WorldWideScience

Sample records for lung transplant rejection

  1. Endothelial cell chimerism associated with graft rejection after human lung transplantation.

    OpenAIRE

    Ratajczak , Philippe; Murata , Hideyuki; Meignin , Véronique; Groussard , Odile; Fournier , Michel; Socié , Gérard; Mal , Hervé; Janin , Anne

    2008-01-01

    International audience; Endotheliitis is a major sign of graft rejection. Recipient-derived endothelial cells found in two series of liver and kidney transplants were related to graft rejection. Here, we assessed the presence and the number of chimeric endothelial cells in lung transplants, and their relation with graft rejection. In six males grafted with female lungs out of 193 lung transplantations, endothelial chimerism was studied by combined XY-fluorescent in situ hybridization with CD3...

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

    Directory of Open Access Journals (Sweden)

    Priscila Cilene León Bueno de Camargo

    2014-08-01

    Full Text Available 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.

  3. CMV driven CD8(+) T-cell activation is associated with acute rejection in lung transplantation.

    Science.gov (United States)

    Roux, Antoine; Mourin, Gisèle; Fastenackels, Solène; Almeida, Jorge R; Iglesias, Maria Candela; Boyd, Anders; Gostick, Emma; Larsen, Martin; Price, David A; Sacre, Karim; Douek, Daniel C; Autran, Brigitte; Picard, Clément; Miranda, Sandra de; Sauce, Delphine; Stern, Marc; Appay, Victor

    2013-07-01

    Lung transplantation is the definitive treatment for terminal respiratory disease, but the associated mortality rate is high. Acute rejection of the transplanted lung is a key determinant of adverse prognosis. Furthermore, an epidemiological relationship has been established between the occurrence of acute lung rejection and cytomegalovirus infection. However, the reasons for this association remain unclear. Here, we performed a longitudinal characterization of CMV-specific T-cell responses and immune activation status in the peripheral blood and bronchoalveolar lavage fluid of forty-four lung transplant patients. Acute rejection was associated with high levels of cellular activation in the periphery, reflecting strong CMV-specific CD8(+) T-cell activity post-transplant. Peripheral and lung CMV-specific CD8(+) T-cell responses were very similar, and related to the presence of CMV in the transplanted organ. These findings support that activated CMV-specific CD8(+) T-cells in the lung may play a role in promoting acute rejection. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Esophageal motor disorders are frequent during pre and post lung transplantation. Can they influence lung rejection?

    Science.gov (United States)

    Ciriza de Los Ríos, Constanza; Canga Rodríguez-Valcárcel, Fernando; de Pablo Gafas, Alicia; Castel de Lucas, Isabel; Lora Pablos, David; Castellano Tortajada, Gregorio

    2018-06-01

    lung transplantation (LTx) is a viable option for most patients with end-stage lung diseases. Esophageal motor disorders (EMD) are frequent in candidates for LTx, but there is very little data about changes in esophageal motility post-LTx. the aim of our study was to assess esophageal motor disorders by high resolution manometry (HRM) both pre-LTx and six months post-LTx in patients with and without organ rejection. HRM (Manoscan®) was performed in 57 patients both pre-LTx and six months post-LTx. HRM plots were analyzed according to the Chicago classification 3.0. EMD were found in 33.3% and in 49.1% of patients pre-LTx and post-LTx, respectively, and abnormal peristalsis was more frequently found post-LTx (p = 0.018). Hypercontractile esophagus was frequently found post-LTx (1.8% and 19.3% pre-LTx and post-LTx, respectively). Esophagogastric junction (EGJ) morphology changed significantly pre-LTx and post-LTx; type I (normal) was more frequent post-LTx (63-2% and 82.5% respectively, p = 0.007). EMD were more frequent post-LTx in both the non-rejection and rejection group, although particularly in the rejection group (43.2% and 69.2% respectively, p = 0.09). EMD such as distal spasm, hypercontractile esophagus and EGJ outflow obstruction were also observed more frequently post-LTx in the rejection group. significant changes in esophageal motility were observed pre-LTx and particularly post-LTx; hypercontractile esophagus was a frequent EMD found post-LTx. EMD were more frequent in the group of patients that experienced organ rejection compared to the non-rejection group. EMD leading to an impaired esophageal clearance should be considered as an additional factor that contributes to LTx failure.

  5. Transplant rejection

    Science.gov (United States)

    ... Antibodies References Abbas AK, Lichtman AH, Pillai S. Transplantation immunology. In: Abbas AK, Lichtman AH, Pillai S, eds. Cellular and Molecular Immunology. 9th ed. Philadelphia, PA: Elsevier; 2018:chap 17. ...

  6. Efficacy of total lymphoid irradiation for chronic allograft rejection following double lung transplantation

    International Nuclear Information System (INIS)

    Diamond, David A.; Michalski, Jeff M.; Trulock, Elbert M.; Lynch, John P.

    1997-01-01

    Purpose: The purpose of this study was to assess the safety and efficacy of total lymphoid irradiation in a series of patients experiencing chronic rejection following bilateral lung transplantation. Patients and Materials: Eleven patients (10 males, 1 female) received total lymphoid irradiation for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Treatment was delivered between March, 1995, and September, 1996. Mean patient age was 33 years (range 15-51). Indications for transplantation included cystic fibrosis (7 patients), alpha 1 anti-trypsin deficiency (2 patients), primary pulmonary hypertension (1 patient), and emphysema (1 patient). Radiation therapy was prescribed as 800 cGy delivered in ten 80 cGy fractions, 2 fractions per week, via AP/PA mantle and inverted-Y fields. Radiation was withheld for total wbc count 3 , absolute neutrophil count 3 , or platelets 3 . Serial pre- and post-radiation therapy pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements (use of methylprednisolone, azathioprine, mycophenolate mofetil, OKT3, and FK506) were monitored. Results: In the 3 months preceding total lymphoid irradiation, the average decrease in FEV 1 was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). At initiation of radiation therapy, the average FEV 1 was 1.4 liters (range 0.77-2.28). Only (4(11)) patients completed all 10 treatment fractions. Reasons for discontinuation included unabated rejection (4 patients), worsening pulmonary infection (2 patients), and persistent thrombocytopenia (1 patient). No treatment course was discontinued because of persistent neutropenia or leukopenia. Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related donor transplants. He is alive and well. Six patients died. Two of these deaths were due

  7. Efficacy of total lymphoid irradiation for chronic allograft rejection following bilateral lung transplantation

    International Nuclear Information System (INIS)

    Diamond, David A.; Michalski, Jeff M.; Lynch, John P.; Trulock, Elbert P.

    1998-01-01

    Purpose: To assess the safety and efficacy of total lymphoid irradiation (TLI) in patients experiencing chronic rejection following bilateral lung transplantation (BLT). Patients and Materials: Eleven patients received TLI for chronic allograft rejection (bronchiolitis obliterans syndrome) refractory to conventional treatment modalities. Radiation therapy (RT) was prescribed as 8 Gy delivered in 10 0.8-Gy fractions, 2 fractions/week, via mantle, paraaortic, and inverted-Y fields. Serial pre- and post-RT pulmonary function values, complete blood counts, and immunosuppressive augmentation requirements [use of methylprednisolone, murine anti-human mature T-cell monoclonal antibody (OKT3), polyclonal antithymocyte globulin (ATG), and tacrolimus] were monitored. Results: In the 3 months preceding TLI, the average decrease in forced expiratory volume in 1 s (FEV 1 ) was 34% (range 0-75%) and the median number of immunosuppression augmentations was 3 (range 0-5). Only 4 of 11 patients completed all 10 TLI treatment fractions. Reasons for discontinuation included progressive pulmonary decline (four patients), worsening pulmonary infection (two patients), and persistent thrombocytopenia (one patient). Seven of the 11 patients failed within 8 weeks of treatment cessation. One patient had unabated rejection and received bilateral living related-donor transplants; he is alive and well. Six patients died. Two of these deaths were due to pulmonary infection from organisms isolated prior to the start of RT; the other four deaths were from progressive pulmonary decline. The four remaining patients had durable positive responses to TLI (mean follow-up of 47 weeks; range 24-72). Comparing the 3 months preceding RT to the 3 months following treatment, these four patients had improvements in average FEV 1 (40% decline vs. 1% improvement) and fewer median number of immunosuppressive augmentations (3.5 vs. 0). None of these patients has developed lymphoproliferative disease or has died

  8. Assessment of pathological changes associated with chronic allograft rejection and tolerance in two experimental models of rat lung transplantation.

    Science.gov (United States)

    Matsumura, Y; Marchevsky, A; Zuo, X J; Kass, R M; Matloff, J M; Jordan, S C

    1995-06-15

    Lung transplantation is now routinely performed for a wide range of end-stage cardiopulmonary disorders. Despite overcoming the problems associated with early acute rejection, chronic rejection (CR) in the form of obliterative bronchiolitis has emerged as the primary cause of late graft loss. The mechanisms involved in the development of CR of lung allografts are poorly understood, and no effective therapy is currently available. To better understand the pathological events associated with CR and tolerance, we examined two models of lung allograft rejection established in our laboratory. First, we exchanged left lung allografts between moderately histoincompatible inbred rat strains (WKY-->F344: n = 42 and F344-->WKY: n = 40). The WKY-->F344 model was previously shown to develop spontaneous tolerance, while the converse model (F344-->WKY) showed persistent acute rejection. The purpose of this investigation was to assess histopathological changes associated with long-term grafts left in place up to 140 days after transplant. To confirm that tolerance had developed, skin-grafting experiments were performed. Five skin grafts from each strain were placed on lung allograft recipients on day 35 after transplant and skin allograft survival was assessed and compared with controls. Acute rejection (AR) was graded histologically (stage O-IV) and the pathologic intensity of inflammation and CR were graded (0-4: 0 = 0%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = 76-100%) on percentage of involvement with the following categories being examined: (a) lymphocytic infiltration (perivascular, peribronchial, and peribronchiolar) and (b) vasculitis, edema, hemorrhage, and necrosis. Finally, chronic rejection was diagnosed by the presence of intimal hyperplasia, interstitial fibrosis, peribronchiolar fibrosis, bronchiolitis obliterans, and bronchiectasis. The WKY-->F344 animals showed progressive AR (stage III, day 21). Thereafter, the AR subsided spontaneously and was stage 0 on day

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

    DEFF Research Database (Denmark)

    Hagedorn, Peter; Burton, Christopher M.; Carlsen, Jørn

    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...

  10. Evaluation of 99Tcm nonspecific polyclonal IgG in the detection of rejection in a single lung transplant canine model

    International Nuclear Information System (INIS)

    Larcos, G.; McLarty, A.J.; McGregor, C.G.A.; Brown, M.L.; Hung, J.C.; O'Connor, M.K.; Tazelaar, H.D.

    1993-01-01

    Acute rejection is an important cause of graft failure in single lung transplantation, however, current noninvasive tests are neither sensitive nor specific for this diagnosis. The aim of this study was to determine whether 99 Tc m -labelled human nonspecific polyclonal IgG ( 99 Tc m -IgG) may serve as a marker for acute pulmonary rejection following allotransplantation in a dog model. Seventeen mongrel dogs were studied, including four controls and thirteen dogs which underwent surgery [right autotransplant recipient right unmodified allotransplant recipient, and right immunosuppressed allotransplant recipient]. At 6 days following surgery, all dogs received 67 Ga-citrate and 99 Tc m -IgG. Two days later all dogs were sacrified. Post-mortem examination revealed acute lung rejection in nine animals. No significant difference was found in the percentage uptake of both 99 Tc m -IgG and 67 Ga-citrate per gram of tissue between rejecting and nonrejecting transplanted lungs. In cases of moderate to severe rejection, only 67 Ga-citrate showed a significant difference in uptake between rejecting and contralateral native lungs, respectively. We conclude that 99 Tc m -IgG does not accurately identify acute lung rejection in the early postoperative period. (author)

  11. Antibody induction therapy for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Møller, Christian H; Penninga, Ida Elisabeth Irene

    2013-01-01

    Lung transplantation has become a valuable and well-accepted treatment option for most end-stage lung diseases. Lung transplant recipients are at risk of transplanted organ rejection, and life-long immunosuppression is necessary. Clear evidence is essential to identify an optimal, safe and effect...... and effective immunosuppressive treatment strategy for lung transplant recipients. Consensus has not yet been achieved concerning use of immunosuppressive antibodies against T-cells for induction following lung transplantation....

  12. Lung Transplant

    Science.gov (United States)

    ... Severity of the recipient's lung disease Recipient's overall health Likelihood that the transplant will be successful Immediately before ... will begin within days of your surgery. Your health care team will likely work with you to design an exercise program that's right for you. Your doctor may ...

  13. Eosinophil count, allergies, and rejection in pediatric heart transplant recipients.

    Science.gov (United States)

    Arbon, Kate S; Albers, Erin; Kemna, Mariska; Law, Sabrina; Law, Yuk

    2015-08-01

    Allograft rejection and long-term immunosuppression remain significant challenges in pediatric heart transplantation. Pediatric recipients are known to have fewer rejection episodes and to develop more allergic conditions than adults. A T-helper 2 cell dominant phenotype, manifested clinically by allergies and an elevated eosinophil count, may be associated with immunologic quiescence in transplant recipients. This study assessed whether the longitudinal eosinophil count and an allergic phenotype were associated with freedom from rejection. This single-center, longitudinal, observational study included 86 heart transplant patients monitored from 1994 to 2011. Post-transplant biannual complete blood counts, allergic conditions, and clinical characteristics related to rejection risk were examined. At least 1 episode of acute cellular rejection (ACR) occurred in 38 patients (44%), antibody-mediated rejection (AMR) occurred in 11 (13%), and 49 patients (57%) were diagnosed with an allergic condition. Patients with ACR or AMR had a lower eosinophil count compared with non-rejectors (p = 0.011 and p = 0.022, respectively). In the multivariable regression analysis, the presence of panel reactive antibodies to human leukocyte antigen I (p = 0.014) and the median eosinophil count (p = 0.011) were the only independent covariates associated with AMR. Eosinophil count (p = 0.010) and female sex (p = 0.009) were independent risk factors for ACR. Allergic conditions or young age at transplant were not protective from rejection. This study demonstrates a novel association between a high eosinophil count and freedom from rejection. Identifying a biomarker for low rejection risk may allow a reduction in immunosuppression. Further investigation into the role of the T-helper 2 cell phenotype and eosinophils in rejection quiescence is warranted. Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  14. Immediate and Catastrophic Antibody-Mediated Rejection in a Lung Transplant Recipient With Anti-Angiotensin II Receptor Type 1 and Anti-Endothelin-1 Receptor Type A Antibodies.

    Science.gov (United States)

    Cozzi, E; Calabrese, F; Schiavon, M; Feltracco, P; Seveso, M; Carollo, C; Loy, M; Cardillo, M; Rea, F

    2017-02-01

    Preexisting donor-specific anti-HLA antibodies (DSAs) have been associated with reduced survival of lung allografts. However, antibodies with specificities other than HLA may have a detrimental role on the lung transplant outcome. A young man with cystic fibrosis underwent lung transplantation with organs from a suitable deceased donor. At the time of transplantation, there were no anti-HLA DSAs. During surgery, the patient developed a severe and intractable pulmonary hypertension associated with right ventriular dysfunction, which required arteriovenous extracorporeal membrane oxygenation. After a brief period of clinical improvement, a rapid deterioration in hemodynamics led to the patient's death on postoperative day 5. Postmortem studies showed that lung specimens taken at the end of surgery were compatible with antibody-mediated rejection (AMR), while terminal samples evidenced diffuse capillaritis, blood extravasation, edema, and microthrombi, with foci of acute cellular rejection (A3). Immunological investigations demonstrated the presence of preexisting antibodies against the endothelin-1 receptor type A (ET A R) and the angiotensin II receptor type 1 (AT 1 R), two of the most potent vasoconstrictors reported to date, whose levels slightly rose after transplantation. These data suggest that preexisting anti-ET A R and anti-AT 1 R antibodies may have contributed to the onset of AMR and to the catastrophic clinical course of this patient. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Thallium kinetics in rat cardiac transplant rejection

    International Nuclear Information System (INIS)

    Barak, J.H.; LaRaia, P.J.; Boucher, C.A.; Fallon, J.T.; Buckley, M.J.

    1988-01-01

    Cardiac transplant rejection is a very complex process involving both cellular and vascular injury. Recently, thallium imaging has been used to assess acute transplant rejection. It has been suggested that changes in thallium kinetics might be a sensitive indicator of transplant rejection. Accordingly, thallium kinetics were assessed in vivo in acute untreated rat heterotopic (cervical) transplant rejection. Male Lewis rats weighing 225-250 g received heterotopic heart transplants from syngeneic Lewis rats (group A; n = 13), or allogeneic Brown Norway rats (group B; n = 11). Rats were imaged serially on the 2nd and the 7th postoperative days. Serial cardiac thallium content was determined utilizing data collected every 150 sec for 2 hr. The data were fit to a monoexponential curve and the decay rate constant (/sec) derived. By day 7 all group B hearts had histological evidence of severe acute rejection, and demonstrated decreased global contraction. Group A hearts showed normal histology and contractility. However, thallium uptakes and washout of the two groups were the same. Peak thallium uptake of group B was +/- 3758 1166 counts compared with 3553 +/- 950 counts in the control group A (P = 0.6395); The 2-hr percentage of washout was 12.1 +/- 1.04 compared with 12.1 +/- 9.3 (P = 1.0000); and the decay constant was -0.00002065 +/- 0.00001799 compared with -0.00002202 +/- 0.00001508 (P = 0.8409). These data indicate that in vivo global thallium kinetics are preserved during mild-to-severe acute transplant rejection. These findings suggest that the complex cellular and extracellular processes of acute rejection limit the usefulness of thallium kinetics in the detection of acute transplant rejection

  16. History of Lung Transplantation.

    Science.gov (United States)

    Dabak, Gül; Şenbaklavacı, Ömer

    2016-04-01

    History of lung transplantation in the world can be traced back to the early years of the 20 th century when experimental vascular anastomotic techniques were developed by Carrel and Guthrie, followed by transplantation of thoracic organs on animal models by Demikhov and finally it was James Hardy who did the first lung transplantation attempt on human. But it was not until the discovery of cyclosporine and development of better surgical techniques that success could be achieved in that field by the Toronto Lung Transplant Group led by Joel Cooper. Up to the present day, over 51.000 lung transplants were performed in the world at different centers. The start of lung transplantation in Turkey has been delayed for various reasons. From 1998 on, there were several attempts but the first successful lung transplant was performed at Sureyyapasa Hospital in 2009. Today there are four lung transplant centers in Turkey; two in Istanbul, one in Ankara and another one in Izmir. Three lung transplant centers from Istanbul which belong to private sector have newly applied for licence from the Ministry of Health.

  17. Lung allograft rejection in the rat. I. Accelerated rejection caused by graft lymphocytes

    International Nuclear Information System (INIS)

    Prop, J.; Nieuwenhuis, P.; Wildevuur, C.R.

    1985-01-01

    To find out to what extent rejection of lungs differs from that of other organs, functional rejection of lung allografts was studied in five combinations of inbred rat strains. Rejection could be monitored accurately by perfusion scintigraphy, and equally well by chest roentgenography. The rejection of lung grafts was found to proceed remarkably fast, when compared with heart grafts, in combinations with strong RT1-incompatibilities. This accelerated rejection pattern could be converted into rejection at a normal pace by pretreatment of the donor with 10 Gy roentgen irradiation one day before transplantation. Donor pretreatment depleted the lung graft's bronchus-associated lymphoid tissue (BALT) of lymphocytes. When grafts were depleted of all other passenger cells as well--by retransplantation from a cyclosporine-treated intermediate host--they showed an even more reduced immunogenicity, probably because of the loss of donor-type dendritic cells. These results indicate that lymphocytes from the BALT of lung grafts are capable of accelerating the rejection response

  18. Lipid raft facilitated ligation of K-α1-tubulin by specific antibodies on epithelial cells: Role in pathogenesis of chronic rejection following human lung transplantation

    International Nuclear Information System (INIS)

    Tiriveedhi, Venkataswarup; Angaswamy, Nataraju; Weber, Joseph; Mohanakumar, T.

    2010-01-01

    Research highlights: → Addition of KAT Abs (+) sera to NHBE culture causes upregulation of growth factors. → Cholesterol depletion causes down regulation of growth factor expression. → Cholesterol depletion is accompanied by loss of membrane bound caveolin. → Thus, we demonstrate lipid raft are critical for efficient ligation of the KAT Abs. -- Abstract: Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-α1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients who develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4 ± 1.1-, 3.2 ± 0.9-, and 3.4 ± 1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the growth factor expression pattern upon depletion and enrichment with lipid raft following the ligation of the epithelial cell membranes with Abs specific for KAT. NHBE cells cultured in the presence of β-methyl cyclodextran (βMCD) had significantly reduced growth factor expression (1.3 ± 0.3, vs βMCD untreated being 6.4 ± 1.1-fold increase) upon stimulation with KAT Abs. Depletion

  19. Lipid raft facilitated ligation of K-{alpha}1-tubulin by specific antibodies on epithelial cells: Role in pathogenesis of chronic rejection following human lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Tiriveedhi, Venkataswarup; Angaswamy, Nataraju [Department of Surgery, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States); Weber, Joseph [Department of Medicine, Washington University School of Medicine, St. Louis, MO (United States); Mohanakumar, T., E-mail: kumart@wustl.edu [Department of Surgery, Pathology and Immunology, Washington University School of Medicine, St. Louis, MO (United States)

    2010-08-20

    Research highlights: {yields} Addition of KAT Abs (+) sera to NHBE culture causes upregulation of growth factors. {yields} Cholesterol depletion causes down regulation of growth factor expression. {yields} Cholesterol depletion is accompanied by loss of membrane bound caveolin. {yields} Thus, we demonstrate lipid raft are critical for efficient ligation of the KAT Abs. -- Abstract: Long term function of human lung allografts is hindered by development of chronic rejection manifested as Bronchiolitis Obliterans Syndrome (BOS). We have previously identified the development of antibodies (Abs) following lung transplantation to K-{alpha}1-tubulin (KAT), an epithelial surface gap junction cytoskeletal protein, in patients who develop BOS. However, the biochemical and molecular basis of the interactions and signaling cascades mediated by KAT Abs are yet to be defined. In this report, we investigated the biophysical basis of the epithelial cell membrane surface interaction between KAT and its specific Abs. Towards this, we analyzed the role of the lipid raft-domains in the membrane interactions which lead to cell signaling and ultimately increased growth factor expression. Normal human bronchial epithelial (NHBE) cells, upon specific ligation with Abs to KAT obtained either from the serum of BOS(+) patients or monoclonal KAT Abs, resulted in upregulation of growth factors VEGF, PDGF, and bFGF (6.4 {+-} 1.1-, 3.2 {+-} 0.9-, and 3.4 {+-} 1.1-fold increase, respectively) all of which are important in the pathogenesis of BOS. To define the role for lipid raft in augmenting surface interactions, we analyzed the changes in the growth factor expression pattern upon depletion and enrichment with lipid raft following the ligation of the epithelial cell membranes with Abs specific for KAT. NHBE cells cultured in the presence of {beta}-methyl cyclodextran ({beta}MCD) had significantly reduced growth factor expression (1.3 {+-} 0.3, vs {beta}MCD untreated being 6.4 {+-} 1.1-fold

  20. MR imaging of renal transplant rejection

    International Nuclear Information System (INIS)

    Hanna, S.; Helenon, O.; Legendre, C.; Chichie, J.F.; Di Stefano, D.; Kreis, H.; Moreau, J.F.; Hopital Necker, 75 - Paris

    1991-01-01

    The results of 62 consecutive MR examinations were correlated with the subsequent clinical course and histologic results. Twenty-six cases of rejection showed a marked diminution of cortico-medullary differentiation (CMD). The renal parenchymal vascular pattern and visibility of renal sinus fat were not markedly altered in rejection and there was no difference between normal and rejected allograft shape. The ability of MR imaging to diagnose renal transplant rejection is only based on CMD, which, however, is non-specific. In 2 cases of severe rejection, T2 weighted images showed an abnormal signal intensity of the cortex due to renal infarction. Our preliminary results in 8 patients with Gd-DOTA injection showed 2 cases with necrosis seen as areas with absent contrast enhancement. This technique seems to be promising in the detection of perfusion defects. (orig.)

  1. Allorecognition pathways in transplant rejection and tolerance.

    Science.gov (United States)

    Ali, Jason M; Bolton, Eleanor M; Bradley, J Andrew; Pettigrew, Gavin J

    2013-10-27

    With the advent of cellular therapies, it has become clear that the success of future therapies in prolonging allograft survival will require an intimate understanding of the allorecognition pathways and effector mechanisms that are responsible for chronic rejection and late graft loss.Here, we consider current understanding of T-cell allorecognition pathways and discuss the most likely mechanisms by which these pathways collaborate with other effector mechanisms to cause allograft rejection. We also consider how this knowledge may inform development of future strategies to prevent allograft rejection.Although both direct and indirect pathway CD4 T cells appear active immediately after transplantation, it has emerged that indirect pathway CD4 T cells are likely to be the dominant alloreactive T-cell population late after transplantation. Their ability to provide help for generating long-lived alloantibody is likely one of the main mechanisms responsible for the progression of allograft vasculopathy and chronic rejection.Recent work has suggested that regulatory T cells may be an effective cellular therapy in transplantation. Given the above, adoptive therapy with CD4 regulatory T cells with indirect allospecificity is a rational first choice in attempting to attenuate the development and progression of chronic rejection; those with additional properties that enable inhibition of germinal center alloantibody responses hold particular appeal.

  2. Antimyosin imaging in cardiac transplant rejection

    International Nuclear Information System (INIS)

    Johnson, L.L.; Cannon, P.J.

    1991-01-01

    Fab fragments of antibodies specific for cardiac myosin have been labeled with indium-111 and injected intravenously into animals and into patients with heart transplants. The antibodies, developed by Khaw, Haber, and co-workers, localize in cardiac myocytes that have been damaged irreversibly by ischemia, myocarditis, or the rejection process. After clearance of the labeled antibody from the cardiac blood pool, planar imaging or single photon emission computed tomography is performed. Scintigrams reveal the uptake of the labeled antimyosin in areas of myocardium undergoing transplant rejection. In animal studies, the degree of antimyosin uptake appears to correlate significantly with the degree of rejection assessed at necropsy. In patients, the correlation between scans and pathologic findings from endomyocardial biopsy is not as good, possibly because of sampling error in the endomyocardial biopsy technique. The scan results at 1 year correlate with either late complications (positive) or benign course (negative). Current limitations of the method include slow blood clearance, long half-life of indium-111, and hepatic uptake. Overcoming these limitations represents a direction for current research. It is possible that from these efforts a noninvasive approach to the diagnosis and evaluation of cardiac transplantation may evolve that will decrease the number of endomyocardial biopsies required to evaluate rejection. This would be particularly useful in infants and children. 31 references

  3. Tacrolimus versus cyclosporin as primary immunosuppression for lung transplant recipients

    DEFF Research Database (Denmark)

    Penninga, Luit; Penninga, Ida Elisabeth Irene; Møller, Christian H

    2013-01-01

    Lung transplantation is a well-accepted treatment for people with most end-stage lung diseases. Although both tacrolimus and cyclosporin are used as primary immunosuppressive agents in lung transplant recipients, it is unclear which of these drugs is better in reducing rejection and death without...

  4. Local graft irradiation in renal transplant rejection

    International Nuclear Information System (INIS)

    Kawamura, Masashi; Kataoka, Masaaki; Itoh, Hisao

    1990-01-01

    From 1977 to 1988, of 142 renal transplantations, seven recipients (4.9%) received local graft irradiation following rejective reaction refractory to antirejection medical managements. Concurrent with the administration of pulsed high dose methylprednisolone and other antirejection medical managements, the graft was irradiated with a total dose of 6.0 Gy-150 cGy per fraction every other day at the midplane of the graft using two opposing portals of 4MX Linac. The fields were defined by palpation and echography. All patients had improvements in serum creatinine on the 10th day after beginning the irradiation. Four patients with peripheral lymphocytosis during the irradiation combined with pulsed high dose methylprednisolone improved in renal functions. On the other hand, out of 3 patients with lymphcytopenic changes, in two the transplanted graft was removed due to deteriorations, and the other patient is currently suffering from chronic rejection. Local graft irradiation can be useful in maintaining a rejective graft and reversing its functions in some patients whose rejective reaction failed to respond to the antirejection medical managements. (author)

  5. Belatacept for Maintenance Immunosuppression in Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Christine Hui PharmD

    2014-06-01

    Full Text Available Belatacept is a novel immunosuppressant that blocks a T-cell costimulation pathway and is approved for use in adult kidney transplant recipients. Its safety and efficacy have not been established after lung transplantation. We present a case of a lung transplant recipient treated with belatacept. A 56-year-old man underwent bilateral lung retransplantation for bronchiolitis obliterans syndrome (BOS. In the third year posttransplant, he developed hemolytic uremic syndrome (HUS attributed to tacrolimus. Tacrolimus was changed to sirolimus. One month later, he presented with worsening renal function and HUS attributed to sirolimus. Plasmapheresis and steroid pulse were initiated with clinical improvement, and sirolimus was switched to belatacept. He experienced no episodes of cellular rejection but developed recurrent BOS. Complications during treatment included anemia and recurrent pneumonias. The safety and efficacy of belatacept in lung transplantation remains unclear; further studies are needed.

  6. In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

    International Nuclear Information System (INIS)

    Forstrom, L.A.; Loken, M.K.; Cook, A.; Chandler, R.; McCullough, J.

    1981-01-01

    Indium-111-labeled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labeling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111-leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients

  7. In-111-labeled leukocytes in the diagnosis of rejection and cytomegalovirus infection in renal transplant patients

    International Nuclear Information System (INIS)

    Forstrom, L.A.; Loken, M.K.; Cook, A.; Chandler, R.; McCullough, J.

    1981-01-01

    Indium-111-labelled (In-111) leukocytes have been shown to be useful in the localization of inflammatory processes, including renal transplant rejection. Using previously reported labelling methods, 63 studies with this agent have been performed in 53 renal transplant patients. Indications for study included suspected rejection or cytomegalovirus (CMV) infection. Studies were performed in 33 men and 20 women, with ages ranging from 6 to 68 years. Autologous cells were normally used for labeling, although leukocytes obtained from ABO-compatible donors were used in three subjects. Rectilinear scanner and/or scintillation camera images were obtained at 24 hours after intravenous administration of 0.1 to 0.6 mCi of In-111 leukocytes. There was abnormal uptake of In-111-leukocytes in the transplanted kidney in 11 of 15 cases of rejection. In three additional cases of increased transplant uptake, CMV infection was present in two. Abnormal lung uptake was present in 13 of 14 patients with CMV infection. In four additional cases, increased lung uptake was associated with other pulmonary inflammatory disease. Increased lung activity was not seen in patients with uncomplicated transplant rejection. These results suggest that In-111-leukocyte imaging may be useful in the differential diagnosis of rejection versus CMV infection in renal transplant patients

  8. Cyclosporine C2 levels have impact on incidence of rejection in de novo lung but not heart transplant recipients: the NOCTURNE study

    DEFF Research Database (Denmark)

    Iversen, Martin; Nilsson, Folke; Sipponen, Jorma

    2009-01-01

    . Abbreviated AUC (AUC(0-4)) was measured at 7 days and 3 months. Primary outcome was C2 relation to the frequency of acute cellular rejection (ACR) needing treatment and possible decline in measured glomerular filtration rate (mGFR). Recipients were divided into lower, middle and upper third C2 groups based...... monitoring, but should be further explored in thoracic organ recipients. METHODS: In a 12-month study we included de novo lung (n = 95) and heart (n = 96) recipients. All participants received cyclosporine (Sandimmun Neoral) monitored by C0 and blood was collected for analysis of C2 retrospectively...... on 2-week post-operative values (tertiles T1 to T3). RESULTS: C2 was the most robust substitute for AUC(0-4) in the group of patients studied. For lung, but not heart, recipients there were differences in mean number of ACRs (p = 0.05), incidence of any rejections (p = 0.04), mean number of any...

  9. Immunological risk stratification of the bronchiolitis obliterans syndrome after lung transplantation

    NARCIS (Netherlands)

    Kwakkel - van Erp, J.M.

    2011-01-01

    The development of chronic allograft rejection after lung transplantation (LTx) is the most common cause of poor long-term survival in lung transplant recipients. This rejection leads to obliteration of the bronchioli. Since this obliteration has a patchy distribution and normal lung tissue obtained

  10. Indium-labeled platelet uptake in rejecting renal transplants

    International Nuclear Information System (INIS)

    Chandler, S.T.; Buckels, J.; Hawker, R.J.; Smith, N.; Barnes, A.D.; McCollum, C.N.

    1983-01-01

    The uptake of 111 In autologous platelets in transplanted kidneys was measured in 16 patients shortly after operation. Each patient was then observed for two years. When transplant radioactivity had increased, despite treatment for acute rejection, the kidney was ultimately lost because of rejection

  11. Acute antibody-mediated rejection in pancreas and kidney transplantation

    NARCIS (Netherlands)

    Kort, Hanneke de

    2013-01-01

    In this thesis, acute rejection after kidney, simultaneous pancreas and kidney (SPKT), and islets of Langerhans transplantation was addressed. The focus is on acute antibody-mediated rejection (AMR) after transplantation and on a potential strategy using cellular immune modulation to prevent acute

  12. Predicting outcome of acute kidney transplant rejection using

    NARCIS (Netherlands)

    Rekers, Niels Vincent

    2014-01-01

    Acute kidney transplant rejection is an important risk factors for adverse graft outcome. Once diagnosed, it remains difficult to predict the risk of graft loss and the response to anti-rejection treatment. The aim of this thesis was to identify biomarkers during acute rejection, which predict the

  13. Endothelial cell chimerism after renal transplantation and vascular rejection.

    NARCIS (Netherlands)

    Lagaaij, E.L.; Cramer-Knijnenburg, G.F.; Kemenade, F.J. van; Es, L.A. van; Bruijn, J.A.; Krieken, J.H.J.M. van

    2001-01-01

    BACKGROUND: The blood vessels of a transplanted organ are the interface between donor and recipient. The endothelium in the blood vessels is thought to be the major target for graft rejection. Endothelial cells of a transplanted organ are believed to remain of donor origin after transplantation. We

  14. Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression.

    Science.gov (United States)

    Hollander, Zsuzsanna; Chen, Virginia; Sidhu, Keerat; Lin, David; Ng, Raymond T; Balshaw, Robert; Cohen-Freue, Gabriela V; Ignaszewski, Andrew; Imai, Carol; Kaan, Annemarie; Tebbutt, Scott J; Wilson-McManus, Janet E; McMaster, Robert W; Keown, Paul A; McManus, Bruce M

    2013-02-01

    Acute rejection in cardiac transplant patients remains a contributory factor to limited survival of implanted hearts. Currently, there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplant acute cellular rejection. Such a development would be of great value in personalizing immunosuppressive treatment. Recipient age, donor age, cold ischemic time, warm ischemic time, panel-reactive antibody, gender mismatch, blood type mismatch and human leukocyte antigens (HLA-A, -B and -DR) mismatch between recipients and donors were tested in 53 heart transplant patients for their power to predict post-transplant acute cellular rejection. Donor transplant biopsy and recipient pre-transplant blood were also examined for the presence of genomic biomarkers in 7 rejection and 11 non-rejection patients, using non-targeted data mining techniques. The biomarker based on the 8 clinical variables had an area under the receiver operating characteristic curve (AUC) of 0.53. The pre-transplant recipient blood gene-based panel did not yield better performance, but the donor heart tissue gene-based panel had an AUC = 0.78. A combination of 25 probe sets from the transplant donor biopsy and 18 probe sets from the pre-transplant recipient whole blood had an AUC = 0.90. Biologic pathways implicated include VEGF- and EGFR-signaling, and MAPK. Based on this study, the best predictive biomarker panel contains genes from recipient whole blood and donor myocardial tissue. This panel provides clinically relevant prediction power and, if validated, may personalize immunosuppressive treatment and rejection monitoring. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  15. Acute rejection episodes after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Hamida Fethi

    2009-01-01

    Full Text Available Acute rejection episodes (AREs are a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains, at least partially, the improvement seen in the results of transplantation in recent years. The objectives of this study are to analyze the incidence and severity of AREs, their risk factors and their influence on graft and patient survival. We retrospectively studied 280 kidney transplants performed in adults at the Charles Nicolle Hospital, Tunis, between 1986 and 2004. The diagnosis of ARE was based on clinical data and response to treatment. Allograft biopsies were performed in ten cases. The treatment of AREs consisted of pulse methylprednisolone and anti-thymocyte globulin. There were 186 males (66.4% and 94 females (33.6%, and their mean age was 31 ± 8.9 years. Overall, the 280 study patients experienced a total of 113 AREs. Of them, 85 had only one ARE, 28 had two to three and none had more than three AREs. A total of 68 AREs were completely re-versible, 42 were partially reversible while three could not be reversed with treatment. The mean inci-dence of AREs was 40.4%. The incidence was > 45% between 1986 and 1997, decreased to 20.5% between 1998 and 2000 and to 9% between 2001 and 2004. Graft survival rates in patients with and without AREs were respectively 91% and 93% at three years, 82% and 90% at five years and 73% and 83% at 10 years. We found a decrease in the incidence of AREs in recent years in our study patients, and this was related to the introduction of sensitized cross-match and the newer immunosuppressive agents, particularly MMF. Additionally, AREs had a deleterious impact on late graft survival in our study population.

  16. Imaging in lung transplants: Checklist for the radiologist

    International Nuclear Information System (INIS)

    Madan, Rachna; Chansakul, Thanissara; Goldberg, Hilary J

    2014-01-01

    Post lung transplant complications can have overlapping clinical and imaging features, and hence, the time point at which they occur is a key distinguisher. Complications of lung transplantation may occur along a continuum in the immediate or longer postoperative period, including surgical and mechanical problems due to size mismatch and vascular as well as airway anastomotic complication, injuries from ischemia and reperfusion, acute and chronic rejection, pulmonary infections, and post-transplantation lymphoproliferative disorder. Life expectancy after lung transplantation has been limited primarily by chronic rejection and infection. Multiple detector computed tomography (MDCT) is critical for evaluation and early diagnosis of complications to enable selection of effective therapy and decrease morbidity and mortality among lung transplant recipients

  17. Early laparotomy after lung transplantation

    DEFF Research Database (Denmark)

    Bredahl, Pia; Zemtsovski, Mikhail; Perch, Michael

    2014-01-01

    BACKGROUND: Gastrointestinal complications after lung transplantation have been reported with incidence rates ranging from 3% to 51%, but the reasons are poorly understood. We aimed to investigate the correlations between pulmonary diseases leading to lung transplantation and early gastrointestinal...... for time on mechanical ventilation. Among pulmonary diseases and demographics of the patients, no other risk factors were identified for laparotomy. CONCLUSIONS: A1AD was the only significant risk factor identified for gastrointestinal complications that required laparotomy within 3 months after lung...

  18. [Lung transplantation in pulmonary fibrosis and other interstitial lung diseases].

    Science.gov (United States)

    Berastegui, Cristina; Monforte, Victor; Bravo, Carlos; Sole, Joan; Gavalda, Joan; Tenório, Luis; Villar, Ana; Rochera, M Isabel; Canela, Mercè; Morell, Ferran; Roman, Antonio

    2014-09-15

    Interstitial lung disease (ILD) is the second indication for lung transplantation (LT) after emphysema. The aim of this study is to review the results of LT for ILD in Hospital Vall d'Hebron (Barcelona, Spain). We retrospectively studied 150 patients, 87 (58%) men, mean age 48 (r: 20-67) years between August 1990 and January 2010. One hundred and four (69%) were single lung transplants (SLT) and 46 (31%) bilateral-lung transplants (BLT). The postoperative diagnoses were: 94 (63%) usual interstitial pneumonia, 23 (15%) nonspecific interstitial pneumonia, 11 (7%) unclassifiable interstitial pneumonia and 15% miscellaneous. We describe the functional results, complications and survival. The actuarial survival was 87, 70 and 53% at one, 3 and 5 years respectively. The most frequent causes of death included early graft dysfunction and development of chronic rejection in the form of bronchiolitis obliterans (BOS). The mean postoperative increase in forced vital capacity and forced expiratory volume in the first second (FEV1) was similar in SLT and BLT. The best FEV1 was reached after 10 (r: 1-36) months. Sixteen percent of patients returned to work. At some point during the evolution, proven acute rejection was diagnosed histologically in 53 (35%) patients. The prevalence of BOS among survivors was 20% per year, 45% at 3 years and 63% at 5 years. LT is the best treatment option currently available for ILD, in which medical treatment has failed. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  19. Lung and renal transplantation

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    Full Text Available Renal transplantation is the most common type of solid organ transplantation and kidney transplant recipients are susceptible to pulmonary complications of immunosuppressive therapy, which are a diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 ( ± 13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 ( ± 18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy. Resumo: O transplante renal é o transplante de órgãos sólidos mais frequente, sendo os transplantados renais alvo de complicações pulmonares inerentes à própria terapêutica imunossupressora, as quais constituem, por vezes, um desafio diagnóstico e terapêutico. Objectivo: Avaliar os doentes admitidos na Unidade de Transplante Renal (UTR do Hospital de S. João com o diagnóstico de patologia respirat

  20. Detection of cardiac transplant rejection with radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Bergmann, S.R.; Lerch, R.A.; Carlson, E.M.; Saffitz, J.E.; Sobel, B.E.

    1982-01-01

    To determine whether rejections of cardiac transplants could be detected specifically and non-invasively by lymphocytes labeled with indium-111 (111In), we studied 36 allogeneic and 14 isogeneic heterotopic cardiac transplants in rats. Allogeneic grafts accumulated autologous 111In-lymphocytes, detectable scintigraphically 24 hours after i.v. injection of the labeled cells. At the time of peak histologic rejection, the allogeneic grafts accumulated 92. +/- 4.8 times more activity than the native hearts (determined by well counting). The tissue-to-blood ratio in the rejecting transplants was 3.7 +/- 2.2; total uptake by the graft was 2.9 +/- 2.1% of the injected dose. Autoradiography confirmed that graft radioactivity was associated with labeled lymphocytes. In contrast, isogeneic grafts showed no signs of rejection and did not accumulate radioactivity. Because conventionally isolated and labeled lymphocytes are often contaminated with platelets, we prepared both 111In-platelets and purified 111In-lymphocytes for use in additional experiments. Allogeneic grafts accumulated platelets and purified lymphocytes independently. Thus, deposition of immunologically active cells in the rejecting graft representing specific pathophysiologic events can be detected. The results suggest that rejection of cardiac transplants can be detected noninvasively, potentially facilitating objective early clinical detection of rejection and titration of antirejection therapy

  1. Balancing rejection and infection with respect to age, race, and gender: clues acquired from 17 years of cardiac transplantation data.

    Science.gov (United States)

    George, James F; Pamboukian, Salpy V; Tallaj, José A; Naftel, David C; Myers, Susan L; Foushee, Margaret T; Brown, Robert N; Pajaro, Octavio E; McGiffin, David C; Kirklin, James K

    2010-09-01

    frequency of rejection/infection events. However, individuals transplanted at younger or older ages, especially non-white recipients in the 10- to 30-year age group, experience significantly more infection or rejection. Therefore, programs should increase the level of surveillance in these patients and consider modification of immunosuppressive regimens in order to lower the frequency of infection and rejection events. Copyright 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  2. Role of Soluble ST2 as a Marker for Rejection after Heart Transplant.

    Science.gov (United States)

    Lee, Ga Yeon; Choi, Jin-Oh; Ju, Eun-Seon; Lee, Yoo-Jung; Jeon, Eun-Seok

    2016-11-01

    Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx. A total of 494 blood samples acquired at the time of endomyocardial biopsy were analyzed in 67 HTx cases from September 2006 to August 2014. Significant rejection was defined as International Society of Heart and Lung Transplant (ISHLT) score ≥2R and humoral rejection accompanied by hemodynamic instability. Twenty cases of HTx with 22 blood samples showed significant rejection in endomyocardial biopsy at 4.0 (2.0-9.0) months after HTx. The level of sST2 showed positive correlation with cardiac troponin I, and N-terminal pro-B-type natriuretic peptide (all prejection) (p=0.003). However, when we studied within-subject effects of sST2 using a mixed model, the sST2 level according to the predefined time point was not different according to the presence of significant rejection (p for interaction=0.94). Although sST2 is known as a promising predictor for cardiovascular events, its role in HTx patients to predict acute allograft rejection seems to be limited.

  3. Role of gastroesophageal reflux disease in lung transplantation

    Science.gov (United States)

    Hathorn, Kelly E; Chan, Walter W; Lo, Wai-Kit

    2017-01-01

    Lung transplantation is one of the highest risk solid organ transplant modalities. Recent studies have demonstrated a relationship between gastroesophageal reflux disease (GERD) and lung transplant outcomes, including acute and chronic rejection. The aim of this review is to discuss the pathophysiology, evaluation, and management of GERD in lung transplantation, as informed by the most recent publications in the field. The pathophysiology of reflux-induced lung injury includes the effects of aspiration and local immunomodulation in the development of pulmonary decline and histologic rejection, as reflective of allograft injury. Modalities of reflux and esophageal assessment, including ambulatory pH testing, impedance, and esophageal manometry, are discussed, as well as timing of these evaluations relative to transplantation. Finally, antireflux treatments are reviewed, including medical acid suppression and surgical fundoplication, as well as the safety, efficacy, and timing of such treatments relative to transplantation. Our review of the data supports an association between GERD and allograft injury, encouraging a strategy of early diagnosis and aggressive reflux management in lung transplant recipients to improve transplant outcomes. Further studies are needed to explore additional objective measures of reflux and aspiration, better compare medical and surgical antireflux treatment options, extend follow-up times to capture longer-term clinical outcomes, and investigate newer interventions including minimally invasive surgery and advanced endoscopic techniques. PMID:28507913

  4. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

    DEFF Research Database (Denmark)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

    2014-01-01

    INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died......% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. CONCLUSION: In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted...

  5. Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

    Science.gov (United States)

    Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

    2017-07-12

    Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  6. Computed tomography of complications of lung transplantation

    International Nuclear Information System (INIS)

    Soyer, P.; Devine, N.; Frachon, I.; Vinatier, I.; Stern, M.; Le Normand, S.; Scherrer, A.

    1997-01-01

    In spite of improvements in single or double lung transplantation (LT) technique, complications after LT are not uncommon; the most frequent ale anastomotic complications, infections and rejection (acute or chronic). Early detection of complications of LT allows the optimal therapeutic option to be taken, yielding decreased morbidity and mortality. In some cases, CT plays a key role in early detection of several complications of LT that may not be depicted with other diagnostic modalities, so that knowledge of their CT features is important. In this pictorial review, the authors describe the spectrum of CT features of the complications of LT (including reimplantation response, mechanical problems, acute and chronic rejection, infection, lymphoproliferative disorders, recurrence of the initial disease and complications involving the pleura and the anastomotic sites). In addition, the authors analyze the value of CT compared to that of the other available modalities for the detection of complications of LT. (orig.). With 19 figs

  7. Redox-Dependent Inflammation in Islet Transplantation Rejection

    Directory of Open Access Journals (Sweden)

    Jessie M. Barra

    2018-04-01

    Full Text Available Type 1 diabetes is an autoimmune disease that results in the progressive destruction of insulin-producing pancreatic β-cells inside the islets of Langerhans. The loss of this vital population leaves patients with a lifelong dependency on exogenous insulin and puts them at risk for life-threatening complications. One method being investigated to help restore insulin independence in these patients is islet cell transplantation. However, challenges associated with transplant rejection and islet viability have prevented long-term β-cell function. Redox signaling and the production of reactive oxygen species (ROS by recipient immune cells and transplanted islets themselves are key players in graft rejection. Therefore, dissipation of ROS generation is a viable intervention that can protect transplanted islets from immune-mediated destruction. Here, we will discuss the newly appreciated role of redox signaling and ROS synthesis during graft rejection as well as new strategies being tested for their efficacy in redox modulation during islet cell transplantation.

  8. Redox-Dependent Inflammation in Islet Transplantation Rejection

    Science.gov (United States)

    Barra, Jessie M.; Tse, Hubert M.

    2018-01-01

    Type 1 diabetes is an autoimmune disease that results in the progressive destruction of insulin-producing pancreatic β-cells inside the islets of Langerhans. The loss of this vital population leaves patients with a lifelong dependency on exogenous insulin and puts them at risk for life-threatening complications. One method being investigated to help restore insulin independence in these patients is islet cell transplantation. However, challenges associated with transplant rejection and islet viability have prevented long-term β-cell function. Redox signaling and the production of reactive oxygen species (ROS) by recipient immune cells and transplanted islets themselves are key players in graft rejection. Therefore, dissipation of ROS generation is a viable intervention that can protect transplanted islets from immune-mediated destruction. Here, we will discuss the newly appreciated role of redox signaling and ROS synthesis during graft rejection as well as new strategies being tested for their efficacy in redox modulation during islet cell transplantation. PMID:29740396

  9. Brain Region-Dependent Rejection of Neural Precursor Cell Transplants

    Directory of Open Access Journals (Sweden)

    Nina Fainstein

    2018-04-01

    Full Text Available The concept of CNS as an immune-privileged site has been challenged by the occurrence of immune surveillance and allogeneic graft rejection in the brain. Here we examined whether the immune response to allogeneic neural grafts is determined by the site of implantation in the CNS. Dramatic regional differences were observed between immune responses to allogeneic neural precursor/stem cell (NPC grafts in the striatum vs. the hippocampus. Striatal grafts were heavily infiltrated with IBA-1+ microglia/macrophages and CD3+ T cells and completely rejected. In contrast, hippocampal grafts exhibited milder IBA-1+ cell infiltration, were not penetrated efficiently by CD3+ cells, and survived efficiently for at least 2 months. To evaluate whether the hippocampal protective effect is universal, astrocytes were then transplanted. Allogeneic astrocyte grafts elicited a vigorous rejection process from the hippocampus. CD200, a major immune-inhibitory signal, plays an important role in protecting grafts from rejection. Indeed, CD200 knock out NPC grafts were rejected more efficiently than wild type NPCs from the striatum. However, lack of CD200 expression did not elicit NPC graft rejection from the hippocampus. In conclusion, the hippocampus has partial immune-privilege properties that are restricted to NPCs and are CD200-independent. The unique hippocampal milieu may be protective for allogeneic NPC grafts, through host-graft interactions enabling sustained immune-regulatory properties of transplanted NPCs. These findings have implications for providing adequate immunosuppression in clinical translation of cell therapy.

  10. ST2 IN REJECTION OF THE TRANSPLANTED HEART

    Directory of Open Access Journals (Sweden)

    O. P. Shevchenko

    2015-01-01

    Full Text Available This review summarizes the current literature devoted to the analysis of prognostic role of ST2 biomarker in rejection of the transplanted heart. ST2 is one of the most promising diagnostic markers of the development and severity of heart failure as well as the mortality risk in patients with cardiovascular diseases. ST2 is expressed in cardiomyocytes in response to a variety of pathological processes and mechanical damage to the heart, which allows diagnosing cardiovascular diseases before clinical manifestations. Presumably, measuring the level of ST2 in heart transplant may have diagnostic and prognostic value in the assessment of graft and risk of rejection. Currently, accumulated clinical data on the role of given biomarker in heart transplantation are not enough, and further research on the relation of ST2 levels with different clinical and laboratory parameters in heart recipients is necessary. 

  11. High-sensitivity cardiac troponin I assay to screen for acute rejection in patients with heart transplant.

    Science.gov (United States)

    Patel, Parag C; Hill, Douglas A; Ayers, Colby R; Lavingia, Bhavna; Kaiser, Patricia; Dyer, Adrian K; Barnes, Aliessa P; Thibodeau, Jennifer T; Mishkin, Joseph D; Mammen, Pradeep P A; Markham, David W; Stastny, Peter; Ring, W Steves; de Lemos, James A; Drazner, Mark H

    2014-05-01

    A noninvasive biomarker that could accurately diagnose acute rejection (AR) in heart transplant recipients could obviate the need for surveillance endomyocardial biopsies. We assessed the performance metrics of a novel high-sensitivity cardiac troponin I (cTnI) assay for this purpose. Stored serum samples were retrospectively matched to endomyocardial biopsies in 98 cardiac transplant recipients, who survived ≥3 months after transplant. AR was defined as International Society for Heart and Lung Transplantation grade 2R or higher cellular rejection, acellular rejection, or allograft dysfunction of uncertain pathogenesis, leading to treatment for presumed rejection. cTnI was measured with a high-sensitivity assay (Abbott Diagnostics, Abbott Park, IL). Cross-sectional analyses determined the association of cTnI concentrations with rejection and International Society for Heart and Lung Transplantation grade and the performance metrics of cTnI for the detection of AR. Among 98 subjects, 37% had ≥1 rejection episode. cTnI was measured in 418 serum samples, including 35 paired to a rejection episode. cTnI concentrations were significantly higher in rejection versus nonrejection samples (median, 57.1 versus 10.2 ng/L; P<0.0001) and increased in a graded manner with higher biopsy scores (P(trend)<0.0001). The c-statistic to discriminate AR was 0.82 (95% confidence interval, 0.76-0.88). Using a cut point of 15 ng/L, sensitivity was 94%, specificity 60%, positive predictive value 18%, and negative predictive value 99%. A high-sensitivity cTnI assay seems useful to rule out AR in cardiac transplant recipients. If validated in prospective studies, a strategy of serial monitoring with a high-sensitivity cTnI assay may offer a low-cost noninvasive strategy for rejection surveillance. © 2014 American Heart Association, Inc.

