment Response of Chronic Lung Diseases of Adult Sheep in the United Kingdom Based upon Ultrasonographic Findings</