  12. Late-onset acute rejection after living donor liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Nobuhisa Akamatsu; Yasuhiko Sugawara; Sumihito Tamura; Junichi Keneko; Yuichi Matsui; Kiyoshi Hasegawa; Masatoshi Makuuchi

    2006-01-01

    AIM: To investigate the incidence and risk factors of late-onset acute rejection (LAR) and to clarify the effectiveness of our immunosuppressive regime consisting of life-long administration of tacrolimus and steroids.METHODS: Adult living donor liver transplantation recipients (n = 204) who survived more than 6 mo after living donor liver transplantation were enrolled.Immunosuppression was achieved using tacrolimus and methylprednisolone. When adverse effects of tacrolimus were detected, the patient was switched to cyclosporine. Six months after transplantation,tacrolimus or cyclosporine was carefully maintained at a therapeutic level. The methylprednisolone dosage was maintained at 0.05 mg/kg per day by oral administration.Acute rejections that occurred more than 6 mo after the operation were defined as late-onset. The median followup period was 34 mo.RESULTS: LAR was observed in 15 cases (7%) and no chronic rejection was observed. The incidence of hyperlipidemia, chronic renal failure, new-onset posttransplantation diabetes, and deep fungal infection were 13%, 2%, 24%, and 17%, respectively. Conversion from tacrolimus to cyclosporine was required in 38 patients (19%). Multivariate analysis revealed that a cyclosporinebased regimen was significantly associated with LAR.CONCLUSION: Both LAR and drug-induced adverse events happen at a low incidence, supporting the safety and efficacy of the present immunosuppression regimen for living donor liver transplantation.

  13. [Lung transplantation: supply and demand in France].

    Science.gov (United States)

    Stern, M; Souilamas, R; Tixier, D; Mal, H

    2008-10-01

    For a decade lung transplantation has suffered from a lack of donor organs which aroused a national debate and led to planned action in collaboration with The French National Agency for Transplantation. Analysis of the stages of the process from potential donor to lung transplantation identified lung procurement as the main priority. An increase in the number of potential lung donors and revision of the acceptance criteria led to a doubling of the annual rate of lung transplantation in less than two years. In the near future we may solve the problem of donor family refusals and establish scientifically based criteria for lung acceptance to increase the rate of lung transplantation. Transplantation from non heart-beating donors and the reconditioning of ex vivo non acceptable lungs might supply additional organs to fulfill demand in the long term. The rate of lung transplantation activity in France doubled as the result of a dramatic increase of donor lung proposals. The current improvement in the results of lung transplantation might create new demands and generate future difficulties in the supply of donor lungs. New approaches, such as transplantation from non heart-beating donors and reconditioning ex vivo non acceptable lungs, should be examined in the near future.

  14. Computed tomography findings of postoperative complications in lung transplantation

    International Nuclear Information System (INIS)

    Hochhegger, Bruno; Irion, Klaus Loureiro; Marchiori, Edson; Bello, Rodrigo; Moreira, Jose; Camargo, Jose Jesus; Universidade Federal do Rio de Janeiro

    2009-01-01

    Due to the increasing number and improved survival of lung transplant recipients, radiologists should be aware of the imaging features of the postoperative complications that can occur in such patients. The early treatment of complications is important for the long-term survival of lung transplant recipients. Frequently, HRCT plays a central role in the investigation of such complications. Early recognition of the signs of complications allows treatment to be initiated earlier, which improves survival. The aim of this pictorial review was to demonstrate the CT scan appearance of pulmonary complications such as reperfusion edema, acute rejection, infection, pulmonary thromboembolism, chronic rejection, bronchiolitis obliterans syndrome, cryptogenic organizing pneumonia, post transplant lymphoproliferative disorder, bronchial dehiscence and bronchial stenosis. (author)

  15. Perturbations in the Urinary Exosome in Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; NG, Yolanda; Lee, Sangho; Nicora, Carrie D.; Qian, Weijun; Smith, Richard D.; Camp, David G.; Sarwal, Minnie M.

    2015-01-05

    Background: Urine exosomes, vesicles exocytosed into urine by all renal epithelial cell types, occur under normal physiologic and disease states. Exosome contents may mirror disease-specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed and for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Methods: Urine exosomes were isolated by centrifugal filtration from mid-stream, second morning void, urine samples collected from kidney transplant recipients with and without biopsy matched acute rejection. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Uexo) underwent mass spectrometry-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR). Results: Identifications of 1018 and 349 proteins, Uw and Uexo fractions, respectively, demonstrated a 279 protein overlap between the two urinary compartments with 25%(70) of overlapping proteins unique to Uexoand represented membrane bound proteins (p=9.31e-7). Of 349 urine exosomal proteins identified in transplant patients 220 were not previously identified in the normal urine exosomal fraction. Uexo proteins (11), functioning in the inflammatory / stress response, were more abundant in patients with biopsy-confirmed acute rejection, 3 of which were exclusive to Uexo. Uexo AR-specific biomarkers (8) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. Conclusions: A rapid urinary exosome isolation method and quantitative measurement of enriched Uexo proteins was applied. Urine proteins specific to the exosomal fraction were detected either in unfractionated urine (at low abundances) or by Uexo fraction analysis. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were

  16. Rechazo y retrasplante corneal Corneal rejection and re-transplantation

    Directory of Open Access Journals (Sweden)

    Miguel O Mokey Castellanos

    2007-06-01

    Full Text Available Se efectuó una investigación observacional análítica retrospectiva, sobre los transplantes corneales efectuados en el Servicio de Oftalmología del Hospital "Hermanos Ameijeiras. Rechazaron 76 pacientes, que se compararon con un control de 89 pacientes, que en un período similar no tuvieron rechazo. El queratocono fue la afección corneal que predominó. El primer lugar en los rechazos correspondió a queratoherpes (43,5 %. El menor índice de rechazo fue para el queratocono (8,8 %. Se analizó la multiplicidad de rechazos; y fue frecuente que se presentara un solo rechazo, aunque sí hubo congruencia entre el número de rechazos y la necesidad de retrasplantes. Se encontró que los resultados de la conducta médica o quirúrgica se relacionaban con la causa. Se calcula un índice de supervivencia (Kaplan-Meier, que concluye que en los primeros dos años existe menos posibilidad de aparición de rechazoAn retrospective observational analytical research was conducted on corneal transplants performed at Ophthalmological Service in “Hermanos Ameijeiras” hospital . Seventy six patients had graft rejection and were compared to a control group of 89 patients that did not present rejection in the same period of time. Keratoconus was the prevailing corneal problem. The highest rejection rate corresponded to keratoherpes (43,5% whereas the lowest rate was for keratoconus (8,8%. Multiplicity of rejections was analyzed and it was found that mostly one graft rejection occured, but number of rejections was associated with the need of re-transplantation. It was found that the results of medical or surgical performance were related to the cause of graft rejection. A survival index (Kaplan-Meier was estimated, which showed that occurence of graf rejection is less probable in the first two years

  17. Pulmonary rehabilitation in lung transplant candidates.

    Science.gov (United States)

    Li, Melinda; Mathur, Sunita; Chowdhury, Noori A; Helm, Denise; Singer, Lianne G

    2013-06-01

    While awaiting lung transplantation, candidates may participate in pulmonary rehabilitation to improve their fitness for surgery. However, pulmonary rehabilitation outcomes have not been systematically evaluated in lung transplant candidates. This investigation was a retrospective cohort study of 345 pre-transplant pulmonary rehabilitation participants who received a lung transplant between January 2004 and June 2009 and had available pre-transplant exercise data. Data extracted included: 6-minute walk tests at standard intervals; exercise training details; health-related quality-of-life (HRQL) measures; and early post-transplant outcomes. Paired t-tests were used to examine changes in the 6MW distance (6MWD), exercise training volume and HRQL during the pre-transplant period. We evaluated the association between pre-transplant 6MWD and transplant hospitalization outcomes. The final 6MWD prior to transplantation was only 15 m less than the listing 6MWD (n = 200; p = 0.002). Exercise training volumes increased slightly from the start of the pulmonary rehabilitation program until transplant: treadmill, increase 0.69 ml/kg/min (n = 238; p volumes are well preserved among lung transplant candidates participating in pulmonary rehabilitation, even in the setting of severe, progressive lung disease. Participants with greater exercise capacity prior to transplantation have more favorable early post-transplant outcomes. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  18. Technology and outcomes assessment in lung transplantation.

    Science.gov (United States)

    Yusen, Roger D

    2009-01-15

    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.

  19. Lung transplantation in children. Specific aspects.

    Science.gov (United States)

    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%. Copyright © 2013 SEPAR. Published by Elsevier Espana. All rights reserved.

  20. Changing Paradigms in the Management of Rejection in Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Mirela Maier

    2017-01-01

    Full Text Available Purpose of review: P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine’s relevance to the various stages of the kidney transplant cycle. Sources of information: A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016 using a combination of subject headings (MeSH and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine. The electronic database search was expanded further on particular subject headings. Findings: Available histocompatibility methods exemplify current applications of the predictive and preventive domains of P4 medicine in kidney transplant recipients’ care. Pharmacogenomics are discussed as means to facilitate personalized immunosuppression regimens and promotion of active patient participation as a means to improve adherence. Limitations: For simplicity, this review focuses on rejection. P4 medicine, however, should more broadly address health concerns in kidney transplant recipients, including competing outcomes such as infections, malignancies, and cardiovascular disease. This review highlights how biomarkers to evaluate these competing outcomes warrant validation and standardization prior to their incorporation into clinical practice. Implications: Consideration of all 4 domains of the P4 medicine framework when caring for and/or studying kidney transplant recipients has the potential of increasing therapeutic efficiency, minimizing adverse effects, decreasing health care costs, and maximizing wellness. Technologies to gauge immune competency, immunosuppression requirements, and early/reversible immune-mediated injuries are required to optimize kidney transplant care.

  1. Changing Paradigms in the Management of Rejection in Kidney Transplantation

    Science.gov (United States)

    Maier, Mirela; Takano, Tomoko; Sapir-Pichhadze, Ruth

    2017-01-01

    Purpose of review: P4 medicine denotes an evolving field of medicine encompassing predictive, preventive, personalized, and participatory medicine. Using the example of kidney allograft rejection because of donor-recipient incompatibility in human leukocyte antigens, this review outlines P4 medicine’s relevance to the various stages of the kidney transplant cycle. Sources of information: A search for English articles was conducted in Medline via OvidSP (up to August 18, 2016) using a combination of subject headings (MeSH) and free text in titles, abstracts, and author keywords for the concepts kidney transplantation and P4 medicine. The electronic database search was expanded further on particular subject headings. Findings: Available histocompatibility methods exemplify current applications of the predictive and preventive domains of P4 medicine in kidney transplant recipients’ care. Pharmacogenomics are discussed as means to facilitate personalized immunosuppression regimens and promotion of active patient participation as a means to improve adherence. Limitations: For simplicity, this review focuses on rejection. P4 medicine, however, should more broadly address health concerns in kidney transplant recipients, including competing outcomes such as infections, malignancies, and cardiovascular disease. This review highlights how biomarkers to evaluate these competing outcomes warrant validation and standardization prior to their incorporation into clinical practice. Implications: Consideration of all 4 domains of the P4 medicine framework when caring for and/or studying kidney transplant recipients has the potential of increasing therapeutic efficiency, minimizing adverse effects, decreasing health care costs, and maximizing wellness. Technologies to gauge immune competency, immunosuppression requirements, and early/reversible immune-mediated injuries are required to optimize kidney transplant care. PMID:28270929

  2. Life after a lung transplant

    DEFF Research Database (Denmark)

    Graarup, Jytte; Mogensen, Elin Lindberg; Missel, Malene

    2017-01-01

    and challenges. They had received a new chance in life and were eager to fulfil their life hopes and dreams. At the same time, they were worried about the future. Having a lung transplant implies rules that have to be followed. What are the healthy choices they are supposed to make? And will there be a tomorrow...... and psychological challenges. The interviewees were happy to get another chance to live, although some of them suffered from medical side effects, postoperative complications and psychological problems. When asked about the future, interviewees stated that life could be described as (3) a balance of joy...... physically and psychologically challenging. Interviewees were aware of the prognosis for patients following lung transplantation. They expressed feelings of worry and insecurity but still had hopes and dreams. RELEVANCE TO CLINICAL PRACTICE: The patients are troubled by both physical and psychological...

  3. Rejection with hemodynamic compromise in the current era of pediatric heart transplantation: a multi-institutional study.

    Science.gov (United States)

    Everitt, Melanie D; Pahl, Elfriede; Schechtman, Kenneth B; Zheng, Jie; Ringewald, Jeremy M; L'ecuyer, Thomas; Naftel, David C; Kirklin, James K; Blume, Elizabeth D; Bullock, Emily A; Canter, Charles E

    2011-03-01

    Survival after pediatric heart transplant has improved over time, as has the incidence of overall rejection. We studied the effect of era on the occurrence and outcome of rejection with hemodynamic compromise (HC). Data from 2227 patients who received allografts between 1993 and 2006 at 36 centers in the Pediatric Heart Transplant Study were analyzed to determine incidence, outcome, and risk factors for rejection with HC in early (1993-1999) and recent (2000-2006) eras. Rejection with HC was classified as severe (RSHC) when inotropes were used for circulatory support and mild (RMHC) when inotropes were not used. Of 1217 patients with any episode of rejection, 541 had rejection with HC. Freedom from RMHC improved at 1 year (81% vs 90%, p RMHC (87% at 1 year and 72% at 5 years, p RMHC was earlier era of transplant (HR, 1.94; 95% CI, 1.56-2.41; p RMHC has declined over time but the same era effect has not occurred with RSHC. Close follow-up after RSHC is crucial because mortality is so high. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  4. Perturbations in the Urinary Exosome in Transplant Rejection

    Directory of Open Access Journals (Sweden)

    Tara eSigdel

    2015-01-01

    Full Text Available Urine exosomes are small vesicles exocytosed into the urine by all renal epithelial cell types under normal physiologic and disease states. Urine exosomal proteins may mirror disease specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Urine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection, which were biopsy matched. The proteomes of unfractionated whole urine (Uw and urine exosomes (Ue underwent mass spectroscopy-based quantitative proteonomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR. A total of 1018 proteins were identified in Uw and 349 proteins in Ue. 279 overlapped between the two urinary compartments and 70 proteins were unique to the Ue compartment. Of 349 exosomal proteins identified from transplant patients,220 had not been previously identified in the normal Ue fraction. 11 Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with acute rejection, 3 of which are exclusive to the Ue fraction. Ue AR-specific biomarkers(8 were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. A rapid urinary exosome isolation method and quantitative measurement of enriched Ue proteins was applied. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were specific to inflammatory responses, and were not observed in the Ue fraction from normal healthy subjects. Ue specific protein alterations in renal disease provide potential mechanistic insights and offer a unique panel of sensitive biomarkers for monitoring AR.

  5. Acute appendicitis mistaken as acute rejection in renal transplant recipients.

    Directory of Open Access Journals (Sweden)

    Talwalkar N

    1994-01-01

    Full Text Available Case histories of 2 renal transplant recipients are reported who had presenting features of fever, leukocytosis and pain/tenderness over right iliac fossa and were diagnosed to be due to acute appendicitis rather than more commonly suspected acute rejection episode which has very similar features. Diagnosis of acute appendicitis was suspected on the basis of rectal examination and later confirmed by laparotomy. The purpose of this communication is to emphasize the need for proper diagnosis in patient with such presentation; otherwise wrong treatment may be received.

  6. Lung transplantation for chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Liou TG

    2013-07-01

    Full Text Available Theodore G Liou, Sanjeev M Raman, Barbara C CahillDivision of Respiratory, Critical Care and Occupational Pulmonary Medicine, Department of Medicine, School of Medicine, University of Utah, Salt Lake City, Utah, USAAbstract: Patients with end-stage chronic obstructive pulmonary disease (COPD comprise the largest single lung disease group undergoing transplantation. Selection of appropriate candidates requires consideration of specific clinical characteristics, prognosis in the absence of transplantation, and likely outcome of transplantation. Increased availability of alternatives to transplantation for end-stage patients and the many efforts to increase the supply of donor organs have complicated decision making for selecting transplant candidates. Many years of technical and clinical refinements in lung transplantation methods have improved survival and quality of life outcomes. Further advances will probably come from improved selection methods for the procedure. Because no prospective trial has been performed, and because of confounding and informative censoring bias inherent in the transplant selection process in studies of the existing experience, the survival effect of lung transplant in COPD patients remains undefined. There is a lack of conclusive data on the impact of lung transplantation on quality of life. For some patients with end-stage COPD, lung transplantation remains the only option for further treatment with a hope of improved survival and quality of life. A prospective trial of lung transplantation is needed to provide better guidance concerning survival benefit, resource utilization, and quality of life effects for patients with COPD.Keywords: outcomes, emphysema, COPD, alpha-1-antitrypsin deficiency, survival, single lung transplant, bilateral sequential single lung transplant, lung volume reduction, referral, guidelines, health related quality of life

  7. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation.

    Science.gov (United States)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold; Zemtsovski, Mikhail; Nilsson, Jens Christian; Seidelin, Casper Tobias; Perch, Michael; Iversen, Martin; Steinbrüchel, Daniel

    2014-03-01

    The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its introduction. The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died of non-EVLP-related causes, but all other recipients were alive with normal graft function at the end of our registration period. All lungs showed an improved PaO2/FiO2 ratio from a median 23.1 kPa (8.8-38.9) within the donor to 58.8 kPa (34.9-76.5) (FiO2 = 1.0) after EVLP, which corresponds to a 155% improved oxygenation. The median time to extubation, time in intensive care unit and the admission period were 1, 7 and 39 days, respectively. In the first year after the introduction of EVLP in Denmark, seven pairs of donor lungs that previously would have been rejected have been transplanted as a result of their improved function. EVLP seems to be a safe way to increase the use of marginal donor lungs. no funding was granted for the present paper. not relevant.

  8. The arcuate artery in renal transplants: An insensitive indicator of rejection

    International Nuclear Information System (INIS)

    McIntire, J.N.; Angtuaco, T.L.; Boyd, C.; Flanigan, W.J.

    1987-01-01

    The authors performed 65 duplex US examinations in 28 patients within 2 years of transplantation. During this time 15 episodes of rejection were diagnosed by US and confirmed clinically. Of the remaining 50 examinations, 14 showed negligible or absent diastolic flow (suggesting rejection) in the arcuate arteries with normal diastolic flow in the main renal, segmental, and interlobar branches. No other criteria for rejection were present in these patients. It is concluded that the arcuate artery is an insensitive indicator of transplant rejection

  9. Psychological rejection of the transplanted organ and graft dysfunction in kidney transplant patients

    Directory of Open Access Journals (Sweden)

    Látos M

    2016-06-01

    Full Text Available Melinda Látos,1 György Lázár,1 Zoltán Horváth,1 Victoria Wittmann,1 Edit Szederkényi,1 Zoltán Hódi,1 Pál Szenohradszky,1 Márta Csabai2 1Department of Surgery, Faculty of Medicine, 2Psychology Institute, University of Szeged, Szeged, Hungary Abstract: Interdisciplinary studies suggest that the mental representations of the transplanted organ may have a significant effect on the healing process. The objective of this study was to examine the representations of the transplanted organ and their relationship with emotional and mood factors, illness perceptions, and the functioning of the transplanted organ. One hundred and sixty-four kidney transplant patients were assessed using the Spielberger Anxiety Inventory, the Beck’s Depression Scale, the Posttraumatic Growth Inventory, the Brief Illness Perception Questionnaire, and the Transplanted Organ Questionnaire. Medical parameters were collected from the routine clinical blood tests (serum creatinine and estimated glomerular filtration rate levels and biopsy results. Our most outstanding results suggest that kidney-transplanted patients’ illness representations are associated with health outcomes. The Transplanted Organ Questionnaire “psychological rejection” subscale was connected with higher serum creatinine and estimated glomerular filtration rate levels. Logistic regression analysis showed that psychological rejection subscale, Brief Illness Perception Questionnaire, and Posttraumatic Growth Questionnaire total scores were associated with graft rejection. These results may serve as a basis for the development of complex treatment interventions, which could help patients to cope with the bio-psycho-social challenges of integrating the new organ as part of their body and self. Keywords: anxiety, depression, illness representations, posttraumatic growth, psychological rejection, renal transplantation

  10. Immune response and histology of humoral rejection in kidney transplantation.

    Science.gov (United States)

    González-Molina, Miguel; Ruiz-Esteban, Pedro; Caballero, Abelardo; Burgos, Dolores; Cabello, Mercedes; Leon, Miriam; Fuentes, Laura; Hernandez, Domingo

    2016-01-01

    The adaptive immune response forms the basis of allograft rejection. Its weapons are direct cellular cytotoxicity, identified from the beginning of organ transplantation, and/or antibodies, limited to hyperacute rejection by preformed antibodies and not as an allogenic response. This resulted in allogenic response being thought for decades to have just a cellular origin. But the experimental studies by Gorer demonstrating tissue damage in allografts due to antibodies secreted by B lymphocytes activated against polymorphic molecules were disregarded. The special coexistence of binding and unbinding between antibodies and antigens of the endothelial cell membranes has been the cause of the delay in demonstrating the humoral allogenic response. The endothelium, the target tissue of antibodies, has a high turnover, and antigen-antibody binding is non-covalent. If endothelial cells are attacked by the humoral response, immunoglobulins are rapidly removed from their surface by shedding and/or internalization, as well as degrading the components of the complement system by the action of MCP, DAF and CD59. Thus, the presence of complement proteins in the membrane of endothelial cells is transient. In fact, the acute form of antibody-mediated rejection was not demonstrated until C4d complement fragment deposition was identified, which is the only component that binds covalently to endothelial cells. This review examines the relationship between humoral immune response and the types of acute and chronic histological lesion shown on biopsy of the transplanted organ. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  11. Lung transplantation in the rat. III. Functional studies in iso- and allografts

    International Nuclear Information System (INIS)

    Marck, K.W.; Prop, J.; Wildevuur, C.R.

    1983-01-01

    Recently a microsurgical technique for orthotopic left lung transplantation in the rat was developed. The aim of this study was to investigate the influence of the operation itself and of an unmodified rejection reaction on the function of the transplanted rat lung. Orthotopic left lung transplantation was performed in 59 rats (34 isografts and 25 allografts). Isografts demonstrated a mean left lung perfusion of 23.1% in the first two postoperative weeks. Seven out of the 10 animals, subjected to a repeated scintigraphy 5-10 weeks later, had an increased graft perfusion, resulting in an almost normal mean left lung perfusion of 34.8%. At that time chest roentgenography revealed a good aeration of the grafts, that at autopsy had a normal aspect. Allografts showed an initial mean left lung perfusion (24.6%) similar to the isografts, which, however, declined sharply a few days later (4.3%). At that time chest roentgenography revealed totally opalescent grafts that at autopsy had the hepatized aspect characteristic of lung allograft rejection. These results of isogeneic and allogeneic lung transplantation in the rat were comparable with those of canine auto- and allotransplantation. For immunogenetic and economical reasons lung transplantation in the rat is a good alternative animal model in lung transplantation research

  12. Soluble CD30 and HLA antibodies as potential risk factors for kidney transplant rejection.

    Science.gov (United States)

    Slavcev, Antonij; Lácha, Jiri; Honsová, Eva; Sajdlová, Helena; Lodererová, Alena; Vitko, Stefan; Skibová, Jelena; Striz, Ilja

    2005-06-01

    Recent literary data suggest that high pre- and post-transplant serum levels of the soluble CD30 (sCD30) molecule may be a risk factor for acute rejection and worse prognosis of the transplanted kidney. The aim of our study was to correlate the concentrations of sCD30 and the presence of HLA antibodies as defined by flow cytometry and ELISA with the clinical course and graft prognosis after transplantation. One hundred and seventeen kidney transplant patients were included into the study. The incidence of rejection episodes, graft function and graft survival for up to 1 year post-transplant were evaluated. Soluble CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. In both patient groups, a significant decrease of sCD30 was detected 2 weeks after transplantation (104.4 U/ml before vs. 37.0 U/ml post-transplant, P sCD30 between rejecting and non-rejecting patients. Patients without rejection had lower sCD30 values (31.2 U/ml post-transplant) compared to patients who experienced rejection episodes (62.9 U/ml), P antigens and elevated concentrations of sCD30 shortly after transplantation were associated with increased risk for acute rejection in the first post-transplant year. Measurement of soluble CD30 after transplantation, taken into consideration with the presence of HLA class II antibodies, might be helpful for evaluating the potential risk for acute rejection.

  13. Post-transplant soluble CD30 levels are associated with early subclinical rejection in kidney transplantation.

    Science.gov (United States)

    Grenzi, Patricia C; Campos, Érika F; Silva, Hélio T; Felipe, Claudia R; Franco, Marcelo F; Soares, Maria F; Medina-Pestana, José O; Gerbase-DeLima, Maria

    2015-03-01

    Several studies have shown association of high pre- or post-transplant levels of soluble CD30 (sCD30) with acute rejection and poor late kidney transplant outcome. Our goal was to investigate whether sCD30 levels at month-3 post-transplant are associated with subclinical rejection, presence of CD30(+) cells within the graft, and expression of immune response genes in peripheral blood mononuclear cells. The study comprised 118 adult first kidney graft recipients, transplanted at a single center, receiving tacrolimus in low concentration. All were submitted to a protocol biopsy at month-3. Subclinical rejection was identified in 10 biopsies and sCD30 levels ≥ 61.88 ng/mL (P = 0.004), younger recipient age (P = 0.030) and non-Caucasian ethnicity (P = 0.011) were independently associated with this outcome. Rare CD30(+) cells were present in only two biopsies. There was a correlation between sCD30 levels and CD30 gene expression in peripheral blood mononuclear cells (r = 0.385, P = 0.043). These results show that high sCD30 levels are independent predictors of graft dysfunction and may contribute to patient selection protocols by indicating those who could benefit from a more thorough evaluation. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Biomarkers for the prediction of the bronchiolitis obliterans syndrome after lung transplantation

    NARCIS (Netherlands)

    Paantjens, A.W.M.

    2011-01-01

    The main limitation for overall survival after lung transplantation (LTx) is the development of chronic rejection, which is represented by the bronchiolitis obliterans syndrome (BOS). The diagnosis BOS is based on lung function testing, however, it is a surrogate marker. And because BOS is an

  15. Suicidal hanging donors for lung transplantation

    Science.gov (United States)

    Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

    2018-01-01

    Abstract In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group. Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed. No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation. PMID:29620623

  16. Lung Transplantation for Lymphangioleiomyomatosis in Japan

    Science.gov (United States)

    Ando, Katsutoshi; Okada, Yoshinori; Akiba, Miki; Kondo, Takashi; Kawamura, Tomohiro; Okumura, Meinoshin; Chen, Fengshi; Date, Hiroshi; Shiraishi, Takeshi; Iwasaki, Akinori; Yamasaki, Naoya; Nagayasu, Takeshi; Chida, Masayuki; Inoue, Yoshikazu; Hirai, Toyohiro; Seyama, Kuniaki; Mishima, Michiaki

    2016-01-01

    Background Lung transplantation has been established as the definitive treatment option for patients with advanced lymphangioleiomyomatosis (LAM). However, the prognosis after registration and the circumstances of lung transplantation with sirolimus therapy have never been reported. Methods In this national survey, we analyzed data from 98 LAM patients registered for lung transplantation in the Japan Organ Transplantation Network. Results Transplantation was performed in 57 patients as of March 2014. Survival rate was 86.7% at 1 year, 82.5% at 3 years, 73.7% at 5 years, and 73.7% at 10 years. Of the 98 patients, 21 had an inactive status and received sirolimus more frequently than those with an active history (67% vs. 5%, p<0.001). Nine of twelve patients who remained inactive as of March 2014 initiated sirolimus before or while on a waiting list, and remained on sirolimus thereafter. Although the statistical analysis showed no statistically significant difference, the survival rate after registration tended to be better for lung transplant recipients than for those who awaited transplantation (p = 0.053). Conclusions Lung transplantation is a satisfactory therapeutic option for advanced LAM, but the circumstances for pre-transplantation LAM patients are likely to alter with the use of sirolimus. PMID:26771878

  17. Neurological complications following adult lung transplantation

    NARCIS (Netherlands)

    Mateen, F. J.; Dierkhising, R. A.; Rabinstein, A. A.; van de Beek, D.; Wijdicks, E. F. M.

    2010-01-01

    The full spectrum of neurologic complications and their impact on survival in lung recipients has not been reported. A retrospective cohort review of the Mayo Clinic Lung Transplant Registry (1988-2008) was performed to determine the range of neurologic complications in a cohort of adult lung

  18. Primary Graft Dysfunction and Long-Term Outcomes Following Lung Transplantation

    OpenAIRE

    DerHovanessian, Ariss

    2012-01-01

    Background: Primary graft dysfunction (PGD) is an early complication of lung transplantation associated with poor early outcomes, however less is known about its prolonged effects on morbidity and mortality. We hypothesized that PGD is associated with long-term mortality and chronic rejection in the form of bronchiolitis obliterans syndrome. Methods: A retrospective study of 279 adult lung transplant recipients between 2000 and 2007 was performed. PGD grade was determined both immediately ...

  19. The Induction of IgM and IgG Antibodies against HLA or MICA after Lung Transplantation

    OpenAIRE

    Paantjens, Annelieke W. M.; van de Graaf, Ed A.; Kwakkel-van Erp, Johanna M.; Hoefnagel, Tineke; van Ginkel, Walter G. J.; Fakhry, Farzia; van Kessel, Diana A.; van den Bosch, Jules M. M.; Otten, Henny G.

    2011-01-01

    The production of IgG HLA antibodies after lung transplantation (LTx) is considered to be a major risk factor for the development of chronic rejection, represented by the bronchiolitis obliterans syndrome (BOS). It has recently been observed that elevated levels of IgM HLA antibodies also correlates with the development of chronic rejection in heart and kidney transplantation. This study investigates the relationship between IgM and IgG antibodies against HLA and MICA after lung transplantati...

  20. Waiting narratives of lung transplant candidates.

    Science.gov (United States)

    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.

  1. Waiting Narratives of Lung Transplant Candidates

    Directory of Open Access Journals (Sweden)

    Maria T. Yelle

    2013-01-01

    Full Text Available 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.

  2. Increase of peripheral Th17 lymphocytes during acute cellular rejection in liver transplant recipients.

    Science.gov (United States)

    Fan, Hua; Li, Li-Xin; Han, Dong-Dong; Kou, Jian-Tao; Li, Ping; He, Qiang

    2012-12-15

    Although many human inflammatory and autoimmune diseases were previously considered to be mediated by T helper type 1 (Th1) cells, the recently described Th17 cells play dominant roles in several of these diseases. We and others speculated that allograft rejection after organ transplantation may also involve Th17 cells. Episodes of acute rejection occur in 30% of liver transplants. This study aimed to determine the frequency of circulating Th17 cells in patients who had received liver transplants for benign end-stage liver disease and to identify any association between acute rejection episodes and levels of Th17 cells in the peripheral blood. A prospective study compared Th17 cells from 76 consecutive benign end-stage liver disease patients who had undergone orthotopic liver transplantation from 2007 to 2011 with those from 20 age-matched healthy individuals. Peripheral blood samples were collected at different time points within one year after transplant. Blood samples and liver biopsies were also collected at the diagnosis of acute rejection. Percentages of circulating CD4+IL-17+ cells were measured by flow cytometry. The transplant patients were classified into two groups: a rejection group consisting of 17 patients who had an episode of acute rejection, and a non-rejection group comprising the remaining 59 patients with no acute rejection episodes. Percentages of circulating Th17 cells were compared between the two groups and controls. The levels of circulating CD4+IL-17+ T cells in the rejection group were higher during acute rejection than those in the non-rejection group (2.56+/-0.43% versus 1.79+/-0.44%, Pblood was positively correlated with the rejection activity index (r=0.79, P=0.0002). Circulating Th17 cells may be useful as a surrogate marker for predicting acute rejection in liver transplant recipients.

  3. Lung Cancer in Renal Transplant Recipients

    Directory of Open Access Journals (Sweden)

    Jozicic Mirela

    2016-06-01

    Full Text Available Introduction. Although the incidence of malignancy has increased after solid organ transplantation, data on lung cancer in this group of patients is scarce. The aim of this study was to determine clinical characteristics and outcome of patients who developed lung cancer after renal transplantation. Methods. Among a cohort of 1658 patients who received a transplant at our institution and were followedup between 1973 and 2014, five patients developed lung cancer. We analyzed risk factors, transplantation characteristics, treatment options and survival. Results. Lung cancer was diagnosed in 5 patients (0.3%. Time to diagnosis after the transplant procedure ranged from 26 to 156 months (mean 115 months. All of them had a smoking history. Tumors were classified as IIB (20%, IIIA (40%, and IV (40%. Histological types included adenocarcinoma (80% and there was one case of sarcomatoid carcinoma (20%. One patient had concomitant thyroid papillary carcinoma. Radiotherapy was applied in 2 patients, 2 underwent chemotherapy (erlotinib and combination of carboplatinum and etopozide in one patient each, and 2 died within one month after the diagnosis from disseminated malignant disease. Patients with stage IIIA survived 14 and 24 months after the diagnosis. The patient with sarcomatoid cancer underwent thoracotomy with a complete resection, lost his graft function and died 7 months after the diagnosis. Conclusion. Lung cancer is relatively rare malignancy in renal transplant recipients, but associated with high mortality. Smoking is a significant risk factor, thus smoking cessation should be promoted among renal transplant recipients, as well as regular screening for lung cancer.

  4. Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody Mediated Rejection After Vascularized Composite Allotransplantation

    Science.gov (United States)

    2017-10-01

    Award Number: W81XWH-16-1-0664 TITLE: Autologous Hematopoietic Stem Cell Transplantation to Prevent Antibody-Mediated Rejection after...Annual 3. DATES COVERED 15 Sep 2016 – 14 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Autologous Hematopoietic Stem Cell Transplantation to...sensitization, autologous hematopoietic stem cell transplantation, antibody mediated rejection, donor specific antibodies 16. SECURITY CLASSIFICATION OF

  5. 111-Indium-labelled platelets for diagnosis of acute kidney transplant rejection and monitoring of prostacyclin anti-rejection treatment

    International Nuclear Information System (INIS)

    Leithner, C.; Pohanka, E.; Schwarz, M.; Sinzinger, H.; Syre, G.

    1984-01-01

    33 patients were examined daily under a gamma camera after weekly injections of 111-In-labelled autologous platelets over a period of at least 4 weeks after transplantation. A group of 33 patients with long-term stable and well-functioning grafts served as controls. By means of a computerized recording technique, platelet trapping in the graft was measured and expressed as platelet-uptake index (PUI). The method worked well for the early diagnosis of acute rejection signified by an increase in PUI, accompanied by a shortening of platelet half life (t/2). 6 patients suffering from acute rejection received infusions of prostacyclin in addition to conventional high-dose methylprednisolone therapy. In 4 cases the PUI decreased again and an improvement in graft function was observed. Prostacyclin infusion treatment was applied also in 12 patients with histologically-proven chronic transplant rejection. Decreased platelet consumption by the graft and a temporary improvement in transplant function were achieved. We suggest that prostacyclin could enrich the possibilities of anti-rejection treatment by providing a tool for the suppression of platelet trapping in the graft. The platelet scan served as a useful method for the early detection of acute rejection, as well as the monitoring of prostacyclin anti-rejection treatment. (Autor)

  6. Lung Transplantation in Patients with Pulmonary Hypertension

    Science.gov (United States)

    ... 00:00 Lung Transplantation in Patients with Pulmonary Hypertension Consensus Statements Issued by the Scientific Leadership Council ... a treatment option for selected patients with pulmonary hypertension (PH) when medical therapy is no longer effective. ...

  7. Late antibody-mediated rejection after ABO-incompatible kidney transplantation during Gram-negative sepsis

    NARCIS (Netherlands)

    A. de Weerd (Annelies); A.G. Vonk (Alieke); H. van der Hoek (Hans); M. van Groningen (Marian); W. Weimar (Willem); M.G.H. Betjes (Michiel); M. Agteren (Madelon)

    2014-01-01

    textabstractBackground: The major challenge in ABO-incompatible transplantation is to minimize antibody-mediated rejection. Effective reduction of the anti-ABO blood group antibodies at the time of transplantation has made ABO-incompatible kidney transplantation a growing practice in our hospital

  8. High pre-transplant soluble CD30 levels are predictive of the grade of rejection.

    Science.gov (United States)

    Rajakariar, Ravindra; Jivanji, Naina; Varagunam, Mira; Rafiq, Mohammad; Gupta, Arun; Sheaff, Michael; Sinnott, Paul; Yaqoob, M M

    2005-08-01

    In renal transplantation, serum soluble CD30 (sCD30) levels in graft recipients are associated with increased rejection and graft loss. We investigated whether pre-transplant sCD30 concentrations are predictive of the grade of rejection. Pre-transplant sera of 51 patients with tubulointerstitial rejection (TIR), 16 patients with vascular rejection (VR) and an age-matched control group of 41 patients with no rejection (NR) were analyzed for sCD30. The transplant biopsies were immunostained for C4d. The median sCD30 level was significantly elevated in the group with VR (248 Units (U)/mL, range: 92-802) when compared with TIR (103 U/mL, range: 36-309, psCD30 levels compared to NR. Based on C4d staining, a TH2 driven process, the median sCD30 levels were significantly raised in C4d+ patients compared with C4d- group (177 U/mL vs. 120 U/mL, psCD30 levels measured at time of transplantation correlate with the grade of rejection. High pre-transplant levels are associated with antibody-mediated rejection which carries a poorer prognosis. sCD30 could be another tool to assess immunological risk prior to transplantation and enable a patient centered approach to immunosuppression.

  9. Unilateral lung transplantation for pulmonary fibrosis.

    Science.gov (United States)

    1986-05-01

    Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

  10. [B-type natriuretic peptide assessment in the diagnosis of rejection after pediatric heart transplant].

    Science.gov (United States)

    Sylos, Cristina de; Azeka, Estela; Kajita, Luis; Benvenutti, Luis; Strunz, Célia Cassaro; Branco, Klébia Castello; Riso, Arlindo Almeida; Tanamati, Carla; Jatene, Marcelo; Barbero-Marcial, Miguel

    2009-03-01

    Rejection is one of the major causes of mortality following pediatric heart transplant. B-type natriuretic peptide (BNP) has been studied as a method for the diagnosis of acute rejection, especially in adult patients undergoing heart transplant. To correlate serum BNP levels with acute rejection as diagnosed by endomyocardial biopsy in patients of the pediatric heart transplant group. A total of 50 BNP samples were collected from 33 children in the postoperative period of heart transplant, and data on age, gender, skin color, blood group, immune panel, follow-up time after transplant, functional class, immunosuppressive regimen used and number of rejections were analyzed. Thirty three children with median age of 10.13 years were analyzed; of these, 54% were females and 78% were Caucasians. BNP levels were determined at a mean time from transplant of 4.25 years. Nine episodes of rejection were diagnosed in eight patients (27%) by means of endomyocardial biopsy; of these, three were grade 3A, five were grade 2, and one had humoral rejection. At the moment of biopsy, most patients were asymptomatic. The mean serum BNP level was 77.18 pg/ml, with 144.22 pg/ml in the group with rejection and 62.46 pg/ml in the group without rejection, with p = 0.02. Asymptomatic children can present acute rejection in the postoperative period of heart transplant. Serum BNP levels show a statistically significant difference in the group with rejection and thus can be an additional method in the diagnosis of cardiac rejection.

  11. The Role of Tissue-Resident Donor T Cells in Rejection of Clinical Face Transplants

    Science.gov (United States)

    2017-10-01

    cells contribute to VCA rejection, and that pathogenic T cells (both donor and recipient-derived) are detectable in blood during rejection to serve as...AWARD NUMBER: W81XWH-16-1-0760 TITLE: The role of tissue-resident donor T cells in rejection of clinical face transplants PRINCIPAL...AND SUBTITLE The role of tissue-resident donor T cells in rejection of clinical face transplants 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1

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

    Science.gov (United States)

    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 donor organs and resulted in successful transplants with lungs that would have otherwise been rejected (ClinicalTrials.gov number: NCT01967953). © 2014 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT.

  13. Peripheral blood transcriptome sequencing reveals rejection-relevant genes in long-term heart transplantation.

    Science.gov (United States)

    Chen, Yan; Zhang, Haibo; Xiao, Xue; Jia, Yixin; Wu, Weili; Liu, Licheng; Jiang, Jun; Zhu, Baoli; Meng, Xu; Chen, Weijun

    2013-10-03

    Peripheral blood-based gene expression patterns have been investigated as biomarkers to monitor the immune system and rule out rejection after heart transplantation. Recent advances in the high-throughput deep sequencing (HTS) technologies provide new leads in transcriptome analysis. By performing Solexa/Illumina's digital gene expression (DGE) profiling, we analyzed gene expression profiles of PBMCs from 6 quiescent (grade 0) and 6 rejection (grade 2R&3R) heart transplant recipients at more than 6 months after transplantation. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out in an independent validation cohort of 47 individuals from three rejection groups (ISHLT, grade 0,1R, 2R&3R). Through DGE sequencing and qPCR validation, 10 genes were identified as informative genes for detection of cardiac transplant rejection. A further clustering analysis showed that the 10 genes were not only effective for distinguishing patients with acute cardiac allograft rejection, but also informative for discriminating patients with renal allograft rejection based on both blood and biopsy samples. Moreover, PPI network analysis revealed that the 10 genes were connected to each other within a short interaction distance. We proposed a 10-gene signature for heart transplant patients at high-risk of developing severe rejection, which was found to be effective as well in other organ transplant. Moreover, we supposed that these genes function systematically as biomarkers in long-time allograft rejection. Further validation in broad transplant population would be required before the non-invasive biomarkers can be generally utilized to predict the risk of transplant rejection. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. Pre-transplant immune state defined by serum markers and alloreactivity predicts acute rejection after living donor kidney transplantation.

    Science.gov (United States)

    Vondran, Florian W R; Timrott, Kai; Kollrich, Sonja; Steinhoff, Ann-Kristin; Kaltenborn, Alexander; Schrem, Harald; Klempnauer, Juergen; Lehner, Frank; Schwinzer, Reinhard

    2014-09-01

    Acute rejection (AR) remains a major cause for long-term kidney allograft failure. Reliable immunological parameters suitable to define the pre-transplant immune state and hence the individual risk of graft rejection are highly desired to preferably adapt the immunosuppressive regimen in advance. Donor and third party alloreactivities were determined by mixed lymphocyte cultures. Soluble forms of CD25, CD30, and CD44 were detected in patients' serum by ELISA. Various lymphocyte subpopulations were measured using flow cytometry. All patients received triple immunosuppression (tacrolimus/mycophenolate mofetil/steroids) and were grouped according to biopsy results within the first year: rejection-free (RF, n = 13), borderline (BL, n = 5), or acute rejection (AR, n = 7). Patients with AR showed the highest pre-transplant alloreactivities and serum levels (sCD25/sCD30/sCD44) according to the pattern RF transplant frequencies of CD4(+) /CD8(+) T cells lacking CD28, but lower numbers of CD8(+) CD161(bright) T cells and NK cells than RF individuals. Pre-transplant immune state defined by alloreactivity, serum markers, and particular lymphocyte subsets seems to correlate with occurrence of graft rejection after kidney transplantation. A prognostic score based on pre-transplant serum levels has shown great potential for prediction of rejection episodes and should be further evaluated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. High serum soluble CD30 does not predict acute rejection in liver transplant patients.

    Science.gov (United States)

    Matinlauri, I; Höckerstedt, K; Isoniemi, H

    2006-12-01

    Increased pre- and posttransplantation values of soluble CD30 (sCD30) have been shown to be associated with acute kidney transplant rejection. We sought to study whether high sCD30 could predict rejection early after liver transplantation. The study population included 54 consecutive liver transplant patients, whose samples were collected before liver transplantation and at discharge, which was at a mean time of 3 weeks after transplantation. During the first 6 months posttransplantation, 22 patients experienced an acute rejection episode. Serum sCD30 concentrations were measured by an enzyme-linked immunoassay; changes in serum sCD30 levels posttransplantation were also expressed as relative values compared with pretransplantation results. Liver patients before transplantation displayed higher serum sCD30 values compared with healthy controls: mean values +/- SD were 93 +/- 58 IU/mL vs 17 +/- 8 IU/mL, respectively. At 3 weeks after transplantation the mean sCD30 concentration in liver transplant patients decreased to 59 +/- 42 IU/mL (P = .005). The mean pretransplantation serum sCD30 value was slightly lower among rejecting vs nonrejecting patients: 78 +/- 43 IU/mL vs 104 +/- 65 IU/mL (P = NS). Posttransplantation values in both groups decreased significantly: 47 +/- 34 IU/mL in patients with rejection (P = .014) vs 69 +/- 45 IU/mL in patients without rejection (P = .012). The relative value at 3 weeks posttransplantation decreased slightly more among patients with vs without rejection (70% vs 88%; NS). No correlation was found between serum sCD30 and anti-HLA class I antibodies or crossmatch positivity. In conclusion, neither pre- nor posttransplantation sCD30 levels were associated with acute rejection in liver transplant patients.

  16. Soluble CD30 in renal transplant recipients: is it a good biomarker to predict rejection?

    Science.gov (United States)

    Azarpira, Negar; Aghdaie, Mahdokht Hosein; Malekpour, Zahra

    2010-01-01

    It has been suggested that the serum soluble CD30 (sCD30) level may be a poten-tial marker for the prediction of acute allograft rejection in kidney transplant recipients. Therefore, its serum concentrations might offer a promising non-invasive tool to recognize patients with an increased risk for developing an acute graft rejection. We retrospectively correlate pre and post transplant level on post transplant graft survival, incidence of acute rejection and graft function using stored serum samples. Ninety-nine patients were divided in two separate groups: Group A in whom sample collection was done one day before transplantation and Group B where sample collection was done five days after transplantation. Younger recipients (aged less than 20 years) had higher sCD30 levels (P= 0.02). There was neither significant difference in the incidence of acute rejection nor incomplete response rate after anti rejection therapy in relation to pre transplant or post transplant sCD30. We could not find a significantly inferior graft survival rate in the high sCD30 group. In conclusion, younger patients had higher sCD30 concentrations however no correlation existed between the serum concentrations and occurrence of rejection episodes or graft survival.

  17. Computed tomography findings of postoperative complications in lung transplantation; Achados tomograficos nas complicacoes pos-operatorias do transplante pulmonar

    Energy Technology Data Exchange (ETDEWEB)

    Hochhegger, Bruno; Irion, Klaus Loureiro; Marchiori, Edson; Bello, Rodrigo; Moreira, Jose; Camargo, Jose Jesus [Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS (Brazil). Postgraduate Program in Respiratory Sciences; Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Postgraduate Program in Radiological Sciences], e-mail: brunorgs@mail.ufsm.br

    2009-03-15

    Due to the increasing number and improved survival of lung transplant recipients, radiologists should be aware of the imaging features of the postoperative complications that can occur in such patients. The early treatment of complications is important for the long-term survival of lung transplant recipients. Frequently, HRCT plays a central role in the investigation of such complications. Early recognition of the signs of complications allows treatment to be initiated earlier, which improves survival. The aim of this pictorial review was to demonstrate the CT scan appearance of pulmonary complications such as reperfusion edema, acute rejection, infection, pulmonary thromboembolism, chronic rejection, bronchiolitis obliterans syndrome, cryptogenic organizing pneumonia, post transplant lymphoproliferative disorder, bronchial dehiscence and bronchial stenosis. (author)

  18. A common rejection module (CRM) for acute rejection across multiple organs identifies novel therapeutics for organ transplantation.

    Science.gov (United States)

    Khatri, Purvesh; Roedder, Silke; Kimura, Naoyuki; De Vusser, Katrien; Morgan, Alexander A; Gong, Yongquan; Fischbein, Michael P; Robbins, Robert C; Naesens, Maarten; Butte, Atul J; Sarwal, Minnie M

    2013-10-21

    Using meta-analysis of eight independent transplant datasets (236 graft biopsy samples) from four organs, we identified a common rejection module (CRM) consisting of 11 genes that were significantly overexpressed in acute rejection (AR) across all transplanted organs. The CRM genes could diagnose AR with high specificity and sensitivity in three additional independent cohorts (794 samples). In another two independent cohorts (151 renal transplant biopsies), the CRM genes correlated with the extent of graft injury and predicted future injury to a graft using protocol biopsies. Inferred drug mechanisms from the literature suggested that two FDA-approved drugs (atorvastatin and dasatinib), approved for nontransplant indications, could regulate specific CRM genes and reduce the number of graft-infiltrating cells during AR. We treated mice with HLA-mismatched mouse cardiac transplant with atorvastatin and dasatinib and showed reduction of the CRM genes, significant reduction of graft-infiltrating cells, and extended graft survival. We further validated the beneficial effect of atorvastatin on graft survival by retrospective analysis of electronic medical records of a single-center cohort of 2,515 renal transplant patients followed for up to 22 yr. In conclusion, we identified a CRM in transplantation that provides new opportunities for diagnosis, drug repositioning, and rational drug design.

  19. Graft rejection after hematopoietic cell transplantation with nonmyeloablative conditioning

    DEFF Research Database (Denmark)

    Masmas, T.N.; Petersen, S.L.; Madsen, H.O.

    2008-01-01

    over time. The storage temperature of the apheresis products was identified as a risk factor for rejection. Storage of the apheresis products at 5 degrees C diminished the risk of rejection. Low donor T cell chimerism at Day +14 significantly increased the risk of rejection. Seven patients were...

  20. Beneficial Immune Effects of Myeloid-Related Proteins in Kidney Transplant Rejection

    NARCIS (Netherlands)

    Rekers, N. V.; Bajema, I. M.; Mallat, M. J. K.; Petersen, B.; Anholts, J. D. H.; Swings, G. M. J. S.; van Miert, P. P. M. C.; Kerkhoff, C.; Roth, J.; Popp, D.; van Groningen, M. C.; Baeten, D.; Goemaere, N.; Kraaij, M. D.; Zandbergen, M.; Heidt, S.; van Kooten, C.; de Fijter, J. W.; Claas, F. H. J.; Eikmans, M.

    2016-01-01

    Acute rejection is a risk factor for inferior long-term kidney transplant survival. Although T cell immunity is considered the main effector in clinical acute rejection, the role of myeloid cells is less clear. Expression of S100 calcium-binding protein A8 (S100A8) and S100A9 was evaluated in 303

  1. Significance of {sup 99m}Tc-tin Colloid Scan in Rejection of Transplanted Kidney

    Energy Technology Data Exchange (ETDEWEB)

    Oh, Ha Young; Kim, Seung Taik; Park, Seon Yang; Kim, Sung Yang; Lee, Myung Chul; Cho, Bo Youn; Lee, Jung Sang; Koh, Chang Soon [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1982-09-15

    Renal transplant uptake of {sup 99m}Tc-tin colloid was evaluated in 26 patients. Seventy-seven examinations were performed comparing transplant with bone marrow activity, clinical and/or pathological diagnosis. There were 13 instances of acute rejection; 7 of these exhibited slight uptake of radiocolloid in the renal transplant, 1 had marked uptake, and 5 had no evidence of uptake. There were 7 instances of chronic rejection; 5 of which demonstrated marked transplant uptake of radiocolloid, 1 had slight uptake, and 1 had no evidence of uptake. There were 2 instances of acute tubular necrosis and 55 instances of normal transplant function, but none of these exhibited transplant uptake of radiocolloid. From the result, the uptake of {sup 99m}Tc-tin colloid by renal transplant appears to signal rejection as long as the vascular supply is not severely compromised. Acute rejection may be represented by slight radiocolloid uptake, and chronic rejection by marked uptake when compared to bone marrow activity.

  2. Role of Soluble ST2 as a Marker for Rejection after Heart Transplant

    OpenAIRE

    Lee, Ga Yeon; Choi, Jin-Oh; Ju, Eun-Seon; Lee, Yoo-Jung; Jeon, Eun-Seok

    2016-01-01

    Background and Objectives Endomyocardial biopsy is obligatory during the first year after heart transplant (HTx) for the surveillance of acute rejection. Previous attempts using cardiac biomarkers for the detection of rejection failed to show enough evidence to substitute endomyocardial biopsy. Therefore, this study sought the possibility of using soluble ST2 (sST2), a novel cardiovascular marker, as a surrogate marker for acute allograft rejection after HTx. Subjects and Methods A total of 4...

  3. Life after a lung transplant: a balance of joy and challenges.

    Science.gov (United States)

    Graarup, Jytte; Mogensen, Elin Lindberg; Missel, Malene; Berg, Selina Kikkenborg

    2017-11-01

    To describe patients' experiences throughout the first four months post-lung transplant. Health professionals are familiar with the fact that patients' average survival after a lung transplant is about seven years and that 74% of these patients reject new organs within the first two years. By contrast, knowledge of these patients' perspectives after lung transplantation is scant. A qualitative study was conducted between May 2013-May 2014 in which 26 interviewees participated - four months post-transplant - based on a semistructured interview guide. The data were inductively analysed using a content thematic approach within a phenomenological and hermeneutic frame. The main findings in the study reveal that (1) having a lung transplant is an overwhelming experience, which for some patients includes (2) troubling physical and psychological challenges. The interviewees were happy to get another chance to live, although some of them suffered from medical side effects, postoperative complications and psychological problems. When asked about the future, interviewees stated that life could be described as (3) a balance of joy and challenges. They had received a new chance in life and were eager to fulfil their life hopes and dreams. At the same time, they were worried about the future. Having a lung transplant implies rules that have to be followed. What are the healthy choices they are supposed to make? And will there be a tomorrow? Having a lung transplant is described as an overwhelming experience because of the improvement in the physical function of the body. Patients were grateful to family, friends and healthcare professionals for supporting them. The first four months post-transplantation were described as both physically and psychologically challenging. Interviewees were aware of the prognosis for patients following lung transplantation. They expressed feelings of worry and insecurity but still had hopes and dreams. The patients are troubled by both physical and

  4. Pulmonary thromboembolism as a complication of lung transplantation

    DEFF Research Database (Denmark)

    Kristensen, Anna Warncke; Mortensen, Jann; Berg, Ronan M G

    2017-01-01

    Post-transplantation mortality after lung transplantation (LTX) is higher than for other solid organ transplantations. Thoracic surgery is associated with increased risk of thromboembolic complications, and as LTX recipients lack the collateral bronchial circulation, pulmonary thromboembolism (PTE...

  5. Ex Vivo Model of Human Penile Transplantation and Rejection: Implications for Erectile Tissue Physiology.

    Science.gov (United States)

    Sopko, Nikolai A; Matsui, Hotaka; Lough, Denver M; Miller, Devin; Harris, Kelly; Kates, Max; Liu, Xiaopu; Billups, Kevin; Redett, Richard; Burnett, Arthur L; Brandacher, Gerald; Bivalacqua, Trinity J

    2017-04-01

    Penile transplantation is a potential treatment option for severe penile tissue loss. Models of human penile rejection are lacking. Evaluate effects of rejection and immunosuppression on cavernous tissue using a novel ex vivo mixed lymphocyte reaction (MLR) model. Cavernous tissue and peripheral blood mononuclear cells (PBMCs) from 10 patients undergoing penile prosthesis operations and PBMCs from a healthy volunteer were obtained. Ex vivo MLRs were prepared by culturing cavernous tissue for 48h in media alone, in media with autologous PBMCs, or in media with allogenic PBMCs to simulate control, autotransplant, and allogenic transplant conditions with or without 1μM cyclosporine A (CsA) or 20nM tacrolimus (FK506) treatment. Rejection was characterized by PBMC flow cytometry and gene expression transplant array. Cavernous tissues were evaluated by histomorphology and myography to assess contraction and relaxation. Data were analyzed using two-way analysis of variance and unpaired Student t test. Flow cytometry and tissue array demonstrated allogenic PBMC activation consistent with rejection. Rejection impaired cavernous tissue physiology and was associated with cellular infiltration and apoptosis. CsA prevented rejection but did not improve tissue relaxation. CsA treatment impaired relaxation in tissues cultured without PBMCs compared with media and FK506. Study limitations included the use of penile tissue with erectile dysfunction and lack of cross-matching data. This model could be used to investigate the effects of penile rejection and immunosuppression. Additional studies are needed to optimize immunosuppression to prevent rejection and maximize corporal tissue physiology. This report describes a novel ex vivo model of human penile transplantation rejection. Tissue rejection impaired erectile tissue physiology. This report suggests that cyclosporin A might hinder corporal physiology and that other immunosuppressant agents, such as FK506, might be better suited

  6. Physical activity levels early after lung transplantation.

    Science.gov (United States)

    Wickerson, Lisa; Mathur, Sunita; Singer, Lianne G; Brooks, Dina

    2015-04-01

    Little is known of the early changes in physical activity after lung transplantation. The purposes of this study were: (1) to describe physical activity levels in patients up to 6 months following lung transplantation and (2) to explore predictors of the change in physical activity in that population. This was a prospective cohort study. Physical activity (daily steps and time spent in moderate-intensity activity) was measured using an accelerometer before and after transplantation (at hospital discharge, 3 months, and 6 months). Additional functional measurements included submaximal exercise capacity (measured with the 6-Minute Walk Test), quadriceps muscle torque, and health-related quality of life (measured with the Medical Outcomes Study 36-Item Short-Form Health Survey 36 [SF-36] and the St George's Respiratory Questionnaire). Thirty-six lung transplant recipients (18 men, 18 women; mean age=49 years, SD=14) completed posttransplant measurements. Before transplant, daily steps were less than a third of the general population. By 3 months posttransplant, the largest improvement in physical activity had occurred, and level of daily steps reached 55% of the general population. The change in daily steps (pretransplant to 3 months posttransplant) was inversely correlated with pretransplant 6-minute walk distance (r=-.48, P=.007), daily steps (r=-.36, P=.05), and SF-36 physical functioning (SF-36 PF) score (r=-.59, P=.0005). The SF-36 PF was a significant predictor of the change in physical activity, accounting for 35% of the variation in change in daily steps. Only individuals who were ambulatory prior to transplant and discharged from the hospital in less than 3 months were included in the study. Physical activity levels improve following lung transplantation, particularly in individuals with low self-reported physical functioning. However, the majority of lung transplant recipients remain sedentary between 3 to 6 months following transplant. The role of exercise

  7. Fusarium Infection in Lung Transplant Patients

    Science.gov (United States)

    Carneiro, Herman A.; Coleman, Jeffrey J.; Restrepo, Alejandro; Mylonakis, Eleftherios

    2013-01-01

    Fusarium is a fungal pathogen of immunosuppressed lung transplant patients associated with a high mortality in those with severe and persistent neutropenia. The principle portal of entry for Fusarium species is the airways, and lung involvement almost always occurs among lung transplant patients with disseminated infection. In these patients, the immunoprotective mechanisms of the transplanted lungs are impaired, and they are, therefore, more vulnerable to Fusarium infection. As a result, fusariosis occurs in up to 32% of lung transplant patients. We studied fusariosis in 6 patients following lung transplantation who were treated at Massachusetts General Hospital during an 8-year period and reviewed 3 published cases in the literature. Cases were identified by the microbiology laboratory and through discharge summaries. Patients presented with dyspnea, fever, nonproductive cough, hemoptysis, and headache. Blood tests showed elevated white blood cell counts with granulocytosis and elevated inflammatory markers. Cultures of Fusarium were isolated from bronchoalveolar lavage, blood, and sputum specimens. Treatments included amphotericin B, liposomal amphotericin B, caspofungin, voriconazole, and posaconazole, either alone or in combination. Lung involvement occurred in all patients with disseminated disease and it was associated with a poor outcome. The mortality rate in this group of patients was high (67%), and of those who survived, 1 patient was treated with a combination of amphotericin B and voriconazole, 1 patient with amphotericin B, and 1 patient with posaconazole. Recommended empirical treatment includes voriconazole, amphotericin B or liposomal amphotericin B first-line, and posaconazole for refractory disease. High-dose amphotericin B is recommended for treatment of most cases of fusariosis. The echinocandins (for example, caspofungin, micafungin, anidulafungin) are generally avoided because Fusarium species have intrinsic resistance to them. Treatment

  8. Psychosocial and financial aspects of lung transplantation.

    Science.gov (United States)

    Smolin, T L; Aguiar, L J

    1996-09-01

    This article summarizes the many psychosocial phases a patient will encounter during his or her transplantation experience and the ways the social worker can assist during this time. These include supportive services such as facilitating support groups and orientation programs, counseling, and crisis intervention. Also of importance is the financing of lung transplantation and its many associated costs, such as immunosuppressive medications and temporary housing. With the rise in managed care, the role of the transplant financial coordinator is of increasing importance from both a fiscal perspective and customer service standpoint for both the patient and the institution.

  9. Pharmacologic strategies in the prevention and treatment of corneal transplant rejection.

    Science.gov (United States)

    Tabbara, Khalid F

    2008-06-01

    Corneal transplantation remains one of the most successful organ transplantation procedures in humans. The unique structure of the cornea, with its absence of blood vessels and corneal lymphatic, allows the survival of corneal allograft. Recent advances in sutures, storage media, microsurgical instrumentation, and new pharmacological strategies have greatly improved the success of corneal transplantation and the prevention of corneal allograft rejection. Our strategies in the management and prevention of corneal graft rejection can modify and improve the survival of corneal allografts. Preoperative evaluation, understanding the risk factors, and management of ocular surface disorders may greatly improve the survival of the corneal transplant. Early recognition of corneal allograft rejection and aggressive treatment may improve the survival of the corneal graft. Furthermore, patients who undergo corneal transplantation should be maintained under close ophthalmic surveillance and patients should be informed to report immediately whenever symptoms of corneal graft rejection occur. The mainstay of therapy is topical corticosteroids. In severe cases, periocular, intravenous, and oral corticosteroids therapy can be rendered. New therapeutic modalities such as cyclosporine, tacrolimus, daclizumab, mycophenolate mofetil, leflunomide, rapamycin, and others may prove to be of help in the prevention and treatment of corneal graft rejection. Early recognition of corneal graft rejection and prompt treatment are mandatory for the successful survival of the corneal allograft.

  10. Increased deoposition of 111indium labelled platelets in chronically rejected kidney transplants

    International Nuclear Information System (INIS)

    Leithner, C.; Syre, G.

    1982-01-01

    Increased deposition of 111 In-oxine labelled autologous platelets in chronically rejected kidney transplants was demonstrated using a gamma-camera and by measurement of a platelet uptake index (PUI). In this group of patients the PUI correlated indirectly with the platelet half-life and was statistically different from the PUI found in stable transplant patients who acted as controls. It is therefore suggested that platelets may play a key role in chronic rejection by the release of a mitogenic factor which promotes the development of obliterative arterial lesions in the transplant. (orig.)

  11. Rhoh deficiency reduces peripheral T-cell function and attenuates allogenic transplant rejection

    DEFF Research Database (Denmark)

    Porubsky, Stefan; Wang, Shijun; Kiss, Eva

    2011-01-01

    better graft function. This effect was independent of the lower T-cell numbers in Rhoh-deficient recipients, because injection of equal numbers of Rhoh-deficient or control T cells into kidney transplanted mice with SCID led again to a significant 60% reduction of rejection. Mixed lymphocyte reaction...... deficiency in a clinically relevant situation, in which T-cell inhibition is desirable. In murine allogenic kidney transplantation, Rhoh deficiency caused a significant 75% reduction of acute and chronic transplant rejection accompanied by 75% lower alloantigen-specific antibody levels and significantly...

  12. A bedside technique for the diagnosis of acute rejection in renal transplants using 111-In platelets

    International Nuclear Information System (INIS)

    Chandler, S.T.; Buckels, J.A.C.; Drolc, Z.; Hawker, R.J.; Barnes, A.D.; McCollum, C.N.

    1982-01-01

    A total of 33 patients was studied with the aim of developing a bedside method for providing early diagnosis of acute rejection using 111-In labelled platelets. Platelet deposition was detected in all patients suffering acute rejection. A significant increase in kidney/aortic arch ratio, as measured by the portable bedside system, preceded the clinical diagnosis in 70% of patients. Using this system, it appeared possible not only to diagnose acute rejection at an earlier stage but also to predict irrecoverable transplant loss even in the presence of tubular necrosis. By labelling the platelets repeatedly for at least two weeks after transplantation, the period of highest risk for acute rejection and other complications. The gamma camera should still be employed in the event of markedly increased platelet deposition to differentiate between rejection and vascular complications

  13. Reviewing the pathogenesis of antibody-mediated rejection and renal graft pathology after kidney transplantation.

    Science.gov (United States)

    Morozumi, Kunio; Takeda, Asami; Otsuka, Yasuhiro; Horike, Keiji; Gotoh, Norihiko; Narumi, Shunji; Watarai, Yoshihiko; Kobayashi, Takaaki

    2016-07-01

    The clinicopathological context of rejection after kidney transplantation was well recognized. Banff conferences greatly contributed to elucidate the pathogenesis and to establish the pathologic criteria of rejection after kidney transplantation. The most important current problem of renal transplantation is de novo donor-specific antibody (DSA) production leading chronic rejection and graft loss. Microvascular inflammation is considered as a reliable pathological marker for antibody-mediated rejection (AMR) in the presence of DSA. Electron microscopic study allowed us to evaluate early changes in peritubular capillaries in T-lymphocyte mediated rejection and transition to antibody-mediated rejection. Severe endothelial injuries with edema and activated lymphocyte invaded into subendothelial space with early multi-layering of peritubular capillary basement membrane suggest T-lymphocyte mediated rejection induce an unbounded chain of antibody-mediated rejection. The risk factors of AMR after ABO-incompatible kidney transplantation are important issues. Anti-ABO blood type antibody titre of IgG excess 32-fold before transplant operation is the only predictable factor for acute AMR. Characteristics of chronic active antibody-mediated rejection (CAAMR) are one of the most important problems. Light microscopic findings and C4d stain of peritubular capillary and glomerular capillary are useful diagnostic criteria of CAAMR. Microvascular inflammation, double contour of glomerular capillary and thickening of peritubular capillary basement are good predictive factors of the presence of de novo DSA. C4d stain of linear glomerular capillary is a more sensitive marker for CAAMR than positive C4d of peritubular capillary. Early and sensitive diagnostic attempts of diagnosing CAAMR are pivotal to prevent chronic graft failure. © 2016 Asian Pacific Society of Nephrology.

  14. Reduction of acute rejection by bone marrow mesenchymal stem cells during rat small bowel transplantation.

    Directory of Open Access Journals (Sweden)

    Yang Yang

    Full Text Available Bone marrow mesenchymal stem cells (BMMSCs have shown immunosuppressive activity in transplantation. This study was designed to determine whether BMMSCs could improve outcomes of small bowel transplantation in rats.Heterotopic small bowel transplantation was performed from Brown Norway to Lewis rats, followed by infusion of BMMSCs through the superficial dorsal veins of the penis. Controls included rats infused with normal saline (allogeneic control, isogeneically transplanted rats (BN-BN and nontransplanted animals. The animals were sacrificed after 1, 5, 7 or 10 days. Small bowel histology and apoptosis, cytokine concentrations in serum and intestinal grafts, and numbers of T regulatory (Treg cells were assessed at each time point.Acute cellular rejection occurred soon after transplantation and became aggravated over time in the allogeneic control rats, with increase in apoptosis, inflammatory response, and T helper (Th1/Th2 and Th17/Treg-related cytokines. BMMSCs significantly attenuated acute cellular rejection, reduced apoptosis and suppressed the concentrations of interleukin (IL-2, IL-6, IL-17, IL-23, tumor necrosis factor (TNF-α, and interferon (IFN-γ while upregulating IL-10 and transforming growth factor (TGF-β expression and increasing Treg levels.BMMSCs improve the outcomes of allogeneic small bowel transplantation by attenuating the inflammatory response and acute cellular rejection. Treatment with BMMSCs may overcome acute cellular rejection in small bowel transplantation.

  15. Pre-transplant soluble CD30 level as a predictor of not only acute rejection and graft loss but pneumonia in renal transplant recipients.

    Science.gov (United States)

    Wang, Dong; Wu, Wei-Zhen; Chen, Jin-Hua; Yang, Shun-Liang; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

    2010-02-01

    Pre-transplant sera of 586 renal graft recipients were tested to investigate whether soluble CD30 (sCD30) is a useful predictor of some severe clinical episodes post-transplant. Correlation analysis showed sCD30 level was significantly correlated with acute rejection (AR) (r=0.242, PsCD30 levels were observed in patients with AR than the others (180.0+/-89.1 vs. 135.3+/-72.7U/ml, Ptransplant sCD30 level than the others (123.2+/-75.5 vs. 150.7+/-79.6U/ml, P=0.003). Based on statistical results, 120 and 240U/ml were selected as the optimal couple of cut-off value to divide patients into three groups: Group High (H), Group Intermedial (I) and Group Low (L). The lowest AR rate of 17.4% was observed in Group L (Ptransplant sCD30 level of renal allograft recipients may reflect an immune state detrimental for renal allograft survival. But sCD30 level lower than transplant sCD30 level is an independent predictor of acute rejection, lung infection, even graft survival. Suitable immunosuppression protocol should be selected according to pre-transplant sCD30 level in an attempt to promote patient and graft survival. Copyright 2010 Elsevier B.V. All rights reserved.

  16. Lung transplantation: overall approach regarding its major aspects

    Science.gov (United States)

    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

  17. Acute rejection after kidney transplantation promotes graft fibrosis with elevated adenosine level in rat.

    Directory of Open Access Journals (Sweden)

    Mingliang Li

    Full Text Available Chronic allograft nephropathy is a worldwide issue with the major feature of progressive allograft fibrosis, eventually ending with graft loss. Adenosine has been demonstrated to play an important role in process of fibrosis. Our study aimed to investigate the relationship between adenosine and fibrosis in renal allograft acute rejection in rat.Wistar rats and SD rats were selected as experimental animals. Our study designed two groups. In the allograft transplantation group, kidneys of Wistar rats were orthotopically transplanted into SD rat recipients, the same species but not genetically identical, to induce acute rejection. Kidney transplantations of SD rats to SD rats which were genetically identical were served as the control. We established rat models and detected a series of indicators. All data were analyzed statistically. P<0.05 was considered statistically significant.Compared with the control group, levels of adenosine increased significantly in the allograft transplantation group, in which acute rejection was induced (P<0.05. Progressive allograft fibrosis as well as collagen deposition were observed.These findings suggested that level of adenosine was upregulated in acute rejection after kidney allograft transplantation in rat. Acute rejection may promote renal allograft fibrosis via the adenosine signaling pathways.

  18. Lung transplant in end-staged chronic obstructive pulmonary disease (COPD) patients: a concise review.

    Science.gov (United States)

    Aziz, Fahad; Penupolu, Sudheer; Xu, Xin; He, Jianxing

    2010-06-01

    Lung transplantation is commonly used for patients with end-stage lung disease. However, there is continuing debate on the optimal operation for patients with chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Single-lung transplantation (SLT) provides equivalent short- and medium-term results compared with bilateral lung transplantation (BLT), but long-term survival appears slightly better in BLT recipients (especially in patients with COPD). The number of available organs for lung transplantation also influences the choice of operation. Recent developments suggest that the organ donor shortage is not as severe as previously thought, making BLT a possible alternative for more patients. Among the different complications, re-implantation edema, infection, rejection, and bronchial complications predominate. Chronic rejection, also called obliterative bronchiolitis syndrome, is a later complication which can be observed in about half of the patients. Improvement in graft survival depends greatly in improvement in prevention and management of complications. Despite such complications, graft survival in fibrosis patients is greater than spontaneous survival on the waiting list; idiopathic fibrosis is associated with the highest mortality on the waiting list. Patients should be referred early for the pre-transplantation work-up because individual prognosis is very difficult to predict.

  19. Drugs in development for prophylaxis of rejection in kidney-transplant recipients

    Directory of Open Access Journals (Sweden)

    Sanders ML

    2015-08-01

    Full Text Available Marion Lee Sanders,1 Anthony James Langone2 1Department of Medicine, Division of Nephrology and Hypertension, University of Iowa, Iowa City, IA, 2Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA Abstract: Transplantation is the preferred treatment option for individuals with end-stage renal disease. Individuals who undergo transplantation must chronically be maintained on an immunosuppression regimen for rejection prophylaxis to help ensure graft survival. Current rejection prophylaxis consists of using a combination of calcineurin inhibitors, mTOR inhibitors, antimetabolite agents, and/or corticosteroids. These agents have collectively improved the short-term outcomes of renal transplantation, but improvements in late/chronic graft loss and recipient survival have lagged significantly behind challenging the field of transplantation to develop novel prophylactic agents. There have been several clinical trials conducted within the last 5 years in an attempt to bring such novel agents to the commercial market. These trials have resulted in the US Food and Drug Administration (FDA approval of extended-release tacrolimus, as well as belatacept, which has the potential to replace calcineurin inhibitors for rejection prophylaxis. Other trials have focused on the development of novel calcineurin inhibitors (voclosporin, costimulation blockade (ASKP1240 and alefacept, kinase inhibitors (tofacitinib and sotrastaurin, and inhibitors of leukocyte migration (efalizumab. While these later agents have not been FDA-approved for use in transplantation, they remain noteworthy, as these agents explore pathways not previously targeted for allograft-rejection prophylaxis. The purpose of this review was to consolidate available clinical trial data with regard to the recent developments in rejection prophylaxis in kidney transplantation. Keywords: rejection, prophylaxis, immunosuppression

  20. Antibody-mediated rejection across solid organ transplants: manifestations, mechanisms, and therapies.

    Science.gov (United States)

    Valenzuela, Nicole M; Reed, Elaine F

    2017-06-30

    Solid organ transplantation is a curative therapy for hundreds of thousands of patients with end-stage organ failure. However, long-term outcomes have not improved, and nearly half of transplant recipients will lose their allografts by 10 years after transplant. One of the major challenges facing clinical transplantation is antibody-mediated rejection (AMR) caused by anti-donor HLA antibodies. AMR is highly associated with graft loss, but unfortunately there are few efficacious therapies to prevent and reverse AMR. This Review describes the clinical and histological manifestations of AMR, and discusses the immunopathological mechanisms contributing to antibody-mediated allograft injury as well as current and emerging therapies.

  1. Diagnosis of Rejection by Analyzing Ventricular Late Potentials in Heart Transplant Patients

    Directory of Open Access Journals (Sweden)

    Vítor Nogueira Mendes

    2016-01-01

    Full Text Available Background: Heart transplant rejection originates slow and fragmented conduction. Signal-averaged ECG (SAECG is a stratification method in the risk of rejection. Objective: To develop a risk score for rejection, using SAECG variables. Methods: We studied 28 transplant patients. First, we divided the sample into two groups based on the occurrence of acute rejection (5 with rejection and 23 without. In a second phase, we divided the sample considering the existence or not of rejection in at least one biopsy performed on the follow-up period (rejection pm1: 18 with rejection and 10 without. Results: On conventional ECG, the presence of fibrosis was the only criterion associated with acute rejection (OR = 19; 95% CI = 1.65-218.47; p = 0.02. Considering the rejection pm1, an association was found with the SAECG variables, mainly with RMS40 (OR = 0.97; 95% CI = 0.87-0.99; p = 0.03 and LAS40 (OR = 1.06; 95% IC = 1.01-1.11; p = 0.03. We formulated a risk score including those variables, and evaluated its discriminative performance in our sample. The presence of fibrosis with increasing of LAS40 and decreasing of RMS40 showed a good ability to distinguish between patients with and without rejection (AUC = 0.82; p < 0.01, assuming a cutoff point of sensitivity = 83.3% and specificity = 60%. Conclusion: The SAECG distinguished between patients with and without rejection. The usefulness of the proposed risk score must be demonstrated in larger follow-up studies.

  2. Panel reactive HLA antibodies, soluble CD30 levels, and acute rejection six months following renal transplant.

    Science.gov (United States)

    Domingues, Elizabeth M F L; Matuck, Teresa; Graciano, Miguel L; Souza, Edison; Rioja, Suzimar; Falci, Mônica C; Monteiro de Carvalho, Deise B; Porto, Luís Cristóvão

    2010-01-01

    Specific anti-human leukocyte antigen antibodies (HLA) in the post-transplant period may be present with acute rejection episodes (ARE), and high soluble CD30 (sCD30) serum levels may be a risk factor for ARE and graft loss. HLA cross-matching, panel reactive antibodies (PRA), and sCD30 levels were determined prior to transplantation in 72 patients. Soluble CD30 levels and PRA were re-assessed at day 7, 14, 21, and 28, and monthly up to the sixth.   Twenty-four subjects had a positive PRA and 17 experienced ARE. Nine of 17 ARE subjects demonstrated positive PRA and 16 had HLA mismatches. Positive PRA was more frequent in ARE subjects (p = 0.03). Eight subjects with ARE had donor-specific antibodies (DSA) in serum samples pre-transplantation, two subjects developed DSA. Three subjects without ARE had positive PRA only in post-transplantation samples. Soluble CD30 levels were higher in pre-transplant samples and ARE subjects than non-ARE subjects (p = 0.03). Post-transplant sCD30 levels were elevated in subjects who experienced rejection and were significantly higher at seven d (p = 0.0004) and six months (p = 0.03). Higher sCD30 levels following transplant were associated with ARE. Elevated sCD30 levels may represent a risk factor for acute rejection. © 2009 John Wiley & Sons A/S.

  3. Total lymphoid irradiation in the treatment of early or recurrent heart transplant rejection

    International Nuclear Information System (INIS)

    Salter, Susan P.; Salter, Merle M.; Kirklin, James K.; Bourge, Robert C.; Naftel, David C.

    1995-01-01

    Purpose: Recurrent acute cardiac allograft rejection is an important cause of repeat hospitalization and a major mode of mortality, particularly during the 6 months immediately following transplant. Total lymphoid irradiation (TLI) has been shown experimentally to induce a state of partial tolerance when administered prior to transplantation. Anecdotal reports of clinical experience have also suggested efficacy of TLI in treatment of recurrent cardiac rejection. The purpose of this study is to evaluate the safety and efficacy of TLI for treatment of early or recurrent heart transplant rejection. Materials and Methods: Between January 1990 and June 1992, 49 patients postallograft cardiac transplant were given courses of TLI for treatment of early or recurrent rejection after conventional therapy with Methylprednisolone, antithymocyte globulin, OKT3, and methotrexate. Two patients failed to complete their therapy and were not evaluated. Two other patients received a second TLI course, making a total of 49 courses delivered. Indications for TLI were early rejection (n = 5), recurrent rejection (n = 38), and recurrent rejection with vasculitis (n = 6). The dose goal of the TLI protocol was 8 Gy in 10 fractions given twice weekly. Three separate fields were used to encompass all major lymph node-bearing areas. The actual mean dose was 7 Gy (range 2.4-8.4 Gy), and the duration of treatment was 8 to 106 days. These variations were secondary to leukopenia or thrombocytopenia. Results: The mean posttransplant follow-up is 15 ± 1.2 months (maximum 27 months). Among patients initiating TLI within 1 month posttransplant (n = 15), the rejection frequency decreased from 1.83 episodes/patient/month pre-TLI to 0.13 episodes/patient/month post-TLI (p < 0.0001). For those who began TLI 1-3 months after transplant (n = 21), rejection decreased from 1.43 to 0.10 episodes/patient/month (p < 0.0001). When TLI was started more than 3 months posttransplant (n = 11), the pre-TLI and post

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

    Science.gov (United States)

    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

    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. 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. 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. 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.

  5. Insights from computational modeling in inflammation and acute rejection in limb transplantation.

    Directory of Open Access Journals (Sweden)

    Dolores Wolfram

    Full Text Available Acute skin rejection in vascularized composite allotransplantation (VCA is the major obstacle for wider adoption in clinical practice. This study utilized computational modeling to identify biomarkers for diagnosis and targets for treatment of skin rejection. Protein levels of 14 inflammatory mediators in skin and muscle biopsies from syngeneic grafts [n = 10], allogeneic transplants without immunosuppression [n = 10] and allografts treated with tacrolimus [n = 10] were assessed by multiplexed analysis technology. Hierarchical Clustering Analysis, Principal Component Analysis, Random Forest Classification and Multinomial Logistic Regression models were used to segregate experimental groups. Based on Random Forest Classification, Multinomial Logistic Regression and Hierarchical Clustering Analysis models, IL-4, TNF-α and IL-12p70 were the best predictors of skin rejection and identified rejection well in advance of histopathological alterations. TNF-α and IL-12p70 were the best predictors of muscle rejection and also preceded histopathological alterations. Principal Component Analysis identified IL-1α, IL-18, IL-1β, and IL-4 as principal drivers of transplant rejection. Thus, inflammatory patterns associated with rejection are specific for the individual tissue and may be superior for early detection and targeted treatment of rejection.

  6. Heat Shock Protein 90α Is a Potential Serological Biomarker of Acute Rejection after Renal Transplantation.

    Directory of Open Access Journals (Sweden)

    Takeshi Maehana

    Full Text Available Heat shock protein 90 (HSP90, a molecular chaperone associated with the activation of client proteins, was recently reported to play an important role in immunologic reactions. To date, the role of HSP90 in solid organ transplantations has remained unknown. The aim of this study was to evaluate the relationship between serum HSP90α levels and acute allograft rejection after organ and tissue transplantation using serum samples from kidney allograft recipients, an in vitro antibody-mediated rejection model, and a murine skin transplantation.Serum HSP90α levels were significantly higher in kidney recipients at the time of acute rejection (AR than in those with no evidence of rejection. In most cases with AR, serum HSP90 decreased to baseline after the treatment. On the other hand, serum HSP90α was not elevated as much in patients with chronic rejection, calcineurin inhibitor nephrotoxicity, or BK virus nephropathy as in AR patients. In vitro study showed that HSP90α concentration in the supernatant was significantly higher in the supernatant of human aortic endothelial cells cocultured with specific anti-HLA IgG under complement attack than in that of cells cocultured with nonspecific IgG. In mice receiving skin transplantation, serum HSP90α was elevated when the first graft was rejected and the level further increased during more severe rejection of the second graft.The results suggest that HSP90α is released into the serum by cell damage due to AR in organ and tissue transplantation, and it is potentially a new biomarker to help detect AR in kidney recipients.

  7. PREVENTION AND TREATMENT OF REJECTION AFTER SIMULTANEOUS PANCREAS-KIDNEY TRANSPLANTATION

    Institute of Scientific and Technical Information of China (English)

    Lei Yang; Yong-feng Liu; Shu-rong Liu; Gang Wu; Jia-lin Zhang; Yi-man Meng; Shao-wei Shong; Gui-chen Li

    2005-01-01

    Objective To explore methods of preventing and reversing rejection after simultaneous pancreas-kidney (SPK) tran splantation. Methods Seventeen patients underwent SPK transplantation from September 1999 to September 2003 were reviewed retrospectively. Immunosuppression was achieved by a triple drug regimen consisting of cyclosporine, mycophenolate mofteil (MMF), and steroids. Three patients were treated with anti-CD3 monoclone antibody (OKT3, 5 mg· d-1) for induction therapy for a mean period of 5-7 days. One patients received IL-2 receptor antibodies (daclizumab) in a dose of 1 mg· kg-1 on the day of transplant and the 5th day posttransplant. One patient was treated with both OKT3 and daclizumab for induction. Results No primary non-functionality of either kidney or pancreas occurred in this series of transplantations. Function of all the kidney grafts recovered within 2 to 4 days after transplantation. The level of serum creatinine was 94 ± 11 μmol/L on the 7th day posttransplant. One patient experienced the accelerated rejection, resulting in the resection of the pancreas and kidney grafts because of the failure of conservative therapy. The incidence of the first rejection episodes at 3 months was 47.1% (8/17). Only the kidney was involved in 35.3% (6/17); and both the pancreas and kidney were involved in 11.8% (2/17). All these patients received a high-dose pulse of methylprednisone (0.5 g·d-1) for 3 days. OKT3 (0.5 mg·d-1) was administered for 7-10 days in two patients with both renal and pancreas rejection. All the grafts were successfully rescued. Conclusion Rejection, particularly acute rejection, is the major cause influencing graft function in SPK transplantation. Monitoring renal function and pancreas exocrine secretion, and reasonable application of immunosuppressants play important roles in the diagnosis and treatment of rejection.

  8. Prediction of acute renal allograft rejection in early post-transplantation period by soluble CD30.

    Science.gov (United States)

    Dong, Wang; Shunliang, Yang; Weizhen, Wu; Qinghua, Wang; Zhangxin, Zeng; Jianming, Tan; He, Wang

    2006-06-01

    To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

  9. [Short-term outcomes of lung transplant recipients using organs from brain death donors].

    Science.gov (United States)

    He, W X; Jiang, C; Liu, X G; Huang, W; Chen, C; Jiang, L; Yang, B; Wu, K; Chen, Q K; Yang, Y; Yu, Y M; Jiang, G N

    2016-12-01

    Objective: To assess short-term outcomes after lung transplantation with organs procured following brain death. Methods: Between April 2015 and July 2016, all 17 recipients after lung transplantation using organs from brain death donors (DBD) at Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine were enrolled in this study. All patients were male, aging (60±7) years, including 11 chronic obstructive pulmonary disease, 5 idiopathic pulmonary fibrosis, 1 silicosis. Seventeen donors were 16 males and 1 female, with 10 traumatic brain injury, 5 cerebrovascular accident and 2 sudden cardiac death. Of 17 recipients receiving DBD lung transplant, 16 were single lung transplant. Data were collected including intubation duration of mechanical ventilation, hospital length of stay, incidence of pulmonary infection bronchus anastomosis complications, primary graft dysfunction (PGD), and acute rejection, bronchiolitis obliterans syndrome (BOS) as well as mortality of 90-day after lung transplantation. Results: Median duration of intubation were 2 (2) days ( M ( Q R )) in recipients after lung transplantation. The incidence of pulmonary infection and bronchus anastomosis complications were 15/17 and 5/17, respectively. Median length of stay in hospital were 56 (19) days. The ratio of readmission 1 month after discharge were 10/17. Mortality of 90-day post-transplant were 2/17. The incidence of PGD and BOS were 1/17 and 2/17, respectively. Conclusion: Recipients with DBD lung transplantation have an acceptable survival during short-term follow-up, but with higher incidences of complications related to infection post-transplantation.

  10. A quantitative study of Indium-111-oxine platelet kinetics in acute and chronic renal transplant rejection

    International Nuclear Information System (INIS)

    Heyns, A. du P.; Pieters, H.; Badenhorst, P.N.; Wessels, P.; Loetter, M.G.; Minnaar, P.C.; Pauw, F.H.

    1982-01-01

    Thirteen patients were investigated on 22 occasions at times varying from 1 day to 10 years after living family donor or cadaver renal transplantation. Platelet survival in the circulation, and in vivo platelet distribution and sites of deposition and sequestration was quantitatively determined with Indium-111-oxine (In-111-oxine) labelled platelets and a scintillation camera interfaced with a computer assisted imaging system. In all patients platelet survival was shortened and the platelet survival curve exponential. In patients with no evidence of transplant rejection and those with chronic rejection, there was no measurable or visible accumulation of labelled platelets in the kidney. The sequestration pattern of In-111 labelled platelets at the end of platelet life span was within normal limits and located in the reticuloendothelial system. In those patients with acute transplant rejection, platelet survival was shortened. Labelled platelets accumulated in the kidney: this was clearly visualized on scintigraphy and reflected by a significant increase in the radioactivity count density of the kidney. Platelets not deposited in the transplant were sequestrated in the reticuloendothelial system. This study demonstrates the diagnostic value of In-111 labelled platelet kinetics in the investigation of acute renal failure after renal transplantation. This investigation appears of limited clinical value in chronic rejection. (orig.)

  11. Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

    Science.gov (United States)

    El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

    2018-01-01

    Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

  12. Ventricular function during the acute rejection of heterotopic transplanted heart: Gated blood pool studies

    International Nuclear Information System (INIS)

    Valette, H.; Bourguignon, M.H.; Desruennes, M.; Merlet, P.; Le Guludec, D.; Syrota, A.

    1991-01-01

    Twenty patients who had undergone a heterotopic heart transplant were studied prospectively to determine the relationship between rejection and ventricular dysfunction assessed from gated blood pool studies. A fully automated method for detecting ventricular edges was implemented; its success rate for the grafted left and right ventricles was 94% and 77%, respectively. The parameters, peak ejection and filling rates, were calculated pixel per pixel using a two-harmonic Fourier algorithm and then averaged over the ventricular region of interest. Peak filling and ejection rates were closely related with the severity of the rejection, while the left ventricular ejection fraction was not. Peak filling rates of both ventricles were the indices closely related to the presence of moderate rejection. Despite the low number of patients, these data suggested that gated blood pool derived indices of ventricular function are associated with ventricular dysfunction resulting from myocarditis rejection. Radionuclide ventriculography provides parametric data which are accurate and reliable for the diagnosis of rejection. (orig.)

  13. Lifetime costs of lung transplantation : Estimation of incremental costs

    NARCIS (Netherlands)

    VanEnckevort, PJ; Koopmanschap, MA; Tenvergert, EM; VanderBij, W; Rutten, FFH

    1997-01-01

    Despite an expanding number of centres which provide lung transplantation, information about the incremental costs of lung transplantation is scarce. From 1991 until 1995, in The Netherlands a technology assessment was performed which provided information about the incremental costs of lung

  14. Noninvasive detection of rejection of transplanted hearts with indium-111-labeled lymphocytes

    International Nuclear Information System (INIS)

    Eisen, H.J.; Eisenberg, S.B.; Saffitz, J.E.; Bolman, R.M. III; Sobel, B.E.; Bergmann, S.R.

    1987-01-01

    To determine whether cardiac transplant rejection can be detected noninvasively with indium-111 ( 111 In)-labeled lymphocytes, we studied 11 dogs with thoracic heterotopic cardiac transplants without immunosuppression and five dogs with transplants treated with cyclosporine (10 mg/kg/day) and prednisone (1 mg/kg/day). All were evaluated sequentially with gamma scintigraphy after administration of 150 to 350 muCi of autologous 111 In-lymphocytes. Technetium-99m-labeled red blood cells (1 to 3 mCi) were used for correction of radioactivity in the blood pool attributable to circulating labeled lymphocytes. Lymphocyte infiltration was quantified as the ratio of indium in the myocardium of the transplant or native heart compared with that in blood (indium excess, IE). Results were correlated with mechanical and electrical activity of allografts and with histologic findings in sequential biopsy specimens. In untreated dogs (n = 11), IE was 15.5 +/- 7.0 (SD) in transplanted hearts undergoing rejection and 0.4 +/- 1.1 in native hearts on the day before animals were killed. In dogs treated with cyclosporine and prednisone (n = 5), IE was minimal in allografts during the course of immunosuppression (0.8 +/- 0.4) and increased to 22.9 +/- 11.1 after immunosuppression was stopped. Scintigraphic criteria of rejection (IE greater than 2 SD above that in native hearts) correlated with results of biopsies indicative of rejection and appeared before electrophysiologic or mechanical manifestations of dysfunction. Thus infiltration of labeled lymphocytes in allografts, indicative of rejection, is detectable noninvasively by gamma scintigraphy and provides a sensitive approach potentially applicable to clinical monitoring for early detection of rejection and guidance for titration of immunosuppressive measures

  15. Acute humoral rejection and C4d immunostaining in ABO blood type-incompatible liver transplantation.

    Science.gov (United States)

    Haga, Hironori; Egawa, Hiroto; Fujimoto, Yasuhiro; Ueda, Mikiko; Miyagawa-Hayashino, Aya; Sakurai, Takaki; Okuno, Tomoko; Koyanagi, Itsuko; Takada, Yasutsugu; Manabe, Toshiaki

    2006-03-01

    Complement C4d deposition in graft capillaries has been reported to be associated with antibody-mediated rejection in kidney and other solid organ transplantation. The correlation of C4d deposits and humoral rejection in liver transplants, however, is not well understood. We investigated the C4d immunostaining pattern in 34 patients whose liver biopsy was taken within the first 3 postoperative weeks for suspected acute rejection after ABO blood type-incompatible liver transplantation. The staining pattern was classified as positive (portal stromal staining), indeterminate (endothelial staining only), and negative (no staining). Positive C4d immunostaining was seen in 17 (50%) patients and was significantly associated with high (x64 or more) postoperative antidonor A/B antibody (immunoglobulin M (IgM)) titers (88 vs. 35%, P = 0.002) and poorer overall survival rate (41 vs. 88%, P = 0.007). Ten of 11 (91%) cases with histological acute humoral rejection (periportal edema and necrosis (PEN) or portal hemorrhagic edema) were positive for C4d, all of which showed high postoperative antibody titers. The other histologies associated with C4d positivity was purulent cholangitis (n = 4), coagulative hepatocyte necrosis (n = 1), acute cellular rejection (n = 1), and hepatocanalicular cholestasis (n = 1). Full clinical recovery was observed in only 6 of 17 (35%) C4d-positive patients, and tended to be associated with a lower rejection activity index (RAI). In conclusion, our study indicates that C4d deposits in the portal stroma can be a hallmark of acute humoral rejection in ABO-incompatible liver transplantation, and allograft damage can be reversible in a minority of cases. Copyright 2006 AASLD

  16. The value of microparticles in detecting acute rejection episodes after liver transplantation.

    Science.gov (United States)

    Morgul, Mehmet Haluk; Splith, Katrin; Leonhardt, Christoph; Raschzok, Nathanael; Reutzel-Selke, Anja; Schmuck, Rosa Bianca; Andreou, Andreas; Atanasov, Georgi; Benzing, Christian; Krenzien, Felix; Hau, Hans-Michael; Felgendreff, Philipp; Klunk, Sergej; Pratschke, Johann; Sauer, Igor Maximillian; Schmelzle, Moritz

    2018-02-01

    Non-invasive markers for diagnosis of acute rejection (AR) following liver transplantation have not been developed, yet. We analyzed the correlation of plasma microparticle levels (MP) with AR. MP (CD4, CD8, CD25, CD31, MHC) of 11 AR patients and 11 controls were analyzed within the first week after transplantation. CD4, CD8 and CD31 positive MP were higher in the AR, whereas overall MP count, CD25 and MHCI positive MP proportions did not differ between both groups. MP dynamics within the first period of transplantation could help to clarify on-going mechanisms of immunomodulation.

  17. Pre-transplant and post-transplant soluble CD30 for prediction and diagnosis of acute kidney allograft rejection.

    Science.gov (United States)

    Nafar, Mohsen; Farrokhi, Farhat; Vaezi, Mohammad; Entezari, Amir-Ebrahim; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Eniollahi, Behzad

    2009-01-01

    Serum levels of soluble CD30 (sCD30) have been considered as a predictor of acute kidney allograft rejection. We have evaluated the pre-transplant and post-transplant levels of sCD30 with the aim of determining its value in predicting and diagnosing kidney rejection. We measured sCD30 serum levels before kidney transplantation, 5 days post-operatively, and at creatinine elevation episodes. The predictive value of sCD30 for diagnosing acute rejection (AR) within the first 6 post-operative months was assessed in 203 kidney recipients from living donors. Pre-transplant and post-operative levels of serum sCD30 were 58.10 +/- 52.55 and 51.55 +/- 49.65 U/ml, respectively (P = 0.12). Twenty-three patients experienced biopsy-proven acute rejection, and 28 had acute allograft dysfunction due to non-immunologic diseases. The pre-transplant sCD30 level was not different between patients with and without AR. However, post-transplant sCD30 was higher in the AR group. The median serum level of post-transplant sCD30 was 52 U/ml in the AR group and 26.3 U/ml in a control group (P sCD30 on day 5 were higher in patients with AR (P = 0.003). Based on post-transplant sCD30 levels, we were able to differentiate between kidney recipients who experienced an AR within 6 months post-surgery and those without an AR (cutoff value 41 U/ml; sensitivity 70%; specificity 71.7%). The level of sCD30 during periods of elevated serum creatinine was not independently associated with the diagnosis of AR. Post-transplant sCD30 levels and their relative changes are higher in patients experiencing AR. We propose further studies on the post-transplant trend of this marker for the prediction of AR.

  18. Soluble CD30 for the prediction and detection of kidney transplant rejection.

    Science.gov (United States)

    Arjona, Alvaro

    2009-09-01

    Although safer and more effective immunosuppressants as well as enhanced immunosuppressive protocols are continuously being developed in order to increase graft survival, they come at the steep price of drug-related complications and important side effects. In addition, the value of panel reactive antibodies determination, which at present is the single most used indicator of an increased risk of transplant rejection, is now being reevaluated. Therefore, effective tailoring of immunosuppressive therapy minimizing the above-mentioned pitfalls requires the existence of dependable biomarkers that adequately monitor rejection risk both before and after transplantation. Here we review the data yielded by studies assessing the usefulness of measuring soluble CD30 levels (sCD30) in kidney transplant rejection. These data collectively show that sCD30 serum content has a considerable predictive/diagnostic value for acute rejection of renal grafts, particularly when measured a few days after transplantation. Copyright 2009 Prous Science, S.A.U. or its licensors. All rights reserved.

  19. Single-shot, high-dose rabbit ATG for rejection prophylaxis after kidney transplantation

    NARCIS (Netherlands)

    R. Zietse (Bob); E.P.M. van Steenberge (E. P M); C.J. Hesse (Cees); L.B. Vaessen (L.); J.N.M. IJzermans (Jan); W. Weimar (Willem)

    1993-01-01

    textabstractWe studied the effects of a single intravenous injection of rabbit ATG (RIVM, Bilthoven, The Netherlands) in a dose of 8 mg/kg body weight administered 6 h after kidney transplantation on graft survival, rejection incidence, T-cell subsets, and cost-effectiveness. A total of 58 (37

  20. Acute and chronic rejection: compartmentalization and kinetics of counterbalancing signals in cardiac transplants.

    Science.gov (United States)

    Kaul, A M K; Goparaju, S; Dvorina, N; Iida, S; Keslar, K S; de la Motte, C A; Valujskikh, A; Fairchild, R L; Baldwin, W M

    2015-02-01

    Acute and chronic rejection impact distinct compartments of cardiac allografts. Intramyocardial mononuclear cell infiltrates define acute rejection, whereas chronic rejection affects large arteries. Hearts transplanted from male to female C57BL/6 mice undergo acute rejection with interstitial infiltrates at 2 weeks that resolve by 6 weeks when large arteries develop arteriopathy. These processes are dependent on T cells because no infiltrates developed in T cell-deficient mice and transfer of CD4 T cells restored T cell as well as macrophage infiltrates and ultimately neointima formation. Markers of inflammatory macrophages were up-regulated in the interstitium acutely and decreased as markers of wound healing macrophages increased chronically. Programmed cell death protein, a negative costimulator, and its ligand PDL1 were up-regulated in the interstitium during resolution of acute rejection. Blocking PDL1:PD1 interactions in the acute phase increased interstitial T cell infiltrates. Toll-like receptor (TLR) 4 and its endogenous ligand hyaluronan were increased in arteries with neointimal expansion. Injection of hyaluronan fragments increased intragraft production of chemokines. Our data indicate that negative costimulatory pathways are critical for the resolution of acute interstitial infiltrates. In the arterial compartment recognition of endogenous ligands including hyaluronan by the innate TLRs may support the progression of arteriopathy. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  1. Lymphocele: a possible relationship with acute cellular rejection in kidney transplantation

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Silva Lipay

    1999-11-01

    Full Text Available CONTEXT: The incidence of lymphocele after renal transplantation varies between 0.6 and 18% of cases, and many factors have been associated to its etiology. Cellular rejection of the kidney allograft has been described as a possible causal factor of lymphocele. OBJECTIVE: To analyze the possible relationship between lymphocele and acute cellular rejection. DESIGN: A retrospective study. SETTING: A referral hospital center. SAMPLE: 170 patients submitted to kidney transplantation from March 1992 to January 1997. A standard technique for renal transplantation was used. RESULTS: Of the 19 patients that developed lymphocele, 16 presented at least one episode of acute cell rejection (84%, and were treated with methylprednisolone. The relation between lymphocele and rejection was statistically significant (p = 0.04. Treatment of lymphocele consisted of peritoneal marsupialization in 3 patients (15.3%, percutaneous drainage in 7 (36.8%, laparascopic marsupialization in 2 (10.5%, and conservative treatment in 7 patients (36.8%. Evolution was favorable in 15 patients (78.9%, 1 patient (5.3% died due to a cause unrelated to lymphocele, and 3 (15.8% lost the graft due to immunological factors. The average follow-up period was 24.5 months. CONCLUSION: The high incidence of acute cell rejection in patients with lymphocele suggests a possible causal relationship between both conditions.

  2. Recurrence of Intravenous Talc Granulomatosis following Single Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Richard C Cook

    1998-01-01

    Full Text Available Advanced pulmonary disease is an unusual consequence of the intravenous injection of oral medications, usually developing over a period of several years. A number of patients with this condition have undergone lung transplantation for respiratory failure. However, a history of drug abuse is often considered to be a contraindication to transplantation in the context of limited donor resources. A patient with pulmonary talc granulomatosis secondary to intravenous methylphenidate injection who underwent successful lung transplantation and subsequently presented with recurrence of the underlying disease in the transplanted lung 18 months after transplantation is reported.

  3. Renal blood flow after transplantation: Effects of acute tubular necrosis, rejection, and cyclosporine toxicity

    International Nuclear Information System (INIS)

    Lear, J.L.; Raff, U.; Jain, R.; Horgan, J.G.

    1988-01-01

    The authors incorporated their recently developed radionuclide first pass-technique for the quantitative measurement of renal transplant perfusion into routine DTPA imaging. Using this technique they investigated the effects of acute tubular necrosis (ATN), rejection, and cyclosporing toxicity on renal blood flow in a series of 80 studies in 35 patients, with independent evaluation of renal function. Transplant flow values were as follows: normal functioning, 439 mL/min +-83; ATN 248 mL/min +-63; rejection, 128 mL/min +-58; cyclosporing toxicity, 284 mL/min +-97; (normal flow in nontransplanted kidneys, approximately 550 mL/min). Differences between normal functioning, ATN, and rejection were significant (P < .05). Interestingly, immediate postsurgical hyperemia frequently occurred, with flow values sometimes exceeding 700 mL/min

  4. Donor-specific anti-HLA antibodies with antibody-mediated rejection and long-term outcomes following heart transplantation.

    Science.gov (United States)

    Clerkin, Kevin J; Farr, Maryjane A; Restaino, Susan W; Zorn, Emmanuel; Latif, Farhana; Vasilescu, Elena R; Marboe, Charles C; Colombo, Paolo C; Mancini, Donna M

    2017-05-01

    Donor-specific anti-HLA antibodies (DSA) are common after heart transplantation and are associated with rejection, cardiac allograft vasculopathy, and mortality. A noninvasive diagnostic test for pathologic antibody-mediated rejection (pAMR) does not exist. From January 1, 2010, through August 31, 2013, 221 consecutive adult patients underwent heart transplantation and were followed through October 1, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included association of DSA (stratified by major histocompatibility complex class and de novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of cardiac allograft vasculopathy. During the study period, 69 patients (31.2%) had DSA (24% had de novo DSA), and there were 74 episodes of pAMR in 38 patients. Sensitivity of DSA at any mean fluorescence intensity to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (odds ratio = 5.37; 95% confidence interval [CI], 1.34-21.47; p = 0.018), adjusting for age, sex, and timing of AMR. Circulating class II DSA after transplantation increased risk of future pAMR (hazard ratio = 2.97; 95% CI, 1.31-6.73; p = 0.009). Patients who developed de novo class II DSA had 151% increased risk of graft loss (contingent on 30-day survival) compared with patients who did not have DSA (95% CI, 1.11-5.69; p = 0.027). DSA were inadequate to diagnose pAMR. Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  5. CD16+ Monocytes and Skewed Macrophage Polarization toward M2 Type Hallmark Heart Transplant Acute Cellular Rejection

    OpenAIRE

    van den Bosch, Thierry P. P.; Caliskan, Kadir; Kraaij, Marina D.; Constantinescu, Alina A.; Manintveld, Olivier C.; Leenen, Pieter J. M.; von der Th?sen, Jan H.; Clahsen-van Groningen, Marian C.; Baan, Carla C.; Rowshani, Ajda T.

    2017-01-01

    textabstractBackground: During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and their polarization status during rejection. Here, we aimed to define and correlate monocyte-macrophage endomyocardial tissue profiles obtained at rejection and time points prior to rejection, with corresponding serial blood samples ...

  6. Antibody-mediated rejection in kidney transplantation: a review of pathophysiology, diagnosis, and treatment options.

    Science.gov (United States)

    Kim, Miae; Martin, Spencer T; Townsend, Keri R; Gabardi, Steven

    2014-07-01

    Antibody-mediated rejection (AMR), also known as B-cell-mediated or humoral rejection, is a significant complication after kidney transplantation that carries a poor prognosis. Although fewer than 10% of kidney transplant patients experience AMR, as many as 30% of these patients experience graft loss as a consequence. Although AMR is mediated by antibodies against an allograft and results in histologic changes in allograft vasculature that differ from cellular rejection, it has not been recognized as a separate disease process until recently. With an improved understanding about the importance of the development of antibodies against allografts as well as complement activation, significant advances have occurred in the treatment of AMR. The standard of care for AMR includes plasmapheresis and intravenous immunoglobulin that remove and neutralize antibodies, respectively. Agents targeting B cells (rituximab and alemtuzumab), plasma cells (bortezomib), and the complement system (eculizumab) have also been used successfully to treat AMR in kidney transplant recipients. However, the high cost of these medications, their use for unlabeled indications, and a lack of prospective studies evaluating their efficacy and safety limit the routine use of these agents in the treatment of AMR in kidney transplant recipients. © 2014 Pharmacotherapy Publications, Inc.

  7. Preventing Rejection

    Science.gov (United States)

    ... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

  8. Time-dependent changes in B-type natriuretic peptide after heart transplantation: correlation with allograft rejection and function.

    Science.gov (United States)

    Bader, Feras M; Rogers, R Kevin; Kfoury, Abdallah G; Gilbert, Edward M; Horne, Ben D; Stehlik, Josef; Renlund, Dale G

    2009-01-01

    Endomyocardial biopsy is the gold standard to diagnose cardiac allograft rejection, although a noninvasive modality such as brain natriuretic peptide (BNP) is attractive. The authors examined the correlation of BNP levels with rejection patterns and allograft function in cardiac allograft recipients followed up to 8 years. One hundred forty-four consecutive patients underwent endomyocardial biopsy, right heart catheterization, and blood sampling. BNP levels decreased during the first 6 months after transplant but then reached a plateau. Time-dependent correlations were made between BNP levels and allograft rejection, left ventricular ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, and serum creatinine. BNP levels were not different between patients with any rejection pattern and no rejection prior to or after 6 months following transplant. BNP levels did not correlate with ejection fraction, pulmonary capillary wedge pressure, right atrial pressure, or creatinine in the first 6 months after transplant. Statistically significant correlations existed between BNP and these parameters after 6 months following transplant. In cardiac transplant recipients, BNP levels decrease in the first 6 months following transplant and then reach a plateau regardless of the presence, type, or severity of allograft rejection. BNP levels do predict allograft rejection but correlate with allograft function after 6 months following transplant.

  9. Radiation therapy for renal transplant rejection refractory to pulse steroids and OKT3

    International Nuclear Information System (INIS)

    Noyes, William R.; Rodriguez, Rey; Knechtle, Stuart J.; Pirsch, John D.; Sollinger, Hans W.; D'Alessandro, Anthony M.; Chappell, Rick; Belzer, Folkert O.; Kinsella, Timothy J.

    1996-01-01

    Purpose: To determine the response rate and kidney graft survival following local irradiation to the transplanted renal graft undergoing persistent rejection after medical management including pulse steroids and OKT3. The role of radiation for renal transplant rejection after failure of OKT3 has not been previously reported. Methods and Materials: From July 1, 1988 to July 1, 1994, 72 consecutive patients with kidney graft rejection were treated with local irradiation to the transplanted renal graft following failure of medical management. All patients received pulse steroids and OKT3, an anti-CD3 immunosuppressant. Patients who failed to respond to methylprednisolone and OKT3 therapy were referred for radiation therapy. The median time from the diagnosis of rejection to irradiation was 8 days. All kidney grafts received local graft irradiation to a total of 8 Gy delivered in four daily fractions. Results: Sixty (83%) patients initially responded to radiotherapy at 7 days after completion of radiotherapy, as defined by a decrease in serum creatinine. Thirty-five responding patients have not experienced a second episode of graft rejection. Overall, 43 (60%) patients have renal graft survival, with a median follow-up of 16 months (range of 6-73 months). Conclusion: It is concluded that there is a subgroup of kidney graft patients undergoing graft rejection who are refractory to pulse steroids and OKT3 therapy where irradiation may be an effective modality with high rates of response and a moderate rate of graft survival. However, a prospective, randomized trial in these medically refractory patients is needed to ascertain whether these results are clinically significant

  10. Physiotherapeutic Intervention in the lung transplant

    International Nuclear Information System (INIS)

    Castro C, Carolyn; Gonzalez M Sonia

    2001-01-01

    The physical therapist just as other health professionals must know, how to detect and control the risk factors that affect the welfare of his patients, this is done by evaluation, education and assistance in order to benefit the biological, psychological, emotional, social and environmental conditions that contribute to their development as human beings. The physical therapist in the lung transplant area can create strategies to promotion, prevent and rehabilitate in the pre and post surgical phases of the intervention, to facilitate the required conditions that allow optimal adaptation of the receiver to the new organ

  11. Clinical Outcomes of Lung Transplantation in Patients with Telomerase Mutations

    Science.gov (United States)

    Tokman, Sofya; Singer, Jonathan P.; Devine, Megan S.; Westall, Glen P.; Aubert, John-David; Tamm, Michael; Snell, Gregory I.; Lee, Joyce S.; Goldberg, Hilary J.; Kukreja, Jasleen; Golden, Jeffrey A.; Leard, Lorriana E.; Garcia, Christine K.; Hays, Steven R.

    2017-01-01

    Background Successful lung transplantation (LT) for patients with pulmonary fibrosis from telomerase mutations is limited by systemic complications of telomerase dysfunction including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes among 14 LT recipients with telomerase mutations. Methods Subjects underwent LT between February 2005 and April 2014 at 5 LT centers. We abstracted data from medical records, focusing on outcomes reflecting post-LT treatment effects likely to be complicated by telomerase mutations. Results The median age of subjects was 60.5 years (IQR 52.0–62.0), 64.3% were male, and the mean post-LT observation time was 3.2 years (SD ±2.9). Eleven subjects had a mutation in telomerase reverse transcriptase, 2 in telomerase RNA component, and 1 had an uncharacterized mutation. Ten subjects were leukopenic post-LT; leukopenia prompted cessation of mycophenolate mofetil in 5 and treatment with filgrastim in 4. Six subjects had recurrent lower respiratory tract infections (LRTI), 7 had acute cellular rejection (ACR) (A1), and 4 developed chronic lung allograft dysfunction (CLAD). Ten LT recipients developed chronic renal insufficiency and 8 experienced acute, reversible renal failure. Three developed cancer, none had cirrhosis. Thirteen subjects were alive at data censorship. Conclusions The clinical course for LT recipients with telomerase mutations is complicated by renal disease, leukopenia prompting a change in the immunosuppressive regimen, and recurrent LTRI. In contrast, cirrhosis was absent, ACR was mild, and development of CLAD was comparable to other LT populations. While posing challenges, lung transplantation may be feasible for patients with pulmonary fibrosis due to telomerase mutations. PMID:26169663

  12. First Danish experience with ex vivo lung perfusion of donor lungs before transplantation

    DEFF Research Database (Denmark)

    Henriksen, Ian Sune Iversen; Møller-Sørensen, Hasse; Møller, Christian Holdfold

    2014-01-01

    INTRODUCTION: The number of lung transplantations is limited by a general lack of donor organs. Ex vivo lung perfusion (EVLP) is a novel method to optimise and evaluate marginal donor lungs prior to transplantation. We describe our experiences with EVLP in Denmark during the first year after its...... introduction. MATERIAL AND METHODS: The study was conducted by prospective registration of donor offers and lung transplantations in Denmark from 1 May 2012 to 30 April 2013. Donor lungs without any contraindications were transplanted in the traditional manner. Taken for EVLP were donor lungs that were...... otherwise considered transplantable, but failed to meet the usual criteria due to possible contusions or because they were from donors with sepsis or unable to pass the oxygenation test. RESULTS: In the study period, seven of 33 Danish lung transplantations were made possible due to EVLP. One patient died...

  13. INTRAVENOUS IMMUNOGLOBULIN ADMINISTRATION FOR DESENSITIZATION BEFORE RENAL TRANSPLANTATION AND MANAGING ANTIBODY-MEDIATED REJECTION

    Directory of Open Access Journals (Sweden)

    A. I. Sushkov

    2011-01-01

    Full Text Available Much attention has been placed recently in transplantation in highly HLA-sensitized patients. In attempts to remove these antibodies and enable successful renal transplantation, several approaches have been developed. Intravenous immunoglobulin (IVIG was found to be effective in the treatment of autoimmune and inflammatory disorders (e. g. Kawasaki disease, Guillain-Barre syndrome. Recently, a beneficial effect of IVIG on the reduc- tion of anti-HLA antibodies was described. The anti-inflammatory effect of IVIG provides hopeful opportunities in antibody-mediated rejection (AMR management. There are several protocols of IVIG administration for pre-transplant desensitization and AMR treatment: high-dose IVIG, low-dose IVIG + plasmapheresis, IVIG + plasmapheresis + rituximab. These advancements have enabled transplantation in patients previously considered untransplantable and in concert with new diagnostic techniques has resulted in new approaches to management of AMR. 

  14. Soluble CD30 does not predict late acute rejection or safe tapering of immunosuppression in renal transplantation.

    Science.gov (United States)

    Valke, Lars L F G; van Cranenbroek, Bram; Hilbrands, Luuk B; Joosten, Irma

    2015-01-01

    Previous reports revealed the potential value of the soluble CD30 level (sCD30) as biomarker for the risk of acute rejection and graft failure after renal transplantation, here we examined its use for the prediction of safe tapering of calcineurin inhibitors as well as late acute rejection. In a cohort of renal transplant patients receiving triple immunosuppressive therapy we examined whether sCD30 can be used as a marker for safe (rejection-free) discontinuation of tacrolimus at six months after transplantation (TDS cohort: 24 rejectors and 44 non-rejecting controls). Also, in a second cohort of patients (n=22, rejectors n=11 and non-rejectors n=11), participating in a clinical trial of rituximab as induction therapy after renal transplantation (RITS cohort), we examined whether sCD30 could predict the occurrence of late (>3months post-transplant) acute rejection episodes. sCD30 was measured by ELISA in serum taken before and at several time points after transplantation. Overall, in the TDS cohort sCD30 decreased after transplantation. No difference in sCD30 was observed between rejectors and non-rejecting controls at any of the time points measured. In addition, in the RITS cohort, sCD30 measured at three months after transplantation were not indicative for the occurrence of late acute rejection. In two prospectively followed cohorts of renal transplant patients we found no association between sCD30 and the occurrence of either late acute rejection or acute rejection after reduction of immunosuppression. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. CARDIAC TRANSPLANT REJECTION AND NON-INVASIVE COMON CAROTID ARTERY WALL FUNCTIONAL INDICES

    Directory of Open Access Journals (Sweden)

    A. O. Shevchenko

    2015-01-01

    Full Text Available Allograft rejection would entail an increase in certain blood biomarkers and active substances derived from activated inflammatory cells which could influence entire vascular endothelial function and deteriorate arterial wall stiffness. We propose that carotid wall functional indices measured with non-invasive ultrasound could we valuable markers of the subclinical cardiac allograft rejection. Aim. Our goal was to analyze the clinical utility of functional common carotid wall (CCW variables measured with high-resolution Doppler ultrasound as a non-invasive screening tool for allograft rejection in cardiac transplant patients (pts. Methods. One hundred and seventy one pts included 93 cardiac recipients, 30 dilated cardiomyopathy waiting list pts, and 48 stable coronary artery disease (SCAD pts without decompensated heart failure were included. Along with resistive index (Ri, pulsative index (Pi, and CCW intima-media thickness (IMT, CCW rigidity index (iRIG was estimated using empirical equation. Non-invasive evaluation was performed in cardiac transplant recipients prior the endomyo- cardial biopsy. Results. Neither of Ri, Pi, or CCW IMT were different in studied subgroups. iRIG was signifi- cantly lower in SCAD pts when compared to the dilated cardiomyopathy subgroup. The later had similar values with cardiac transplant recipients without rejection. Antibody-mediated and cellular rejection were found in 22 (23.7% and 17 (18.3% cardiac recipients, respectively. Mean iRIG in pts without rejection was significantly lower in comparison to antibody-mediated rejection and cell-mediated (5514.7 ± 2404.0 vs 11856.1 ± 6643.5 and 16071.9 ± 10029.1 cm/sec2, respectively, p = 0.001. Area under ROC for iRIG was 0.90 ± 0.03 units2. Analysis showed that iRIG values above estimated treshold 7172 cm/sec2 suggested relative risk of any type of rejection 17.7 (95%CI = 6.3–49.9 sensitivity 80.5%, specificity – 81.1%, negative predictive value – 84

  16. Early extracellular matrix changes are associated with later development of bronchiolitis obliterans syndrome after lung transplantation

    DEFF Research Database (Denmark)

    Müller, Catharina; Andersson-Sjöland, Annika; Schultz, Hans Henrik

    2017-01-01

    are largely unknown. The aim of this study was to identify potential early changes in the extracellular matrix (ECM) in different compartments of the transplanted lung prior to the development of BOS. Methods: Transbronchial biopsies from a cohort of 58 lung transplantation patients at the Copenhagen...... and immunohistochemistry. Results: A time-specific and compartment-specific pattern of ECM changes was detected. Alveolar total collagen (p=0.0190) and small airway biglycan (p=0.0199) increased between 3 and 12 months after transplantation in patients developing BOS, while collagen type IV (p=0.0124) increased...... in patients without BOS. Patients with early-onset BOS mirrored this increase. Patients developing grade 3 BOS showed distinct ECM changes already at 3 months. Patients with BOS with treated acute rejections displayed reduced alveolar total collagen (p=0.0501) and small airway biglycan (p=0.0485) at 3 months...

  17. Level of soluble CD30 after kidney transplantation correlates with acute rejection episodes.

    Science.gov (United States)

    Yang, J L; Hao, H J; Zhang, B; Liu, Y X; Chen, S; Na, Y Q

    2008-12-01

    Measurement of soluble CD30 (sCD30) levels may predict acute rejection episodes (ARE). To explore the value of sCD30 after transplantation, we tested serum sCD30 levels in 58 kidney transplant cases at 1 day before and 7 and 28 days after transplantation by enzyme-linked immunosorbent assay (ELISA). The incidences of ARE after kidney transplantation were recorded simultaneously. Meanwhile, 31 healthy individuals were selected as a control group. The results showed a relationship between sCD30 level in serum before kidney transplantation and the incidence of ARE. However, the relationship was more significant between serum sCD30 levels at day 7 after kidney transplantation and the incidence of ARE. There was no obvious relationship between serum sCD30 levels at day 28 after kidney transplantation and the incidence of ARE. These results suggested that the level of sCD30 at day 7 posttransplantation provides valuable data to predict ARE.

  18. Tacrolimus in preventing transplant rejection in Chinese patients – optimizing use

    Directory of Open Access Journals (Sweden)

    Li CJ

    2015-01-01

    Full Text Available Chuan-Jiang Li,1,* Liang Li2,* 1Department of Surgery, Nanfang Hospital, 2Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, People’s Republic of China *The authors contributed equally to this work Abstract: Tacrolimus is a product of fermentation of Streptomyces, and belongs to the family of calcineurin inhibitors. It is a widely used immunosuppressive drug for preventing solid-organ transplant rejection. Compared to cyclosporine, tacrolimus has greater immunosuppressive potency and a lower incidence of side effects. It has been accepted as first-line treatment after liver and kidney transplantation. Tacrolimus has specific features in Chinese transplant patients; its in vivo pharmacokinetics, treatment regimen, dose and administration, and adverse-effect profile are influenced by multiple factors, such as genetics and the spectrum of primary diseases in the Chinese population. We reviewed the clinical experience of tacrolimus use in Chinese liver- and kidney-transplant patients, including the pharmacology of tacrolimus, the immunosuppressive effects of tacrolimus versus cyclosporine, effects of different factors on tacrolimus metabolism on Chinese patients, personalized medicine, clinical safety profile, and patient satisfaction and adherence. This article provides guidance for the rational and efficient use of tacrolimus in Chinese organ-transplant patients. Keywords: tacrolimus, liver transplantation, kidney transplant, Chinese, personalized medicine

  19. Lung transplantation in the most critically-III: forging ahead.

    Science.gov (United States)

    Mulvihill, Michael S; Hartwig, Matthew G; Daneshmand, Mani A

    2017-09-01

    Lung transplantation is the gold standard therapy for patients with end-stage lung disease. The use of the lung allocation score (LAS) has permitted improved allocation of scarce pulmonary allografts. Recently, Crawford et al. examined the experience in the United States in lung transplantation in candidates with the highest LAS, demonstrating that outcomes for candidates with the highest LAS scores have improved significantly. This editorial places these data in the broader context of thoracic transplantation, and highlights the critical need for ongoing examination of this critically-ill patient population.

  20. Impact of pretransplant anti-HLA antibodies on outcomes in lung transplant candidates.

    Science.gov (United States)

    Kim, Miae; Townsend, Keri R; Wood, Isabelle G; Boukedes, Steve; Guleria, Indira; Gabardi, Steven; El-Chemaly, Souheil; Camp, Phillip C; Chandraker, Anil K; Milford, Edgar L; Goldberg, Hilary J

    2014-05-15

    The prevalence of anti-HLA antibodies in lung transplant candidates and their impact on waitlist and transplant outcomes is not known. We examined the prevalence of pretransplant anti-HLA antibodies at varying thresholds and evaluated their impact on outcomes before and after lung transplantation. We performed a single-center retrospective cohort study including all patients listed for lung transplantation between January 2008 and August 2012. Per protocol, transplant candidates were assessed by solid phase LABscreen mixed Class I and II and LABscreen Single Antigen assays. Among 224 patients, 34% had anti-HLA antibodies at mean fluorescent intensity (MFI) greater than or equal to 3,000 (group III), and 24% had antibodies at MFI 1,000 to 3,000 (group II). Ninety percent of the patients with pretransplant anti-HLA antibodies had class I antibodies, whereas only seven patients developed class II alone. Patients in group III were less likely to receive transplants than patients without any anti-HLA antibodies (group I) (45.5 vs. 67.7%, P = 0.005). Wait time to transplant was longer in group III than group I, although this difference did not meet statistical significance, and waitlist mortality was similar. Among transplant recipients, antibody-mediated rejection (AMR) was more frequent in group III than in group II (20% vs. 0%, P = 0.01) or group I (6.3%, P = 0.05). The presence of anti-HLA antibodies at the high MFI threshold (>3,000) was associated with lower transplant rate and higher rates of AMR. Screening for anti-HLA antibodies using the 3,000 MFI threshold may be important in managing transplant candidates and recipients.

  1. Patient-reported non-adherence and immunosuppressant trough levels are associated with rejection after renal transplantation.

    Science.gov (United States)

    Scheel, Jennifer; Reber, Sandra; Stoessel, Lisa; Waldmann, Elisabeth; Jank, Sabine; Eckardt, Kai-Uwe; Grundmann, Franziska; Vitinius, Frank; de Zwaan, Martina; Bertram, Anna; Erim, Yesim

    2017-03-29

    Different measures of non-adherence to immunosuppressant (IS) medication have been found to be associated with rejection episodes after successful transplantation. The aim of the current study was to investigate whether graft rejection after renal transplantation is associated with patient-reported IS medication non-adherence and IS trough level variables (IS trough level variability and percentage of sub-therapeutic IS trough levels). Patient-reported non-adherence, IS trough level variability, percentage of sub-therapeutic IS trough levels, and acute biopsy-proven late allograft rejections were assessed in 267 adult renal transplant recipients who were ≥12 months post-transplantation. The rate of rejection was 13.5%. IS trough level variability, percentage of sub-therapeutic IS trough levels as well as patient-reported non-adherence were all significantly and positively associated with rejection, but not with each other. Logistic regression analyses revealed that only the percentage of sub-therapeutic IS trough levels and age at transplantation remained significantly associated with rejection. Particularly, the percentage of sub-therapeutic IS trough levels is associated with acute rejections after kidney transplantation whereas IS trough level variability and patient-reported non-adherence seem to be of subordinate importance. Patient-reported non-adherence and IS trough level variables were not correlated; thus, non-adherence should always be measured in a multi-methodological approach. Further research concerning the best combination of non-adherence measures is needed.

  2. Long-term experience of plasmapheresis in antibody-mediated rejection in renal transplantation.

    LENUS (Irish Health Repository)

    Brown, C M

    2009-11-01

    Antibody-mediated rejection (AMR) continues to pose a serious challenge in renal transplantation with potentially devastating consequences. Treatment options for this condition include plasmapheresis, high-dose intravenous immunoglobulin (IVIG), plasmapheresis with low-dose IVIG, and the use of rituximab (anti-CD20 chimeric antibody). We previously reported on the short-term outcome of plasmapheresis as a rescue therapy for AMR in our centre. We now report on the long-term follow up.

  3. Association of Endothelial Nitric Oxide Synthase Gene Polymorphisms With Acute Rejection in Liver Transplant Recipients.

    Science.gov (United States)

    Azarpira, Negar; Namazi, Soha; Malahi, Sayan; Kazemi, Kourosh

    2016-06-01

    Polymorphisms of the endothelial nitric oxide synthase gene have been associated with altered endothelial nitric oxide synthase activity. The purpose of this study was to investigate the relation between endothelial nitric oxide synthase -786T/C and 894G/T polymorphism and their haplotypes on the occurrence of acute rejection episodes in liver transplant recipients. We conducted a case control study in which 100 liver transplant recipients and 100 healthy controls were recruited from Shiraz Transplant Center. The patients used triple therapy including tacrolimus, mycophenolate mofetil, and prednisolone for immunosuppression maintenance. DNA was extracted from peripheral blood and endothelial nitric oxide synthase polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Patients included 60 men and 40 women (mean age, 32.35 ± 10.2 y). There was a significant association of endothelial nitric oxide synthase 894G/T and acute rejection episode. The GT* gen-otype and acute rejection episodes had a significant association (odds ratio, 2.42; 95% confidence interval, 0.97-6.15; P = .03). The GG and GT* genotype and T* allele frequency were significantly different between patients and control subjects (P = .001). Haplotype TT* was higher in recipients than control subjects (odds ratio, 2.17; 95% confidence interval, 1.12-4.25; P = .01). Haplotype TG was higher in the control group (odds ratio, 0.62; 95% confidence interval, 0.40-0.96; P = .02). Our results suggest a relation between different endothelial nitric oxide synthase geno-types and risk of acute rejection episodes. However, further study is necessary to determine genetic susceptibility for transplant patients.

  4. Cytokine profiles in early rejection following OKT3 treatment in liver transplant patients

    Directory of Open Access Journals (Sweden)

    Sasan Roayaie

    2000-01-01

    Full Text Available OKT3, a murine monoclonal antibody specific to the human CD3 complex, induces immunosuppression by depletion of T cells. Administration of OKT3 results in significant release of proinflammatory cytokines, such as TNFα and IL1β. Liver recipients who experience rejection within 3 weeks after transplantation with OKT3 prophylaxis recover their T cells by postoperative day 10 despite complete initial clearance.

  5. The Perfect Storm: HLA Antibodies, Complement, FcγRs and Endothelium in Transplant Rejection

    OpenAIRE

    Thomas, Kimberly A.; Valenzuela, Nicole M.; Reed, Elaine F.

    2015-01-01

    The pathophysiology of antibody-mediated rejection (AMR) in solid organ transplants is multi-faceted and predominantly caused by antibodies directed against polymorphic donor human leukocyte antigens (HLA). Despite the clearly detrimental impact of HLA antibodies (HLA-Ab) on graft function and survival, the prevention, diagnosis and treatment of AMR remain a challenge. Histological manifestations of AMR reflect signatures of HLA-Ab-triggered injury, specifically endothelial changes, recipient...

  6. Integrated Kidney Exosome Analysis for the Detection of Kidney Transplant Rejection.

    Science.gov (United States)

    Park, Jongmin; Lin, Hsing-Ying; Assaker, Jean Pierre; Jeong, Sangmoo; Huang, Chen-Han; Kurdi, A; Lee, Kyungheon; Fraser, Kyle; Min, Changwook; Eskandari, Siawosh; Routray, Sujit; Tannous, Bakhos; Abdi, Reza; Riella, Leonardo; Chandraker, Anil; Castro, Cesar M; Weissleder, Ralph; Lee, Hakho; Azzi, Jamil R

    2017-11-28

    Kidney transplant patients require life-long surveillance to detect allograft rejection. Repeated biopsy, albeit the clinical gold standard, is an invasive procedure with the risk of complications and comparatively high cost. Conversely, serum creatinine or urinary proteins are noninvasive alternatives but are late markers with low specificity. We report a urine-based platform to detect kidney transplant rejection. Termed iKEA (integrated kidney exosome analysis), the approach detects extracellular vesicles (EVs) released by immune cells into urine; we reasoned that T cells, attacking kidney allografts, would shed EVs, which in turn can be used as a surrogate marker for inflammation. We optimized iKEA to detect T-cell-derived EVs and implemented a portable sensing system. When applied to clinical urine samples, iKEA revealed high level of CD3-positive EVs in kidney rejection patients and achieved high detection accuracy (91.1%). Fast, noninvasive, and cost-effective, iKEA could offer new opportunities in managing transplant recipients, perhaps even in a home setting.

  7. Prevention of organ rejection in renal and liver transplantation with extended release tacrolimus

    Directory of Open Access Journals (Sweden)

    Reschen ME

    2014-09-01

    Full Text Available Michael E Reschen, Christopher A O’Callaghan Henry Wellcome Building, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom Abstract: Tacrolimus is the key immunosuppressant used to prevent allograft rejection in kidney and liver transplant recipients. Despite the efficacy of tacrolimus and adjunctive immunosuppressants, a substantial number of patients experience episodes of acute rejection and late graft loss. Nonadherence is an etiological factor in both acute rejection and graft loss. In 2007, a prolonged release version of tacrolimus became available that allows once daily administration, thus halving the pill burden compared to the standard twice-daily tacrolimus. An increasing number of studies in de novo transplantation and in treatment conversion have evaluated the pharmacokinetic profile, efficacy, and safety of prolonged-release tacrolimus. We have reviewed the literature on the use of prolonged-release tacrolimus and hope that this will be of value in the design of protocols for transplant immunosuppression.Keywords: immunosuppression, kidney, hepatic, allograft, adherence

  8. CD16+ monocytes and skewed macrophage polarization toward M2 type hallmark heart transplant acute cellular rejection

    NARCIS (Netherlands)

    T.P.P. van den Bosch (Thierry); K. Caliskan (Kadir); M.D. Kraaij (Marina); A.A. Constantinescu (Alina); O.C. Manintveld (Olivier); P.J. Leenen (Pieter); J. von der Thusen (Jan); M.C. Clahsen-van Groningen (Marian); C.C. Baan (Carla); A.T. Rowshani (Ajda)

    2017-01-01

    textabstractBackground: During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and their polarization status during

  9. Kidney Transplant Recipients With Primary Membranous Glomerulonephritis Have a Higher Risk of Acute Rejection Compared With Other Primary Glomerulonephritides

    Directory of Open Access Journals (Sweden)

    Tripti Singh, MD

    2017-11-01

    Conclusions. Patients with MN have higher incidence of acute rejection after kidney transplant but have similar 10-year allograft survival in comparison to the other glomerular diseases like IgAN, FSGS, and LN.

  10. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    A 44-year-old woman underwent left single-lung transplantation for end-stage emphysema due to α1-antitrypsin deficiency in January 2010. Cyclosporine, azathioprine, and prednisolone were administered for immunosuppression and antithymocyte globulin for induction therapy at the time...... of transplantation. Routine examination of a lung biopsy, 4 months after transplantation, showed nonspecific, diffuse interstitial inflammation with alveolar septal fibrosis. The patient's clinical status and imaging studies, consistent with nonspecific interstitial pneumonitis, which was considered as signs......, posttransplant antirejection drug regimen. We have since successfully treated with alemtuzumab three additional patients who developed interstitial lung injury after lung transplantation, who are also summarized in this report....

  11. Towards non-invasive diagnostic techniques for early detection of acute renal transplant rejection: A review

    Directory of Open Access Journals (Sweden)

    Elizabeth Hollis

    2017-03-01

    Full Text Available The kidney is a very important complicated filtering organ of the body. When the kidney reaches stage 5 chronic kidney disease, end stage renal failure, the preeminent therapy is renal transplantation. Although it is the best form of treatment, lack of kidney donors is still challenging. Therefore, all efforts should be employed to prolong the survival rate of the transplanted kidney. However, graft dysfunction (e.g., acute rejection is one of the serious barriers to long term kidney transplant survival. Currently, graft dysfunction’s gold standard of diagnosis is renal biopsy. Although renal biopsy is helpful, it is not preferred due to its invasive nature, high morbidity rates, and expensiveness. Therefore, noninvasive imaging techniques have become the subject of extensive research and interest, giving a strong promise to replace, or at least to decrease, biopsy usage in diagnosing graft dysfunction. This survey will discuss not only the current diagnosis and treatment of graft dysfunction but also the state-of-the-art imaging techniques in detecting acute renal transplant rejection.

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

    Science.gov (United States)

    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.

  13. [The relationship between acute rejection and expression of sCD30 for the patients after kidney transplantation].

    Science.gov (United States)

    Yang, Jian-Lin; Hao, Hong-Jun; Qin, Bin; Bang, Ling-Qing; Zhang, Zhi-Hong; Xin, Dian-Qi; Guo, Ying-Lu; Na, Yan-Qun

    2005-03-16

    To study the relationship between the sCD30 and acute rejection. We tested the sCD30 level in serum for 58 cases with kidney transplantation before and the 7th day and 28th day after operation by ELISA. 31 healthy individual for control group, and simultaneously recorded the incidence of rejection after kidney transplantation. The results showed that there is an obviously relation before kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 4.843, P = 0.028, P kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 7.201, P = 0.007, P kidney transplantation between the sCD30 level in serum and the incidence of acute rejection (chi = 2.095, P = 0.148, P > 0.05). The results suggested that the expressions of sCD30 are related to acute rejection. We speculated that the expressions of sCD30 could play an important role in acute rejection.

  14. TPMT genetic variants are associated with increased rejection with azathioprine use in heart transplantation.

    Science.gov (United States)

    Liang, Jackson J; Geske, Jennifer R; Boilson, Barry A; Frantz, Robert P; Edwards, Brooks S; Kushwaha, Sudhir S; Kremers, Walter K; Weinshilboum, Richard M; Pereira, Naveen L

    2013-12-01

    Azathioprine (AZA) is an important immunosuppressant drug used in heart transplantation (HTX). Consensus guidelines recommend that patients with thiopurine S-methyltransferase (TPMT) genetic variants be started on lower AZA dose because of higher active metabolite levels and risk of adverse events. However, in-vitro lymphocyte proliferation assays performed in participants with inactive TPMT alleles have suggested that AZA use may result in decreased immunosuppressant efficacy as compared with wild-type (WT) individuals. The objective of this study was therefore to determine the effect of TPMT genetic variation on AZA efficacy or prevention of rejection in HTX recipients treated with AZA. We genotyped 93 HTX recipients treated with AZA and measured erythrocyte TPMT enzyme activity. Acute rejection was monitored by routine endomyocardial biopsies. There were 83 WT and 10 heterozygote (HZ) HTX recipients. TPMT activity level was lower in HZ compared with WT (13.1±2.8 vs. 21±4.5 U/ml red blood cell, Prejection earlier (Prejection score was higher (P=0.02) than WT. AZA was discontinued more frequently in HZ (P=0.01) because of rejection. The incidence of leukopenia was similar between the groups (40 vs. 43%, P=1.0). HTX recipients with TPMT genetic variant alleles who are treated with AZA develop acute rejection earlier, more frequently, and of greater severity. These patients, despite having lower TPMT enzymatic activity, should be monitored carefully for possible increased risk of acute rejection.

  15. Significance of single lung transplantation in the current situation of severe donor shortage in Japan.

    Science.gov (United States)

    Miyoshi, Ryo; Chen-Yoshikawa, Toyofumi F; Hijiya, Kyoko; Motoyama, Hideki; Aoyama, Akihiro; Menju, Toshi; Sato, Toshihiko; Sonobe, Makoto; Date, Hiroshi

    2016-02-01

    Although bilateral lung transplantation is the procedure of choice internationally, single lung transplantation is preferred in Japan because of the severe donor shortage except in cases of contraindications to single lung transplantation. This study aimed to evaluate the clinical characteristics of single lung transplant recipients and outcomes of this procedure at one of the largest lung transplant centers in Japan. Between April 2002 and May 2015, 57 cadaveric lung transplantations (33 single and 24 bilateral) were performed in Kyoto University Hospital. The clinical characteristics of the lung transplant recipients and outcomes of these procedures, including overall survival and postoperative complications, were investigated. Overall, the 1-, 3-, and 5-year survival rates were 86, 77, and 72 %, respectively, with a median follow-up period of 1.9 years. There was no significant difference in survival between patients who underwent single lung transplantations and those who underwent bilateral lung transplantations (p = 0.92). The median waiting time was significantly shorter for single lung transplant patients than for bilateral lung transplant patients (p = 0.02). Native lung complications were seen in 14 out of 33 patients (42 %) who underwent single lung transplantation. There was no significant difference in survival between patients with and without postoperative native lung complications. Single lung transplantation has been performed with acceptable outcomes in our institution. In the current situation of severe donor shortage in Japan, single lung transplantation can remain the first choice of treatment except in cases of contraindications to single lung transplantation.

  16. CD16+ Monocytes and Skewed Macrophage Polarization toward M2 Type Hallmark Heart Transplant Acute Cellular Rejection.

    Science.gov (United States)

    van den Bosch, Thierry P P; Caliskan, Kadir; Kraaij, Marina D; Constantinescu, Alina A; Manintveld, Olivier C; Leenen, Pieter J M; von der Thüsen, Jan H; Clahsen-van Groningen, Marian C; Baan, Carla C; Rowshani, Ajda T

    2017-01-01

    During acute heart transplant rejection, infiltration of lymphocytes and monocytes is followed by endothelial injury and eventually myocardial fibrosis. To date, no information is available on monocyte-macrophage-related cellular shifts and their polarization status during rejection. Here, we aimed to define and correlate monocyte-macrophage endomyocardial tissue profiles obtained at rejection and time points prior to rejection, with corresponding serial blood samples in 25 heart transplant recipients experiencing acute cellular rejection. Additionally, 33 healthy individuals served as control. Using histology, immunohistochemistry, confocal laser scan microscopy, and digital imaging expression of CD14, CD16, CD56, CD68, CD80, and CD163 were explored to define monocyte and macrophage tissue profiles during rejection. Fibrosis was investigated using Sirius Red stainings of rejection, non-rejection, and 1-year biopsies. Expression of co-stimulatory and migration-related molecules on circulating monocytes, and production potential for pro- and anti-inflammatory cytokines were studied using flow cytometry. At tissue level, striking CD16+ monocyte infiltration was observed during rejection ( p  rejection compared to barely present CD68+CD80+ M1 macrophages. Rejection was associated with severe fibrosis in 1-year biopsies ( p  rejection status, decreased frequencies of circulating CD16+ monocytes were found in patients compared to healthy individuals. Rejection was reflected by significantly increased CD54 and HLA-DR expression on CD16+ monocytes with retained cytokine production potential. CD16+ monocytes and M2 macrophages hallmark the correlates of heart transplant acute cellular rejection on tissue level and seem to be associated with fibrosis in the long term.

  17. Bilateral versus single lung transplant for idiopathic pulmonary fibrosis.

    Science.gov (United States)

    Lehmann, Sven; Uhlemann, Madlen; Leontyev, Sergey; Seeburger, Joerg; Garbade, Jens; Merk, Denis R; Bittner, Hartmuth B; Mohr, Friedrich W

    2014-10-01

    It is unknown if uni- or bilateral lung transplant is best for treatment of usual idiopathic pulmonary fibrosis. We reviewed our single-center experience comparing both treatments. Between 2002 and 2011, one hundred thirty-eight patients at our institution underwent a lung transplant. Of these, 58 patients presented with idiopathic pulmonary fibrosis (56.9%) and were the focus of this study. Thirty-nine patients received a single lung transplant and 19 patients a bilateral sequential lung transplant. The mean patient age was 54 ± 10 years, and 69% were male. The intraoperative course was uneventful, save for 7 patients who needed extracorporeal membrane oxygenation support. Three patients had respiratory failure before the lung transplant that required mechanical ventilation and was supported by extracorporeal membrane oxygenation. Elevated pulmonary artery pressure > 40 mm Hg was identified as an independent predictor of early mortality by uni- and multivariate analysis (P = .01; OR 9.7). Using a Cox regression analysis, postoperative extracorporeal membrane oxyge-nation therapy (P = .01; OR 10.2) and the need for > 10 red blood cell concentrate during the first 72 hours after lung transplant (P = .01; OR 5.6) were independent predictors of long-term survival. Actuarial survival at 1 and 5 years was 65.6% and 55.3%, with no significant between-group differences (70.6% and 54.3%). Lung transplant is a safe and curative treatment for idiopathic pulmonary fibrosis. According to our results, unilateral lung transplant for idiopathic pulmonary fibrosis is an alternative to bilateral lung transplant and may affect the allocation process.

  18. Surfactant treatment before reperfusion improves the immediate function of lung transplants in rats

    NARCIS (Netherlands)

    Erasmus, ME; Petersen, AH; Hofstede, G; Haagsman, HP; Oetomo, SB; Prop, J

    An impaired function of alveolar surfactant can cause lung transplant dysfunction early after reperfusion. In this study it was investigated whether treatment with surfactant before reperfusion improves the immediate function of lung transplants and whether an improved transplant function was

  19. Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

    NARCIS (Netherlands)

    Moes, Dirk Jan A. R.; Press, Rogier R.; Ackaert, Oliver; Ploeger, Bart A.; Bemelman, Frederike J.; Diack, Cheikh; Wessels, Judith A. M.; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F.; van der Heide, Jaap J. Homan; Guchelaar, Henk Jan; de Fijter, Johan W.

    AIMS This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). METHODS Adult renal transplant recipients (n = 361) on cyclosporine-based

  20. Exploring genetic and non-genetic risk factors for delayed graft function, acute and subclinical rejection in renal transplant recipients

    NARCIS (Netherlands)

    Moes, Dirk Jan A. R.; Press, Rogier R.; Ackaert, Oliver; Ploeger, Bart A.; Bemelman, Frederike J.; Diack, Cheikh; Wessels, Judith A. M.; van der Straaten, Tahar; Danhof, Meindert; Sanders, Jan-Stephan F.; Homan van der Heide, Jaap J.; Guchelaar, Henk Jan; de Fijter, Johan W.

    2016-01-01

    This study aimed at identifying pharmacological factors such as pharmacogenetics and drug exposure as new predictive biomarkers for delayed graft function (DGF), acute rejection (AR) and/or subclinical rejection (SCR). Adult renal transplant recipients (n = 361) on cyclosporine-based

  1. Urinary granzyme A mRNA is a biomarker to diagnose subclinical and acute cellular rejection in kidney transplant recipients

    NARCIS (Netherlands)

    van Ham, S. Marieke; Heutinck, Kirstin M.; Jorritsma, Tineke; Bemelman, Fréderike J.; Strik, Merel C. M.; Vos, Wim; Muris, Jettie J. F.; Florquin, Sandrine; ten Berge, Ineke J. M.; Rowshani, Ajda T.

    2010-01-01

    The distinction between T-cell-mediated rejection (TCMR) and other causes of kidney transplant dysfunction such as tubular necrosis requires biopsy. Subclinical rejection (SCR), an established risk factor for chronic allograft dysfunction, can only be diagnosed by protocol biopsy. A specific

  2. Computational chemical imaging for cardiovascular pathology: chemical microscopic imaging accurately determines cardiac transplant rejection.

    Directory of Open Access Journals (Sweden)

    Saumya Tiwari

    Full Text Available Rejection is a common problem after cardiac transplants leading to significant number of adverse events and deaths, particularly in the first year of transplantation. The gold standard to identify rejection is endomyocardial biopsy. This technique is complex, cumbersome and requires a lot of expertise in the correct interpretation of stained biopsy sections. Traditional histopathology cannot be used actively or quickly during cardiac interventions or surgery. Our objective was to develop a stain-less approach using an emerging technology, Fourier transform infrared (FT-IR spectroscopic imaging to identify different components of cardiac tissue by their chemical and molecular basis aided by computer recognition, rather than by visual examination using optical microscopy. We studied this technique in assessment of cardiac transplant rejection to evaluate efficacy in an example of complex cardiovascular pathology. We recorded data from human cardiac transplant patients' biopsies, used a Bayesian classification protocol and developed a visualization scheme to observe chemical differences without the need of stains or human supervision. Using receiver operating characteristic curves, we observed probabilities of detection greater than 95% for four out of five histological classes at 10% probability of false alarm at the cellular level while correctly identifying samples with the hallmarks of the immune response in all cases. The efficacy of manual examination can be significantly increased by observing the inherent biochemical changes in tissues, which enables us to achieve greater diagnostic confidence in an automated, label-free manner. We developed a computational pathology system that gives high contrast images and seems superior to traditional staining procedures. This study is a prelude to the development of real time in situ imaging systems, which can assist interventionists and surgeons actively during procedures.

  3. Experimental high-frequency ultrasound can detect graft rejection after small bowel transplantation.

    Science.gov (United States)

    Yang, R; Liu, Q; Wu, E X; Pescovitz, M D; Collins, M H; Kopecky, K K; Grosfeld, J L

    1994-02-01

    Early diagnosis of graft rejection after small bowel transplantation (SBT) can allow prompt institution of vigorous immunosuppressive therapy, with resultant reversal of the rejection process. The current method for graft monitoring is random mucosal biopsy from a stomal site or through an endoscope. However, because early rejection often has a patchy distribution, it could be missed by random biopsy. We hypothesized that the pathological process of rejection would alter acoustic impedance of the tissue and thus change the ultrasonic patterns of the graft intestinal wall. If this hypothesis is correct, then high-frequency endoscopic ultrasound (US) could be used to monitor the entire transplanted bowel and guide the biopsy, with improved yields. This hypothesis was tested in a rat orthotopic SBT model. Sixty-two intestinal specimens (9 isografts, 12 allografts treated with cyclosporine A [CsA], 22 untreated allografts, and 19 intestines from normal rats) were collected for in vitro transluminal US imaging (30 MHz) and histopathologic study. The echo pattern of normal rat intestinal wall consisted of five echo layers that correlated spatially with the histological layers: the innermost hyperechoic layer 1, plus hypoechoic layer 2, corresponded to the mucosa; hyperechoic layer 3, the submucosa; anechoic layer 4, the muscularis propria; and hyperechoic layer 5, the serosa. The isografts and CsA-treated allografts were identical histologically and ultrasonically to normal intestine. However, the echo patterns of the untreated allografts had progressive loss of architectural stratification, with worsening rejection. The change began with patchy indistinctness and disruption of hyperechoic layers 1, 3 and 5, and progressed to total obliteration of the layers, with the intestinal wall becoming a nonstratified hypoechoic structure.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. mRNA Expression of Interferon Regulatory Factors during Acute Rejection of Liver Transplants in Patients with Autoimmune Hepatitis.

    Science.gov (United States)

    Nasiri, M; Geramizadeh, B; Nabavizadeh, S H; Male-Hosseini, S A; Karimi, M H; Saadat, I

    2018-01-01

    Interferon regulatory factors (IRFs) can play a critical role in the regulation of many facets of innate and adaptive immune responses through transcriptional activation of type I interferons, other proinflammatory cytokines, and chemokines. However, their roles in transplantation immunity still remain to be elucidated. To evaluate the time course of mRNA expression of all 9 members of IRFs family of transcription factors during liver allograft acute rejection. Blood samples of 19 patients with autoimmune hepatitis receiving liver transplants were collected on days 1, 3, 5, and 7 post-transplantation. The patients were followed for 6 months after transplantation and divided into two groups of acute rejection (AR) (n=4) and non-acute rejection (non-AR) (n=15). All of the studied transcription factors were down-regulated in AR-group on days 3, 5, and 7 post-transplantation compared to non-AR group. The mean±SEM IRF5 on day 7 post-transplantation was significantly (p=0.005) lower in AR-group than in non-AR group (0.7±0.21 vs . 1.91±0.27, respectively); expression of other IRFs family members was not significantly different between the two groups on days 3, 5, and 7 post-transplantation. IRF5 may have an important role during the acute rejection of liver transplants.

  5. Antibody-Mediated Rejection in a Blood Group A-Transgenic Mouse Model of ABO-Incompatible Heart Transplantation.

    Science.gov (United States)

    Motyka, Bruce; Fisicaro, Nella; Wang, Szu-I; Kratochvil, Annetta; Labonte, Katrina; Tao, Kesheng; Pearcey, Jean; Marshall, Thuraya; Mengel, Michael; Sis, Banu; Fan, Xiaohu; dʼApice, Anthony J F; Cowan, Peter J; West, Lori J

    2016-06-01

    ABO-incompatible (ABOi) organ transplantation is performed owing to unremitting donor shortages. Defining mechanisms of antibody-mediated rejection, accommodation, and tolerance of ABOi grafts is limited by lack of a suitable animal model. We report generation and characterization of a murine model to enable study of immunobiology in the setting of ABOi transplantation. Transgenesis of a construct containing human A1- and H-transferases under control of the ICAM-2 promoter was performed in C57BL/6 (B6) mice. A-transgenic (A-Tg) mice were assessed for A-antigen expression by histology and flow cytometry. B6 wild-type (WT) mice were sensitized with blood group A-human erythrocytes; others received passive anti-A monoclonal antibody and complement after heart transplant. Serum anti-A antibodies were assessed by hemagglutination. "A-into-O" transplantation (major histocompatibility complex syngeneic) was modeled by transplanting hearts from A-Tg mice into sensitized or nonsensitized WT mice. Antibody-mediated rejection was assessed by morphology/immunohistochemistry. A-Tg mice expressed A-antigen on vascular endothelium and other cells including erythrocytes. Antibody-mediated rejection was evident in 15/17 A-Tg grafts in sensitized WT recipients (median titer, 1:512), with 2 showing hyperacute rejection and rapid cessation of graft pulsation. Hyperacute rejection was observed in 8/8 A-Tg grafts after passive transfer of anti-A antibody and complement into nonsensitized recipients. Antibody-mediated rejection was not observed in A-Tg grafts transplanted into nonsensitized mice. A-Tg heart grafts transplanted into WT mice with abundant anti-A antibody manifests characteristic features of antibody-mediated rejection. These findings demonstrate an effective murine model to facilitate study of immunologic features of ABOi transplantation and to improve potential diagnostic and therapeutic strategies.

  6. Early plasmapheresis and rituximab for acute humoral rejection after ABO-compatible liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Nassim Kamar; Laurence Lavayssière; Fabrice Muscari; Janick Selves; Céline Guilbeau-Frugier; Isabelle Cardeau; Laure Esposito; Olivier Cointault; Marie Béatrice Nogier; Jean Marie Peron; Philippe Otal; Marylise Fort; Lionel Rostaing

    2009-01-01

    Acute humoral rejection (AHR) is uncommon after ABOcompatible liver transplantation. Herein, we report two cases of AHR treated with plasmapheresis and rituximab in two ABO-compatible liver-transplant patients with preformed anti-human leukocyte antigen donor-specific antibodies. Patient 1 experienced a biopsy-proven AHR at day 10 post-transplant. She was treated by steroid pulses, and OKT3. Because of persisting signs of biopsy-proven AHR at day 26, she was treated by plasmapheresis and rituximab. Liver enzyme levels did not improve, and she died on day 41. Patient 2 experienced a biopsy-proven AHR on day 10 post-transplant. She was treated by steroid pulses, plasmapheresis, and rituximab.Liver enzymes returned to within normal range 18 dafter diagnosis. Liver biopsies, at 3 and 9 mo post-transplant,showed complete resolution of AHR. We conclude that plasmapheresis should be started as soon as AHR is diagnosed, and be associated with a B-cell depleting agent. Rituximab may be considered as a first-line therapy.

  7. Obesity in pediatric kidney transplant recipients and the risks of acute rejection, graft loss and death.

    Science.gov (United States)

    Ladhani, Maleeka; Lade, Samantha; Alexander, Stephen I; Baur, Louise A; Clayton, Philip A; McDonald, Stephen; Craig, Jonathan C; Wong, Germaine

    2017-08-01

    Obesity is prevalent in children with chronic kidney disease (CKD), but the health consequences of this combination of comorbidities are uncertain. The aim of this study was to evaluate the impact of obesity on the outcomes of children following kidney transplantation. Using data from the ANZDATA Registry (1994-2013), we assessed the association between age-appropriate body mass index (BMI) at the time of transplantation and the subsequent development of acute rejection (within the first 6 months), graft loss and death using adjusted Cox proportional hazards models. Included in our analysis were 750 children ranging in age from 2 to 18 (median age 12) years with a total of 6597 person-years of follow-up (median follow-up 8.4 years). Overall, at transplantation 129 (17.2%) children were classified as being overweight and 61 (8.1%) as being obese. Of the 750 children, 102 (16.2%) experienced acute rejection within the first 6 months of transplantation, 235 (31.3%) lost their allograft and 53 (7.1%) died. Compared to children with normal BMI, the adjusted hazard ratios (HR) for graft loss in children who were underweight, overweight or diagnosed as obese were 1.05 [95% confidence interval (CI) 0.70-1.60], 1.03 (95% CI 0.71-1.49) and 1.61 (95% CI 1.05-2.47), respectively. There was no statistically significant association between BMI and acute rejection [underweight: HR 1.07, 95% CI 0.54-2.09; overweight: HR 1.42, 95% CI 0.86-2.34; obese: HR 1.83, 95% CI 0.95-3.51) or patient survival (underweight: HR 1.18, 95% CI 0.54-2.58, overweight: HR 0.85, 95% CI 0.38-1.92; obese: HR 0.80, 95% CI 0.25-2.61). Over 10 years of follow-up, pediatric transplant recipients diagnosed with obesity have a substantially increased risk of allograft failure but not acute rejection of the graft or death.

  8. Functional evaluation of transplanted kidneys in normal function and acute rejection using BOLD MR imaging

    International Nuclear Information System (INIS)

    Xiao Wenbo; Xu Jingjing; Wang Qindong; Xu Ying; Zhang Minming

    2012-01-01

    In this study, we evaluated a large number of subjects using BOLD MRI to provide more information about oxygen metabolism in the normal function of transplanted kidneys and to distinguish acute graft rejection from normal function kidneys. This study included 122 subjects (20 volunteers, 72 patients with normal functioning transplants, and 21 patients with acute rejection), and 9 patients had normal function grafts received examination while grafts dysfunction occurred within 6 months during the follow-up. The R2* (1/s) values in the cortex and medulla as well as the R2* ratio of the medulla to cortex (R2* ratio of M/C) were recorded. The R2* values of the medulla were higher than those of the cortex in the normal function group and the volunteers which have a steep R2* ratio of M/C. All the R2* values in the acute rejection group were lower than those in the normal function grafts group (P 1.1) is an important reason for keeping clinical normal function.

  9. Advanced pulmonary arterial hypertension: mechanical support and lung transplantation

    Directory of Open Access Journals (Sweden)

    Sonja Bartolome

    2017-12-01

    Full Text Available The development of targeted therapies has transformed the outlook for patients with pulmonary arterial hypertension (PAH; however, some patients fail to achieve an adequate clinical response despite receiving maximal treatment. For these patients, lung transplantation remains an important therapeutic option, and recommendations for transplantation are included in the current European Society of Cardiology/European Respiratory Society guidelines for the diagnosis and treatment of pulmonary hypertension. Although lung transplantation is not without risk, overall long-term survival rates are good and substantial improvements in quality of life have been reported for lung transplant recipients. In this review, we describe the important considerations prior to, during and after transplantation, including the role of mechanical support, in patients with advanced PAH.

  10. The perfect storm: HLA antibodies, complement, FcγRs, and endothelium in transplant rejection.

    Science.gov (United States)

    Thomas, Kimberly A; Valenzuela, Nicole M; Reed, Elaine F

    2015-05-01

    The pathophysiology of antibody-mediated rejection (AMR) in solid organ transplants is multifaceted and predominantly caused by antibodies directed against polymorphic donor human leukocyte antigens (HLAs). Despite the clearly detrimental impact of HLA antibodies (HLA-Abs) on graft function and survival, the prevention, diagnosis, and treatment of AMR remain a challenge. The histological manifestations of AMR reflect the signatures of HLA-Ab-triggered injury, specifically endothelial changes, recipient leukocytic infiltrate, and complement deposition. We review the interconnected mechanisms of HLA-Ab-mediated injury that might synergize in a 'perfect storm' of inflammation. Characterization of antibody features that are critical for effector functions may help to identify HLA-Abs that are more likely to cause rejection. We also highlight recent advances that may pave the way for new, more effective therapies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Induction of MHC-mismatched Mouse Lung Allograft Acceptance with Combined Donor Bone Marrow: Lung Transplant using a 12-Hour Nonmyeloablative Conditioning Regimen

    Science.gov (United States)

    Vulic, Ante; Panoskaltsis-Mortari, Angela; McDyer, John F.; Luznik, Leo

    2016-01-01

    Background Despite broad and intense conventional immunosuppression, long-term survival after lung transplantation lags behind that for other solid organ transplants, primarily because of allograft rejection. Therefore, new strategies to promote lung allograft acceptance are urgently needed. The purpose of the present study was to induce allograft tolerance with a protocol compatible with deceased donor organ utilization. Methods Using the MHC-mismatched mouse orthotopic lung transplant model, we investigated a conditioning regimen consisting of pretransplant T cell depletion, low dose total body irradiation and posttransplant (donor) bone marrow and splenocyte infusion followed by posttransplantation cyclophosphamide (PTTT-PTB/PTCy). Results Our results show that C57BL/6 recipients of BALB/c lung allografts undergoing this complete short-duration nonmyeloablative conditioning regimen had durable lung allograft acceptance. Mice that lacked 1 or more components of this regimen exhibited significant graft loss. Mechanistically, animals with lung allograft acceptance had established higher levels of donor chimerism, lymphocyte responses which were attenuated to donor antigens but maintained to third-party antigens, and clonal deletion of donor-reactive host Vβ T cells. Frequencies of Foxp3+ T regulatory cells were comparable in both surviving and rejected allografts implying that their perturbation was not a dominant cell-regulatory mechanism. Donor chimerism was indispensable for sustained tolerance, as evidenced by acute rejection of allografts in established chimeric recipients of PTTT-PTB/PTCy following a chimerism-ablating secondary recipient lymphocyte infusion. Conclusion Together, these data provide proof-of-concept for establishing lung allograft tolerance with tandem donor bone marrow transplantation (BMT) using a short-duration nonmyeloablative conditioning regimen and PTCy. PMID:27861294

  12. The Induction of IgM and IgG Antibodies against HLA or MICA after Lung Transplantation

    Directory of Open Access Journals (Sweden)

    Annelieke W. M. Paantjens

    2011-01-01

    Full Text Available The production of IgG HLA antibodies after lung transplantation (LTx is considered to be a major risk factor for the development of chronic rejection, represented by the bronchiolitis obliterans syndrome (BOS. It has recently been observed that elevated levels of IgM HLA antibodies also correlates with the development of chronic rejection in heart and kidney transplantation. This study investigates the relationship between IgM and IgG antibodies against HLA and MICA after lung transplantation. Serum was collected from 49 patients once prior to transplantation and monthly for up to 1 year after lung transplantation was analyzed by Luminex to detect IgM and IgG antibodies against HLA and MICA. The presence of either IgM or IgG HLA and/or MICA antibodies prior to or after transplantation was not related to survival, gender, primary disease, or the development of BOS. Additionally, the production of IgG alloantibodies was not preceded by an increase in levels of IgM, and IgM levels were not followed by an increase in IgG. Under current immune suppressive regimen, although the presence of IgM antibodies does not correlate with BOS after LTx, IgM high IgG low HLA class I antibody titers were observed more in patients with BOS compared to patients without BOS.

  13. Vascular endothelium as a target of immune response in renal transplant rejection

    Directory of Open Access Journals (Sweden)

    Giovanni ePiotti

    2014-10-01

    Full Text Available This review of clinical and experimental studies aims at analysing the interplay between graft endothelium and host immune system in renal transplantation, and how it affects the survival of the graft. Graft endothelium is indeed the first barrier between self and non-self that is encountered by host lymphocytes upon reperfusion of vascularised solid transplants. Endothelial cells express all the major sets of antigens that elicit host immune response, and therefore represent a preferential target in organ rejection.Some of the antigens expressed by endothelial cells are target of the antibody-mediated response, such as the AB0 blood group system, the HLA and MICA systems, and the endothelial cell-restricted antigens; for each of these systems, the mechanisms of interaction and damage of both preformed and de novo donor-specific antibodies are reviewed along with their impact on renal graft survival. Moreover the rejection process can force injured endothelial cells to expose cryptic self-antigens, toward which an auto-immune response mounts, overlapping to the allo-immune response in the damaging of the graft. Not only are endothelial cells a passive target of the host immune response, but also an active player in lymphocyte activation; therefore their interaction with allogenic T-cells is analysed on the basis of experimental in vitro and in vivo studies, according to the patterns of expression of the HLA class I and II and the co-stimulatory molecules specific for cytotoxic and helper T-cells.Finally, as the response that follows transplantation has proven to be not necessarily destructive, the factors that foster graft endothelium functioning in spite of rejection, and how they could be therapeutically harnessed to promote long-term graft acceptance, are described: accommodation that is resistance of endothelial cells to donor-specific antibodies, and endothelial cell ability to induce Foxp3+ Regulatory T-cells, that are crucial mediators of

  14. Donor-specific alloreactive T cells can be quantified from whole blood, and may predict cellular rejection after renal transplantation.

    Science.gov (United States)

    Fischer, Michaela; Leyking, Sarah; Schäfer, Marco; Elsäßer, Julia; Janssen, Martin; Mihm, Janine; van Bentum, Kai; Fliser, Danilo; Sester, Martina; Sester, Urban

    2017-07-01

    Preformed cellular alloreactivity can exist prior to transplantation and may contribute to rejection. Here, we used a rapid flow-cytometric whole-blood assay to characterize the extent of alloreactive T cells among 1491 stimulatory reactions from 61 renal transplant candidates and 75 controls. The role of preformed donor-specific alloreactive T cells in cellular rejection was prospectively analyzed in 21 renal transplant recipients. Alloreactive CD8 + T cells were more frequent than respective CD4 + T cells, and these levels were stable over time. CD8 + T cells were effector-memory T cells largely negative for expression of CD27, CD62L, and CCR7, and were susceptible to steroid and calcineurin inhibitor inhibition. Alloreactivity was more frequent in samples with higher number of HLA mismatches. Moreover, the percentage of individuals with alloreactive T cells was higher in transplant candidates than in controls. Among transplant candidates, 5/61 exhibited alloreactive CD8 + T cells against most stimulators, 23/61 toward a limited number of stimulators, and 33/61 did not show any alloreactivity. Among 21 renal transplant recipients followed prospectively, one had donor-specific preformed T-cell alloreactivity. She was the only patient who developed cellular rejection posttransplantation. In conclusion, donor-specific alloreactive T cells may be rapidly quantified from whole blood, and may predict cellular rejection after transplantation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Early diagnosis of acute postoperative renal transplant rejection by indium-111-labeled platelet scintigraphy

    International Nuclear Information System (INIS)

    Tisdale, P.L.; Collier, B.D.; Kauffman, H.M.

    1986-01-01

    A prospective evaluation of 111 In-labeled platelet scintigraphy (IPS) for the early diagnosis of acute postoperative renal transplant rejection (TR) was undertaken. The results of IPS were compared with in vitro biochemical tests, the clinical finding of graft tenderness, and combined [/sup 99m/Tc]DTPA and [ 131 I]orthoiodohippurate scintigraphy. With a sensitivity of 0.93 and a specificity of 0.95, IPS provided otherwise unavailable diagnostic information. Furthermore, postoperative IPS was a good predictor of long-term allograft survival

  16. Fish oil enhances recovery of intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplant.

    Directory of Open Access Journals (Sweden)

    Qiurong Li

    Full Text Available BACKGROUND: The intestinal chronic rejection (CR is the major limitation to long-term survival of transplanted organs. This study aimed to investigate the interaction between intestinal microbiota and epithelial integrity in chronic rejection of intestinal transplantation, and to find out whether fish oil enhances recovery of intestinal microbiota and epithelial integrity. METHODS/PRINCIPAL FINDINGS: The luminal and mucosal microbiota composition of CR rats were characterized by DGGE analysis at 190 days after intestinal transplant. The specific bacterial species were determined by sequence analysis. Furthermore, changes in the localization of intestinal TJ proteins were examined by immunofluorescent staining. PCR-DGGE analysis revealed that gut microbiota in CR rats had a shift towards Escherichia coli, Bacteroides spp and Clostridium spp and a decrease in the abundance of Lactobacillales bacteria in the intestines. Fish oil supplementation could enhance the recovery of gut microbiota, showing a significant decrease of gut bacterial proportions of E. coli and Bacteroides spp and an increase of Lactobacillales spp. In addition, CR rats showed pronounced alteration of tight junction, depicted by marked changes in epithelial cell ultrastructure and redistribution of occuldin and claudins as well as disruption in TJ barrier function. Fish oil administration ameliorated disruption of epithelial integrity in CR, which was associated with an improvement of the mucosal structure leading to improved tight junctions. CONCLUSIONS/SIGNIFICANCE: Our study have presented novel evidence that fish oil is involved in the maintenance of epithelial TJ integrity and recovery of gut microbiota, which may have therapeutic potential against CR in intestinal transplantation.

  17. Primary Nocardia Infection Causing a Fluorodeoxyglucose-Avid Right Renal Mass in a Redo Lung Transplant Recipient

    Directory of Open Access Journals (Sweden)

    Sreeja Biswas Roy

    2018-01-01

    Full Text Available Immunosuppression after lung transplantation may increase susceptibility to opportunistic infection and is associated with early and delayed deaths in lung transplant recipients. Factors that may predispose lung transplant recipients to opportunistic bacterial and fungal infections include prolonged corticosteroid use, renal impairment, treatment of acute rejection, and post-transplant diabetes mellitus. We present a unique case of a 63-year-old woman with diabetes mellitus who underwent redo lung transplantation. Three years after her right-sided single redo lung transplant, she presented with right-sided abdominal pain, nausea, and vomiting. Upon examination, computed tomography showed a 4.5 × 3.3 cm heterogeneous, enhancing right renal mass with a patent renal vein. Magnetic resonance imaging confirmed a T1/T2 hypointense, diffusion-restricting, right mid-renal mass that was fluorodeoxyglucose-avid on positron emission tomography. We initially suspected primary renal cell carcinoma. However, after a right nephrectomy, no evidence of neoplasia was observed; instead, a renal abscess containing filamentous bacteria was noted, raising suspicion for infection of the Nocardia species. Special stains confirmed a diagnosis of Nocardia renal abscess. Computed tomography of the chest and brain revealed no lesions consistent with infection. We initiated a long-term therapeutic regimen of anti-Nocardia therapy with imipenem and trimethoprim-sulfamethoxazole.

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

    Energy Technology Data Exchange (ETDEWEB)

    McKay, Clare, E-mail: clmck7@student.monash.edu; Knight, Kellie A; Wright, Caroline [Department of Medical Imaging and Radiation Sciences, School of Biomedical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria (Australia)

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

    International Nuclear Information System (INIS)

    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

  20. The value of ventilation scintigraphy after single lung transplantation

    NARCIS (Netherlands)

    Ouwens, JP; van der Bij, W; van der Mark, TW; Piers, DA; Koeter, GH

    Background: A decrease in forced expiratory volume in 1 second (FEV1) as a diagnostic criterion for bronchiolitis obliterans syndrome (BOS) after single lung transplantation may be influenced significantly by the presence of the native lung. To quantify and to discriminate between the relative

  1. Torque Teno Virus Load-Inverse Association With Antibody-Mediated Rejection After Kidney Transplantation.

    Science.gov (United States)

    Schiemann, Martin; Puchhammer-Stöckl, Elisabeth; Eskandary, Farsad; Kohlbeck, Philip; Rasoul-Rockenschaub, Susanne; Heilos, Andreas; Kozakowski, Nicolas; Görzer, Irene; Kikić, Željko; Herkner, Harald; Böhmig, Georg A; Bond, Gregor

    2017-02-01

    Antibody-mediated rejection (AMR) represents one of the cardinal causes of late allograft loss after kidney transplantation, and there is great need for noninvasive tools improving early diagnosis of this rejection type. One promising strategy might be the quantification of peripheral blood DNA levels of the highly prevalent and apathogenic Torque Teno virus (TTV), which might mirror the overall level of immunosuppression and thus help determine the risk of alloimmune response. To assess the association between TTV load in the peripheral blood and AMR, 715 kidney transplant recipients (median, 6.3 years posttransplantation) were subjected to a systematical cross-sectional AMR screening and, in parallel, TTV quantification. Eighty-six of these recipients had donor-specific antibodies and underwent protocol biopsy, AMR-positive patients (n = 46) showed only 25% of the TTV levels measured in patients without AMR (P = 0.003). In a generalized linear model, higher TTV levels were associated with a decreased risk for AMR after adjustment for potential confounders (risk ratio 0.94 per TTV log level; 95% confidence interval 0.90-0.99; P = 0.02). Future studies will have to clarify whether longitudinal assessment of TTV load might predict AMR risk and help guide the type and intensity of immunosuppression to prevent antibody-mediated graft injury.

  2. State of the Art in Pediatric Lung Transplantation.

    Science.gov (United States)

    Lancaster, Timothy S; Eghtesady, Pirooz

    2018-04-24

    Pediatric lung transplantation is a highly specialized therapy for end stage pulmonary disease in children, performed in only a handful of transplant centers around the world. Advancement in the field has been made on many fronts in recent years, including in public policy and organ allocation strategies, donor selection and management, emerging technologies for donor lung rehabilitation and bridge-to-transplant support of listed candidates, and ongoing refinement of surgical techniques. Despite this progress, children continue to suffer discrepant waitlist mortality and longer waiting times than their adult counterparts, and face special challenges of donor availability and size matching. Here we review the current state of the art in pediatric lung transplantation, reviewing progress made to date and further opportunities to improve care for this unique group of patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  3. Pulmonary hypertension as a risk factor of mortality after lung transplantation

    DEFF Research Database (Denmark)

    Andersen, Kasper H; Schultz, Hans Henrik L; Nyholm, Benjamin

    2016-01-01

    PURPOSE: Pulmonary hypertension (PH) is recognized as a risk factor in lung transplantation as reflected in the lung allocation score (LAS). We examined the impact of PH on outcome after lung transplantation, with special emphasis on pre- and post-capillary PH. METHODS: Consecutive lung transplant...

  4. Pattern and Predictors of Hospital Readmission During the First Year After Lung Transplantation.

    Science.gov (United States)

    Alrawashdeh, M; Zomak, R; Dew, M A; Sereika, S; Song, M K; Pilewski, J M; DeVito Dabbs, A

    2017-05-01

    Hospital readmission after lung transplantation negatively affects quality of life and resource utilization. A secondary analysis of data collected prospectively was conducted to identify the pattern of (incidence, count, cumulative duration), reasons for and predictors of readmission for 201 lung transplant recipients (LTRs) assessed at 2, 6, and 12 mo after discharge. The majority of LTRs (83.6%) were readmitted, and 64.2% had multiple readmissions. The median cumulative readmission duration was 19 days. The main reasons for readmission were other than infection or rejection (55.5%), infection only (25.4%), rejection only (9.9%), and infection and rejection (0.7%). LTRs who required reintubation (odds ratio [OR] 1.92; p = 0.008) or were discharged to care facilities (OR 2.78; p = 0.008) were at higher risk for readmission, with a 95.7% cumulative incidence of readmission at 12 mo. Thirty-day readmission (40.8%) was not significantly predicted by baseline characteristics. Predictors of higher readmission count were lower capacity to engage in self-care (incidence rate ratio [IRR] 0.99; p = 0.03) and discharge to care facilities (IRR 1.45; p = 0.01). Predictors of longer cumulative readmission duration were older age (arithmetic mean ratio [AMR] 1.02; p = 0.009), return to the intensive care unit (AMR 2.00; p = 0.01) and lower capacity to engage in self-care (AMR 0.99; p = 0.03). Identifying LTRs at risk may assist in optimizing predischarge care, discharge planning and long-term follow-up. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    Science.gov (United States)

    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. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  6. Recurrence of lymphangioleiomyomatosis: Nine years after a bilateral lung transplantation.

    Science.gov (United States)

    Zaki, Khawaja S; Aryan, Zahra; Mehta, Atul C; Akindipe, Olufemi; Budev, Marie

    2016-03-24

    Lymphangioleiomyomatosis (LAM) is a rare, slowly progressive lethal lung disease primary afflicting young women. LAM is characterized by proliferation of abnormal smooth muscle cells that target the lungs, causing cystic destruction and eventual respiratory failure leading to death. Recent ten year mortality due to end stage LAM has been reported to be approximately 10%-20%, but may vary. The decline in lung function in LAM is gradual, occurring at a rate of about 3% to 15% per year but can vary from patient to patient. But recently therapy with mammalian target of rapamycin (mTOR) inhibitors such as sirolimus has shown promising results in the stabilization of lung function and reduction of chylous effusions in LAM. Lung transplantation is a viable option for patients who continue to have decline in lung function despite mTOR therapy. Unique issues that may occur post-transplant in a recipient with LAM include development of chylous effusion and a risk of recurrence. We describe a case of LAM recurrence in a bilateral lung transplant recipient who developed histological findings of LAM nine years after transplantation.

  7. Late acute antibody mediated rejection after nine years of renal transplantation

    Directory of Open Access Journals (Sweden)

    Halim Medhat

    2010-01-01

    Full Text Available Acute Antibody Mediated Rejection (AMR is rarely reported as a long-term com-plication of renal transplantation, and it can present on top of another chronic pathology affecting the graft. A 45-year-old gentleman with chronic kidney disease due to unknown etiology received renal transplantation from his sister with 4 HLA mismatches. He received antithymocte globulin induction therapy and was maintained on steroids, azathioprine (AZA and cyclosporine A (CsA. Up to eight years post-transplantation he was clinically and biochemically stable. He lost follow-up for about one year, and then presented with nephritic nephrotic syndrome and rise of serum creatinine (SCr. to 210 μmol/L. Graft biopsy revealed picture suggestive of acute AMR on top of de novo membranoprolipherative glomerulonephritis (MPGN with focal crescent formation, diffuse immune complex deposition and peri-tubular capillaries C4d positivity. Anti-HLA donor specific antibodies were highly positive for B and T cells class I and class II. The patient was treated with intravenous immunoglobulin, plasma exchange and anti-CD20 (rituximab. AZA was changed to mycophenolate mofetil and CsA to tacrolimus. He had partial response, but SCr. continued at 220 μmol/L.

  8. Coronary blood flow and thallium 201 uptake in rejecting rat heart transplantations

    International Nuclear Information System (INIS)

    Bergsland, J.; Hwang, K.; Driscoll, R.; Carr, E.A.; Wright, J.R.; Curran-Everett, D.C.; Carroll, M.; Krasney, E.; Krasney, J.A.

    1989-01-01

    The effects of rejection on coronary flow (CAF) in heart allografts are unclear, although previous evidence with cardiac imaging agents indicates impaired flow during advanced rejection. The purpose of this study was to measure CAF in heterotopically placed heart grafts. Lewis rats (LEW) received grafts from either syngeneic Lewis rats (LEW/LEW group) or allogeneic ACI rats (ACI/LEW group). CAF was measured in both the transplanted and native hearts with radiolabeled microspheres. Rejection was measured histologically (grades 0 [absent] to 4+ [severe]). In addition systemic blood pressure and cardiac outputs of the native hearts were determined with microspheres. Different animals were studied during relatively early (4 days) and late (6 days) rejection. Among the 4-day animals a cyclosporine-treated group was included (ACI/LEW CyA). In 6-day rats CAF in allografts was lower (0.56 +/- .06 ml/gm/min) compared with syngeneic grafts (1.72 +/- 0.4 ml/gm/min) (p less than 0.05). The CAF in the native hearts did not differ significantly but was higher than in the grafts in both groups. Heart rates were reduced in allografts (p less than 0.05). It is interesting that arterial pressure and cardiac output were significantly lower in animals bearing allogeneic than syngeneic grafts. In rats studied at 4 days graft CAF was lower than in the native heart in both the LEW/LEW and ACI/LEW groups, but there was no significant difference in behavior between groups. The same was true for a cyclosporine-treated group. Graft heart rates were similar in all 4-day rats

  9. Detection of acute renal allograft rejection by analysis of renal tissue proteomics in rat models of renal transplantation

    Directory of Open Access Journals (Sweden)

    Dai Yong

    2008-01-01

    Full Text Available At present, the diagnosis of renal allograft rejection requires a renal biopsy. Clinical management of renal transplant patients would be improved if rapid, noninvasive and reliable biomarkers of rejection were available. This study is designed to determine whether such protein biomarkers can be found in renal-graft tissue proteomic approach. Orthotopic kidney transplantations were performed using Fisher (F344 or Lewis rats as donors and Lewis rats as recipients. Hence, there were two groups of renal transplant models: one is allograft (from F344 to Lewis rats; another is syngrafts (from Lewis to Lewis rats serving as control. Renal tissues were collected 3, 7 and 14 days after transplantation. As many as 18 samples were analyzed by 2-D Electrophoresis and mass spectrometry (MALDI-TOF-TOF-MS. Eleven differentially expressed proteins were identified between groups. In conclusion, proteomic technology can detect renal tissue proteins associated with acute renal allograft rejection. Identification of these proteins as diagnostic markers for rejection in patients′ urine or sera may be useful and non-invasive, and these proteins might serve as novel therapeutic targets that also help to improve the understanding of mechanism of renal rejection.

  10. Interaction between Pseudomonas and CXC Chemokines Increases Risk of Bronchiolitis Obliterans Syndrome and Death in Lung Transplantation

    Science.gov (United States)

    Wang, Xiaoyan; Weigt, S. Sam; Palchevskiy, Vyacheslav; Lynch, Joseph P.; Ross, David J.; Kubak, Bernard M.; Saggar, Rajan; Fishbein, Michael C.; Ardehali, Abbas; Li, Gang; Elashoff, Robert; Belperio, John A.

    2013-01-01

    Rationale: Pseudomonas aeruginosa is the most commonly isolated gram-negative bacterium after lung transplantation and has been shown to up-regulate glutamic acid–leucine–arginine–positive (ELR+) CXC chemokines associated with bronchiolitis obliterans syndrome (BOS), but the effect of pseudomonas on BOS and death has not been well defined. Objectives: To determine if the influence of pseudomonas isolation and ELR+ CXC chemokines on the subsequent development of BOS and the occurrence of death is time dependent. Methods: A three-state model was developed to assess the likelihood of transitioning from lung transplant (state 1) to BOS (state 2), from transplant (state 1) to death (state 3), and from BOS (state 2) to death (state 3). This Cox semi-Markovian approach determines state survival rates and cause-specific hazards for movement from one state to another. Measurements and Main Results: The likelihood of transition from transplant to BOS was increased by acute rejection, CXCL5, and the interaction between pseudomonas and CXCL1. The pseudomonas effect in this transition was due to infection rather than colonization. Movement from transplant to death was facilitated by pseudomonas infection and single lung transplant. Transition from BOS to death was affected by the length of time in state 1 and by the interactions between any pseudomonas isolation and CXCL5 and aspergillus, either independently or in combination. Conclusions: Our model demonstrates that common post-transplantation events drive movement from one post-transplantation state to another and influence outcomes differently depending upon when after transplantation they occur. Pseudomonas and the ELR+ CXC chemokines may interact to negatively influence lung transplant outcomes. PMID:23328531

  11. Esophageal motor disease and reflux patterns in patients with advanced pulmonary disease undergoing lung transplant evaluation.

    Science.gov (United States)

    Seccombe, J; Mirza, F; Hachem, R; Gyawali, C P

    2013-08-01

    Advanced pulmonary disorders are linked to esophageal hypomotility and reflux disease. However, characterization of esophageal function using high resolution manometry (HRM) and ambulatory pH monitoring, segregation by pulmonary pathology, and comparison to traditional reflux disease are all limited in the literature. Over a 4 year period, 73 patients (55.2 ± 1.3 years, 44F) were identified who underwent esophageal function testing as part of lung transplant evaluation for advanced pulmonary disease (interstitial lung disease, ILD = 47, obstructive lung disease, OLD = 24, other = 2). Proportions of patients with motor dysfunction (≥ 80% failed sequences = severe hypomotility) and/or abnormal reflux parameters (acid exposure time, AET ≥ 4%) were determined, and compared to a cohort of 1081 patients (48.4 ± 0.4 years, 613F) referred for esophageal function testing prior to antireflux surgery (ARS). The proportion of esophageal body hypomotility was significantly higher within advanced pulmonary disease categories (35.6%), particularly ILD (44.7%), compared to ARS patients (12.1%, P esophageal motor pattern or reflux evidence. Interstitial lung disease has a highly significant association with esophageal body hypomotility. Consequently, prevalence of abnormal esophageal acid exposure is high, but implications for post lung transplant chronic rejection remain unclear. © 2013 John Wiley & Sons Ltd.

  12. Nephro and neurotoxicity of calcineurin inhibitors and mechanisms of rejections: A review on tacrolimus and cyclosporin in organ transplantation.

    Science.gov (United States)

    Tolou-Ghamari, Zahra

    2012-04-01

    In the meadow of medical sciences substituting a diseased organ with a healthy one from another individual, dead or alive, to allow a human to stay alive could be consider as the most string event. In this article we review the history of transplantation, mechanisms of rejection, nephro-neurotoxicity of tacrolimus and cyclosporin in organ transplantations. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. The first reference to the concept of organ transplantation and replacement for therapeutic purposes appears to be to Hua-To (136 to 208 A.D), who replaced diseased organs with healthy ones in patients under analgesia induced with a mixture of Indian hemp. In 1936, the first human renal transplant performed by Voronoy in Russia. The first liver transplant in humans was performed on March 1, 1963 by Starzl in Denver, USA. Medawar was the first to assert that rejection was an immunological response, with the inflammatory reaction due to lymphocyte infiltration. Consequently, rational immunosuppressive therapies could inhibit deleterious T-cell responses in an antigen specific manner. Searching related to the history of organ transplantation from mythic to modern times suggests that, to prevent graft rejection, minimize nephro and neuro toxicity monitoring of immunosupressive concentrations could provide an invaluable and essential aid in adjusting dosage to ensure adequate immunosuppression.

  13. Dangerous drug interactions leading to hemolytic uremic syndrome following lung transplantation

    Directory of Open Access Journals (Sweden)

    Parissis Haralabos

    2010-09-01

    Full Text Available Abstract Background To report our experience of a rather uncommon drug interaction, resulting in hemolytic uremic syndrome (HUS. Methods Two consecutive cases of hemolytic uremic syndrome were diagnosed in our service. In both patients the use of macrolides in patients taking Tacrolimus, resulted in high levels of Tacrolimus. Results The first patient was a 48 years old female with Bilateral emphysema. She underwent Single Sequential Lung Transplantation. She developed reperfusion injury requiring prolonged stay. Tacrolimus introduced (Day 51. The patient remained well up till 5 months later; Erythromycin commenced for chest infection. High Tacrolimus levels and a clinical diagnosis of HUS were made. She was treated with plasmapheresis successfully. The second case was a 57 years old female with Emphysema & A1 Antithrypsin deficiency. She underwent Right Single Lung Transplantation. A2 rejection with mild Obliterative Bronchiolitis diagnosed 1 year later and she switched to Tacrolimus. She was admitted to her local Hospital two and a half years later with right middle lobe consolidation. The patient commenced on amoxicillin and clarithromycin. Worsening renal indices, high Tacrolimus levels, hemolytic anemia & low Platelets were detected. HUS diagnosed & treated with plasmapheresis. Conclusions There are 21 cases of HUS following lung transplantation in the literature that may have been induced by high tacrolimus levels. Macrolides in patients taking Cyclosporin or Tacrolimus lead to high levels. Mechanism of action could be glomeruloconstrictor effect with reduced GFR increased production of Endothelin-1 and increased Platelet aggregation.

  14. Depressive Symptoms, Exercise Capacity, and Clinical Outcomes After Lung Transplantation.

    Science.gov (United States)

    Smith, Patrick J; Byrd, Rebecca; Lusby, Megan; Clausen, Emily; Snyder, Laurie D

    2018-05-01

    Depressive symptoms are common among lung transplant recipients and have been associated with worse clinical outcomes. However, few studies have examined the association between depressive symptoms assessed at multiple time points or behavioral mechanisms by which posttransplant depressive symptoms may confer greater clinical risk. We therefore examined the associations between depressive symptoms, exercise capacity, chronic lung allograft dysfunction (CLAD), and mortality prospectively in a large sample of lung transplant recipients. Between July 2009 and February 2016, 251 lung transplant recipients were assessed before transplantation and again approximately 3 weeks and 3 months after transplant. Depressive symptoms were assessed using the Centers for Epidemiologic Studies of Depression scale. Functional exercise capacity was assessed using the 6-minute walk test. Cox proportional hazards models were used to examine the associations between depressive symptoms, exercise capacity, CLAD, and mortality. During a median (range) follow-up of 4.5 (0.1 to 6.3) years, 53 participants (21%) died. Greater depressive symptoms (hazard ratio [HR] = 1.39 [95% CI = 1.05 to 1.84], p = .021) and poorer exercise capacity (HR = 0.58 [95% CI = 0.38 to 0.90], p = .021) assessed 3 months after transplant were both independently associated with mortality. Although greater depressive symptoms were associated with lower exercise capacity (β = -0.14, p = .039), exercise capacity did not mediate the association between depressive symptoms and mortality. In secondary analyses, depressive symptoms were independently predictive of CLAD (HR = 1.29 [95% CI = 1.01 to 1.65], p = .045) and the composite outcome of CLAD and mortality in a clustered event model (HR = 1.30 [1.09 to 1.56], p = .005). Depressive symptoms are associated with mortality and CLAD after lung transplantation, independent of exercise capacity.

  15. Early bedside detection of ischemia and rejection in liver transplants by microdialysis.

    Science.gov (United States)

    Håugaa, Håkon; Thorgersen, Ebbe B; Pharo, Anne; Boberg, Kirsten M; Foss, Aksel; Line, Pål Dag; Sanengen, Truls; Almaas, Runar; Grindheim, Guro; Pischke, Soeren Erik; Mollnes, Tom Eirik; Tønnessen, Tor Inge

    2012-07-01

    This study was performed to explore whether lactate, pyruvate, glucose, and glycerol levels sampled via microdialysis catheters in the transplanted liver could be used to detect ischemia and/or rejection. The metabolites were measured at the bedside every 1 to 2 hours after the operation for a median of 10 days. Twelve grafts with biopsy-proven rejection and 9 grafts with ischemia were compared to a reference group of 39 grafts with uneventful courses. The median lactate level was significantly higher in both the ischemia group [5.8 mM (interquartile range = 4.0-11.1 mM)] and the rejection group [2.1 mM (interquartile range = 1.9-2.4 mM)] versus the reference group [1.5 mM (interquartile range = 1.1-1.9 mM), P interquartile range = 155-206 μM)] versus the reference group [124 μM (interquartile range = 102-150 μM), P interquartile range = 23.9-156.7) and 138 μM (interquartile range = 26-260 μM)] versus the reference group [11.8 (interquartile range = 10.6-13.6), P interquartile range = 9-24 μM), P = 0.002]. Ischemia was detected with 100% sensitivity and greater than 90% specificity when a positive test was repeated after 1 hour. In 3 cases of hepatic artery thrombosis, ischemia was detected despite normal blood lactate levels. Consecutive pathological measurements for 6 hours were used to diagnose rejection with greater than 80% sensitivity and specificity at a median of 4 days before the activity of alanine aminotransferase, the concentration of bilirubin in serum, or both increased. In conclusion, bedside measurements of intrahepatic lactate and pyruvate levels were used to detect ischemia and rejection earlier than current standard methods could. Discrimination from an uneventful patient course was achieved. Consequently, intrahepatic graft monitoring with microdialysis may lead to the earlier initiation of graft-saving treatment. Copyright © 2012 American Association for the Study of Liver Diseases.

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

    Science.gov (United States)

    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

  17. Pulmonary rehabilitation programs in lung transplant: a literature review

    Directory of Open Access Journals (Sweden)

    Juliana Maria de Sousa Pinto

    2015-09-01

    Full Text Available Objective: To analyze, using a literature review, Pulmonary Rehabilitation (RP Programs in lung transplant. Methods: A literature review in July 2014 in Ebsco Host, Periódicos Capes, BVS and Science Direct data bases using descriptors in English (“lung transplantation”, “lung transplant” AND/OR “rehabilitation” and Portuguese (“reabilitação” AND/OR “transplante pulmonar”. The eligibility criterions were interventional studies of PR before and/or after lung transplant; participants who were candidates to lung transplant or lung transplant recipients; studies that applied any kind of PR program (hospital-based, homebased or outpatient and articles published in English, Spanish or Portuguese. Literature reviews, guidelines and case reports were excluded. The search process yielded 46 articles of which two were duplicated. After title and abstract screening 13 articles remained for full text reading. Six studies met the inclusion eligibility and were included in the review. Results: The studies involved patients with Chronic Obstructive Pulmonary Disease, Cystic Fibrosis, Pulmonary Hypertension, Interstitial Lung Disease and Pulmonary Fibrosis. Pulmonary function, exercise capacity, quality of life (QoL and quadriceps force were evaluated. Most interventions were outpatient programs with three months duration, three times a week and session with at least one hour. Protocols included physical training, educational approach and just one included nutritional, psychiatric and social assistant follow-up. The studies presented significant change in the six-minute walking distance, QoL and quadriceps force after PR programs. Conclusion: This review showed the benefits of the PR in the QoL and exercise capacity contributing to the Health Promotion of the patients.

  18. The role of indium-111 antimyosin (Fab) imaging as a noninvasive surveillance method of human heart transplant rejection

    International Nuclear Information System (INIS)

    De Nardo, D.; Scibilia, G.; Macchiarelli, A.G.

    1989-01-01

    The identification of rejection after heart transplantation in patients receiving cyclosporine immunosuppressive therapy requires the endomyocardial biopsy, an invasive method associated with a finite morbidity. To evaluate the role of indium-111 antimyosin (Fab) scintigraphy as a noninvasive surveillance method of heart transplant rejection, the Fab fragment of murine monoclonal antimyosin antibodies labeled with indium-111 was administered intravenously in 30 scintigraphic studies to 10 consecutive heart transplant recipients. Endomyocardial biopsy specimens were obtained 72 hours after each scintigraphic study. Nineteen scintigraphic studies had negative findings; no false negative finding was obtained. Eleven antimyosin scintigraphic studies had positive findings, and in these studies endomyocardial biopsy revealed mild rejection in two cases, moderate acute rejection with myocyte necrosis in two cases, myocyte necrosis as a consequence of ischemic injury in six cases, and possibly cytotoxic damage in one case. Antimyosin scintigraphy may represent a reliable screening method for the surveillance of heart transplant patients. In the presence of a negative finding from antimyosin scintigraphy, it may be possible to avoid endomyocardial biopsy. Conversely, in patients who have a positive finding from antimyosin scintigraphy, the endomyocardial biopsy is mandatory to establish the definitive diagnosis by histologic examination of the myocardium

  19. Effect of dietary fish oil on renal function and rejection in cyclosporine-treated recipients of renal transplants

    NARCIS (Netherlands)

    van der Heide, J. J.; Bilo, H. J.; Donker, J. M.; Wilmink, J. M.; Tegzess, A. M.

    1993-01-01

    Dietary fish oil exerts effects on renal hemodynamics and the immune response that may benefit renal-transplant recipients treated with cyclosporine. To evaluate this possibility, we studied the effect of fish oil on renal function, blood pressure, and the incidence of acute rejection episodes in

  20. Intragraft interleukin 2 mRNA expression during acute cellular rejection and left ventricular total wall thickness after heart transplantation

    NARCIS (Netherlands)

    de Groot-Kruseman, H A; Baan, C C; Hagman, E M; Mol, W M; Niesters, H G; Maat, A P; Zondervan, P E; Weimar, W; Balk, A H

    OBJECTIVE: To assess whether diastolic graft function is influenced by intragraft interleukin 2 (IL-2) messenger RNA (mRNA) expression in rejecting cardiac allografts. DESIGN: 16 recipients of cardiac allografts were monitored during the first three months after transplantation. The presence of IL-2

  1. Postoperative rebound of antiblood type antibodies and antibody-mediated rejection after ABO-incompatible living-related kidney transplantation.

    Science.gov (United States)

    Ishida, Hideki; Kondo, Tsunenori; Shimizu, Tomokazu; Nozaki, Taiji; Tanabe, Kazunari

    2015-03-01

    The purpose of this study is to examine whether postoperative antiblood type antibody rebound is attributed to kidney allograft rejection in ABO blood type-incompatible (ABO-I) living-related kidney transplantation (KTx). A total of 191 ABO-I recipients who received ABO-I living-related KTx between 2001 and 2013 were divided into two groups: Group 1 consisted of low rebound [(≦1:32), N = 170] and Group 2 consisted of high rebound [(≧1:64), N = 21], according to the levels of the rebounded antiblood type antibodies within 1 year after transplantation. No prophylactic treatment for rejection was administered for elevated antiblood type antibodies, regardless of the levels of the rebounded antibodies. Within 1 year after transplantation, T-cell-mediated rejection was observed in 13 of 170 recipients (13/170, 8%) in Group 1 and in 2 of 21 recipients (2/21, 10%) in Group 2 (Groups 1 vs. 2, P = 0.432). Antibody-mediated rejection was observed in 15 of 170 recipients (15/170, 9%) and 2 of 21 recipients (2/21, 10%) in Groups 1 and 2, respectively (P = 0.898). In this study, we found no correlation between the postoperative antiblood type antibody rebound and the incidence of acute rejection. We concluded that no treatment is necessary for rebounded antiblood type antibodies. © 2014 Steunstichting ESOT.

  2. Detection of acute renal allograft rejection by analysis of Renal TissueProteomics in rat models of renal transplantation

    International Nuclear Information System (INIS)

    Dai, Y.; Lv, T.; Wang, K.; Li, D.; Huang, Y.; Liu, J.

    2008-01-01

    At present, the diagnosis of renal allograft rejection requires a renalbiopsy. Clinical management of renal transplant patients would be improved ifrapid, noninvasive and reliable biomarkers of rejection were available. Thisstudy is designed to determine whether such protein biomarkers can be foundin renal graft tissue proteomic approach. Orthotopic kidney transplantationswere performed using Fisher (F344) or Lewis rats as donors and Lewis rats asrecipients. Hence, there were two groups of renal transplant models: one isallograft (from F344 to Lewis rats); another is syngrafts (from Lewis toLewis rats) serving as control. Renal tissues were collected 3, 7 and 14 daysafter transplantation. As many 18 samples were analyzed by 2-DElectrophoresis and mass spectrometry (MALDI-TOF-TOF-MS). Elevendifferentially expressed proteins were identified between groups. Inconclusion, proteomic technology can detect renal tissue proteins associatedwith acute renal allograft rejection. Identification of these proteins asdiagnostic markers for rejection in patient's urine or sera may be useful andnon-invasive, and these proteins might serve as novel therapeutic targetsthat also help to improve the understanding of mechanisms of renal rejection.(author)

  3. Spirometric assessment of lung transplant patients: one year follow-up

    Directory of Open Access Journals (Sweden)

    Paulo M. Pêgo-Fernandes

    2009-06-01

    Full Text Available OBJECTIVE: The purpose of this study was to compare spirometry data between patients who underwent single-lung or double-lung transplantation the first year after transplantation. INTRODUCTION: Lung transplantation, which was initially described as an experimental method in 1963, has become a therapeutic option for patients with advanced pulmonary diseases due to improvements in organ conservation, surgical technique, immunosuppressive therapy and treatment of post-operative infections. METHODS: We retrospectively reviewed the records of the 39 patients who received lung transplantation in our institution between August 2003 and August 2006. Twenty-nine patients survived one year post-transplantation, and all of them were followed. RESULTS: The increase in lung function in the double-lung transplant group was more substantial than that of the single-lung transplant group, exhibiting a statistical difference from the 1st month in both the forced expiratory volume in one second (FEV1 and the forced vital capacity (FVC in comparison to the pre-transplant values (p <0.05. Comparison between double-lung transplant and single lung-transplant groups of emphysema patients demonstrated a significant difference in lung function beginning in the 3rd month after transplantation. DISCUSSION: The analyses of the whole group of transplant recipients and the sub-group of emphysema patients suggest the superiority of bilateral transplant over the unilateral alternative. Although the pre-transplant values of lung function were worse in the double-lung group, this difference was no longer significant in the subsequent months after surgery. CONCLUSION: Although both groups demonstrated functional improvement after transplantation, there was a clear tendency to greater improvement in FVC and FEV1 in the bilateral transplant group. Among our subjects, double-lung transplantation improved lung function.

  4. Circulating angiotensin type II receptor: Possible marker for antibody mediated rejection after renal transplantation?

    Science.gov (United States)

    Kimball, Pamela M; Gupta, Gaurav; McDougan, Felecia

    2017-10-01

    Presence of antibody [Ab] against angiotensin receptor [AT1R] indicates heightened risk for antibody mediated rejection [AMR] after transplantation but is insufficient as a marker. We speculated AT1R might be released systemically because of AMR and might be a useful biomarker. AT1R was measured in blood from 73 Normals and 72 renal patients pre- and post-transplantation. Patients were stratified as AMR-free [Gp1], AMR1yr [Gp3]. AT1R was higher [13±26vs.367±537, p<0.01)] and more prevalent [20% vs. 92%, p<0.01] among renal patients than Normals. Pretransplant levels were similar [p=ns] between groups. One-year posttransplant levels approached [p<0.01] normalcy for Gps1+3 but spiked during AMR and remained elevated [155±58, p<0.01] for 50% Gp2 patients. One-year AT1R levels were higher among subsequent graft failures than surviving grafts [171±267vs. 38±50, p<0.01]. Pretransplant AT1R was abnormally elevated: possibly indicating ongoing tissue injury. Pretransplant AT1R didn't predict risk for AMR. However, AT1R spiked during early AMR and sustained elevations were associated with poorer outcomes. Copyright © 2017. Published by Elsevier Inc.

  5. Scintigraphy at 3 months after single lung transplantation and observations of primary graft dysfunction and lung function

    DEFF Research Database (Denmark)

    Belmaati, Esther Okeke; Iversen, Martin; Kofoed, Klaus F

    2012-01-01

    procedure 3 months after single lung transplantation (SLTX). A total of 41 patients were included in the study: 20 women and 21 men with the age span of patients at transplantation being 38-66 years (mean ± SD: 54.2 ± 6.0). Patient records also included lung function tests and chest X-ray images. We found......Scintigraphy has been used as a tool to detect dysfunction of the lung before and after transplantation. The aims of this study were to evaluate the development of the ventilation-perfusion relationships in single lung transplant recipients in the first year, at 3 months after transplantation...

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

    Science.gov (United States)

    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

  7. Lung ultrasound for the diagnosis of post-operative complications after lung transplantation

    DEFF Research Database (Denmark)

    Rømhild Davidsen, Jesper; Lawaetz Schultz, Hans Henrik; Henriksen, Daniel Pilsgaard

    2017-01-01

    Lung ultrasound (LUS) has a high diagnostic accuracy for the identification of pleural effusion, pneumonia, and interstitial syndrome (IS), all of which are common complications in the early phase after lung transplantation (LTx), and may be associated with primary graft dysfunction, bleeding, or...... after LTx, and could be an alternative to conventional and more time-consuming thoracic imaging....

  8. Development of cytochrome P450 2D6-specific LKM-autoantibodies following liver transplantation for Wilson's disease -- possible association with a steroid-resistant transplant rejection episode.

    Science.gov (United States)

    Lohse, A W; Obermayer-Straub, P; Gerken, G; Brunner, S; Altes, U; Dienes, H P; Manns, M P; Meyer zum Büschenfelde, K H

    1999-07-01

    Antibodies to cytochrome P450 2D6, also known as LKM1-autoantibodies, are characteristic for a subgroup of patients with autoimmune hepatitis, but can also occasionally be found in hepatitis C. We observed the occurrence of LKM1-autoantibodies 4 months after liver transplantation for Wilson's disease, in close association with a steroid-resistant rejection episode, in the absence of evidence for autoimmune hepatitis or hepatitis C. Sera from several time points prior to and following transplantation were tested for LKM-reactivity by immunofluorescence, ELISA and Western blotting. Antigen specificity was confirmed by Western blotting analysis on different cytochrome P450 isoenzymes. The absence of viral hepatitis C and hepatitis G virus infection was confirmed by polymerase chain reaction. The serum of the organ donor was also tested. All the sera prior to transplantation and up to 4 months after transplantation were LKM-negative by all assay systems used. In the course of a steroid-resistant rejection episode at this time, the patient developed LKM antibodies at high titre (70% in inhibition ELISA) and has remained positive since (now more than 4 years). Reactivity was exclusively to the cytochrome isoenzyme 2D6. Hepatitis C infection never occurred, but hepatitis G was transiently present many years prior to transplantation. The donor serum was negative for all autoantibodies and for hepatitis C and G virus infection. We here describe a patient developing LKM1-autoantibodies without evidence of autoimmune or viral hepatitis. The close temporal association with a transplant rejection episode suggests immunological mechanisms of rejection together with hepatocellular injury as a pathogenetic mechanism.

  9. Lung function after allogeneic hematopoietic stem cell transplantation in children

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Larsen Bang, Cæcilie; Christensen, Ib Jarle

    2013-01-01

    Reduction in pulmonary function (PF) has been reported in up to 85% of pediatric patients during the first year after hematopoietic stem cell transplantation (HSCT). Our understanding of the etiology for this decrease in lung function is, however, sparse. The aim of this study was to describe PF...

  10. Mycobacterium bovis hip bursitis in a lung transplant recipient.

    Science.gov (United States)

    Dan, J M; Crespo, M; Silveira, F P; Kaplan, R; Aslam, S

    2016-02-01

    We present a report of extrapulmonary Mycobacterium bovis infection in a lung transplant recipient. M. bovis is acquired predominantly by zoonotic transmission, particularly from consumption of unpasteurized foods. We discuss epidemiologic exposure, especially as relates to the Mexico-US border, clinical characteristics, resistance profile, and treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Superficial herpes simplex virus wound infection following lung transplantation.

    Science.gov (United States)

    Karolak, Wojtek; Wojarski, Jacek; Zegleń, Sławomir; Ochman, Marek; Urlik, Maciej; Hudzik, Bartosz; Wozniak-Grygiel, Elzbieta; Maruszewski, Marcin

    2017-08-01

    Surgical site infections (SSIs) are infections of tissues, organs, or spaces exposed by surgeons during performance of an invasive procedure. SSIs are classified into superficial, which are limited to skin and subcutaneous tissues, and deep. The incidence of deep SSIs in lung transplant (LTx) patients is estimated at 5%. No reports have been published as to the incidence of superficial SSIs specifically in LTx patients. Common sense would dictate that the majority of superficial SSIs would be bacterial. Uncommonly, fungal SSIs may occur, and we believe that no reports exist as to the incidence of viral wound infections in LTx patients, or in any solid organ transplant patients. We report a de novo superficial wound infection with herpes simplex virus following lung transplantation, its possible source, treatment, and resolution. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. The effect of ABO blood incompatibility on corneal transplant failure in conditions with low-risk of graft rejection.

    Science.gov (United States)

    Dunn, Steven P; Stark, Walter J; Stulting, R Doyle; Lass, Jonathan H; Sugar, Alan; Pavilack, Mark A; Smith, Patricia W; Tanner, Jean Paul; Dontchev, Mariya; Gal, Robin L; Beck, Roy W; Kollman, Craig; Mannis, Mark J; Holland, Edward J

    2009-03-01

    To determine whether corneal graft survival over a 5-year follow-up period was affected by ABO blood type compatibility in participants in the Cornea Donor Study undergoing corneal transplantation principally for Fuchs dystrophy or pseudophakic corneal edema, conditions at low-risk for graft rejection. Multi-center prospective, double-masked, clinical trial. ABO blood group compatibility was determined for 1,002 donors and recipients. During a 5-year follow-up period, episodes of graft rejection were documented, and graft failures were classified as to whether or not they were attributable to immunologic rejection. Endothelial cell density was determined by a central reading center for a subset of subjects. ABO donor-recipient incompatibility was not associated with graft failure attributable to any cause including graft failure because of rejection, or with the occurrence of a rejection episode. The 5-year cumulative incidence of graft failure attributable to rejection was 32 (6%) for recipients with ABO recipient-donor compatibility and 12 (4%) for those with ABO incompatibility (hazard ratio, 0.65; 95% confidence interval, 0.33 to 1.25; P = .20). The 5-year incidence for a definite rejection episode, irrespective of whether graft failure ultimately occurred, was 64 (12%) for ABO compatible compared with 25 (8%) for ABO incompatible cases (P = .09). Among clear grafts at 5 years, percent loss of endothelial cells was similar in ABO compatible and incompatible cases. In patients undergoing penetrating keratoplasty for Fuchs dystrophy or pseudophakic corneal edema, ABO matching is not indicated since ABO incompatibility does not increase the risk of transplant failure attributable to graft rejection.

  13. Transplantes cardiopulmonar e pulmonar com doador em localidade distante Distant donor procurement for heart-lung and lung transplantation

    Directory of Open Access Journals (Sweden)

    Luis Sérgio Fragomeni

    1988-12-01

    Full Text Available Em situações específicas, os transplantes clínicos cardiopulmonar e pulmonar são, hoje, formas estabelecidas de tratamento para estágio final de doença cardiopulmonar e pulmonar. A obtenção de doadores adequados permanece o maior problema e a remoção de órgãos em localidades distantes é, hoje, uma necessidade. Embora muitos métodos de preservação pulmonar possam ser empregados, para períodos isquémicos de até 5 horas, a hipotermia e o uso de solução cardioplégica com infusão da solução de Collins modificada no tronco pulmonar tem sido método simples e eficiente para preservação do bloco coração-pulmão. Descrevemos, aqui, o método corrente que empregamos, com o qual os transplantes cardiopulmonar e pulmonar combinados foram sucedidos de excelente função cárdio-respiratória.In special situations, clinical heart-lung and lung transplantation are today established methods of therapy for end stage cardiopulmonary and pulmonary disease. Adequate donor availability remains a major problem and distant organ procurement is today a necessity. Although many methods of lung preservation can be used, for periods of up to 5 hours, hypothermic storage with cardioplegic arrest and pulmonary artery flush with modified Collins solution has proven to be a simple and reliable method of heart-lung preservation. We here describe our current method of heart-lung block protection, in which heart-lung and double lung transplantation were performed followed by excelent cardiac and pulmonary function.

  14. Detection and surveillance of rejection reactions after heart transplant by means of a sequence of MRI of 'black blood' type

    International Nuclear Information System (INIS)

    David, N.; Escanye, J.M.; Marwan, N.S.; Marie, P.Y.; Perlot, P.; Angioi, M.; Walker, P.; Quiri, N.; Arsena, T.; Hassan, N.; Villemot, J.P.; Mattei, S.; Karcher, G.; Bertrand, A.

    1997-01-01

    A echocardiography and a MRI (Magnetic Resonance Imaging) investigation were achieved at 3 months to 7 years after heart transplant in 61 patients among whose 35 were suspected of rejection and 32 have had a myocardial biopsy. The myocardial (T 2 ) transversal relaxation time was determined by using an inversion-recovery/spin-echo upon a magnet of 0.5 T. The rejection diagnosis criteria by echography was compared with that of a anomalistic high value of T 2 : 1. the MRI was positive but the echography not in 5 cases, all having positive biopsies; 2. the echography was positive but the MRI was not in 10 cases among which all the biopsies were negative; 3. the MRI and the echography gave concordant results in 46 cases (7 positives and 39 negatives) among which an agreement with the biopsy results was observed in 91% (20/22) of cases. The 12 patients having a positive MRI have had a new examination at 2 to 15 days after the anti-rejection treatment; the T 2 values got normalized. In conclusion, the determination of the myocardial T 2 by means of a 'black blood' MRI sequence appears to be superior to an echocardiography in detecting the rejections after heart transplant and could be utilised to evaluate the efficiency of anti-rejection treatment

  15. Macrophage Uptake of Ultra-Small Iron Oxide Particles for Magnetic Resonance Imaging in Experimental Acute Cardiac Transplant Rejection

    International Nuclear Information System (INIS)

    Penno, E.; Johnsson, C.; Johansson, L.; Ahlstroem, H.

    2006-01-01

    Purpose: To discriminate between acutely rejecting and non-rejecting transplanted hearts using a blood pool contrast agent and T2 magnetic resonance imaging (MRI) in a clinical 1.5T scanner. Material and Methods: Allogeneic and syngeneic heterotopic heart transplantations were performed in rats. One allogeneic and one syngeneic group each received either the ultra-small iron oxide particle (USPIO), at two different doses, or no contrast agent at all. MRI was performed on postoperative day 6. Immediately after the MR scanning, contrast agent was injected and a further MRI was done 24 h later. Change in T2 was calculated. Results: No significant difference in change in T2 could be seen between rejecting and non-rejecting grafts in either of the doses, or in the control groups. There was a difference between the allogeneic group that received the higher contrast agent dose and the allogeneic group that did not receive any contrast agent at all. Conclusion: In our rat model, measurements of T2 after myocardial macrophage uptake of AMI-227 in a clinical 1.5T scanner were not useful for the diagnosis of acute rejection

  16. Fiber optic probe enabled by surface-enhanced Raman scattering for early diagnosis of potential acute rejection of kidney transplant

    Science.gov (United States)

    Chi, Jingmao; Chen, Hui; Tolias, Peter; Du, Henry

    2014-06-01

    We have explored the use of a fiber-optic probe with surface-enhanced Raman scattering (SERS) sensing modality for early, noninvasive and, rapid diagnosis of potential renal acute rejection (AR) and other renal graft dysfunction of kidney transplant patients. Multimode silica optical fiber immobilized with colloidal Ag nanoparticles at the distal end was used for SERS measurements of as-collected urine samples at 632.8 nm excitation wavelength. All patients with abnormal renal graft function (3 AR episodes and 2 graft failure episodes) who were clinically diagnosed independently show common unique SERS spectral features in the urines collected just one day after transplant. SERS-based fiber-optic probe has excellent potential to be a bedside tool for early diagnosis of kidney transplant patients for timely medical intervention of patients at high risk of transplant dysfunction.

  17. Novel Non-Histocompatibility Antigen Mismatched Variants Improve the Ability to Predict Antibody-Mediated Rejection Risk in Kidney Transplant

    Directory of Open Access Journals (Sweden)

    Silvia Pineda

    2017-12-01

    Full Text Available Transplant rejection is the critical clinical end-point limiting indefinite survival after histocompatibility antigen (HLA mismatched organ transplantation. The predominant cause of late graft loss is antibody-mediated rejection (AMR, a process whereby injury to the organ is caused by donor-specific antibodies, which bind to HLA and non-HLA (nHLA antigens. AMR is incompletely diagnosed as donor/recipient (D/R matching is only limited to the HLA locus and critical nHLA immunogenic antigens remain to be identified. We have developed an integrative computational approach leveraging D/R exome sequencing and gene expression to predict clinical post-transplant outcome. We performed a rigorous statistical analysis of 28 highly annotated D/R kidney transplant pairs with biopsy-confirmed clinical outcomes of rejection [either AMR or T-cell-mediated rejection (CMR] and no-rejection (NoRej, identifying a significantly higher number of mismatched nHLA variants in AMR (ANOVA—p-value = 0.02. Using Fisher’s exact test, we identified 123 variants associated mainly with risk of AMR (p-value < 0.001. In addition, we applied a machine-learning technique to circumvent the issue of statistical power and we found a subset of 65 variants using random forest, that are predictive of post-tx AMR showing a very low error rate. These variants are functionally relevant to the rejection process in the kidney and AMR as they relate to genes and/or expression quantitative trait loci (eQTLs that are enriched in genes expressed in kidney and vascular endothelium and underlie the immunobiology of graft rejection. In addition to current D/R HLA mismatch evaluation, additional mismatch nHLA D/R variants will enhance the stratification of post-tx AMR risk even before engraftment of the organ. This innovative study design is applicable in all solid organ transplants, where the impact of mitigating AMR on graft survival may be greater, with considerable benefits on

  18. Relation between pretransplant serum levels of soluble CD30 and acute rejection during the first 6 months after a kidney transplant.

    Science.gov (United States)

    Shooshtarizadeh, Tina; Mohammadali, Ali; Ossareh, Shahrzad; Ataipour, Yousef

    2013-06-01

    The immunologic status of kidney allograft recipients affects transplant outcome. High levels of pretransplant serum soluble CD30 correlate with an increased risk of acute rejection. Studies show conflicting results. We evaluated the relation between pretransplant serum sCD30 levels with the risk of posttransplant acute kidney rejection in renal transplant recipients. This prospective cohort study was performed between March 2010 and March 2011 on 77 kidney transplant recipients (53 men [68.8%], 24 women [31.2%]; mean age, 41 ± 14 y). Serum samples were collected 24 hours before transplant and analyzed for soluble CD30 levels by enzyme-linked immunosorbent assay. Patients were followed for 6 months after transplant. Acute biopsy-proven rejection episodes were recorded, serum creatinine levels were measured, and glomerular filtration rates were calculated at the first and sixth months after transplant. Preoperative serum soluble CD30 levels were compared in patients with and without rejection. The mean pretransplant serum soluble CD30 level was 92.1 ± 47.3 ng/mL. At 6 months' follow-up, 10 patients experienced acute rejection. Mean pretransplant soluble CD30 levels were 128.5 ± 84 ng/mL versus 86.7 ± 37 ng/mL in patients with and without acute rejection episodes (P = .008). At 100 ng/mL, the sensitivity, specificity, and positive and negative predictive values of pretransplant serum soluble CD30 level to predict acute rejection were 70%, 73.6%, 29.1%, and 94.3%. We showed a significant relation between pretransplant serum soluble CD30 levels and acute allograft rejection. High pretransplant levels of serum soluble CD30 can be a risk factor for kidney transplant rejection, and its high negative predictive value at various cutoffs make it useful to find candidates with a low risk of acute rejection after transplant.

  19. Lung transplant curriculum in pulmonary/critical care fellowship training.

    Science.gov (United States)

    Hayes, Don; Diaz-Guzman, Enrique; Berger, Rolando; Hoopes, Charles W

    2013-01-01

    Lung transplantation is an evolving specialty with the number of transplants growing annually. A structured lung transplant curriculum was developed for Pulmonary/Critical Care (Pulm/CC) fellows. Scores on pulmonary in-training examinations (ITE) 2 years prior to and 3 years after implementation were reviewed as well as completion of satisfaction surveys. The mean pulmonary ITE score of 1st-year fellows increased from 54.2 ± 2.5 to 63.6 ± 1.2 (M ± SD), p = .002, whereas mean pulmonary ITE score for 2nd-year fellows increased from 63.0 ± 3.0 to 70.7 ± 1.2, p = .019. The combined mean pulmonary ITE score increased from 58.6 ± 2.3 to 67.1 ± 1.2, p = .001. Satisfaction surveys revealed that fellow perception of the curriculum was that the experience contributed to an overall improvement in their knowledge base and clinical skills while opportunity to perform transbronchial biopsies was available. A structured educational lung transplant curriculum was associated with improved performance on the pulmonary ITE and was perceived by fellows to be beneficial in their education and training while providing opportunities for fellows to perform transbronchial biopsies.

  20. Delayed hyperacute rejection in a patient who developed clostridium difficile infection after ABO-incompatible kidney transplantation

    Directory of Open Access Journals (Sweden)

    Gerald S Lipshutz

    2010-11-01

    the surface of bacterial cell wall occurring before the firm establishment of accommodation can trigger the onset of acute antibody-mediated rejection. We herein report a case of delayed hyperacute rejection in an A1 to O, ABO incompatible transplant recipient following an episode of Clostridium difficile infection.Keywords: ABO incompatible transplantation, delayed hyperacute rejection, kidney transplantation, Clostridium difficile infection

  1. A type I interferon signature characterizes chronic antibody-mediated rejection in kidney transplantation.

    Science.gov (United States)

    Rascio, Federica; Pontrelli, Paola; Accetturo, Matteo; Oranger, Annarita; Gigante, Margherita; Castellano, Giuseppe; Gigante, Maddalena; Zito, Anna; Zaza, Gianluigi; Lupo, Antonio; Ranieri, Elena; Stallone, Giovanni; Gesualdo, Loreto; Grandaliano, Giuseppe

    2015-09-01

    Chronic antibody-mediated rejection (CAMR) represents the main cause of kidney graft loss. To uncover the molecular mechanisms underlying this condition, we characterized the molecular signature of peripheral blood mononuclear cells (PBMCs) and, separately, of CD4(+) T lymphocytes isolated from CAMR patients, compared to kidney transplant recipients with normal graft function and histology. We enrolled 29 patients with biopsy-proven CAMR, 29 stable transplant recipients (controls), and 8 transplant recipients with clinical and histological evidence of interstitial fibrosis/tubular atrophy. Messenger RNA and microRNA profiling of PBMCs and CD4(+) T lymphocytes was performed using Agilent microarrays in eight randomly selected patients per group from CAMR and control subjects. Results were evaluated statistically and by functional pathway analysis (Ingenuity Pathway Analysis) and validated in the remaining subjects. In PBMCs, 45 genes were differentially expressed between the two groups, most of which were up-regulated in CAMR and were involved in type I interferon signalling. In the same patients, 16 microRNAs were down-regulated in CAMR subjects compared to controls: four were predicted modulators of six mRNAs identified in the transcriptional analysis. In silico functional analysis supported the involvement of type I interferon signalling. To further confirm this result, we investigated the transcriptomic profiles of CD4(+) T lymphocytes in an independent group of patients, observing that the activation of type I interferon signalling was a specific hallmark of CAMR. In addition, in CAMR patients, we detected a reduction of circulating BDCA2(+) dendritic cells, the natural type I interferon-producing cells, and their recruitment into the graft along with increased expression of MXA, a type I interferon-induced protein, at the tubulointerstitial and vascular level. Finally, interferon alpha mRNA expression was significantly increased in CAMR compared to control

  2. Alveolar epithelial fluid transport capacity in reperfusion lung injury after lung transplantation.

    Science.gov (United States)

    Ware, L B; Golden, J A; Finkbeiner, W E; Matthay, M A

    1999-03-01

    Reperfusion lung injury is an important cause of morbidity and mortality after orthotopic lung transplantation. The purpose of this study was to investigate the function of the alveolar epithelium in the setting of reperfusion lung injury. Simultaneous samples of pulmonary edema fluid and plasma were collected from eight patients with severe post-transplantation reperfusion edema. The edema fluid to plasma protein ratio was measured, an indicator of alveolar-capillary barrier permeability. The initial edema fluid to plasma protein ratio was > 0.75 in six of eight patients, confirming the presence of increased permeability of the alveolar-capillary barrier. Graft ischemic time was positively correlated with the degree of permeability (r = 0.77, p mean +/- SD). Alveolar fluid clearance was calculated from serial samples in six patients. Intact alveolar fluid clearance correlated with less histologic injury, rapid resolution of hypoxemia, and more rapid resolution of radiographic infiltrates. The two patients with no net alveolar fluid clearance had persistent hypoxemia and more severe histologic injury. This study provides the first direct evidence that increased permeability to protein is the usual cause of reperfusion edema after lung transplantation, with longer ischemic times associated with greater permeability to protein in the transplanted lung. The high rates of alveolar fluid clearance indicate that the fluid transport capacity of the alveolar epithelium may be well preserved in the allograft despite reperfusion lung injury. The ability to reabsorb fluid from the alveolar space was a marker of less severe reperfusion injury, whereas the degree of alveolar-capillary barrier permeability to protein was not. Measurement of alveolar fluid clearance may be useful to assess the severity of reperfusion lung injury and to predict outcome when pulmonary edema develops after lung transplantation.

  3. Depression, social support, and clinical outcomes following lung transplantation: a single-center cohort study.

    Science.gov (United States)

    Smith, Patrick J; Snyder, Laurie D; Palmer, Scott M; Hoffman, Benson M; Stonerock, Gregory L; Ingle, Krista K; Saulino, Caroline K; Blumenthal, James A

    2018-05-01

    Depressive symptoms are common among lung transplant candidates and have been associated with poorer clinical outcomes in some studies. Previous studies have been plagued by methodologic problems, including small sample sizes, few clinical events, and uncontrolled confounders, particularly perioperative complications. In addition, few studies have examined social support as a potential protective factor. We therefore examined the association between pretransplant depressive symptoms, social support, and mortality in a large sample of lung transplant recipients. As a secondary aim, we also examined the associations between psychosocial factors, perioperative outcomes [indexed by hospital length of stay (LOS)], and mortality. We hypothesized that depression would be associated with longer LOS and that the association between depression, social support, and mortality would be moderated by LOS. Participants included lung transplant recipients, transplanted at Duke University Medical Center from January 2009 to December 2014. Depressive symptoms were evaluated using the Beck Depression Inventory (BDI-II) and social support using the Perceived Social Support Scale (PSSS). Medical risk factors included forced vital capacity (FVC), partial pressure of carbon dioxide (PCO 2 ), donor age, acute rejection, and transplant type. Functional status was assessed using six-minute walk distance (6MWD). We also controlled for demographic factors, including age, gender, and native disease. Transplant hospitalization LOS was examined as a marker of perioperative clinical outcomes. Participants included 273 lung recipients (174 restrictive, 67 obstructive, 26 cystic fibrosis, and six "other"). Pretransplant depressive symptoms were common, with 56 participants (21%) exhibiting clinically elevated levels (BDI-II ≥ 14). Greater depressive symptoms were associated with longer LOS [adjusted b = 0.20 (2 days per 7-point higher BDI-II score), P social support (P social support were

  4. Antibody Desensitization Therapy in Highly Sensitized Lung Transplant Candidates

    Science.gov (United States)

    Snyder, L. D.; Gray, A. L.; Reynolds, J. M.; Arepally, G. M.; Bedoya, A.; Hartwig, M. G.; Davis, R. D.; Lopes, K. E.; Wegner, W. E.; Chen, D. F.; Palmer, S. M.

    2015-01-01

    As HLAs antibody detection technology has evolved, there is now detailed HLA antibody information available on prospective transplant recipients. Determining single antigen antibody specificity allows for a calculated panel reactive antibodies (cPRA) value, providing an estimate of the effective donor pool. For broadly sensitized lung transplant candidates (cPRA ≥ 80%), our center adopted a pretransplant multimodal desensitization protocol in an effort to decrease the cPRA and expand the donor pool. This desensitization protocol included plasmapheresis, solumedrol, bortezomib and rituximab given in combination over 19 days followed by intravenous immunoglobulin. Eight of 18 candidates completed therapy with the primary reasons for early discontinuation being transplant (by avoiding unacceptable antigens) or thrombocytopenia. In a mixed-model analysis, there were no significant changes in PRA or cPRA changes over time with the protocol. A sub-analysis of the median fluorescence intensity (MFI) change indicated a small decline that was significant in antibodies with MFI 5000–10 000. Nine of 18 candidates subsequently had a transplant. Posttransplant survival in these nine recipients was comparable to other pretransplant-sensitized recipients who did not receive therapy. In summary, an aggressive multi-modal desensitization protocol does not significantly reduce pretransplant HLA antibodies in a broadly sensitized lung transplant candidate cohort. PMID:24666831

  5. Evaluation of serum sCD30 in renal transplantation patients with and without acute rejection.

    Science.gov (United States)

    Cervelli, C; Fontecchio, G; Scimitarra, M; Azzarone, R; Famulari, A; Pisani, F; Battistoni, C; Di Iulio, B; Fracassi, D; Scarnecchia, M A; Papola, F

    2009-05-01

    Despite new immunosuppressive approaches, acute rejection episodes (ARE) are still a major cause of early kidney dysfunction with a negative impact on long-term allograft survival. Noninvasive markers able to identify renal ARE earlier than creatinine measurement include sCD30. We sought to establish whether circulating levels of sCD30 in pretransplantation and posttransplantation periods were of clinical relevance to avoid graft damage. Quantitative detection of serum sCD30 was performed using an enzyme-linked immunosorbent assay. Our results demonstrated that the mean concentrations of sCD30 were significantly higher in the sera of renal transplant recipients with ARE (30.04 U/mL) and in uremic patients on the waiting list (37.7 U/mL) compared with healthy controls (HC; 9.44 U/mL), but not nonrejecting patients (12.01 U/mL). Statistical analysis revealed a strong association between high sCD30 levels in posttransplantation sera and ARE risk. This study suggested that sCD30 levels were a reliable predictor of ARE among deceased-donor kidney recipients.

  6. Cytomegalovirus infection in living-donor and cadaveric lung transplantations.

    Science.gov (United States)

    Ohata, Keiji; Chen-Yoshikawa, Toyofumi F; Takahashi, Koji; Aoyama, Akihiro; Motoyama, Hideki; Hijiya, Kyoko; Hamaji, Masatsugu; Menju, Toshi; Sato, Toshihiko; Sonobe, Makoto; Takakura, Shunji; Date, Hiroshi

    2017-11-01

    Cytomegalovirus (CMV) infection remains a major cause of morbidity after lung transplantation. Some studies have reported prognostic factors for the postoperative development of CMV infection in cadaveric lung transplantation (CLT), but no research has been performed in living-donor lobar lung transplantation (LDLLT). Therefore, we analysed the possible risk factors of post-transplant CMV infection and the differences between LDLLT and CLT. The development of CMV disease and viraemia in 110 patients undergoing lung transplantation at Kyoto University Hospital in 2008-2015 were retrospectively assessed. The prognostic factors in the development of CMV infection and the differences between LDLLT and CLT were analysed. Among 110 patients, 58 LDLLTs and 52 CLTs were performed. The 3-year freedom rates from CMV disease and viraemia were 92.0% and 58.5%, respectively. There was no difference in the development of CMV infection between LDLLT and CLT (disease: 94.6% vs 91.0%, P = 0.58 and viraemia: 59.3% vs 57.2%, P = 0.76). In preoperative anti-CMV immunoglobulin status, R-D+ recipients (recipient: negative, donor: positive) and R-D- recipients (recipient: negative, donor: negative) tended to have higher and lower cumulative incidences, respectively, of CMV infection (disease: P = 0.34 and viraemia: P = 0.24) than that with R+ recipients (recipient: seropositive). Significantly lower cumulative incidence of CMV viraemia was observed in patients receiving 12-month prophylactic medication (70.6% vs 36.8%, P CLT. We found that there was no difference in the development of CMV infection between LDLLT and CLT. Twelve-month prophylaxis protocol provides beneficial effect without increased toxicity also in LDLLT. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  7. Treatment of distal bronchial stenosis after bilateral lung transplantation

    Directory of Open Access Journals (Sweden)

    S. V. Golovinskiy

    2017-01-01

    Full Text Available The effi ciency of lung transplantation is considerably limited by the complications associated with the bronchial pathologies. Despite the progress of the treatment methods, bronchial complications are still remaining as an actual problem in the postoperative period with frequency of occurrence from 7 to 29%. However, the bronchial stenosis are the most common bronchial complications after lung transplantation with mortality from 2 to 4%.Aim. To study an experience of our center of bronchial stenosis treatment in lung recipients. Materials and methods. 34 patients underwent lung transplantation from September 2014 to January 2017. 6 (16% of them had a stenosis of lobar or segmental bronchi from 84 to 494 postoperative day. 5 (83% of them have demonstrated multifocal lesions. In all of the cases there was performed an endoscopic bougienage, which involved a balloon dilatation and electrocoagulated incision of granular tissue under X-ray control. After that the patients were administrated by everolimus.Results. Restenosis was formed in 132,0 ± 94,2 postoperative day after primary treatment in all patients. In four cases (67% we used nitinol stent placement under X-ray control. There were no complications. In 3 cases stents were dislocated distally, so we needed to use repeated endoscopic bougienage to replace the stent. Using of everolimus has allowed to decrease the rate of restenosis, but it need future research.Conclusion. Distal bronchial stenosis after lung transplantation can be managed with endoscopic bougienage and stent placement. Adding everolimus has not signifi cantly affected the risk of frequency of restenosis.

  8. Anesthesia for Pediatric Lung Transplantation: Case Presentation and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Premal M Trivedi

    2017-08-01

    Full Text Available The first pediatric lung transplant was performed in 1987 at the University of Toronto in a 15-year-old with familial pulmonary fibrosis. Since that time, over 2000 children have received lung transplants worldwide, with an annual number ranging between 99 and 137 over the past decade. For the anesthesiologist charged with managing these rare patients, an understanding of the indications that lead to transplantation, their pathophysiology, and the physiology of the transplanted lungs are critical. To provide a context for the anesthetic management of the child undergoing lung transplantation, we discuss the case of a 2-month-old who underwent bilateral lung transplantation for intractable respiratory failure. Both the unique aspects of this case and pediatric lung transplantation, in general, are presented. Then a review of the literature is discussed.

  9. FEATURES OF PLASMAPHERESIS IN THE TREATMENT OF GRAFT REJECTION AFTER KIDNEY TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    A. V. Vatazin

    2015-01-01

    Full Text Available Introduction. The development of immunological confl ict in the form of host-versus-graft reaction has always been main problem in transplantation. The worst case is the development of humoral rejection with the presence of circulating immune complexes and antibodies. There are several methods for quick removal of antibodies; among those are traditional plasmapheresis (PA and double fi ltration plasmapheresis (DFPF. In this paper we present our experience with these two methods and give a comparative evaluation of the effectiveness in the treatment of acute humoral rejection in renal allograft. Aim: to compare the effectiveness of traditional and double fi ltration plasmapheresis while processing different volumes of plasma in the treatment of host-versus-graft disease after kidney transplantation.Methods. The study included 58 patients after kidney transplantation. All patients had increased activity of humoral immunity, which was confi rmed by immunofl uorescence with luminescence C4d complement component. In 26 patients we performed DFPF, in 32 patients – traditional PA. We divided the DFPF patients into 4 subgroups depending on the amount of processed plasma: > 50% (5 patients, 50–100% (8 patients, 100–150% (7 patients, 150–200% (6 patients of circulating plasma volume. We also divided PA patients into four subgroups depending on the volume of plasma removed: >50% (8 patients, 50–70% (12 patients, 70–90% (7 patients, 90–110% (5 patients of the volume of circulating plasma. We monitored the immune status with markers of humoral immunity activation IgM, IgG before and after each of the procedures.Results. Each procedure of traditional PA and DFPF was accompanied by a marked decrease in blood concentrations of IgM and IgG antibodies. Their level decreased by an average of 30–55% of the original. However, some patients in both groups showed an increase in the concentration of these immunoglobulins in 1–2 days

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

    Science.gov (United States)

    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. Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  11. Eicosapentenoic Acid Attenuates Allograft Rejection in an HLA-B27/EGFP Transgenic Rat Cardiac Transplantation Model.

    Science.gov (United States)

    Liu, Zhong; Hatayama, Naoyuki; Xie, Lin; Kato, Ken; Zhu, Ping; Ochiya, Takahiro; Nagahara, Yukitoshi; Hu, Xiang; Li, Xiao-Kang

    2012-01-01

    The development of an animal model bearing definite antigens is important to facilitate the evaluation and modulation of specific allo-antigen responses after transplantation. In the present study, heterotopic cardiac transplantation was performed from F344/EGFPTg and F344/HLA-B27Tg rats to F344 rats. The F344 recipients accepted the F344/EGFPTg transplants, whereas they rejected the cardiac tissue from the F344/HLA-B27Tg rats by 39.4 ± 6.5 days, due to high production of anti-HLA-B27 IgM- and IgG-specific antibodies. In addition, immunization of F344 rats with skin grafts from F344/HLA-B27Tg rats resulted in robust production of anti- HLA-B27 IgM and IgG antibodies and accelerated the rejection of a secondary cardiac allograft (7.4 ± 1.9 days). Of interest, the F344 recipients rejected cardiac grafts from double transgenic F344/HLA-B27&EGFPTg rats within 9.0 ± 3.2 days, and this was associated with a significant increase in the infiltration of lymphocytes by day 7, suggesting a role for cellular immune rejection. Eicosapentenoic acid (EPA), one of the ω-3 polyunsaturated fatty acids in fish oil, could attenuate the production of anti-HLA IgG antibodies and B-cell proliferation, significantly prolonging double transgenic F344HLA-B27&EGFPTg to F344 rat cardiac allograft survival (36.1 ± 13.6 days). Moreover, the mRNA expression in the grafts was assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), revealing an increase in the expression of the HO-1, IL-10, TGF-β, IDO, and Foxp3 genes in the EPA-treated group. Hence, our data indicate that HLA-B27 and/or GFP transgenic proteins are useful for establishing a unique animal transplantation model to clarify the mechanism underlying the allogeneic cellular and humoral immune response, in which the transplant antigens are specifically presented. Furthermore, we also demonstrated that EPA was effective in the treatment of rat cardiac allograft rejection and may allow the development of

  12. Anti-interleukin-2 receptor antibodies—basiliximab and daclizumab—for the prevention of acute rejection in renal transplantation

    Directory of Open Access Journals (Sweden)

    Junichiro Sageshima

    2009-06-01

    Full Text Available Junichiro Sageshima, Gaetano Ciancio, Linda Chen, George W Burke IIIDewitt Daughtry Family Department of Surgery, Division of Kidney and Pancreas Transplantation, The Lillian Jean Kaplan Renal Transplant Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL, USAAbstract: The use of antibody induction after kidney transplantation has increased from 25% to 63% in the past decade and roughly one half of the induction agent used is anti-interleukin-2 receptor antibody (IL-2RA, ie, basiliximab or daclizumab. When combined with calcineurin inhibitor (CNI-based immunosuppression, IL-2RAs have been shown to reduce the incidence of acute rejection, one of the predictors of poor graft survival, without increasing risks of infections and malignancies in kidney transplantation. For low-immunological-risk patients, IL-2RAs, as compared with lymphocyte-depleting antibodies, are equally efficacious and have better safety profiles. For high-risk patients, however, IL-2RAs may be inferior to lymphocyte-depleting antibodies for the prophylaxis of acute rejection. In an effort to reduce toxicities of other immunosuppressive medications without increasing the risk of acute rejection and chronic graft loss, IL-2RAs have often been combined with steroid- and CNI-sparing immunosuppression protocols. More data support the benefits of early steroid withdrawal with IL-2RA in low-risk patients, but preferred induction therapy for high-risk patients has yet to be determined. Although CNI-sparing protocols with IL-2RA may preserve renal function and improve long-term survival in selected patients, further studies are needed to identify those who benefit most from this strategy.Keywords: basiliximab, daclizumab, interleukin-2 receptor antagonist, kidney transplantation, monoclonal antibody

  13. Celecoxib plays a multiple role to peripheral blood lymphocytes and allografts in acute rejection in rats after cardiac transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xue-feng; ZHANG Fan; LIU Hong-yu; SUN Guo-dong; LIU Zong-hong; L(U) Hang; CHI Chao; LI Chun-yu

    2009-01-01

    Background Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is a non-steroidal anti-inflammatory drug used as an adjuvant to sensitize cancer cells to apoptosis. However, in rats suffering from acute rejection, celecoxib reduced apoptosis of myocardial cells. We hypothesize that celecoxib reduces myocardial apoptosis either by inducing apoptosis in peripheral blood lymphocytes (PBLs) or by altering the percentage of CD4+ and CD8+ lymphocytes. Methods After cardiac transplantation, rats were administered intragastrically with celecoxib (50 mg/kg per day) for 3, 5 or 7 days, at which time the graft was excised and evaluated for organ rejection. In addition, PBLs were isolated from the blood to determine PBLs apoptosis, and the percentage of CD4+ and CD8+ lymphocytes. Results Celecoxib induced PBLs apoptosis in 3 days, but protected the cells from apoptosis at 5 and 7 days. Also, the percentage of CD4+ lymphocytes decreased only at 3 days, but a reduction in the percentage of CD8+ lymphocytes was not seen until 7 days after the transplant surgery. Celecoxib only decreased acute rejection at 5 days, with no discernible difference in rejection after 3 and 7 days. Conclusions The results suggested that celecoxib displayed a multiple physiological function in a time-dependent manner.

  14. Quality of life before and after lung transplantation in patients with emphysema versus other indications

    NARCIS (Netherlands)

    TenVergert, EM; Vermeulen, KM; van Enckevort, PJ

    2001-01-01

    Whether lung transplantation improves Health-related Quality of Life in patients with emphysema and other end-stage lung diseases before and after lung transplantation was examined. Between 1992 and 1999, 23 patients with emphysema and 19 patients with other indications completed self-administered

  15. An association of particulate air pollution and traffic exposure with mortality after lung transplantation in Europe

    NARCIS (Netherlands)

    Ruttens, David; Verleden, Stijn E.; Bijnens, Esmee M.; Winckelmans, Ellen; Gottlieb, Jens; Warnecke, Gregor; Meloni, Federica; Morosini, Monica; van der Bij, Wim; Verschuuren, Erik A.; Sommerwerck, Urte; Weinreich, Gerhard; Kamler, Markus; Roman, Antonio; Gomez-Olles, Susana; Berastegui, Cristina; Benden, Christian; Holm, AreMartin; Iversen, Martin; Schultz, Hans Henrik; Luijk, Bart; Oudijk, Erik-Jan; Erp, Johanna M. Kwakkel-van; Jaksch, Peter; Klepetko, Walter; Kneidinger, Nikolaus; Neurohr, Claus; Corris, Paul. A.; Fisher, Andrew J.; Lordan, James; Meachery, Gerard; Piloni, Davide; Vandermeulen, Elly; Bellon, Hannelore; Hoffmann, Barbara; Vienneau, Danielle; Hoek, Gerard; de Hoogh, Kees; Nemery, Benoit; Verleden, Geert M.; Vos, Robin; Nawrot, Tims.; Vanaudenaerde, Bart M.

    2017-01-01

    Air pollution from road traffic is a serious health risk, especially for susceptible individuals. Single-centre studies showed an association with chronic lung allograft dysfunction (CLAD) and survival after lung transplantation, but there are no large studies. 13 lung transplant centres in 10

  16. Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection.

    Science.gov (United States)

    Wang, Dong; Wu, Guo-Jun; Wu, Wei-Zhen; Yang, Shun-Liang; Chen, Jin-Hua; Wang, He; Lin, Wen-Hong; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

    2007-06-01

    Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (PsCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (PsCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

  17. Aspiration, Localized Pulmonary Inflammation, and Predictors of Early-Onset Bronchiolitis Obliterans Syndrome after Lung Transplantation

    Science.gov (United States)

    Fisichella, P Marco; Davis, Christopher S; Lowery, Erin; Ramirez, Luis; Gamelli, Richard L; Kovacs, Elizabeth J

    2014-01-01

    BACKGROUND We hypothesized that immune mediator concentrations in the bronchoalveolar fluid (BALF) are predictive of bronchiolitis obliterans syndrome (BOS) and demonstrate specific patterns of dysregulation, depending on the presence of acute cellular rejection, BOS, aspiration, and timing of lung transplantation. STUDY DESIGN We prospectively collected 257 BALF samples from 105 lung transplant recipients. The BALF samples were assessed for absolute and differential white blood cell counts and 34 proteins implicated in pulmonary immunity, inflammation, fibrosis, and aspiration. RESULTS There were elevated BALF concentrations of interleukin (IL)-15, IL-17, basic fibroblast growth factor, tumor necrosis factor–α, and myeloperoxidase, and reduced concentrations of α1-antitrypsin, which were predictive of early-onset BOS. Patients with BOS had an increased percentage of BALF lymphocytes and neutrophils, with a reduced percentage of macrophages (p < 0.05). The BALF concentrations of IL-1β; IL-8; interferon-γ–induced protein 10; regulated upon activation, normal T-cell expressed and secreted; neutrophil elastase; and pepsin were higher in patients with BOS (p < 0.05). Among those with BOS, BALF concentrations of IL-1RA; IL-8; eotaxin; interferon-γ–induced protein 10; regulated upon activation, normal T-cell expressed and secreted; myeloperoxidase; and neutrophil elastase were positively correlated with time since transplantation (p < 0.01). Those with worse grades of acute cellular rejection had an increased percentage of lymphocytes in their BALF (p < 0.0001) and reduced BALF concentrations of IL-1β, IL-7, IL-9, IL-12, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, interferon-γ, and vascular endothelial growth factor (p ≤ 0.001). Patients with aspiration based on detectable pepsin had increased percentage of neutrophils (p < 0.001) and reduced BALF concentrations of IL-12 (p < 0.001). CONCLUSIONS The BALF levels

  18. Discrepancy between severity of lung impairment and seniority on the lung transplantation list.

    Science.gov (United States)

    Travaline, J M; Cordova, F C; Furukawa, S; Criner, G J

    2004-12-01

    Organ allocation for lung transplantation, based mainly on accrued time on a waiting list, may not be an equitable system of organ allocation. To provide an objective view of the current practice concerning lung allocation, and timing for transplantation, we examined illness severity and list seniority in patients on a lung transplantation waiting list. Adult patients awaiting lung transplantation underwent testing for mean pulmonary artery pressure (mPpa), maximum oxygen consumption (VO2 max), 6-minute walk distance (6MWD), forced expiratory volume in 1 second, mean partial pressure of carbon dioxide, partial pressure of oxygen/fractional concentration of inspired oxygen, and diffusing capacity of the lung for carbon monoxide. Relationships between physiological variables and waiting list rankings were then determined. Thirty-four patients were tested and there was no correlation between time spent waiting on the list and mPpa (r=0.01; P=.94), VO2 max percentage predicted (r=0.07; P=.71), or 6MWD (r=0.15; P=.42). Many patients with functional impairments as indicated by low maximum VO2 or by short 6MWD are scheduled to receive their transplant after patients with levels that indicate a lower degree of risk. When compared with a hypothetical reranking based on mean Ppa, 24 of the 34 patients (71%) on our current waiting list were found to be 5 positions higher or lower than this new risk-based ranking. Sixteen patients (47%) were 10 or more positions away from their hypothetical severity-based ranking, and 9 (26%) were at least 15 positions out of place. Sixteen of the 34 patients were ranked lower than they would be based on a severity of illness using the pulmonary artery pressure alone, 17 were ranked higher than "should be" based on pulmonary artery mean, and only 1 patient (ranked in position 15) was appropriately positioned based on seniority and severity of disease based on PA mean. Rank order for lung transplantation has no relationship with illness

  19. Indium-111-monoclonal antimyosin antibody studies after the first year of heart transplantation. Identification of risk groups for developing rejection during long-term follow-up and clinical implications

    International Nuclear Information System (INIS)

    Ballester, M.; Obrador, D.; Carrio, I.; Auge, J.M.; Moya, C.; Pons-Llado, G.; Caralps-Riera, J.M.

    1990-01-01

    The long-term clinical course and results of biopsies in 21 patients studied with monoclonal antimyosin antibodies more than 12 months after heart transplantation according to the presence and degree of antimyosin-antibody uptake is described. Eighteen men and three women aged 20-52 years (39 +/- 9 years) were studied with antimyosin antibodies 12-40 months (mean, 22 +/- 9 months) after heart transplantation, and followed for a mean of 18 months (10-28 months). The number of biopsies performed during follow-up was 102. Results showed normal antimyosin-antibody studies in nine patients and abnormal studies in 12 patients. Myocyte damage was identified in 18 of the 102 biopsies (17.6%), one in the normal antimyosin-antibody group of patients and 17 in those patients with myocardial antimyosin-antibody uptake. Patients who developed rejection comprised 11% and 67% of each respective group; the mean number of rejection episodes per patient was 0.11 +/- 0.33 and 1.41 +/- 1.41, respectively (p less than 0.01). A trend was noted by which higher heart-to-lung ratios were associated with greater probability of rejection. Conclusively, (1) antimyosin-antibody studies performed after more than 1 year after heart transplantation indicate the presence and level of rejection activity, (2) groups of patients at risk for developing rejection at biopsy during long-term follow-up may be detected by antimyosin-antibody study, and (3) surveillance for rejection and the degree of immunosuppression should be tailored to meet individual patient needs

  20. Ureaplasma Transmitted From Donor Lungs Is Pathogenic After Lung Transplantation.

    Science.gov (United States)

    Fernandez, Ramiro; Ratliff, Amy; Crabb, Donna; Waites, Ken B; Bharat, Ankit

    2017-02-01

    Hyperammonemia is a highly fatal syndrome in lung recipients that is usually refractory to medical therapy. We recently reported that infection by a Mollicute, Ureaplasma, is causative for hyperammonemia and can be successfully treated with antimicrobial agents. However, it remains unknown whether the pathogenic strain of Ureaplasma is donor or recipient derived. Here we provide evidence that donor-derived Ureaplasma infection can be pathogenic. As such, we uncover a previously unknown lethal donor-derived opportunistic infection in lung recipients. Given the high mortality associated with hyperammonemia, strategies for routine donor screening or prophylaxis should be further evaluated in prospective studies. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  1. Ingraft chimerism in lung transplantation - a study in a porcine model of obliterative bronchiolitis

    Directory of Open Access Journals (Sweden)

    Rubes Jiri

    2011-04-01

    Full Text Available Abstract Background Bronchial epithelium is a target of the alloimmune response in lung transplantation, and intact epithelium may protect allografts from rejection and obliterative bronchiolitis (OB. Herein we study the influence of chimerism on bronchial epithelium and OB development in pigs. Methods A total of 54 immunosuppressed and unimmunosuppressed bronchial allografts were serially obtained 2-90 days after transplantation. Histology (H&E was assessed and the fluorescence in situ hybridization (FISH method for Y chromosomes using pig-specific DNA-label was used to detect recipient derived cells in graft epithelium and bronchial wall, and donor cell migration to recipient organs. Ingraft chimerism was studied by using male recipients with female donors, whereas donor cell migration to recipient organs was studied using female recipients with male donors. Results Early appearance of recipient-derived cells in the airway epithelium appeared predictive of epithelial destruction (R = 0.610 - 0.671 and p R = 0.698 and p p p Conclusions In this study we demonstrate that early appearance of Y chromosomes in the airway epithelium predicts features characteristic of OB. Chimerism occurred in all allografts, including those without features of OB. Therefore we suggest that ingraft chimerism may be a mechanism involved in the repair of alloimmune-mediated tissue injury after transplantation.

  2. When the Battle is Lost and Won: Delayed Chest Closure After Bilateral Lung Transplantation.

    Science.gov (United States)

    Soresi, Simona; Sabashnikov, Anton; Weymann, Alexander; Zeriouh, Mohamed; Simon, André R; Popov, Aron-Frederik

    2015-10-12

    In this article we summarize benefits of delayed chest closure strategy in lung transplantation, addressing indications, different surgical techniques, and additional perioperative treatment. Delayed chest closure seems to be a valuable and safe strategy in managing patients with various conditions after lung transplantation, such as instable hemodynamics, need for high respiratory pressures, coagulopathy, and size mismatch. Therefore, this approach should be considered in lung transplant centers to give patients time to recover before the chest is closed.

  3. Lung Abscess: An Early Complication of Lung Transplantation in a Patient with Cystic Fibrosis.

    Science.gov (United States)

    Markelić, I; Jakopović, M; Klepetko, W; Džubur, F; Hećimović, A; Makek, M J; Samaržija, M; Dugac, A V

    2017-01-01

    A 22-year-old woman with cystic fibrosis (CF) developed lung abscess, as a rare complication caused by multidrug-resistant (MDR) Acinetobacter baumannii infection, after lung transplantation (LT). After 6 months of long-term antibiotic therapy, the abscess was successfully eliminated. In reviewed published literature, no previous report was found describing this kind of complication caused by MDR A. baumannii in post-LT patient with CF. In our experience, lung abscess in LT recipients with CF can be successfully treated with prolonged antibiotic therapy.

  4. Transplant rejection and tolerance – advancing the field through integration of computational and experimental investigation

    Energy Technology Data Exchange (ETDEWEB)

    Raimondi, Giorgio [Johns Hopkins Univ., Baltimore, MD (United States); Wood, Kathryn [Univ. of Oxford (United Kingdom); Perelson, Alan S. [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Arciero, Julia C [Indiana Univ.-Purdue Univ., Indianapolis, IN (United States)

    2017-05-31

    This Research Topic provides a venue for stimulating these interdisciplinary conversations in the context of transplantation. The articles collected under this Research Topic introduce new theoretical and experimental studies that describe novel techniques and methods for understanding the interactions between the immune response and transplants and for establishing more effective strategies of diagnosis and intervention that will promote transplant tolerance.

  5. The clinical utility of indium-111 labelled platelet scintigraphy in the diagnoses of renal transplant rejection

    International Nuclear Information System (INIS)

    Desir, G.V.; Bia, M.; Lange, R.C.; Smith, E.O.; Flye, W.; Kashgarian, M.; Schiff, M.; Ezekowitz, M.D.

    1990-01-01

    It is demonstrated that indium-111 labelled platelet scintigraphy is a highly accurate test for detecting acute untreated renal allograft rejection and it is shown that changes in platelet uptake can precede signs and symptoms of rejection by at least 48 hours. (author). 34 refs.; 2 figs.; 1 tab

  6. Comparative evaluation of renal transplant rejection with radioiodinated fibrinogen, /sup 99m/Tc--sulfur colloid, and 67Ga-citrate

    International Nuclear Information System (INIS)

    George, E.A.; Codd, J.E.; Newton, W.T.; Haibach, H.; Donati, R.M.

    1976-01-01

    The diagnostic accuracy, ease, and technical feasibility of imaging with 131 I- or 125 I-fibrinogen, 99 /sup m/Tc-sulfur colloid, and 67 Ga-citrate in renal transplant rejection are compared. Radiofibrinogen data resulted from literature review, radio-colloid data from 125 studies in 52 transplant patients, and gallium citrate data from 24 examinations in seven renal transplant patients performed simultaneously with the radiocolloid studies. Specificity of graft labeling during rejection appears to be similar with radiofibrinogen, 99 /sup m/Tc-sulfur colloid, and 67 Ga-citrate. For routine clinical use 99 /sup m/Tc-sulfur colloid surpasses radiofibrinogen and radiogallium because of its better imaging qualities with a permissible radiation dose, leading to better separation of positive and negative results. The 99 /sup m/Tc-sulfur colloid accumulates in areas of intravascular fibrin thrombosis in acute and chronic rejecting renal transplants. Hence, the mechanisms for accumulation of 99 /sup m/Tc-sulfur colloid and labeled fibrinogen in rejecting transplants would seem to be similar. Such physiologic properties as rapid blood clearance and such physical properties as short physical half-life combine to produce reliable graft visualization with adequate definition, thus favoring 99 /sup m/Tc-sulfur colloid as the single agent of choice for clinical evaluation of renal transplant rejection at this time

  7. Restrictive allograft syndrome after lung transplantation: new radiological insights

    Energy Technology Data Exchange (ETDEWEB)

    Dubbeldam, Adriana; Barthels, Caroline; Coolen, Johan; Verschakelen, Johny A.; Wever, Walter de [University Hospitals Leuven, Department of Radiology, Leuven (Belgium); Verleden, Stijn E.; Vos, Robin; Verleden, Geert M. [University Hospitals Leuven, Department of Pneumology, Leuven (Belgium)

    2017-07-15

    To describe the CT changes in patients with restrictive allograft syndrome (RAS) after lung transplantation, before and after clinical diagnosis. This retrospective study included 22 patients with clinical diagnosis of RAS. Diagnosis was based on a combination of forced expiratory volume (FEV1) decline (≥20 %) and total lung capacity (TLC) decline (≥10 %). All available CT scans after transplantation were analyzed for the appearance and evolution of lung abnormalities. In 14 patients, non-regressing nodules and reticulations predominantly affecting the upper lobes developed an average of 13.9 months prior to the diagnosis of RAS. Median graft survival after onset of non-regressing abnormalities was 33.5 months, with most patients in follow-up (9/14). In eight patients, a sudden appearance of diffuse consolidations mainly affecting both upper and lower lobes was seen an average of 2.8 months prior to the diagnosis of RAS. Median graft survival was 6.4 months after first onset of non-regressing abnormalities, with graft loss in most patients (6/8). RAS has been previously described as a homogenous group. However, our study shows two different groups of RAS-patients: one with slow progression and one with fast progression. The two groups show different onset and progression patterns of CT abnormalities. (orig.)

  8. Pretransplant soluble CD30 level has limited effect on acute rejection, but affects graft function in living donor kidney transplantation.

    Science.gov (United States)

    Kim, Myoung Soo; Kim, Hae Jin; Kim, Soon Il; Ahn, Hyung Joon; Ju, Man Ki; Kim, Hyun Jung; Jeon, Kyung Ock; Kim, Yu Seun

    2006-12-27

    Serum soluble CD30 (sCD30) levels might be a useful marker of immunologic status in pre transplant (Tx) recipients. We retrospectively correlated preTx sCD30 levels (high versus low) on postTx graft survival, incidence of acute rejection, and graft function using stored preTx serum. Of 254 recipients who underwent kidney Tx, 120 recipients were enrolled under the uniform criteria (living donor, age >25 years, viral hepatitis free, diabetes free). The preTx sCD30 was not significantly associated with differences in graft survival rate during 47.5+/-11.4 months of follow-up (P = 0.5901). High sCD30 (> or =115 U/ml) was associated with a higher incidence of clinically or pathologically defined acute rejection than low sCD30, but the difference was not statistically significant (33.9% vs. 22.4%, P = 0.164). The response rate to antirejection therapy in patients with high sCD30 was inferior to those with low sCD30, but also was not statistically significant (33.3% vs. 7.7%, P = 0.087). However, mean serum creatinine levels in high sCD30 patients at one month, one year, and three years postTx were significantly different from those with low sCD30 (P acute rejection episodes, donor age, kidney weight/recipient body weight ratio, and preTx sCD30 levels were independent variables affecting the serum creatinine level three years postTx. PreTx sCD30 level has a limited effect on the incidence of acute rejection and response to antirejection treatment, but inversely and independently affects serum creatinine level after living donor kidney transplantation.

  9. Dynamic MRI-based computer aided diagnostic systems for early detection of kidney transplant rejection: A survey

    Science.gov (United States)

    Mostapha, Mahmoud; Khalifa, Fahmi; Alansary, Amir; Soliman, Ahmed; Gimel'farb, Georgy; El-Baz, Ayman

    2013-10-01

    Early detection of renal transplant rejection is important to implement appropriate medical and immune therapy in patients with transplanted kidneys. In literature, a large number of computer-aided diagnostic (CAD) systems using different image modalities, such as ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), and radionuclide imaging, have been proposed for early detection of kidney diseases. A typical CAD system for kidney diagnosis consists of a set of processing steps including: motion correction, segmentation of the kidney and/or its internal structures (e.g., cortex, medulla), construction of agent kinetic curves, functional parameter estimation, diagnosis, and assessment of the kidney status. In this paper, we survey the current state-of-the-art CAD systems that have been developed for kidney disease diagnosis using dynamic MRI. In addition, the paper addresses several challenges that researchers face in developing efficient, fast and reliable CAD systems for the early detection of kidney diseases.

  10. Transplantation of hamster lung lesions induced by 239PuO2 or benz(a)pyrene

    International Nuclear Information System (INIS)

    McDonald, K.E.; Sanders, C.L.

    1980-01-01

    None(0%) of 1000 recipients of lung lesions for 239 PuO 2 -exposed hamsters that were transplanted into other hamsters' cheek pouches, developed tumors, whereas 90% of transplants from benz(a)pyrene-induced lung lesions were malignant

  11. Emotions while awaiting lung transplantation: A comprehensive qualitative analysis

    Science.gov (United States)

    Brügger, Aurelia; Aubert, John-David

    2014-01-01

    Patients awaiting lung transplantation are at risk of negative emotional and physical experiences. How do they talk about emotions? Semi-structured interviews were performed (15 patients). Categorical analysis focusing on emotion-related descriptions was organized into positive–negative–neutral descriptions: for primary and secondary emotions, evaluation processes, coping strategies, personal characteristics, emotion descriptions associated with physical states, (and) contexts were listed. Patients develop different strategies to maintain positive identity and attitude, while preserving significant others from extra emotional load. Results are discussed within various theoretical and research backgrounds, in emphasizing their importance in the definition of emotional support starting from the patient’s perspective. PMID:28070345

  12. Mycoplasma hominis periaortic abscess following heart-lung transplantation.

    Science.gov (United States)

    Hagiya, Hideharu; Yoshida, Hisao; Yamamoto, Norihisa; Kimura, Keigo; Ueda, Akiko; Nishi, Isao; Akeda, Yukihiro; Tomono, Kazunori

    2017-06-01

    We report the first case of Mycoplasma hominis periaortic abscess after heart-lung transplantation. The absence of sternal wound infection delayed the diagnosis, but the patient successfully recovered with debridement surgeries and long-term antibiotic therapy. Owing to the difficulty in detection and the intrinsic resistance to beta-lactams, M. hominis infections are prone to being misdiagnosed and undertreated. M. hominis should be suspected in cases where conventional microbiological identification and treatment approaches fail. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Emotions while awaiting lung transplantation: A comprehensive qualitative analysis.

    Science.gov (United States)

    Brügger, Aurelia; Aubert, John-David; Piot-Ziegler, Chantal

    2014-07-01

    Patients awaiting lung transplantation are at risk of negative emotional and physical experiences. How do they talk about emotions? Semi-structured interviews were performed (15 patients). Categorical analysis focusing on emotion-related descriptions was organized into positive-negative-neutral descriptions: for primary and secondary emotions, evaluation processes, coping strategies, personal characteristics, emotion descriptions associated with physical states, (and) contexts were listed. Patients develop different strategies to maintain positive identity and attitude, while preserving significant others from extra emotional load. Results are discussed within various theoretical and research backgrounds, in emphasizing their importance in the definition of emotional support starting from the patient's perspective.

  14. Emotions while awaiting lung transplantation: A comprehensive qualitative analysis

    Directory of Open Access Journals (Sweden)

    Aurelia Brügger

    2014-12-01

    Full Text Available Patients awaiting lung transplantation are at risk of negative emotional and physical experiences. How do they talk about emotions? Semi-structured interviews were performed (15 patients. Categorical analysis focusing on emotion-related descriptions was organized into positive–negative–neutral descriptions: for primary and secondary emotions, evaluation processes, coping strategies, personal characteristics, emotion descriptions associated with physical states, (and contexts were listed. Patients develop different strategies to maintain positive identity and attitude, while preserving significant others from extra emotional load. Results are discussed within various theoretical and research backgrounds, in emphasizing their importance in the definition of emotional support starting from the patient’s perspective.

  15. Pretransplantation soluble CD30 level as a predictor of acute rejection in kidney transplantation: a meta-analysis.

    Science.gov (United States)

    Chen, Yile; Tai, Qiang; Hong, Shaodong; Kong, Yuan; Shang, Yushu; Liang, Wenhua; Guo, Zhiyong; He, Xiaoshun

    2012-11-15

    The question of whether high pretransplantation soluble CD30 (sCD30) level can be a predictor of kidney transplant acute rejection (AR) is under debate. Herein, we performed a meta-analysis on the predictive efficacy of sCD30 for AR in renal transplantation. PubMed (1966-2012), EMBASE (1988-2012), and Web of Science (1986-2012) databases were searched for studies concerning the predictive efficacy of sCD30 for AR after kidney transplantation. After a careful review of eligible studies, sensitivity, specificity, and other measures of the accuracy of sCD30 were pooled. A summary receiver operating characteristic curve was used to represent the overall test performance. Twelve studies enrolling 2507 patients met the inclusion criteria. The pooled estimates for pretransplantation sCD30 in prediction of allograft rejection risk were poor, with a sensitivity of 0.70 (95% confidence interval (CI), 0.66-0.74), a specificity of 0.48 (95% CI, 0.46-0.50), a positive likelihood ratio of 1.35 (95% CI, 1.20-1.53), a negative likelihood ratio of 0.68 (95% CI, 0.55-0.84), and a diagnostic odds ratio of 2.07 (95% CI, 1.54-2.80). The area under curve of the summary receiver operating characteristic curve was 0.60, indicating poor overall accuracy of the serum sCD30 level in the prediction of patients at risk for AR. The results of the meta-analysis show that the accuracy of pretransplantation sCD30 for predicting posttransplantation AR was poor. Prospective studies are needed to clarify the usefulness of this test for identifying risks of AR in transplant recipients.

  16. Organotypic lung culture: A new model for studying ischemia and ex vivo perfusion in lung transplantation.

    Science.gov (United States)

    Baste, Jean-Marc; Gay, Arnaud; Smail, Hassiba; Noël, Romain; Bubenheim, Michael; Begueret, Hugues; Morin, Jean-Paul; Litzler, Pierre-Yves

    2015-01-01

    Donors after cardiac death (DCD) in lung transplantation is considered as a solution for organ shortage. However, it is characterized by warm ischemic period, which could be involved in severe Ischemia-Reperfusion lesion (IR) with early graft dysfunction. We describe a new hybrid model combining in vivo ischemia followed by in vitro reoxygenation using organ-specific culture. A hybrid model using in vivo ischemic period followed by in vitro lung slice reoxygenation was set up in rat to mimic DCD in lung transplantation with in vitro perfusion. Different markers (bioenergetics, oxidant stress assays, and histology) were measured to evaluate the viability of lung tissue after different ischemic times (I-0, I-1, I-2, I-4, I-15 hours) and reoxygenation times (R-0, R-1, R-4, R-24 hours). No differences were found in cell viability, ATP concentrations, extracellular LDH assays or histology, demonstrating extensive viability of up to 4 hours in lung tissue warm ischemia. We found oxidative stress mainly during the ischemic period with no burst at reoxygenation. Cytosolic anti-oxidant system was involved first (I-0,I-1,I-2) followed by mitochondrial anti-oxidant system for extensive ischemia (I-4). Histological features showed differences in this model of ischemia-reoxygenation between bronchial epithelium and lung parenchymal cells, with epithelium regeneration after 2 hours of warm ischemia and 24 hours of perfusion. The results of our hybrid model experiment suggest extensive lung viability of up to 4 hours ischemia. Our model could be an interesting tool to evaluate ex vivo reconditioning techniques after different in vivo lung insults.

  17. Recurrence of sarcoid granulomas in lung transplant recipients is common and does not affect overall survival

    DEFF Research Database (Denmark)

    Schultz, Hans Henrik Lawaetz; Andersen, Claus Bøgelund; Steinbrüchel, D

    2014-01-01

    Background: Sarcoidosis represents 2,5% of all indications for lung transplantation and criteria are generally assumed to be the same as for pulmonary fibrosis. Recurrence of granulomas in transplanted lungs has earlier been proved to derive from recipient immune cells, but its role in relation t...

  18. Survival benefit of cardiopulmonary bypass support in bilateral lung transplantation for emphysema patients

    NARCIS (Netherlands)

    Hepkema, BG; Loef, BG; van der Bij, W; Verschuuren, EAM; Lems, SPM; Ebels, T

    2002-01-01

    Background. This study is designed to examine a possible association of cardiopulmonary bypass (CPB) support and outcome of lung transplantation in a well-balanced group of emphysema patients. Methods. We performed a retrospective analysis of 62 consecutive primary bilateral lung transplantations

  19. Effective Prolonged Therapy with Voriconazole in a Lung Transplant Recipient with Spondylodiscitis Induced by Scedosporium apiospermum

    OpenAIRE

    Luijk, B.; Ekkelenkamp, M. B.; De Jong, P. A.; Kwakkel-van Erp, J. M.; Grutters, J. C.; van Kessel, D. A.; van de Graaf, E. A.

    2011-01-01

    Scedosporium/Pseudallescheria species are frequently seen in cystic fibrosis patients. However, disseminated forms after lung transplantation in these patients are rarely seen, but often with poor outcome. In this case report we describe a lung transplant recipient with cystic fibrosis who developed a spondylodiscitis that was caused by Scedosporium apiospermu...

  20. Cytomegalovirus Viral Load in Bronchoalveolar Lavage to Diagnose Lung Transplant Associated CMV Pneumonia

    DEFF Research Database (Denmark)

    Lodding, Isabelle Paula; Schultz, Hans Henrik; Jensen, Jens-Ulrik

    2018-01-01

    BACKGROUND: The diagnostic yield for cytomegalovirus (CMV) PCR viral load in Bronchoalveolar Lavage (BAL) or in plasma to diagnose CMV pneumonia in lung transplant recipients remains uncertain, and was investigated in a large cohort of consecutive lung transplant recipients. METHODS: Bronchoscopi...

  1. Histone deacetylase 2 is decreased in peripheral blood pro-inflammatory CD8+ T and NKT-like lymphocytes following lung transplant.

    Science.gov (United States)

    Hodge, Greg; Hodge, Sandra; Holmes-Liew, Chien-Li; Reynolds, Paul N; Holmes, Mark

    2017-02-01

    Immunosuppression therapy following lung transplantation fails to prevent chronic rejection in many patients, which is associated with lack of suppression of cytotoxic mediators and pro-inflammatory cytokines in peripheral blood T and natural killer T (NKT)-like cells. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) upregulate/downregulate pro-inflammatory gene expression, respectively; however, differences in the activity of these enzymes following lung transplant are unknown. We hypothesized decreased HDAC2 expression and increased HAT expression in pro-inflammatory lymphocytes following lung transplant. Blood was collected from 18 stable lung transplant patients and 10 healthy age-matched controls. Intracellular pro-inflammatory cytokines and HAT/HDAC2 expression were determined in lymphocyte subsets following culture using flow cytometry. A loss of HDAC2 in cluster of differentiation (CD) 8+ T and NKT-like cells in transplant patients compared with controls was noted (CD8+ T: 28 ± 10 (45 ± 10), CD8+NKT-like: 30 ± 13 (54 ± 16) (mean ± SD transplant) (control)). Loss of HDAC2 was associated with an increased percentage of CD8+ T and NKT-like cells expressing perforin, granzyme b, interferon gamma (IFN-γ) and TNF-α (no change in HAT expression in any lymphocyte subset). There was a negative correlation between loss of HDAC2 expression by CD8+ T cells with cumulative dose of prednisolone and time post-transplant. Treatment with 10 mg/L theophylline + 1 µmol/L prednisolone or 2.5 ng/mL cyclosporine A synergistically upregulated HDAC2 and inhibited IFN-γ and TNF-α production by CD8+ T and NKT-like lymphocytes. HDAC2 is decreased in CD8+ T and NKT-like pro-inflammatory lymphocytes following lung transplant. Treatment options that increase HDAC2 may improve graft survival. © 2016 Asian Pacific Society of Respirology.

  2. Serial perfusion in native lungs in patients with idiopathic pulmonary fibrosis and other interstitial lung diseases after single lung transplantation.

    Science.gov (United States)

    Sokai, Akihiko; Handa, Tomohiro; Chen, Fengshi; Tanizawa, Kiminobu; Aoyama, Akihiro; Kubo, Takeshi; Ikezoe, Kohei; Nakatsuka, Yoshinari; Oguma, Tsuyoshi; Hirai, Toyohiro; Nagai, Sonoko; Chin, Kazuo; Date, Hiroshi; Mishima, Michiaki

    2016-04-01

    Lung perfusions after single lung transplantation (SLT) have not been fully clarified in patients with interstitial lung disease (ILD). The present study aimed to investigate temporal changes in native lung perfusion and their associated clinical factors in patients with ILD who have undergone SLT. Eleven patients were enrolled. Perfusion scintigraphy was serially performed up to 12 months after SLT. Correlations between the post-operative perfusion ratio in the native lung and clinical parameters, including pre-operative perfusion ratio and computed tomography (CT) volumetric parameters, were evaluated. On average, the perfusion ratio of the native lung was maintained at approximately 30% until 12 months after SLT. However, the ratio declined more significantly in idiopathic pulmonary fibrosis (IPF) than in other ILDs (p = 0.014). The perfusion ratio before SLT was significantly correlated with that at three months after SLT (ρ = 0.64, p = 0.048). The temporal change of the perfusion ratio in the native lung did not correlate with those of the CT parameters. The pre-operative perfusion ratio may predict the post-operative perfusion ratio of the native lung shortly after SLT in ILD. Perfusion of the native lung may decline faster in IPF compared with other ILDs. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Nontuberculous Mycobacterial Disease Is Not a Contraindication to Lung Transplantation in Patients With Cystic Fibrosis

    DEFF Research Database (Denmark)

    Qvist, Tavs; Pressler, Tanja; Thomsen, V O

    2013-01-01

    of these died of non-NTM-related causes whereas two developed deep Mycobacterium abscessus wound infections and one was transiently culture negative until M abscessus was reactivated. One patient was subsequently cured; the other two remained on therapy with good performance status. The study supports...... infection poses a contraindication to lung transplantation. All CF patients with current or prior NTM who had undergone lung transplantation were identified. Out of 52 lung transplant patients with CF 9 (17%) had NTM disease. Five patients had known infection at the time of transplantation. Two...

  4. Quantitative evaluation of native lung hyperinflation after single lung transplantation for emphysema using three-dimensional computed tomography volumetry.

    Science.gov (United States)

    Motoyama, H; Chen, F; Ohsumi, A; Hijiya, K; Takahashi, M; Ohata, K; Yamada, T; Sato, M; Aoyama, A; Bando, T; Date, H

    2014-04-01

    Although double lung transplantation is performed more frequently for emphysema, single lung transplantation (SLT) continues to be performed owing to limited donor organ availability. Native lung hyperinflation (NLH) is a unique complication following SLT for emphysema. Three-dimensional computed tomography (3D-CT) volumetry has been introduced into the field of lung transplantation, which we used to assess NLH in emphysema patients undergoing SLT. The primary purpose of this study was to confirm the effectiveness of 3D-CT volumetry in the evaluation of NLH following SLT for emphysema. In 5 emphysema patients undergoing SLT at Kyoto University Hospital, 3D-CT volumetry data, pulmonary function test results, and clinical and radiological findings were retrospectively evaluated. Three patients did not develop a significant mediastinal shift, whereas the other 2 patients developed a mediastinal shift. In the 3 patients without a mediastinal shift, 3D-CT volumetry did not show a significant increase in native lung volume. These patients had a history of sternotomy prior to lung transplantation and firm adhesion on the mediastinal side was detected during lung transplantation. One of 2 patients with a mediastinal shift developed severe dyspnea with significantly decreased pulmonary function, and 3D-CT volumetry showed a significant increase in the native lung volume. However, the other patient did not show any dyspnea and his native lung volume decreased postoperatively (preoperatively to 6 months postoperatively: +981 mL and -348 mL, respectively). Although bilateral lung transplantation has become preferable for emphysema patients owing to postoperative NLH with SLT, patients with a history of sternotomy prior to lung transplantation might be good candidates for SLT. 3D-CT volumetry may be a useful method for detection of NLH. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The Effect of Cortex/Medulla Proportions on Molecular Diagnoses in Kidney Transplant Biopsies: Rejection and Injury Can Be Assessed in Medulla.

    Science.gov (United States)

    Madill-Thomsen, K S; Wiggins, R C; Eskandary, F; Böhmig, G A; Halloran, P F

    2017-08-01

    Histologic assessment of kidney transplant biopsies relies on cortex rather than medulla, but for microarray studies, the proportion cortex in a biopsy is typically unknown and could affect the molecular readings. The present study aimed to develop a molecular estimate of proportion cortex in biopsies and examine its effect on molecular diagnoses. Microarrays from 26 kidney transplant biopsies divided into cortex and medulla components and processed separately showed that many of the most significant differences were in glomerular genes (e.g. NPHS2, NPHS1, CLIC5, PTPRO, PLA2R1, PLCE1, PODXL, and REN). Using NPHS2 (podocin) to estimate proportion cortex, we examined whether proportion cortex influenced molecular assessment in the molecular microscope diagnostic system. In 1190 unselected kidney transplant indication biopsies (Clinicaltrials.govNCT01299168), only 11% had Molecular scores for antibody-mediated rejection, T cell-mediated rejection, and injury were independent of proportion cortex. Rejection was diagnosed in many biopsies that were mostly or all medulla. Agreement in molecular diagnoses in paired cortex/medulla samples (23/26) was similar to biological replicates (32/37). We conclude that NPHS2 expression can estimate proportion cortex; that proportion cortex has little influence on molecular diagnosis of rejection; and that, although histology cannot assess medulla, rejection does occur in medulla as well as cortex. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Post-transplant survival in idiopathic pulmonary fibrosis patients concurrently listed for single and double lung transplantation.

    Science.gov (United States)

    Chauhan, Dhaval; Karanam, Ashwin B; Merlo, Aurelie; Tom Bozzay, P A; Zucker, Mark J; Seethamraju, Harish; Shariati, Nazly; Russo, Mark J

    2016-05-01

    Lung transplantation is a widely accepted treatment for patients with end-stage lung disease related to idiopathic pulmonary fibrosis (IPF). However, there are conflicting data on whether double lung transplant (DLT) or single lung transplant (SLT) is the superior therapy in these patients. The purpose of this study was to determine whether actuarial post-transplant graft survival among IPF patients concurrently listed for DLT and SLT is greater for recipients undergoing the former or the latter. The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant candidates with IPF listed between January 1, 2001 and December 31, 2009 (n = 3,411). The study population included 1,001 (29.3%) lung transplant recipients concurrently listed for DLT and SLT, all ≥18 years of age. The primary outcome measure was actuarial post-transplant graft survival, expressed in years. Among the study population, 433 (43.26%) recipients underwent SLT and 568 (56.74%) recipients underwent DLT. The analysis included 2,722.5 years at risk, with median graft survival of 5.31 years. On univariate (p = 0.317) and multivariate (p = 0.415) regression analyses, there was no difference in graft survival between DLT and SLT. Among IPF recipients concurrently listed for DLT and SLT, there is no statistical difference in actuarial graft survival between recipients undergoing DLT vs SLT. This analysis suggests that increased use of SLT for IPF patients may increase the availability of organs to other candidates, and thus increase the net benefit of these organs, without measurably compromising outcomes. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  7. The Effect of Local Irradiation in Prevention and Reversal of Acute Rejection of Transplanted Kidney with High-dose Steroid Pulse

    International Nuclear Information System (INIS)

    Kim, I. H.; Ha, S. W.; Park, C. I.; Kim, S. T.

    1986-01-01

    From 1979 to 1984, 39 local allograft irradiations were given to 29 patients: 10 irradiations were administered for prevention and 29 for reversal of acute rejection of transplanted kidney. Three doses of 150 cGy every other day were combined with high-dose of methylprednisolone pulse (1 gm/day) for 3 days. For prevention of acute rejection, local irradiation was delivered on the days 1, 3, and 5 after the transplantation, and for reversal, irradiation started after the diagnosis of acute rejection. Eight out of 10 patients irradiated for prevention had acute allograft rejection, and, what is more, there was no surviving graft at 15 months after transplantation. Reversal of acute rejection was achieved in 71%. When the pre-irradiation level of serum creatinine was below 5.5 mg%, the reversal rate was 93%, but above 5.5 mg% the reversal rate was only 17% (p<0.01). Reirradiation after failure was not successful. Among 15 reversed patients, 7 (47%) had subsequent rejection (s). The functional graft survivals at 6 month, 1, 2, and 3 year were 70%, 65%, 54%, and 65%, respectively. Therapeutic irradiation resulted in better graft survival when serum creatinine was below 5.5 mg% (p<0.001) or when irradiation started within 15 days after the diagnosis of acute rejection (p<0.001)

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

    Science.gov (United States)

    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. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. [Lung transplantation in sporadic lymphangioleiomyomatosis: study of 7 cases].

    Science.gov (United States)

    Ansótegui Barrera, Emilio; Mancheño Franch, Nuria; Peñalver Cuesta, Juan Carlos; Vera-Sempere, Francisco; Padilla Alarcón, José

    2013-10-19

    Sporadic lymphangioleiomyomatosis (S-LAM) is a rare disease that affects only women. It is characterized by an abnormal proliferation of immature smooth muscle cells (LAM cells) that grow in an aberrant manner in the airway, parenchymal lung lymph and blood vessels, determining the onset of pulmonary cystic lesions. The disease has no treatment, progressing to respiratory failure, and lung transplantation (LT) may be a treatment option at this stage. Our goal was to study 7 patients undergoing LT for S-LAM. We studied a series of clinical and demographic characteristics, diagnostic modality and post-transplant outcomes. We performed a descriptive analysis of the series. The Kaplan-Meier method was used to estimate survival. The mean age of onset of symptoms was 35 years, the diagnosis of 37 years and that of LT 38 years. The most common symptom was dyspnea. Four patients had a history of pneumothorax and pleural effusion. The mean forced expiratory volume in one second was 32.7% and the diffusing capacity for carbon monoxide was 29%. All patients were subjected to LT and survival was 100, 85.7 and 57.1% at one, 3 and 5 years, respectively. Three died of bronchiolitis obliterans and 2 necropsies did not show evidence of disease recurrence. LT is a therapeutic option in patients with S-LAM with an advanced respiratory functional impairment. Copyright © 2013 Elsevier España, S.L. All rights reserved.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. An objective measure to identify pediatric liver transplant recipients at risk for late allograft rejection related to non-adherence.

    Science.gov (United States)

    Venkat, Veena L; Nick, Todd G; Wang, Yu; Bucuvalas, John C

    2008-02-01

    Non-adherence to a prescribed immunosuppressive regimen increases risk for late allograft rejection (LAR). We implemented a protocol for immunosuppression management which decreased variation in calcineurin inhibitor blood levels in pediatric liver transplant recipients by controlling for confounders such as physician practice variability. We hypothesized that patients with increased variation in tacrolimus blood levels despite implementation of the immunosuppression management protocol were at increased risk for LAR. We conducted a single center retrospective cohort study of 101 pediatric liver transplant recipients who were at least one year post liver transplantation and receiving tacrolimus for immunosuppression. The primary outcome variable was biopsy proven allograft rejection. Primary candidate predictor variables were the standard deviation (SD) of tacrolimus blood levels (a marker of drug level variability), mean tacrolimus blood level, age, and insurance type. SD of tacrolimus blood levels was determined for each patient from a minimum of four outpatient levels during the study period. Unadjusted and adjusted logistic regression models were used to determine the prognostic value of candidate predictors. The median and interquartile range of the SD of tacrolimus blood levels was 1.6 (1.1, 2.1). Eleven episodes of LAR occurred during the study period. Ten of the 11 episodes occurred in patients with tacrolimus blood level SD > 2. Insurance type, mean tacrolimus blood level and SD of tacrolimus blood levels were significantly related to LAR in the unadjusted analyses (ptype, mean and SD of tacrolimus blood levels was significantly associated with LAR (validated C-statistic = 0.88, p = 0.012). The adjusted odds of rejection for a one unit increase in the SD of tacrolimus blood level was 3.49 (95% CI 1.31 to 9.29). Effects of age and insurance status on LAR did not provide independent prognostic value after controlling for SD. Variation in tacrolimus blood

  13. Lobar lung transplantation from deceased donors: A systematic review.

    Science.gov (United States)

    Eberlein, Michael; Reed, Robert M; Chahla, Mayy; Bolukbas, Servet; Blevins, Amy; Van Raemdonck, Dirk; Stanzi, Alessia; Inci, Ilhan; Marasco, Silvana; Shigemura, Norihisa; Aigner, Clemens; Deuse, Tobias

    2017-02-24

    To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio. We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx. Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx ( n = 138) was associated with a lower one-year-survival compared to conventional-LTx ( n = 539) (65.1% vs 84.1%, P < 0.001). Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option.

  14. Elevated mRNA levels of CTLA-4, FoxP3, and granzyme B in BAL, but not in blood, during acute rejection of lung allografts

    DEFF Research Database (Denmark)

    Madsen, Caroline B; Nørgaard, Astrid; Iversen, Martin

    2010-01-01

    Regulatory T cells (Tregs) have been related to acute rejection as have the cytotoxic T cells, their immunological counterpart. High expression of cytotoxic markers has been related to acute rejection incidents following both kidney and intestine transplantation, while the correlation between Fox...

  15. Critical appraisal of belatacept for prophylaxis of rejection in kidney transplant patients

    OpenAIRE

    Chandraker, Anil; Gabardi,Steven; Martin,Spencer; Tsapepas,

    2011-01-01

    Spencer T Martin1, Demetra Tsapepas1, Steven Gabardi2–5, Anil Chandraker2,31Department of Pharmacy, New York-Presbyterian Hospital, New York City, NY, USA; 2Harvard Medical School, Boston, MA, USA; 3Renal Division, 4Department of Pharmacy Services, 5Department of Transplant Surgery, Brigham and Women's Hospital, Boston, MA, USAAbstract: Belatacept (LEA29Y) is an intravenous biologic for long-term maintenance immunosuppressive therapy in renal transplant recipients. It is cur...

  16. Evaluation of Lung Function in Liver Transplant Candidates.

    Science.gov (United States)

    Roque, L; Sankarankutty, A K; Silva, O C; Mente, E D

    2018-04-01

    A wide variety of pulmonary conditions are found in cirrhotic patients and may compromise the pleura, diaphragm, parenchyma, and pulmonary vasculature, influencing the results of liver transplantation. To evaluate the pulmonary function (lung capacities, volumes, and gasometric study) of patients with liver cirrhosis awaiting liver transplantation. Cirrhotic patients, subdivided into 3 groups stratified by liver disease severity using the Child-Pugh-Turcotte score, were compared with a control group of healthy volunteers. In spirometry, the parameters evaluated were total lung capacity, forced volume in the first second, and the relationship between forced volume in the first minute and forced vital capacity. Blood gas analysis was performed. In the control group, arterial oxygenation was evaluated by peripheral oxygen saturation by pulse oximetry. Of the 55 patients (75% men, 51 ± 12.77 years), 11 were Child A (73% men, 52 ± 14.01 years), 23 were Child B (75% men, 51 ± 12.77 years), and 21 were Child C (95% men, 50 ± 12.09 years). The control group had 20 individuals (50% men, 47 ± 8.15 years). Pulmonary capacities and volumes by the parameters evaluated were within the normal range. Arterial blood gas analysis detected no hypoxemia, but a tendency to low partial gas pressure was noted. In this population of cirrhotic patients the parameters of spirometry were normal in relation to the lung capacities and volumes in the different groups. No hypoxemia was detected, but a tendency to hypocapnia in the blood gas was noted. Copyright © 2018. Published by Elsevier Inc.

  17. Donor-derived, tolerogenic dendritic cells suppress immune rejection in the indirect allosensitization-dominant setting of corneal transplantation.

    Science.gov (United States)

    Hattori, Takaaki; Saban, Daniel R; Emami-Naeini, Parisa; Chauhan, Sunil K; Funaki, Toshinari; Ueno, Hiroki; Dana, Reza

    2012-04-01

    Significant interest has been focused on the use of ex vivo-manipulated DCs to optimally induce transplant tolerance and promote allograft survival. Although it is understood that donor-derived, tolerogenic DCs suppress the direct pathway of allosensitization, whether such DCs can similarly suppress the indirect pathway remains unclear. We therefore used the murine model of corneal transplantation to address this, as these allografts are rejected in an indirect pathway-dominant manner. Interestingly, recipients administered with donor bone marrow-derived DCregs, generated via culturing with GM-CSF, IL-10, and TGF-β1, significantly prolonged survival of corneal allografts. Correspondingly, these recipients demonstrated a potent reduction in the frequency of indirectly allosensitized T cells, as determined by ELISPOT. Examination of DCregs relative to mDCs or iDCs showed a resistance to up-regulation of MHC-II and costimulatory molecules, as well as an impaired capacity to stimulate MLRs. In vivo, DCreg administration in corneal-allografted recipients led to inhibition of CD4(+)IFN-γ(+) T cell frequencies and an associated increase in Foxp3 expression in the Treg compartment. We conclude that donor-derived, tolerogenic DCs significantly suppress the indirect pathway, thereby identifying a novel regulatory mechanism for these cells in transplantation.

  18. Determinant Factors in Graft Rejection Using Cox Regression, among the Recipients of Second Renal Transplant in Imam Khomeini Hospital in Urmia, 1988-2000

    Directory of Open Access Journals (Sweden)

    Rahim Tahmasebi

    2010-09-01

    Full Text Available Background: The objective of this study was to evaluate graft survival among the recipients of second renal transplant in Imam Khomeini centre hospital in Urmia. Methods: The study population consisted of 50 patients receiving renal grafts for the second time between 1988 and 2008 in Imam Khomeini centre hospital in Urmia. Two survival outcomes, first and second graft survival, were analyzed. Graft survival was defined from date of transplant until its rejection. For the purpose of graft survival analysis, graft failure was defined as return to dialysis, and death due to the functioning graft. Data were collected through individual patient questionnaires. Demographic and clinical factors, transfusion history, type of immunosuppressive drugs, levels of serum creatinine, triglyceride, cholesterol, and LDL at 3 and 6 months after transplantation were collected. Cox-proportional hazard model and Kaplan-Meier were used to data analysis. Results: First graft survival at 1, 2, 3, and 5 years was 74%, 66%, 53%, and 41%, respectively. Second graft survival at 1, 2, 3, and 5 years was 81%, 74%, 70%, and 61%, respectively. Causes of graft loss in first renal transplantation were 6% sever acute graft rejection, 12% acute graft rejection and 82% chronic graft rejection. In the multivariate analysis, only serum creatinine, blood pressure, and immunosuppressive drugs predicted first graft loss and serum creatinine, immunosuppressive drugs, and related donor family predicted second graft rejection. Conclusion: The serum creatinine and immunosuppressive drugs including cyclosporine, cellcept, and prednisolone are the most influential factors on graft survival.

  19. Pulsed-wave transmitral Doppler do not diagnose moderate acute rejection after heart transplantation

    NARCIS (Netherlands)

    Mannaerts, H. F.; Simoons, M. L.; Balk, A. H.; Tijssen, J.; van der Borden, S. G.; Zondervan, P. E.; Mochtar, B.; Weimar, W.; Roelandt, J. R.

    1993-01-01

    The value of pulsed-wave transmitral Doppler for the diagnosis of moderate acute rejection was examined in a total of 347 Doppler recordings obtained in 32 consecutive cardiac allograft recipients. Serial Doppler examinations (median, 11 per patient; range, 1 to 23) were performed simultaneously

  20. PULSED-WAVE TRANSMITRAL DOPPLER DO NOT DIAGNOSE MODERATE ACUTE REJECTION AFTER HEART-TRANSPLANTATION

    NARCIS (Netherlands)

    MANNAERTS, HF; SIMOONS, ML; BALK, AH; TIJSSEN, J; VANDERBORDEN, SG; ZONDERVAN, PE; MOCHTAR, B; WEIMAR, W; ROELANDT, [No Value

    1993-01-01

    The value of pulsed-wave transmitral Doppler for the diagnosis of moderate acute rejection was examined in a total of 347 Doppler recordings obtained in 32 consecutive cardiac allograft recipients. Serial Doppler examinations (median, 11 per patient; range, 1 to 23) were performed simultaneously

  1. The prevalence and extent of gastroesophageal reflux disease correlates to the type of lung transplantation.

    Science.gov (United States)

    Fisichella, Piero Marco; Davis, Christopher S; Shankaran, Vidya; Gagermeier, James; Dilling, Daniel; Alex, Charles G; Kovacs, Elizabeth J; Joehl, Raymond J; Love, Robert B

    2012-02-01

    Evidence is increasingly convincing that lung transplantation is a risk factor of gastroesophageal reflux disease (GERD). However, it is still not known if the type of lung transplant (unilateral, bilateral, or retransplant) plays a role in the pathogenesis of GERD. The records of 61 lung transplant patients who underwent esophageal function tests between September 2008 and May 2010, were retrospectively reviewed. These patients were divided into 3 groups based on the type of lung transplant they received: unilateral (n=25); bilateral (n=30), and retransplant (n=6). Among these groups we compared: (1) the demographic characteristics (eg, sex, age, race, and body mass index); (2) the presence of Barrett esophagus, delayed gastric emptying, and hiatal hernia; and (3) the esophageal manometric and pH-metric profile. Distal and proximal reflux were more prevalent in patients with bilateral transplant or retransplant and less prevalent in patients after unilateral transplant, regardless of the cause of their lung disease. The prevalence of hiatal hernia, Barrett esophagus, and the manometric profile were similar in all groups of patients. Although our data show a discrepancy in prevalence of GERD in patients with different types of lung transplantation, we cannot determine the exact cause for these findings from this study. We speculate that the extent of dissection during the transplant places the patients at risk for GERD. On the basis of the results of this study, a higher level of suspicion of GERD should be held in patients after bilateral or retransplantation.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2012-01-01

    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. A prospective, repeated measures design was used to describe the symptom experience of 85 lung transplant recipients between 2000 and 2005. The transplant symptom inventory was administered before and at one, three, six, nine, and 12 months post-transplant. Ridit analysis provided a unique method for describing symptom experiences and changes. After lung transplantation, significant (p<0.05) 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 time since transplant. 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 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" change or lack of change in patients' symptoms from pre- to post-lung transplant. © 2012 John Wiley & Sons A/S.

  4. Computed tomography findings of postoperative complications in lung transplantation Achados tomográficos nas complicações pós-operatórias do transplante pulmonar

    Directory of Open Access Journals (Sweden)

    Bruno Hochhegger

    2009-03-01

    Full Text Available Due to the increasing number and improved survival of lung transplant recipients, radiologists should be aware of the imaging features of the postoperative complications that can occur in such patients. The early treatment of complications is important for the long-term survival of lung transplant recipients. Frequently, HRCT plays a central role in the investigation of such complications. Early recognition of the signs of complications allows treatment to be initiated earlier, which improves survival. The aim of this pictorial review was to demonstrate the CT scan appearance of pulmonary complications such as reperfusion edema, acute rejection, infection, pulmonary thromboembolism, chronic rejection, bronchiolitis obliterans syndrome, cryptogenic organizing pneumonia, post-transplant lymphoproliferative disorder, bronchial dehiscence and bronchial stenosis.Com o número cada vez maior e uma melhor sobrevida dos pacientes submetidos ao transplante pulmonar, os radiologistas devem estar cientes das diversas possibilidades de complicações associadas ao transplante de pulmão. O tratamento precoce das complicações é importante para a sobrevida a longo prazo dos receptores de transplante pulmonar. Com frequência, a TCAR desempenha um papel central na investigação de tais complicações. O reconhecimento precoce dos sinais de complicações proporciona um tratamento rápido e melhora a sobrevida. O objetivo desta revisão pictórica foi proporcionar uma visão sobre as complicações mais prevalentes na TC, tais como edema de reperfusão, rejeição aguda, infecção, tromboembolismo pulmonar, rejeição crônica, síndrome da bronquiolite obliterante, pneumonia em organização criptogênica, doença linfoproliferativa pós-transplante, deiscência brônquica e estenose brônquica.

  5. Long-term persistence of human donor alveolar macrophages in lung transplant recipients

    DEFF Research Database (Denmark)

    Eguíluz-Gracia, Ibon; Schultz, Hans Henrik Lawaetz; Sikkeland, Liv I. B.

    2016-01-01

    and life span of human AMFs is scarce. METHODS: To follow the origin and longevity of AMFs in patients with lung transplantation for more than 100 weeks, we obtained transbronchial biopsies from 10 gender-mismatched patients with lung transplantation. These were subjected to combined in situ hybridisation...... transplantation we found that recipient monocytes seeded the alveoli early after transplantation, and showed subsequent phenotypical changes consistent with differentiation into proliferating mature AMFs. This resulted in a stable mixed chimerism between donor and recipient AMFs throughout the 2-year period...

  6. Transplantation immunity in the American cockroach, Periplaneta americana: the rejection of integumentary grafts from Blatta orientalis.

    Science.gov (United States)

    Karp, R D; Meade, C C

    1993-01-01

    The results from several previous studies have indicated that the American cockroach is able to respond to integumentary xenografts, but doubt remained as to whether cockroaches could effectively discriminate between self and allogeneic differences. This was emphasized by the fact that while one study reported that Periplaneta americana responded to grafts donated by the closely related genus Blatta orientalis, the data reported elsewhere, using a different assay system, found no such reactivity. Since we have subsequently reported, using a direct histological assay, that Periplaneta can in fact recognize and destroy integumentary allografts, we initiated a study to hopefully sort out the enigma presented by previous data using Blatta as a transplant donor. Integument from Blatta orientalis was transplanted orthotopically onto Periplaneta americana, and at various time points post-transplant, scored histologically for the survival of the subcuticular epidermal layer. The results clearly demonstrated that Periplaneta reacted to the Blatta tissue, because approximately 82% of the grafts had the epidermal layer destroyed by day 7 posttransplant. The kinetics of the response to Blatta was more in line with our allograft data, which would be in agreement with other work indicating that the closer the donor and recipient are on the phylogenetic tree, the less intense the reactivity to the foreign transplant.

  7. Epidemiology, risk factors, and outcome of Clostridium difficile infection in heart and heart-lung transplant recipients.

    Science.gov (United States)

    Bruminhent, Jackrapong; Cawcutt, Kelly A; Thongprayoon, Charat; Petterson, Tanya M; Kremers, Walter K; Razonable, Raymund R

    2017-06-01

    Clostridium difficile is a major cause of diarrhea in thoracic organ transplant recipients. We investigated the epidemiology, risk factors, and outcome of Clostridium difficile infection (CDI) in heart and heart-lung transplant (HT) recipients. This is a retrospective study from 2004 to 2013. CDI was defined by diarrhea and a positive toxigenic C. difficile in stool measured by toxin enzyme immunoassay (2004-2006) or polymerase chain reaction (2007-2013). Cox proportional hazards regression was used to model the association of risk factors with time to CDI and survival with CDI following transplantation. There were 254 HT recipients, with a median age of 53 years (IQR, 45-60); 34% were female. During the median follow-up of 3.1 years (IQR, 1.3-6.1), 22 (8.7%) patients developed CDI. In multivariable analysis, risk factors for CDI were combined heart-lung transplant (HR 4.70; 95% CI, 1.30-17.01 [P=.02]) and retransplantation (HR 7.19; 95% CI, 1.61-32.12 [P=.01]). Acute cellular rejection was associated with a lower risk of CDI (HR 0.34; 95% CI, 0.11-0.94 [P=.04]). CDI was found to be an independent risk factor for mortality (HR 7.66; 95% CI, 3.41-17.21 [PClostridium difficile infection after HT is more common among patients with combined heart-lung and those undergoing retransplantation. CDI was associated with a higher risk of mortality in HT recipients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Soluble CD30 and ELISA-detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients.

    Science.gov (United States)

    Billing, Heiko; Sander, Anja; Süsal, Caner; Ovens, Jörg; Feneberg, Reinhard; Höcker, Britta; Vondrak, Karel; Grenda, Ryszard; Friman, Stybjorn; Milford, David V; Lucan, Mihai; Opelz, Gerhard; Tönshoff, Burkhard

    2013-03-01

    Biomarker-based post-transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well-controlled prospective randomized trial was analyzed pre- and post-transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T-cell reactivity, and anti-human leukocyte antigen (anti-HLA) antibody reactivity, a biomarker for B-cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy-proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut-off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut-off (P = 0.004). For pre- and post-transplant anti-HLA class II reactivities by enzyme-linked immunosorbent assay, a cut-off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti-HLA reactivities. An increased post-transplant sCD30 serum concentration and positive pre- and post-transplant anti-HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG-506-02-43). © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation. Published by Blackwell Publishing Ltd.

  9. Guardians of 'the gift': the emotional challenges of heart and lung transplant professionals in Denmark.

    Science.gov (United States)

    Jensen, Anja M B

    2017-04-01

    This paper deals with the emotional challenges encountered by doctors and nurses caring for heart and lung transplant patients. Organ transplantation enables body parts from the dead to become usable in patients with no other life-saving option. These exchanges are not possible without transplant professionals carefully selecting, guiding and interacting with organ recipients before, during and after the transplant. Based on anthropological fieldwork at a Danish heart and lung transplant unit, the paper explores how doctors and nurses experience and handle the emotional challenges of their working life. By focusing on the everyday life of the transplant unit which, contrary to public understanding of transplant miracles, is sometimes characterised by sad cases and devastation, this paper argues that transplant professionals operate in the presence of death. Medically and emotionally they are at risk. They must take the difficult decisions of whether to admit critically ill patients onto the organ waiting list; face the distress of post-transplant sufferings and deaths; and deal with organ recipients who do not behave according to post-transplant recommendations. Drawing on a familiar metaphor for donated organs, it is suggested that transplant doctors and nurses are 'guardians of the gift'. Attention to the emotional burdens and rewards of this particular position enables new understandings of the practices of transplant medicine, of gift exchange theory, and of the role of emotion in medical practice.

  10. Repeated measurements of NT-pro-B-type natriuretic peptide, troponin T or C-reactive protein do not predict future allograft rejection in heart transplant recipients.

    Science.gov (United States)

    Battes, Linda C; Caliskan, Kadir; Rizopoulos, Dimitris; Constantinescu, Alina A; Robertus, Jan L; Akkerhuis, Martijn; Manintveld, Olivier C; Boersma, Eric; Kardys, Isabella

    2015-03-01

    Studies on the prognostic value of serial biomarker assays for future occurrence of allograft rejection (AR) are scarce. We examined whether repeated measurements of NT-pro-B-type natriuretic peptide (NT-proBNP), troponin T (TropT) and C-reactive protein (CRP) predict AR. From 2005 to 2010, 77 consecutive heart transplantation (HTx) recipients were included. The NT-proBNP, TropT, and CRP were measured at 16 ± 4 (mean ± standard deviation) consecutive routine endomyocardial biopsy surveillance visits during the first year of follow-up. Allograft rejection was defined as International Society for Heart and Lung Transplantation (ISHLT) grade 2R or higher at endomyocardial biopsy. Joint modeling was used to assess the association between repeated biomarker measurements and occurrence of future AR. Joint modeling accounts for dependence among repeated observations in individual patients. The mean age of the patients at HTx was 49 ± 9.2 years, and 68% were men. During the first year of follow-up, 1,136 biopsies and concurrent blood samples were obtained, and 56 patients (73%) experienced at least one episode of AR. All biomarkers were elevated directly after HTx and achieved steady-state after ∼ 12 weeks, both in patients with or without AR. No associations were present between the repeated measurements of NT-proBNP, TropT, or CRP and AR both early (weeks 0-12) and late (weeks 13-52) in the course after HTx (hazard ratios for weeks 13-52: 0.96 (95% confidence interval, 0.55-1.68), 0.67 (0.27-1.69), and 1.44 (0.90-2.30), respectively, per ln[unit]). Combining the three biomarkers in one model also rendered null results. The temporal evolution of NT-proBNP, TropT, and CRP before AR did not predict occurrence of acute AR both in the early and late course of the first year after HTx.

  11. Intravenous immunoglobulins and rituximab therapy for severe transplant glomerulopathy in chronic antibody-mediated rejection: a pilot study.

    Science.gov (United States)

    Bachelet, Thomas; Nodimar, Celine; Taupin, Jean-Luc; Lepreux, Sebastien; Moreau, Karine; Morel, Delphine; Guidicelli, Gwendaline; Couzi, Lionel; Merville, Pierre

    2015-05-01

    Outcome of patients with transplant glomerulopathy (TG) is poor. Using B-cell targeting molecules represent a rational strategy to treat TG during chronic antibody-mediated rejection. In this pilot study, 21 patients with this diagnosis received four doses of intravenous immunoglobulins and two doses of rituximab (IVIG/RTX group). They were retrospectively compared with a untreated control group of 10 patients. At 24 months post-biopsy, graft survival was similar and poor between the treated and the untreated group, 47% vs. 40%, respectively, p = 0.69. This absence of response of IVIG/RTX treatment was observed, regardless the phenotype of TG. Baseline estimated glomerular filtration rate (eGFR) and decline in eGFR during the first six months after the treatment were risk factors associated with 24-month graft survival. The IVIG/RTX therapy had a modest effect on the kinetics of donor-specific alloantibodies at M24, compared to the untreated group, not associated with an improvement in graft survival. The mean number of adverse events per patient was higher in the IVIG/RTX group than in the control group (p = 0.03). Taken together, IVIG/RTX treatment for severe TG during chronic antibody-mediated rejection does not seem to change the natural history of TG and is associated with a high incidence of adverse events. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Plugged percutaneous biopsy of the liver in living-donor liver transplantation recipients suspected to have graft rejection.

    Science.gov (United States)

    Kim, Sung Jung; Won, Je Hwan; Kim, Young Bae; Wang, Hee-Jung; Kim, Bong-Wan; Kim, Haeryoung; Kim, Jinoo

    2017-07-01

    Background Percutaneous biopsy is a widely-accepted technique for acquiring histologic samples of the liver. When there is concern for bleeding, plugged percutaneous biopsy (PPB) may be performed, which involves embolization of the biopsy tract. Purpose To evaluate the efficacy and safety of PPB of the liver in patients suspected to have graft rejection after living-donor liver transplantation (LDLT). Material and Methods During January 2007 and December 2013, 51 patients who underwent PPB of the liver under the suspicion of post-LDLT graft rejection were retrospectively analyzed. A total of 73 biopsies were performed. Biopsy was performed with a 17-gauge core needle and 18-gauge cutting needle. The needle tract was embolized using gelatin sponge (n = 44) or N-butyl cyanoacrylate (NBCA) (n = 29). The specimens were reviewed to determine their adequacy for histologic diagnosis. We reviewed all medical records after PPB. Results Specimens were successfully acquired in all procedures (100%). They were adequate for diagnosis in 70 cases (95.9%) and inadequate in three (1.3%). Average of 9.8 complete portal tracts was counted per specimen. One minor complication (1.4%) occurred where the patient had transient fever after the procedure. Conclusion PPB is easy and safe to perform in LDLT recipients and provides high diagnostic yield.

  13. Pulmonary Rehabilitation in Lung Transplant Candidates: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Stefanie Tonguino Rosero

    2013-09-01

    Full Text Available Pulmonary rehabilitation (PR aims to improve physical fitness and to decrease symptoms in patients with chronic lung disease; however there is not clear evidence regarding the benefits of PR in candidates for lung transplantation (LT. Objective. To determine the effectiveness of PR in LT candidates and also to find out how quality of life and exercise tolerance affects the survival of these patients. Methodology. Electronic databases (Medline, Cochrane, PEDro, Scient Direct and SciELO Search of articles in spanish, english or portuguese; controlled clinical trials and cohort studies published between 2000-2011 regarding PR in candidates for LT, the model of Cochrane systematic reviews was used. Results. The papers included were four cohort, two of which regarded of survival pre LT using the six minutes walking test (6MWT; a study of quality of life related to post LT survival and an exercise tolerance study. Controlled clinical trial was not found. Conclusions. The information found in the included studies had clinical and methodological heterogeneity therefore a meta-analysis could not been undertaken. The PR should be considered as an essential part to maintain the exercise tolerance and the patient’s survival. Research regarding this subject is important and should be carried out.

  14. Contrasting roles of donor and recipient TGFB1 and IFNG gene polymorphic variants in chronic kidney transplant rejection.

    Science.gov (United States)

    Coelho, Verônica Porto Carreiro de Vasconcellos; Ioschpe, Rafael; Caldas, Cristina; Spadafora-Ferreira, Monica; Fonseca, João Americo; Cardoso, Maria Regina Alves; Palacios, Selma Aliotti; Kalil, Jorge; Goldberg, Anna Carla

    2011-03-01

    To assess the long-term impact (minimum of 3 years follow-up) of polymorphisms in cytokine genes in donor:recipient pairs on the results of the transplant. We compared genetic cytokine polymorphisms and the primary factors of risk for the development of chronic rejection in paired groups of renal transplant patients with and without chronic allograft nephropathy [CAN]. Multivariate analysis indicated that the presence of the high-production TT genotype (codon 10) of the transforming growth factor beta-1 (TGFB1) was protective in receptors (p=0.017), contrasting with the increased risk when present in donor samples (p=0.049). On the other hand, in the case of the gamma interferon studied, the greater frequency of the high production allele was protective in the analysis of the donor group (p=0.013), increasing the risk of chronic nephropathy of the allograft when present in the recipients (p=0.036). Our results highlight the importance of TGFB1 genotyping in donors, and indicate that polymorphisms in the gene of this cytokine in donor cells might contribute to the development of chronic allograft nephropathy.

  15. Pre-transplant donor-specific T-cell alloreactivity is strongly associated with early acute cellular rejection in kidney transplant recipients not receiving T-cell depleting induction therapy.

    Directory of Open Access Journals (Sweden)

    Elena Crespo

    Full Text Available Preformed T-cell immune-sensitization should most likely impact allograft outcome during the initial period after kidney transplantation, since donor-specific memory T-cells may rapidly recognize alloantigens and activate the effector immune response, which leads to allograft rejection. However, the precise time-frame in which acute rejection is fundamentally triggered by preformed donor-specific memory T cells rather than by de novo activated naïve T cells is still to be established. Here, preformed donor-specific alloreactive T-cell responses were evaluated using the IFN-γ ELISPOT assay in a large consecutive cohort of kidney transplant patients (n = 90, to assess the main clinical variables associated with cellular sensitization and its predominant time-frame impact on allograft outcome, and was further validated in an independent new set of kidney transplant recipients (n = 67. We found that most highly T-cell sensitized patients were elderly patients with particularly poor HLA class-I matching, without any clinically recognizable sensitizing events. While one-year incidence of all types of biopsy-proven acute rejection did not differ between T-cell alloreactive and non-alloreactive patients, Receiver Operating Characteristic curve analysis indicated the first two months after transplantation as the highest risk time period for acute cellular rejection associated with baseline T-cell sensitization. This effect was particularly evident in young and highly alloreactive individuals that did not receive T-cell depletion immunosuppression. Multivariate analysis confirmed preformed T-cell sensitization as an independent predictor of early acute cellular rejection. In summary, monitoring anti-donor T-cell sensitization before transplantation may help to identify patients at increased risk of acute cellular rejection, particularly in the early phases after kidney transplantation, and thus guide decision-making regarding the use of induction

  16. Association Between Donor MBL Promoter Haplotype and Graft Survival and the Development of BOS After Lung Transplantation

    NARCIS (Netherlands)

    Munster, Janna M.; van der Bij, Wim; Breukink, Myrte B.; van der Steege, Gerrit; Zuurman, Mike W.; Hepkema, Bouke G.; Verschuuren, Erik A. M.; van Son, Willem J.; Seelen, Marc A. J.

    2008-01-01

    Background. Lung transplantation is a well accepted therapy for end-stage lung disease, despite high mortality rates. Mortality after transplantation is mainly caused by allograft failure in the first years after transplantation. Mannose binding lectin (MBL), a recognition molecule of innate

  17. Metalloproteinase Profiling in Lung Transplant Recipients With Good Outcome and Bronchiolitis Obliterans Syndrome

    NARCIS (Netherlands)

    Heijink, Irene H.; Rozeveld, Dennie; van der Heide, Sicco; Bij, van der Wim; Bischoff, Rainer; Oosterhout, van Antoon J,; van der Toorn, Marco

    Background. Bronchiolitis obliterans syndrome (BOS), the major cause of death on lung transplantation, is characterized by bronchiolar inflammation and tissue remodeling. Matrix metalloproteinases (MMPs) have been implicated in these processes, although it is still unclear whether MMP activity and

  18. First Report of Lung Transplantation in a Patient With Active Pulmonary Mycobacterium simiae Infection

    DEFF Research Database (Denmark)

    Qvist, T; Katzenstein, Terese Lea; Lillebaek, T

    2013-01-01

    bilateral lung transplantation for end-stage idiopathic bronchiectasis and chronic M simiae infection. The disease proved manageable on a regimen of clarithromycin, moxifloxacin, and cotrimoxazole with a successful outcome 1-year posttransplantation. There is increasing evidence that nontuberculous...

  19. Donor Specific Anti-HLA Antibodies with Antibody Mediated Rejection and Long-term Outcomes Following Heart Transplantation

    Science.gov (United States)

    Clerkin, Kevin J.; Farr, Maryjane A.; Restaino, Susan W.; Zorn, Emmanuel; Latif, Farhana; Vasilescu, Elena R.; Marboe, Charles C.; Colombo, Paolo C.; Mancini, Donna M.

    2017-01-01

    Introduction Donor specific anti-HLA antibodies (DSA) are common following heart transplantation and are associated with rejection, cardiac allograft vasculopathy (CAV), and mortality. Currently a non-invasive diagnostic test for pathologic AMR (pAMR) does not exist. Methods 221 consecutive adult patients underwent heart transplantation from January 1st, 2010 through August 31th, 2013 and followed through October 1st, 2015. The primary objective was to determine whether the presence of DSA could detect AMR at the time of pathologic diagnosis. Secondary analyses included the association of DSA (stratified by MHC Class and de-novo status) during AMR with new graft dysfunction, graft loss (mortality or retransplantation), and development of CAV. Results During the study period 69 individual patients (31.2%) had DSA (24% had de-novo DSA) and there were 74 episodes of pAMR in 38 unique patients. The sensitivity of DSA at any MFI to detect concurrent pAMR was only 54.3%. The presence of any DSA during pAMR increased the odds of graft dysfunction (OR 5.37, 95% CI 1.34–21.47, p=0.018), adjusting for age, gender, and timing of AMR. Circulating Class II DSA after transplantation increased the risk of future pAMR (HR 2.97, 95% CI 1.31–6.73, p=0.009). Patients who developed de-novo Class II DSA had a 151% increase in risk of graft loss (contingent on 30-day survival) compared with those who did not have DSA (95% CI 1.11–5.69, p=0.027). Conclusions DSA were inadequate to diagnose pAMR, but Class II DSA provided prognostic information regarding future pAMR, graft dysfunction with pAMR, and graft loss. PMID:27916323

  20. Single-Lung Transplant Results in Position Dependent Changes in Regional Ventilation: An Observational Case Series Using Electrical Impedance Tomography

    Directory of Open Access Journals (Sweden)

    Kollengode Ramanathan

    2016-01-01

    Full Text Available Background. Lung transplantation is the optimal treatment for end stage lung disease. Donor shortage necessitates single-lung transplants (SLT, yet minimal data exists regarding regional ventilation in diseased versus transplanted lung measured by Electrical Impedance Tomography (EIT. Method. We aimed to determine regional ventilation in six SLT outpatients using EIT. We assessed end expiratory volume and tidal volumes. End expiratory lung impedance (EELI and Global Tidal Variation of Impedance were assessed in supine, right lateral, left lateral, sitting, and standing positions in transplanted and diseased lungs. A mixed model with random intercept per subject was used for statistical analysis. Results. EELI was significantly altered between diseased and transplanted lungs whilst lying on right and left side. One patient demonstrated pendelluft between lungs and was therefore excluded for further comparison of tidal variation. Tidal variation was significantly higher in the transplanted lung for the remaining five patients in all positions, except when lying on the right side. Conclusion. Ventilation to transplanted lung is better than diseased lung, especially in lateral positions. Positioning in patients with active unilateral lung pathologies will be implicated. This is the first study demonstrating changes in regional ventilation, associated with changes of position between transplanted and diseased lung.

  1. Growing experience with extracorporeal membrane oxygenation as a bridge to lung transplantation.

    Science.gov (United States)

    Shafii, Alexis E; Mason, David P; Brown, Chase R; Vakil, Nakul; Johnston, Douglas R; McCurry, Kenneth R; Pettersson, Gosta B; Murthy, Sudish C

    2012-01-01

    Extracorporeal membrane oxygenation (ECMO) is rarely used as a bridge to lung transplantation (BTT) because of its associated morbidity and mortality. However, recent advancements in perfusion technology and critical care have revived interest in this application of ECMO. We retrospectively reviewed our utilization of ECMO as BTT and evaluated our early and midterm results. Nineteen patients were placed on ECMO with the intent to transplant of which 14 (74%) were successfully transplanted. Early and midterm survival of transplanted patients was 75% (1 year) and 63% (3 years), respectively, with the most favorable results observed in interstitial lung disease patients supported in the venovenous configuration. Extracorporeal membrane oxygenation-bridged transplant survival rates were equivalent to nonbridged recipients, but early morbidity and mortality are high and the failure to bridge to transplant is significant. Overall, successfully bridged patients can derive a tangible benefit, albeit with considerable consumption of resources.

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

    DEFF Research Database (Denmark)

    Nysom, K; Holm, K; Hesse, B

    1996-01-01

    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...... 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....

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

    Science.gov (United States)

    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. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  4. The role of mTOR inhibitors in the prevention of organ rejection in adult liver transplant patients: a focus on everolimus

    Directory of Open Access Journals (Sweden)

    Casanovas T

    2014-06-01

    Full Text Available Teresa Casanovas Liver Transplant Unit, Bellvitge University Hospital, Barcelona, Spain Abstract: Liver transplantation remains the therapy of choice for patients with end-stage liver disease and in selected cases of hepatocellular carcinoma. While short-term allograft survival has improved significantly in recent years, there has been little improvement in long-term survival after liver transplantation. A growing body of evidence on factors influencing the long-term outcomes and the safety profiles of existing immunosuppressive agents after liver transplant points to a need to continue searching for alternative strategies. The calcineurin inhibitors (CNIs (cyclosporine and tacrolimus currently represent the backbone of most immunosuppressor regimens. They have had a revolutionary effect on the overall success of transplantation, as is reflected in greatly reduced rates of acute rejection. However, the CNIs have significant toxicities that produce renal dysfunction, cardiovascular disease, and other unwanted effects, such as malignancies. The recognition of these risk factors has sparked interest in regimens that limit exposure to CNIs. Nowadays, the use of immunosuppressive drugs with different mechanisms of action, which allow for a reduction or avoidance of CNIs, is common. Everolimus, which belongs to the mammalian target-of-rapamycin inhibitor family and is best known for its use in kidney and heart transplantation, has recently been approved for liver transplantation. This overview discusses the emerging evidence on the role of everolimus in the prevention of rejection after liver transplantation, in de novo transplants, conversion regimens, or as a rescue therapy. In addition, some of the most relevant and current clinical problems related to everolimus in this field are discussed. Keywords: everolimus, mTOR inhibitors, tacrolimus, liver transplant, cyclosporine, renal impairment

  5. Tsukamurella tyrosinosolvens - An unusual case report of bacteremic pneumonia after lung transplantation

    Directory of Open Access Journals (Sweden)

    Dromer Claire

    2009-11-01

    Full Text Available Abstract Background Lung transplant recipients have an increased risk for actinomycetales infection secondary to immunosuppressive regimen. Case presentation A case of pulmonary infection with bacteremia due to Tsukamurella tyrosinosolvens in a 54-year old man who underwent a double lung transplantation four years previously is presented. Conclusion The identification by conventional biochemical assays was unsuccessful and hsp gene sequencing was used to identify Tsukamurella tyrosinosolvens.

  6. Lung Transplantation in Cystic Fibrosis and the Impact of Extracorporeal Circulation.

    Science.gov (United States)

    Jauregui, Alberto; Deu, Maria; Romero, Laura; Roman, Antonio; Moreno, Antonio; Armengol, Manuel; Solé, Juan

    2018-03-10

    Lung disease is the major cause of death among cystic fibrosis (CF) patients, affecting 80% of the population. The impact of extracorporeal circulation (ECC) during transplantation has not been fully clarified. This study aimed to evaluate the outcomes of lung transplantation for CF in a single center, and to assess the impact of ECC on survival. We performed a retrospective observational study of all trasplanted CF patients in a single center between 1992 and 2011. During this period, 64 lung transplantations for CF were performed. Five- and 10-year survival of trasplanted patients was 56.7% and 41.3%, respectively. Pre-transplantation supplemental oxygen requirements and non-invasive mechanical ventilation (NIMV) do not seem to affect survival (P=.44 and P=.63, respectively). Five- and 10-year survival among patients who did not undergo ECC during transplantation was 75.69% and 49.06%, respectively, while in those did undergo ECC during the procedure, 5- and 10-year survival was 34.14% and 29.87%, respectively (P=.001). PaCO 2 is an independent risk factor for the need for ECC. The survival rates of CF patients undergoing lung transplantation in our hospital are similar to those described in international registries. Survival is lower among patients receiving ECC during the procedure. PaCO 2 is a risk factor for the need for ECC during lung transplantation. Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Effects of early surfactant treatment persisting for one week after lung transplantation in rats

    NARCIS (Netherlands)

    Erasmus, ME; Hofstede, GJH; Petersen, AH; Haagsman, HP; Oetomo, SB; Prop, J

    We investigated whether pulmonary surfactant in rat lung transplants recovered during the first week post-transplantation, along with symptoms of the reimplantation response, and whether this recovery was affected by early surfactant treatment. The severity of pulmonary injury was varied by

  8. Adherence to immunosuppression in adult lung transplant recipients : Prevalence and risk factors

    NARCIS (Netherlands)

    Bosma, Otto H.; Vermeulen, Karin M.; Verschuuren, Erik A.; Erasmus, Michiel E.; van der Bij, Wim

    2011-01-01

    BACKGROUND: Adherence to medication is a favourable with regard to survival after kidney, heart and liver transplantation. Little is known about adherence to medication in lung transplant recipients. To determine the prevalence of adherence and identify risk factors of non-adherence (NA) we

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

    NARCIS (Netherlands)

    Vermeulen, KM; van der Bij, W; Erasmus, ME; Duiverman, EJ; Koeter, GH; TenVergert, EM

    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 CIF patients

  10. P. aeruginosa in the paranasal sinuses and transplanted lungs have similar adaptive mutations as isolates from chronically infected CF lungs

    DEFF Research Database (Denmark)

    Ciofu, Oana; Johansen, Helle Krogh; Aanaes, Kasper

    2013-01-01

    BACKGROUND: Pseudomonas aeruginosa cells are present as biofilms in the paranasal sinuses and the lungs of chronically infected cystic fibrosis (CF) patients. Since different inflammatory responses and selective antibiotic pressures are acting in the sinuses compared with the lungs, we compared...... the adaptive profiles of mucoid and non-mucoid isolates from the two locations. METHODS: We studied the genetic basis of phenotypic diversification and gene expression profiles in sequential lung and sinus P. aeruginosa isolates from four chronically infected CF patients, including pre- and post-lung...... transplantation isolates. RESULTS: The same phenotypes caused by similar mutations and similar gene expression profiles were found in mucoid and non-mucoid isolates from the paranasal sinuses and from the lungs before and after transplantation. CONCLUSION: Bilateral exchange of P. aeruginosa isolates between...

  11. Ethical and equity issues in lung transplantation and lung volume reduction surgery.

    Science.gov (United States)

    Glanville, A R

    2006-01-01

    New medical and scientific disciplines are often developed in haste with rampant enthusiasm and scant regard for the balance between action and thoughtful deliberation. Driven by the desire to prolong life and provide a better quality of life for desperately sick individuals, the twin modalities of lung transplantation and lung volume reduction therapy have only just reached their majority. Both are invested with the capacity to help and to harm so it is right to consider carefully their ethical and equitable distribution. Much has been learned in the last 20 years to assist in these deliberations. First, how can we ensure equity of access to transplant services and equality of outcomes? How do we balance resource allocation of a precious and scarce resource with individual recipient needs? Does the concept of distributive justice prevail in our daily work in this field? How do we honour the donor and their family? How do we as practitioners avoid ethical dilemmas related to personal bias and justifiable reward for services rendered? Finally, how do we learn to incorporate ethical forethought and planning guided by experts in the area into everyday behaviour?

  12. Therapeutic effect of 15-deoxyspergualin on acute graft rejection detected by 31P nuclear magnetic resonance spectrography, and its effect on rat heart transplantation

    International Nuclear Information System (INIS)

    Suzuki, S.; Kanashiro, M.; Watanabe, H.; Amemiya, H.

    1988-01-01

    We investigated the effect of 15-deoxyspergualin (DSG) on graft rejection, starting administration at the onset of rejection and on the induction of immunologic unresponsiveness. Hearts from WKAH rats were transplanted into the neck of ACI rats. The energy metabolism of the grafted hearts was followed by 31 P nuclear magnetic resonance spectroscopy. The day that energy metabolism started to fall was defined as the onset of rejection, and intraperitoneal administration of DSG was initiated at 5 mg/kg/day for 15 days from this day. The grafted heart arrested in 2 of 10 rats 9 and 11 days after transplantation, respectively, but the remaining 8 recovered from rejection and 5 of them showed evidence of immunologic unresponsiveness. Of 10 rats treated with DSG from the day of transplantation, only 1 rat showed evidence of unresponsiveness. The initiation of DSG treatment from the onset of rejection resulted in a higher percentage of induction of unresponsiveness. Therefore, DSG was considered to specifically inhibit lymphocyte clone expansion at the onset of rejection. Spleen cells obtained from recipients 7-10 days after the end of DSG treatment were administered to syngeneic ACI rats grafted with WKAH hearts. Graft survival was significantly prolonged, but long-term unresponsiveness could not be transferred. However, immunologic unresponsiveness could be adoptively transferred in 3 of 5 rats receiving spleen cells from syngeneic rats that had recovered from rejection after DSG treatment and had acquired long-term unresponsiveness. These results suggest that suppressor cells are resistant to DSG and are spared and participate in the maintenance of immunologic unresponsiveness

  13. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation.

    Science.gov (United States)

    Sayah, David M; Mallavia, Beñat; Liu, Fengchun; Ortiz-Muñoz, Guadalupe; Caudrillier, Axelle; DerHovanessian, Ariss; Ross, David J; Lynch, Joseph P; Saggar, Rajan; Ardehali, Abbas; Ware, Lorraine B; Christie, Jason D; Belperio, John A; Looney, Mark R

    2015-02-15

    Primary graft dysfunction (PGD) causes early mortality after lung transplantation and may contribute to late graft failure. No effective treatments exist. The pathogenesis of PGD is unclear, although both neutrophils and activated platelets have been implicated. We hypothesized that neutrophil extracellular traps (NETs) contribute to lung injury in PGD in a platelet-dependent manner. To study NETs in experimental models of PGD and in lung transplant patients. Two experimental murine PGD models were studied: hilar clamp and orthotopic lung transplantation after prolonged cold ischemia (OLT-PCI). NETs were assessed by immunofluorescence microscopy and ELISA. Platelet activation was inhibited with aspirin, and NETs were disrupted with DNaseI. NETs were also measured in bronchoalveolar lavage fluid and plasma from lung transplant patients with and without PGD. NETs were increased after either hilar clamp or OLT-PCI compared with surgical control subjects. Activation and intrapulmonary accumulation of platelets were increased in OLT-PCI, and platelet inhibition reduced NETs and lung injury, and improved oxygenation. Disruption of NETs by intrabronchial administration of DNaseI also reduced lung injury and improved oxygenation. In bronchoalveolar lavage fluid from human lung transplant recipients, NETs were more abundant in patients with PGD. NETs accumulate in the lung in both experimental and clinical PGD. In experimental PGD, NET formation is platelet-dependent, and disruption of NETs with DNaseI reduces lung injury. These data are the first description of a pathogenic role for NETs in solid organ transplantation and suggest that NETs are a promising therapeutic target in PGD.

  14. Early diagnosis of fungal infections in lung transplant recipients, colonization versus invasive disease?

    Science.gov (United States)

    Herrera, Sabina; Husain, Shahid

    2018-05-21

    The diagnosis of invasive aspergillosis remains challenging in solid organ transplants in general, and in lung transplant recipients, in particular, because of colonization. Lung transplant recipients may be over treated with antifungal drugs because of the lack of appropriate diagnostic tools. A review of the new developments of diagnostic tools and whether this help distinguishing colonization from invasive disease is presented. Efforts are being made to develop new tools that will allow us to identify which patients will develop IPA, and those who will be able to control the disease.

  15. Median sternotomy for double lung transplantation with cardiopulmonary bypass in seven consecutive patients

    DEFF Research Database (Denmark)

    Kohno, Mitsutomo; Steinbrüchel, Daniel A

    2012-01-01

    We describe our technique of using median sternotomy to perform double lung transplantations with cardiopulmonary bypass. By sparing the respiratory muscles, median sternotomy is probably less invasive and preserves lung function. Furthermore, it causes less long-term discomfort than intercostal...

  16. Lung transplantation for bronchiolitis obliterans syndrome after allo-SCT.

    Science.gov (United States)

    Holm, A M; Riise, G C; Hansson, L; Brinch, L; Bjørtuft, O; Iversen, M; Simonsen, S; Fløisand, Y

    2013-05-01

    Chronic GVHD (cGVHD) associated bronchiolitis obliterans syndrome (BOS) is a serious complication after allo-SCT, and lung transplantation (LTx) may be the ultimate treatment option. To evaluate this treatment, data on all patients with LTx after allo-SCT ever performed in Sweden, Norway, Denmark and Finland were recorded and compared with survival data from the Scandiatransplant registry. In total, LTx after allo-SCT had been performed in 13 patients. Allo-SCT was done because of AML (n=6), CML (n=3), ALL (n=2), immunodeficiency (n=1) and aplastic anemia (n=1). All developed clinical cGVHD, with median interval from allo-SCT to LTx of 8.2 (0.7-16) years. Median age at LTx was 34 (16-55) years, and the median postoperative observation time was 4.2 (0.1-15) years. Two patients died, one due to septicemia, the other of relapsing leukemia, after 2 and 14 months, respectively. Four developed BOS, one of these was retransplanted. The survival did not significantly differ from the survival in matched LTx controls, being 90% 1 year and 75% 5 years after LTx compared with 85% and 68% in the controls. We therefore suggest that LTx may be considered in carefully selected patients with BOS due to cGVHD after allo-SCT.

  17. A shift in the collagen V antigenic epitope leads to T helper phenotype switch and immune response to self-antigen leading to chronic lung allograft rejection.

    Science.gov (United States)

    Tiriveedhi, V; Angaswamy, N; Brand, D; Weber, J; Gelman, A G; Hachem, R; Trulock, E P; Meyers, B; Patterson, G; Mohanakumar, T

    2012-01-01

    Immune responses to human leucocyte antigen (HLA) and self-antigen collagen V (Col-V) have been proposed in the pathogenesis of chronic rejection (bronchiolitis obliterans syndrome, BOS) following human lung transplantation (LTx). In this study, we defined the role for the shift in immunodominant epitopes of Col-V in inducing T helper phenotype switch leading to immunity to Col-V and BOS. Sera and lavage from BOS(+) LTx recipients with antibodies to Col-V were analysed. Two years prior to BOS, patients developed antibodies to both Col-V,α1(V) and α2(V) chains. However, at clinical diagnosis of BOS, antibodies became restricted to α1(V). Further, lung biopsy from BOS(+) patients bound to antibodies to α1(V), indicating that these epitopes are exposed. Fourteen Col-V peptides [pep1-14, pep1-4 specific to α1(V), pep5-8 to α1,2(V) and pep9-14 to α2(V)] which bind to HLA-DR4 and -DR7, demonstrated that prior to BOS, pep 6, 7, 9, 11 and 14 were immunodominant and induced interleukin (IL)-10. However, at BOS, the response switched to pep1, 4 and 5 and induced interferon (IFN)-γ and IL-17 responses, but not IL-10. The T helper (Th) phenotype switch is accompanied by decreased frequency of regulatory T cells (T(regs) ) in the lavage. LTx recipients with antibodies to α1(V) also demonstrated increased matrix metalloproteinase (MMP) activation with decreased MMP inhibitor, tissue inhibitor of metalloproteinase (TIMP), suggesting that MMP activation may play a role in the exposure of new Col-V antigenic epitopes. We conclude that a shift in immunodominance of self-antigenic determinants of Col-V results in induction of IFN-γ and IL-17 with loss of tolerance leading to autoimmunity to Col-V, which leads to chronic lung allograft rejection. © 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.

  18. Late acute humoral rejection in low-risk renal transplant recipients induced with an interleukin-2 receptor antagonist and maintained with standard therapy: preliminary communication.

    Science.gov (United States)

    Morales, J; Contreras, L; Zehnder, C; Pinto, V; Elberg, M; Araneda, S; Herzog, C; Calabran, L; Aguiló, J; Ferrario, M; Buckel, E; Fierro, J A

    2011-01-01

    Low-risk renal transplant recipients treated with standard immunosuppressive therapy including interleukin-2 receptor (IL-2R) antagonist show a low incidence of early rejection episodes but few reports have examined the incidence and severity of late rejection processes. This study evaluated retrospectively cellular and antibody-mediated rejection (AMR) among 42 recipients selected because they showed low panel-reactive-antibodies, short cold ischemia time, no delayed graft function, and therapy including basiliximab (Simulect) induction. The mean observation time was 6.6 years. Sixty-seven percent of donors were deceased. Ten-year patient and death-censored graft survivals were 81% and 78%, respectively. Seven patients lost their kidneys due to nonimmunologic events. The seven recipients who experienced cellular rejection episodes during the first posttransplant year had them reversed with steroids. Five patients displayed late acute AMR causing functional deterioration in four cases including 1 graft loss. De novo sensitization occurred in 48% of recipients including patients without clinical rejection. In conclusion, long-term follow-up of kidney transplant recipients selected by a low immunologic risk showed a persistent risk of de novo sensitization evolving to acute AMR in 11% of cases. Although immunologic events were related to late immunosuppressive reduction, most graft losses were due to nonimmunologic factors. Copyright © 2011 Elsevier Inc. All rights reserved.

  19. C1 Inhibitor in Acute Antibody-Mediated Rejection Nonresponsive to Conventional Therapy in Kidney Transplant Recipients: A Pilot Study.

    Science.gov (United States)

    Viglietti, D; Gosset, C; Loupy, A; Deville, L; Verine, J; Zeevi, A; Glotz, D; Lefaucheur, C

    2016-05-01

    Complement inhibitors have not been thoroughly evaluated in the treatment of acute antibody-mediated rejection (ABMR). We performed a prospective, single-arm pilot study to investigate the potential effects and safety of C1 inhibitor (C1-INH) Berinert added to high-dose intravenous immunoglobulin (IVIG) for the treatment of acute ABMR that is nonresponsive to conventional therapy. Kidney recipients with nonresponsive active ABMR and acute allograft dysfunction were enrolled between April 2013 and July 2014 and received C1-INH and IVIG for 6 months (six patients). The primary end point was the change in eGFR at 6 months after inclusion (M+6). Secondary end points included the changes in histology and DSA characteristics and adverse events as evaluated at M+6. All patients showed an improvement in eGFR between inclusion and M+6: from 38.7 ± 17.9 to 45.2 ± 21.3 mL/min/1.73 m(2) (p = 0.0277). There was no change in histological features, except a decrease in the C4d deposition rate from 5/6 to 1/6 (p = 0.0455). There was a change in DSA C1q status from 6/6 to 1/6 positive (p = 0.0253). One deep venous thrombosis was observed. In a secondary analysis, C1-INH patients were compared with a similar historical control group (21 patients). C1-INH added to IVIG is safe and may improve allograft function in kidney recipients with nonresponsive acute ABMR. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

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

    Directory of Open Access Journals (Sweden)

    Nathan C. Bahr

    2015-01-01

    Full Text Available 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.

  1. Lung transplant recipients holding companion animals: impact on physical health and quality of life.

    Science.gov (United States)

    Irani, S; Mahler, C; Goetzmann, L; Russi, E W; Boehler, A

    2006-02-01

    Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.

  2. Pulmão e transplante renal Lung and renal transplantation

    Directory of Open Access Journals (Sweden)

    Patrícia Caetano Mota

    2009-11-01

    diagnostic and therapeutic challenge. Aim: To evaluate patients admitted to the Renal Transplant Unit (RTU of Hospital de S. João with respiratory disease. Subject and methods: We performed a retrospective study of all patients admitted to RTU with respiratory disease during a period of 12 months. Results: Thirty-six patients were included. Mean age 55.2 (±13.4 years; 61.1% male. Immunosuppressive agents most frequently used were prednisolone and mycophenolate mofetil associated with ciclosporin (38.9% or tacrolimus (22.2% or rapamycin (13.9%. Thirty-one patients (86.1% presented infectious respiratory disease. In this group the main diagnoses were 23 (74.2% pneumonias, 5 (16.1% opportunistic infections, 2 (6.5% tracheobronchitis, and 1 case (3.2% of lung abscesses. Microbiological agent was identified in 7 cases (22.6%. Five patients (13.9% presented rapamycin-induced lung disease. Fibreoptic bronchoscopy was performed in 15 patients (41.7%, diagnostic in 10 cases (66.7%. Mean hospital stay was 17.1 (±18.5 days and no related death was observed. Conclusion: Respiratory infections were the main complications in these patients. Drug-induced lung disease implies recognition of its features and a rigorous monitoring of drug serum levels. A more invasive diagnostic approach was determinant in the choice of an early and more specific therapy.

  3. Donor Smoking and Older Age Increases Morbidity and Mortality After Lung Transplantation

    DEFF Research Database (Denmark)

    Schultz, H H; Møller, C H; Zemtsovski, M

    2017-01-01

    survival as well as CLAD-free survival was significantly lower with donors ≥55 years. CONCLUSIONS: Donor smoking history and older donor age impact lung function, mortality, and CLAD-free survival after transplantation. Because of a shortage of organs, extended donor criteria may be considered while taking......BACKGROUND: The lack of lung transplant donors has necessitated the use of donors with a smoking history and donors of older age. We have evaluated the effects of donor smoking history and age on recipient morbidity and mortality with baseline values of pulmonary function and survival free...... of chronic lung allograft dysfunction (CLAD) as morbidity variables. METHODS: This is a retrospective analysis of 588 consecutive lung transplant recipients and their corresponding 454 donors. Donors were divided into three groups: group 1 included smokers, group 2 nonsmokers, and group 3 had unknown smoking...

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

    Science.gov (United States)

    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. Copyright © 2013 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.

  5. Expression of a Chimeric Antigen Receptor Specific for Donor HLA Class I Enhances the Potency of Human Regulatory T Cells in Preventing Human Skin Transplant Rejection.

    Science.gov (United States)

    Boardman, D A; Philippeos, C; Fruhwirth, G O; Ibrahim, M A A; Hannen, R F; Cooper, D; Marelli-Berg, F M; Watt, F M; Lechler, R I; Maher, J; Smyth, L A; Lombardi, G

    2017-04-01

    Regulatory T cell (Treg) therapy using recipient-derived Tregs expanded ex vivo is currently being investigated clinically by us and others as a means of reducing allograft rejection following organ transplantation. Data from animal models has demonstrated that adoptive transfer of allospecific Tregs offers greater protection from graft rejection compared to polyclonal Tregs. Chimeric antigen receptors (CAR) are clinically translatable synthetic fusion proteins that can redirect the specificity of T cells toward designated antigens. We used CAR technology to redirect human polyclonal Tregs toward donor-MHC class I molecules, which are ubiquitously expressed in allografts. Two novel HLA-A2-specific CARs were engineered: one comprising a CD28-CD3ζ signaling domain (CAR) and one lacking an intracellular signaling domain (ΔCAR). CAR Tregs were specifically activated and significantly more suppressive than polyclonal or ΔCAR Tregs in the presence of HLA-A2, without eliciting cytotoxic activity. Furthermore, CAR and ΔCAR Tregs preferentially transmigrated across HLA-A2-expressing endothelial cell monolayers. In a human skin xenograft transplant model, adoptive transfer of CAR Tregs alleviated the alloimmune-mediated skin injury caused by transferring allogeneic peripheral blood mononuclear cells more effectively than polyclonal Tregs. Our results demonstrated that the use of CAR technology is a clinically applicable refinement of Treg therapy for organ transplantation. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  6. Predictive equations for lung volumes from computed tomography for size matching in pulmonary transplantation.

    Science.gov (United States)

    Konheim, Jeremy A; Kon, Zachary N; Pasrija, Chetan; Luo, Qingyang; Sanchez, Pablo G; Garcia, Jose P; Griffith, Bartley P; Jeudy, Jean

    2016-04-01

    Size matching for lung transplantation is widely accomplished using height comparisons between donors and recipients. This gross approximation allows for wide variation in lung size and, potentially, size mismatch. Three-dimensional computed tomography (3D-CT) volumetry comparisons could offer more accurate size matching. Although recipient CT scans are universally available, donor CT scans are rarely performed. Therefore, predicted donor lung volumes could be used for comparison to measured recipient lung volumes, but no such predictive equations exist. We aimed to use 3D-CT volumetry measurements from a normal patient population to generate equations for predicted total lung volume (pTLV), predicted right lung volume (pRLV), and predicted left lung volume (pLLV), for size-matching purposes. Chest CT scans of 400 normal patients were retrospectively evaluated. 3D-CT volumetry was performed to measure total lung volume, right lung volume, and left lung volume of each patient, and predictive equations were generated. The fitted model was tested in a separate group of 100 patients. The model was externally validated by comparison of total lung volume with total lung capacity from pulmonary function tests in a subset of those patients. Age, gender, height, and race were independent predictors of lung volume. In the test group, there were strong linear correlations between predicted and actual lung volumes measured by 3D-CT volumetry for pTLV (r = 0.72), pRLV (r = 0.72), and pLLV (r = 0.69). A strong linear correlation was also observed when comparing pTLV and total lung capacity (r = 0.82). We successfully created a predictive model for pTLV, pRLV, and pLLV. These may serve as reference standards and predict donor lung volume for size matching in lung transplantation. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  7. Preventing acute rejection, Epstein-Barr virus infection, and posttransplant lymphoproliferative disorders after kidney transplantation: Use of aciclovir and mycophenolate mofetil in a steroid-free immunosuppressive protocol

    DEFF Research Database (Denmark)

    Birkeland, S.A.; Andersen, H.K.; Hamilton-Dutoit, Stephen Jacques

    1999-01-01

    Background: A widely held view is that any increase in the potency of an immunosuppressive agent will lead to an increase in infection and malignancy, such as life-threatening Epstein-Barr virus (EBV) induced posttransplant lymphoproliferative disorders (PTLD), We tested this paradigm by studying......; the effect of adding mofetil to a steroid-free protocol under cover of high-dose aciclovir prophylaxis on the number of acute rejections, EBV infections and PTLDs after kidney transplantation. Methods: EBV serology was performed in 267 consecutive renal transplantations (1990-1997), All were treated...

  8. Acute Antibody-Mediated Rejection in Presence of MICA-DSA and Successful Renal Re-Transplant with Negative-MICA Virtual Crossmatch.

    Directory of Open Access Journals (Sweden)

    Yingzi Ming

    Full Text Available The presence of donor-specific alloantibodies (DSAs against the MICA antigen results in high risk for antibody-mediated rejection (AMR of a transplanted kidney, especially in patients receiving a re-transplant. We describe the incidence of acute C4d+ AMR in a patient who had received a first kidney transplant with a zero HLA antigen mismatch. Retrospective analysis of post-transplant T and B cell crossmatches were negative, but a high level of MICA alloantibody was detected in sera collected both before and after transplant. The DSA against the first allograft mismatched MICA*018 was in the recipient. Flow cytometry and cytotoxicity tests with five samples of freshly isolated human umbilical vein endothelial cells demonstrated the alloantibody nature of patient's MICA-DSA. Prior to the second transplant, a MICA virtual crossmatch and T and B cell crossmatches were used to identify a suitable donor. The patient received a second kidney transplant, and allograft was functioning well at one-year follow-up. Our study indicates that MICA virtual crossmatch is important in selection of a kidney donor if the recipient has been sensitized with MICA antigens.

  9. Quality of life in caregivers providing care for lung transplant candidates.

    Science.gov (United States)

    Lefaiver, Cheryl A; Keough, Vicki A; Letizia, Marijo; Lanuza, Dorothy M

    2009-06-01

    Caregivers are essential members of the health care team who provide care, valued at more than $250 billion each year, to millions of persons who require assistance with health and daily care. Patients with respiratory diseases who are waiting for a lung transplant are required to have an identified caregiver. The caregivers are rarely studied. To explore the relationships among the health status of caregivers of lung transplant candidates, caregivers' reaction to caregiving, and caregivers' perceived quality of life. This descriptive study examined the quality of life of lung transplant caregivers from a multidimensional perspective. Twenty-nine dyads of lung transplant candidates and their caregivers were recruited from a Midwestern medical center. Data were collected by self-report: caregivers completed the Quality of Life Index, SF-12 health survey, Profile of Mood States-Short Form, and the Caregiver Reaction Assessment. Caregivers reported favorable levels of quality of life, physical health, and mood during the pretransplant waiting phase. However, problem areas for caregivers during this time included fatigue, depression, and the financial impact of the transplant. Data analyses indicated that depression, caregiver general health, impact on finances, and lack of family support had the greatest effect on caregivers' quality of life. Nurses are urged to recognize the role of caregivers in the transplant process, ask about and listen to caregivers' needs, and include caregivers in the plan of care.

  10. The roles of social support and psychological distress in lung transplant candidacy.

    Science.gov (United States)

    Phillips, Kristin M; Burker, Eileen J; White, Hayley C

    2011-09-01

    Social support appears to be an important component in lung transplantation. However, the relationship between social support, psychological distress, and listing status has not been evaluated in lung transplant candidates. To evaluate the relationships between depression, anxiety, and social support in patients with end-stage lung disease being evaluated for transplantation and determine (1) relationships between social support, depression, anxiety, and coping via seeking emotional and instrumental support; (2) whether social support explains a significant proportion of the variance in depression and anxiety; and (3) whether these factors were associated with whether a patient was listed for transplant. For this observational study, patients completed self-report questionnaires after their pretransplant evaluations. Listing status was subsequently obtained from medical records. Participants were patients with end-stage lung disease evaluated for transplantation at a major hospital. Medical Outcomes Study Social Support Survey, COPE Inventory, Beck Depression Inventory, and State-Trait Anxiety Inventory. Social support was associated with depression, anxiety, and seeking support (P values social support explained a significant proportion of the variance in depression (9%), state anxiety (8%), and trait anxiety (7%; all P values anxiety, trait anxiety, or availability of social support. Results highlight the important role that coping via seeking support plays in transplant candidacy.

  11. Extracorporeal membrane oxygenation as a bridge to lung transplantation: A single-center experience in the present era.

    Science.gov (United States)

    Todd, Emily M; Biswas Roy, Sreeja; Hashimi, A Samad; Serrone, Rosemarie; Panchanathan, Roshan; Kang, Paul; Varsch, Katherine E; Steinbock, Barry E; Huang, Jasmine; Omar, Ashraf; Patel, Vipul; Walia, Rajat; Smith, Michael A; Bremner, Ross M

    2017-11-01

    Extracorporeal membrane oxygenation has been used as a bridge to lung transplantation in patients with rapid pulmonary function deterioration. The reported success of this modality and perioperative and functional outcomes are varied. We retrospectively reviewed all patients who underwent lung transplantation at our institution over 1 year (January 1, 2015, to December 31, 2015). Patients were divided into 2 groups depending on whether they required extracorporeal membrane oxygenation support as a bridge to transplant; preoperative characteristics, lung transplantation outcomes, and survival were compared between groups. Of the 93 patients, 12 (13%) received bridge to transplant, and 81 (87%) did not. Patients receiving bridge to transplant were younger, had higher lung allocation scores, had lower functional status, and were more often on mechanical ventilation at listing. Most patients who received bridge to transplant (n = 10, 83.3%) had pulmonary fibrosis. Mean pretransplant extracorporeal membrane oxygenation support was 103.6 hours in duration (range, 16-395 hours). All patients who received bridge to transplant were decannulated immediately after lung transplantation but were more likely to return to the operating room for secondary chest closure or rethoracotomy. Grade 3 primary graft dysfunction within 72 hours was similar between groups. Lung transplantation success and hospital discharge were 100% in the bridge to transplant group; however, these patients experienced longer hospital stays and higher rates of discharge to acute rehabilitation. The 1-year survival was 100% in the bridge to transplant group and 91% in the non-bridge to transplant group (log-rank, P = .24). The 1-year functional status was excellent in both groups. Extracorporeal membrane oxygenation can be used to safely bridge high-acuity patients with end-stage lung disease to lung transplantation with good 30-day, 90-day, and 1-year survival and excellent 1-year functional status

  12. Fungal infection by Mucorales order in lung transplantation: 4 case reports.

    Science.gov (United States)

    Neto, F M F D; Camargo, P C L B; Costa, A N; Teixeira, R H O B; Carraro, R M; Afonso, J E; Campos, S V; Samano, M N; Fernandes, L M; Abdalla, L G; Pêgo-Fernandes, P M

    2014-01-01

    Mucorales is a fungus that causes systemic, highly lethal infections in immunocompromised patients. The overall mortality of pulmonary mucormycosis can reach 95%. This work is a review of medical records of 200 lung transplant recipients between the years of 2003 and 2013, in order to identify the prevalence of Mucorales in the Lung Transplantation service of Heart Institute (InCor), Hospital das Clínicas da Universidade de São Paulo, Brazil, by culture results from bronchoalveolar lavage and necropsy findings. We report 4 cases found at this analyses: 3 in patients with cystic fibrosis and 1 in a patient with bronchiectasis due to Kartagener syndrome. There were 2 unfavorable outcomes related to the presence of Mucorales, 1 by reduction of immunosuppression, another by invasive infection. Another patient died from renal and septic complications from another etiology. One patient was diagnosed at autopsy just 5 days after lung transplantation, with the Mucor inside the pulmonary vein with a precise, well-defined involvement only of donor's segment, leading to previous colonization hypothesis. There are few case reports of Mucorales infection in lung transplantation in the literature. Surveillance for the presence of Mucor can lead to timely fungal treatment and reduce morbidity and mortality in the immunocompromised patients, especially lung transplant recipients. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Combined HLA matched limbal stem cells allograft with amniotic membrane transplantation as a prophylactic surgical procedure to prevent corneal graft rejection after penetrating keratoplasty: case report

    Directory of Open Access Journals (Sweden)

    Paolo Capozzi

    2014-09-01

    Full Text Available Purpose. To determine if the use of combined HLA matched limbal stem cells allograft with amniotic membrane transplantation (AMT is a safe and effective prophylactic surgical procedure to prevent corneal graft after penetrating keratoplasty (PK. Methods. We report the case of a 17 years old patient with a history of congenital glaucoma, trabeculectomy and multiple corneal graft rejections, presenting total limbal cell deficiency. To reduce the possibility of graft rejection in the left eye after a new PK, a two step procedure was performed. At first the patient underwent a combined HLA matched limbal stem cells allograft (LAT and AMT and then, 10 months later, a new PK. Results. During 12 months of follow-up, the corneal graft remained stable and smooth, with no sign of graft rejection. Conclusions. In our patient, the prophylactic use of LAT from HLA-matched donors and AMT before PK, may result in a better prognosis of corneal graft survival.

  14. Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

    Science.gov (United States)

    Revell, M P; Lewis, M E; Llewellyn-Jones, C G; Wilson, I C; Bonser, R S

    2000-12-01

    We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

  15. Hyperosmolar nonketotic hyperglycemic coma induced by methylprednisolone pulse therapy for acute rejection after liver transplantation: a case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Zhou J

    2014-12-01

    Full Text Available Jian Zhou,* Weiqiang Ju,* Xiaopeng Yuan, Xiaofeng Zhu, Dongping Wang, Xiaoshun HeOrgan Transplant Center, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China *These authors contributed equally to this work Abstract: Hyperosmolar nonketotic hyperglycemic coma (HNKHC is a serious, rare complication induced by methylprednisolone (MP pulse therapy for acute rejection after orthotopic liver transplantation (OLT. Herein, we report an unusual case of a 58-year-old woman who experienced acute rejection at 30 months after OLT, only one case in which HNKHC resulted in MP pulse therapy for acute rejection in all 913 recipients in our center. The general morbidity of HNKHC was 1.09‰ in this study. HNKHC is characterized by rapid onset, rapid progression, and a lack of specific clinical manifestations. High-dose MP management was a clear risk factor. The principle of treatment included rapid rehydration, low-dose insulin infusion, and correcting disorders of electrolytes and acidosis. In conclusion, clinicians considering MP pulse therapy after OLT should be alert to the occurrence of HNKHC. Keywords: liver transplantation, complications, hyperosmolar nonketotic hyperglycemic coma, methylprednisolone pulse therapy, principle of treatment

  16. Gastroesophageal reflux symptoms are not sufficient to guide esophageal function testing in lung transplant candidates.

    Science.gov (United States)

    Posner, S; Zheng, J; Wood, R K; Shimpi, R A; Hartwig, M G; Chow, S-C; Leiman, D A

    2018-05-01

    Gastroesophageal reflux disease and esophageal dysmotility are prevalent in patients with advanced lung disease and are associated with graft dysfunction following lung transplantation. As a result, many transplant centers perform esophageal function testing as part of the wait-listing process but guidelines for testing in this population are lacking. The aim of this study is to describe whether symptoms of gastroesophageal reflux correlate with abnormal results on pH-metry and high-resolution manometry and can be used to identify those who require testing. We performed a retrospective cohort study of 226 lung transplant candidates referred for high-resolution manometry and pH-metry over a 12-month period in 2015. Demographic data, results of a standard symptom questionnaire and details of esophageal function testing were obtained. Associations between the presence of symptoms and test results were analyzed using Fisher's exact tests and multivariable logistic regression. The most common lung disease diagnosis was interstitial lung disease (N = 131, 58%). Abnormal pH-metry was seen in 116 (51%) patients and the presence of symptoms was significantly associated with an abnormal study (p advanced lung disease, symptoms of gastroesophageal reflux increase the likelihood of elevated acid exposure on pH-metry but were not associated with dysmotility. Given the proportion of asymptomatic patients with abnormal studies and associated post-transplant risks, a practice of universal high-resolution manometry and pH-metry testing in this population is justifiable.

  17. Intestine Transplant

    Science.gov (United States)

    ... After the transplant Preventing rejection Post-transplant medications Types of immunosuppressants Switching immunosuppressants Side effects Other medications Generic and brand name drugs Post-transplant tests Infections and immunity Lifestyle changes Health concerns Back to work or ...

  18. [What the family doctor must know about lung transplant (Part 1)].

    Science.gov (United States)

    Zurbano, L; Zurbano, F

    2017-09-01

    Lung transplant is a therapeutic, medical-surgical procedure indicated for pulmonary diseases (except lung cancer), that are terminal and irreversible with current medical treatment. More than 3,500 lung transplants have been performed in Spain, with a rate of over 6 per million and increasing. In this review, an analysis is made of the types of transplants, their indications and contraindications, the procedures, immunosuppressive treatments, their side effects and medical interactions, current prophylaxis. A list of easily accessible literature references is also include, the majority being by national authors. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Detection of HLA-G in serum and graft biopsy associated with fewer acute rejections following combined liver-kidney transplantation: possible implications for monitoring patients.

    Science.gov (United States)

    Creput, Caroline; Le Friec, Gaëlle; Bahri, Rajia; Amiot, Laurence; Charpentier, Bernard; Carosella, Edgardo; Rouas-Freiss, Nathalie; Durrbach, Antoine

    2003-11-01

    Human leukocyte antigen G (HLA-G) is a regulatory molecule that is expressed in the cytotrophoblast during implantation and is thought to allow the tolerance and the development of the semiallogeneic embryo. In vitro, HLA-G inhibits natural killer (NK) cell and CD8 T-cell cytotoxicity. HLA-G also decreases CD4 T-cell expansion. This suggests that it participates in the acceptance of allogeneic organ transplants in humans. We here describe the detection of high concentration of HLA-G in serum from liver-kidney transplant patients, but not in kidney transplant patients. This finding is supported by the ectopic expression of HLA-G in graft biopsies. Finally, its association with a low number of acute transplant rejections, especially in liver-kidney transplant patients led us to propose that HLA-G may serve to monitor transplant patients who are likely to accept their allograft and, thus, may benefit of a reduced immunosuppressive treatment.

  20. Factors Predicting Risk for Antibody-mediated Rejection and Graft Loss in Highly Human Leukocyte Antigen Sensitized Patients Transplanted After Desensitization.

    Science.gov (United States)

    Vo, Ashley A; Sinha, Aditi; Haas, Mark; Choi, Jua; Mirocha, James; Kahwaji, Joseph; Peng, Alice; Villicana, Rafael; Jordan, Stanley C

    2015-07-01

    Desensitization with intravenous immunoglobulin and rituximab (I+R) significantly improves transplant rates in highly sensitized patients, but antibody-mediated rejection (ABMR) remains a concern. Between July 2006 and December 2012, 226 highly sensitized patients received transplants after desensitization. Most received alemtuzumab induction and standard immunosuppression. Two groups were examined: ABMR (n = 181) and ABMR (n = 45, 20%). Risk factors for ABMR, pathology, and outcomes were assessed. Significant risks for ABMR included previous transplants and pregnancies as sensitizing events, donor-specific antibody (DSA) relative intensity scores greater than 17, presence of both class I and II DSAs at transplant and time on waitlist. The ABMR showed a significant benefit for graft survival and glomerular filtration rate at 5 years (P desensitized with I+R who remain ABMR have long-term graft and patient survival. The ABMR patients have significantly reduced graft survival and glomerular filtration rate at 5 years, especially TMA. Severe ABMR episodes benefit from treatment with PLEX + Eculizumab. The DSA-relative intensity scores at transplant was a strong predictor of ABMR. Donor-specific antibody avoidance and reduction strategies before transplantation are critical to avoiding ABMR and improving long-term outcomes.

  1. A novel patient-centered "intention-to-treat" metric of U.S. lung transplant center performance.

    Science.gov (United States)

    Maldonado, Dawn A; RoyChoudhury, Arindam; Lederer, David J

    2018-01-01

    Despite the importance of pretransplantation outcomes, 1-year posttransplantation survival is typically considered the primary metric of lung transplant center performance in the United States. We designed a novel lung transplant center performance metric that incorporates both pre- and posttransplantation survival time. We performed an ecologic study of 12 187 lung transplant candidates listed at 56 U.S. lung transplant centers between 2006 and 2012. We calculated an "intention-to-treat" survival (ITTS) metric as the percentage of waiting list candidates surviving at least 1 year after transplantation. The median center-level 1-year posttransplantation survival rate was 84.1%, and the median center-level ITTS was 66.9% (mean absolute difference 19.6%, 95% limits of agreement 4.3 to 35.1%). All but 10 centers had ITTS values that were significantly lower than 1-year posttransplantation survival rates. Observed ITTS was significantly lower than expected ITTS for 7 centers. These data show that one third of lung transplant candidates do not survive 1 year after transplantation, and that 12% of centers have lower than expected ITTS. An "intention-to-treat" survival metric may provide a more realistic expectation of patient outcomes at transplant centers and may be of value to transplant centers and policymakers. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. SP-A-enriched surfactant for treatment of rat lung transplants with SP-A deficiency after storage and reperfusion

    NARCIS (Netherlands)

    Erasmus, ME; Hofstede, GJH; Petersen, AH; Batenburg, JJ; Haagsman, HP; Oetomo, SB; Prop, J

    2002-01-01

    Background. The function of pulmonary surfactant is affected by lung transplantation, contributing to impaired lung transplant function. A decreased amount of surfactant protein-A (SP-A) after reperfusion is believed to contribute to the impaired surfactant function. Surfactant treatment has been

  3. Monitoring pharmacologically induced immunosuppression by immune repertoire sequencing to detect acute allograft rejection in heart transplant patients: a proof-of-concept diagnostic accuracy study.

    Directory of Open Access Journals (Sweden)

    Christopher Vollmers

    2015-10-01

    Full Text Available It remains difficult to predict and to measure the efficacy of pharmacological immunosuppression. We hypothesized that measuring the B-cell repertoire would enable assessment of the overall level of immunosuppression after heart transplantation.In this proof-of-concept study, we implemented a molecular-barcode-based immune repertoire sequencing assay that sensitively and accurately measures the isotype and clonal composition of the circulating B cell repertoire. We used this assay to measure the temporal response of the B cell repertoire to immunosuppression after heart transplantation. We selected a subset of 12 participants from a larger prospective cohort study (ClinicalTrials.gov NCT01985412 that is ongoing at Stanford Medical Center and for which enrollment started in March 2010. This subset of 12 participants was selected to represent post-heart-transplant events, with and without acute rejection (six participants with moderate-to-severe rejection and six without. We analyzed 130 samples from these patients, with an average follow-up period of 15 mo. Immune repertoire sequencing enables the measurement of a patient's net state of immunosuppression (correlation with tacrolimus level, r = -0.867, 95% CI -0.968 to -0.523, p = 0.0014, as well as the diagnosis of acute allograft rejection, which is preceded by increased immune activity with a sensitivity of 71.4% (95% CI 30.3% to 94.9% and a specificity of 82.0% (95% CI 72.1% to 89.1% (cell-free donor-derived DNA as noninvasive gold standard. To illustrate the potential of immune repertoire sequencing to monitor atypical post-transplant trajectories, we analyzed two more patients, one with chronic infections and one with amyloidosis. A larger, prospective study will be needed to validate the power of immune repertoire sequencing to predict rejection events, as this proof-of-concept study is limited to a small number of patients who were selected based on several criteria including the

  4. Pulmonary nodules and masses in lung transplant recipients: clinical and CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Morla, Olivier; Liberge, Renan; Arrigoni, Pierre Paul; Frampas, Eric [Service de Radiologie Centrale, C.H.U. Hotel Dieu, Nantes (France)

    2014-09-15

    The purpose of this study was to review the clinical and CT findings of pulmonary nodules and masses in lung transplant recipients and to determine distinguishing features among the various aetiologies. This retrospective study included 106 lung transplant recipients who had a chest CT performed over a 7-year period in a single institution. Twenty-four cases of pulmonary nodules and masses were observed on CT. Among the single lesions, three (50 %) were due to infections, one (17 %) to organizing pneumonia, and two (33 %) remained of undetermined origin. Among the multiple lesions, 14 (78 %) were due to infection, three to post-transplant lymphoproliferative disorder (17 %), and one to bronchogenic carcinoma (5 %). The two main microorganisms were P. aeruginosa and Aspergillus spp. Among 12 solid nodules > 1 cm, four (33 %) were due to malignancy: three post-transplant lymphoproliferative disorders (25 %), and one bronchogenic carcinoma (8 %). Among five cavitary nodules four (80 %) were due to aspergillosis. Infection is the most frequent aetiology of pulmonary nodules and masses in lung transplant recipients, but other causes such as post-transplant lymphoproliferative disorder, bronchogenic carcinoma, or organizing pneumonia should be considered. (orig.)

  5. A simple technique can reduce cardiopulmonary bypass use during lung transplantation

    Directory of Open Access Journals (Sweden)

    Marcos N. Samano

    2016-04-01

    Full Text Available Cardiopulmonary bypass causes an inflammatory response and consumption of coagulation factors, increasing the risk of bleeding and neurological and renal complications. Its use during lung transplantation may be due to pulmonary hypertension or associated cardiac defects or just for better exposure of the pulmonary hilum. We describe a simple technique, or open pericardium retraction, to improve hilar exposure by lifting the heart by upward retraction of the pericardial sac. This technique permits lung transplantation without cardiopulmonary bypass when bypass use is recommended only for better exposure.

  6. Methylene Blue for Vasoplegia When on Cardiopulmonary Bypass During Double-Lung Transplantation.

    Science.gov (United States)

    Carley, Michelle; Schaff, Jacob; Lai, Terrance; Poppers, Jeremy

    2015-10-15

    Vasoplegia syndrome, characterized by hypotension refractory to fluid resuscitation or high-dose vasopressors, low systemic vascular resistance, and normal-to-increased cardiac index, is associated with increased morbidity and mortality after cardiothoracic surgery. Methylene blue inhibits inducible nitric oxide synthase and guanylyl cyclase, and has been used to treat vasoplegia during cardiopulmonary bypass. However, because methylene blue is associated with increased pulmonary vascular resistance, its use in patients undergoing lung transplantion has been limited. Herein, we report the use of methylene blue to treat refractory vasoplegia during cardiopulmonary bypass in a patient undergoing double-lung transplantation.

  7. Esophageal Dysmotility, Gastro-esophageal Reflux Disease, and Lung Transplantation: What Is the Evidence?

    Science.gov (United States)

    Wood, Richard K

    2015-12-01

    Lung transplantation is an effective and life-prolonging therapy for patients with advanced lung disease (ALD). However, long-term patient survival following lung transplantation is primarily limited by development of an inflammatory and fibrotic process involving the lung allograft known as bronchiolitis obliterans syndrome (BOS). Although the precise cause of BOS remains uncertain and is likely multifactorial, chronic aspiration of gastro-duodenal contents is one possible contributing factor. Multiple small, cross-sectional studies performed over the past two decades have reported a high prevalence of gastro-esophageal reflux disease (GERD) and esophageal dysmotility in the ALD population and several investigations suggest the prevalence may increase following lung transplantation. More recent studies evaluating the direct effect of gastro-duodenal contents on airways have demonstrated a possible biologic link between GERD and BOS. Despite the recent advances in our understanding of BOS, further investigations are needed to establish GERD as a causative factor in its development. This review will discuss the existing literature that has identified an association of GERD with ALD and post-transplant populations, with a focus on recent advances in the field.

  8. Clinical characteristics of cystic fibrosis patients prior to lung transplantation: An international comparison between Canada and the United States.

    Science.gov (United States)

    Quon, Bradley S; Sykes, Jenna; Stanojevic, Sanja; Marshall, Bruce C; Petren, Kristofer; Ostrenga, Josh; Fink, Aliza; Elbert, Alexander; Faro, Albert; Goss, Christopher H; Stephenson, Anne L

    2018-03-01

    Cystic fibrosis (CF) patients from Canada have better-reported post-lung transplant survival compared to patients from the United States. We hypothesized the clinical characteristics of CF patients prior to lung transplant differ between the two countries. Population-based cohort study utilizing combined Canadian CF Registry and US CF Foundation Patient Registry data from 1986 to 2013. Demographic and clinical variables were analyzed prior to lung transplant. Between 1986 and 2013, 607 (10.2%) CF patients underwent lung transplantation in Canada and 3428 (7.5%) in the United States. A lower proportion of recipients had growth of B. cepacia complex prior to transplant in the United States compared to Canada (0.8% vs 4.3%). Lung function was similar between recipients from the two countries. The proportion of patients classified as underweight was significantly higher in the United States compared to Canada (39.8% vs 28.0%; SD 26.1) despite higher rates of feeding tube use (42.5% vs 28.6%; SD 29.0). CF lung transplant recipients from the United States have similar lung function, lower rates of B. cepacia complex, and worse nutritional parameters prior to transplant compared to counterparts in Canada. Future studies are necessary to evaluate the impact of these differences on post-transplant survival. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients

    Directory of Open Access Journals (Sweden)

    Irai Luis Giacomelli

    Full Text Available ABSTRACT Objective: Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. Methods: From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. Results: We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%; cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%; and mediastinal lymph node enlargement (in 15.7%. Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. Conclusions: The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease.

  10. High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients

    Energy Technology Data Exchange (ETDEWEB)

    Giacomelli, Irai Luis; Schuhmacher Neto, Roberto; Nin, Carlos Schuller; Cassano, Priscilla de Souza; Pereira, Marisa; Moreira, Jose da Silva; Nascimento, Douglas Zaione; Hochhegger, Bruno, E-mail: iraigiacomelli@gmail.com [Complexo Hospitalar Santa Casa de Porto Alegre, RS (Brazil)

    2017-07-15

    Objective: Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. Methods: From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. Results: We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%); cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%); and mediastinal lymph node enlargement (in 15.7%). Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. Conclusions: The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease. (author)

  11. High-resolution computed tomography findings of pulmonary tuberculosis in lung transplant recipients.

    Science.gov (United States)

    Giacomelli, Irai Luis; Schuhmacher Neto, Roberto; Nin, Carlos Schuller; Cassano, Priscilla de Souza; Pereira, Marisa; Moreira, José da Silva; Nascimento, Douglas Zaione; Hochhegger, Bruno

    2017-01-01

    Respiratory infections constitute a major cause of morbidity and mortality in solid organ transplant recipients. The incidence of pulmonary tuberculosis is high among such patients. On imaging, tuberculosis has various presentations. Greater understanding of those presentations could reduce the impact of the disease by facilitating early diagnosis. Therefore, we attempted to describe the HRCT patterns of pulmonary tuberculosis in lung transplant recipients. From two hospitals in southern Brazil, we collected the following data on lung transplant recipients who developed pulmonary tuberculosis: gender; age; symptoms; the lung disease that led to transplantation; HRCT pattern; distribution of findings; time from transplantation to pulmonary tuberculosis; and mortality rate. The HRCT findings were classified as miliary nodules; cavitation and centrilobular nodules with a tree-in-bud pattern; ground-glass attenuation with consolidation; mediastinal lymph node enlargement; or pleural effusion. We evaluated 402 lung transplant recipients, 19 of whom developed pulmonary tuberculosis after transplantation. Among those 19 patients, the most common HRCT patterns were ground-glass attenuation with consolidation (in 42%); cavitation and centrilobular nodules with a tree-in-bud pattern (in 31.5%); and mediastinal lymph node enlargement (in 15.7%). Among the patients with cavitation and centrilobular nodules with a tree-in-bud pattern, the distribution was within the upper lobes in 66.6%. No pleural effusion was observed. Despite treatment, one-year mortality was 47.3%. The predominant HRCT pattern was ground-glass attenuation with consolidation, followed by cavitation and centrilobular nodules with a tree-in-bud pattern. These findings are similar to those reported for immunocompetent patients with pulmonary tuberculosis and considerably different from those reported for AIDS patients with the same disease.

  12. Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients.

    Science.gov (United States)

    Sugimoto, Seiichiro; Yamane, Masaomi; Otani, Shinji; Kurosaki, Takeshi; Okahara, Shuji; Hikasa, Yukiko; Toyooka, Shinichi; Kobayashi, Motomu; Oto, Takahiro

    2018-04-21

    Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

  13. Decrease of Airway Allergies After Lung Transplantation Is Associated With Reduced Basophils and Eosinophils.

    Science.gov (United States)

    Niedzwiecki, M; Yamada, Y; Inci, I; Weder, W; Jungraithmayr, W

    2016-01-01

    Allergies are hypersensitive reactions of the immune system on antigen exposure similar to immune reactions after transplantation (Tx). Their activity can change after Tx. The lung as a transplantable organ is challenged two-fold, by antigens from the blood and the air environment. Herein we analyzed if airway allergies change after lung Tx. We systematically reviewed patients' airway allergies before and after lung Tx between 1992 and 2014. The course of lymphocytes, thrombocytes, and leukocytes, among them neutrophils, eosinophils, and basophils, was analyzed in patients in whom airway allergies have changed and in whom they did not change. From 362 lung transplanted patients, 44 patients had suffered from allergies before Tx (12.2%). In 20 of these patients (45.5%), airway allergies disappeared completely within 1 year after lung Tx and were persistently absent thereafter. In these patients, basophils and eosinophils decreased significantly (P allergies did not disappear. Leukocytes overall, and in particular, neutrophils, decreased significantly in patients whose allergy disappeared (P allergies disappeared in almost half of cases after lung Tx. Along with this reduction, basophils and eosinophils decreased as potentially responsible cells for this phenomenon. These findings may stimulate intensified research on basophils and eosinophils as major drivers of airway allergies. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Detection of the immunologic rejection after xeno-islet transplantation: a study by MR imaging enhanced with superparamagnetic iron oxide marking CD4+ T cell antibody

    International Nuclear Information System (INIS)

    Nie Wei; Tang Yiya; Rong Pengfei; Ye Bin; Ye Zheng; Tong Qiongjuan; Wang Wei

    2008-01-01

    Objective: To evaluate the feasibility of the diagnosis of the early immunologic rejection after xeno-islet transplantation by MR imaging enhanced with superparamagnetic iron oxide (SPIO) marking CD4 + T cell antibody. Methods: Two thousand neonatal porcine islets (NPI)were transplanted under the left renal capsule of BALB/C nude mice. When the grafts could be observed by MRI, 10 7 human PBMC was intraperitoneal injected to nude mouse models to reconstitute the human immunologic system, 20 mice were reconstituted. Before and 3,7,14 days after reconstitution of human immunologic system on BALB/C nude mice, MRI imaging was performed half an hour after intravenous injection of nano-immunomagnetic beads via vena caudatis to observe the grafts' MRI signal. BALB/C nude mice were sacrificed after MRI scanning immediately, the histopathologic examination was assessed on grafts, the results were compared with MRI results. And calculate the sensitivity, specificity, Youden index number and coincidence of the MRI for immunologic rejection. Results: Grafts can be observed by MRI 3 weeks after islet cell transplantation (before immunologic rejection modeling), there is no abnormal MRI signal detected in nude mice' graft region after microbeads injected. Seven days after building of immunologic rejection model, MRI hypo-signal in graft site is shown in the T 2 WI sequence after nano-bioprober injected. Histopathologic assessments were employed on grafts in nude mice immediately (HE and immunohistochemistry staining), the results shown that there are a lot of T lymphocyts infiltrated in graft region, implying the occurrence of immunologic rejection. And the sensitivity, specificity, Youden index number and coincidence is: (72.96±0.24)%, 100%, 0.73±0.24, (88.46±0.13)% respectively. The correct Kappa between the MRI and the imunohistochemistry staining was 0.76. Conclusion: The cellular immunological rejection to xeno-islet grarts can be assessed with nano-bioprobe with anti-CD4

  15. Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease

    NARCIS (Netherlands)

    Verschuuren, E; van der Bij, W; de Boer, W; Timens, W; Middeldorp, J; The, TH

    The Epstein-Barr virus (EBV)-specific antibody response was studied in lung transplant patients to assess their value in the diagnosis and prognosis of post-transplant lymphoproliferative disease. Recently developed synthetic peptides representing Epstein-Barr nuclear antigen-1 (EBNA-1), diffuse

  16. Quantitative Epstein-Barr virus (EBV) serology in lung transplant recipients with primary EBV infection and/or post-transplant lymphoproliferative disease.

    NARCIS (Netherlands)

    Verschuuren, E; van der Bij, W; Boer, W.; Timens, W.; Middeldorp, J.M.; The, T.H.

    2003-01-01

    The Epstein-Barr virus (EBV)-specific antibody response was studied in lung transplant patients to assess their value in the diagnosis and prognosis of post-transplant lymphoproliferative disease. Recently developed synthetic peptides representing Epstein-Barr nuclear antigen-1 (EBNA-1), diffuse

  17. The kSORT assay to detect renal transplant patients at high risk for acute rejection: results of the multicenter AART study.

    Directory of Open Access Journals (Sweden)

    Silke Roedder

    2014-11-01

    Full Text Available Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR.We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART study. Gene expression was assessed by quantitative real-time PCR (QPCR in one center. A 17-gene set--the Kidney Solid Organ Response Test (kSORT--was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91-0.98, validated in 124 independent samples (AUC = 0.95; 95% CI 0.88-1.0 and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy. A novel reference-based algorithm (using 13 12-gene models was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86-0.99. Further validation of kSORT is planned in prospective clinical observational and interventional trials.The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary.

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

    DEFF Research Database (Denmark)

    Uhlving, Hilde Hylland; Andersen, Claus B; Christensen, Ib Jarle

    2015-01-01

    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...

  19. Unusual case of a vanishing bronchus of the left allograft in a lung transplant recipient

    Directory of Open Access Journals (Sweden)

    Don Hayes

    2013-01-01

    Full Text Available We present an interesting case of a complete vanishing of the left main bronchus in a lung transplant recipient who had a successful outcome due to acute respiratory support with venovenous extracorporeal membrane oxygenation in order to perform airway dilation.

  20. Long-term leukopenia in a lung transplanted patient with cystic fibrosis treated with zoledronic acid

    DEFF Research Database (Denmark)

    Karahasanovic, A; Thorsteinsson, A-L; Bjarnason, N H

    2016-01-01

    report a case of a young woman with CF, lung transplantation and low bone mass developing long-term leukopenia after treatment with zoledronic acid. The leukopenia, with a strong affection of the neutrocytes, lasted for 4 months and the condition only went into remission after granulocyte-colony...

  1. Bronchiolitis obliterans syndrome after lung transplantation and health-related quality of life

    NARCIS (Netherlands)

    van den Berg, JWK; van der Bij, W; Koeter, GH; Postma, DS; ten Vergert, EM

    The present study was undertaken to assess the relationship between health-related quality of life (HRQOL) and bronchiolitis obliterans syndrome (BOS), as both represent important parameters of outcome after lung transplantation. HRQOL was measured both cross-sectionally and longitudinally by

  2. Scintigraphic diagnosis of silent aspiration following double-sided lung transplantation

    International Nuclear Information System (INIS)

    Toenshoff, G.; Stock, U.; Bohuslavizki, K.H.; Brenner, W.; Costard-Jaeckle, A.; Cremer, J.; Clausen, M.

    1996-01-01

    We present a case of a 25 year old patient who underwent double-sided lung transplantation and suffered from recurrent pneumonia. Silent aspiration was suspected clinically. Aspiration was proved by scintigraphy enabling to discriminate between direct oro-pulmonal aspiration and aspiration after gastro-esophageal reflux. (orig.) [de

  3. Lung transplantation for high-risk patients with idiopathic pulmonary fibrosis.

    Science.gov (United States)

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

    2016-10-07

    Survival for patients with idiopathic pulmonary fibrosis (IPF) and high lung allocation score (LAS) values may be significantly reduced in comparison to those with lower LAS values. To evaluate outcomes for high-risk IPF patients as defined by LAS values ≥46 (N=42) versus recipients with LAS values pulmonary complications was increased for the higher LAS group versus recipients with LAS <46, 30-day mortality and actuarial survival did not differ between the two cohorts. Although lung transplantation in patients with IPF and high LAS values is associated with increased risk of early post-transplant complications, long-term post-transplant survival for our high-LAS cohort was equivalent to that for the lower LAS recipients.

  4. Suicidal hanging donors for lung transplantation: Is this chapter still closed? Midterm experience from a single center in United Kingdom.

    Science.gov (United States)

    Ananiadou, Olga; Schmack, Bastian; Zych, Bartlomiej; Sabashnikov, Anton; Garcia-Saez, Diana; Mohite, Prashant; Weymann, Alexander; Mansur, Ashham; Zeriouh, Mohamed; Marczin, Nandor; De Robertis, Fabio; Simon, Andre Rüdiger; Popov, Aron-Frederik

    2018-04-01

    In the context of limited donor pool in cardiothoracic transplantation, utilization of organs from high risk donors, such as suicidal hanging donors, while ensuring safety, is under consideration. We sought to evaluate the outcomes of lung transplantations (LTx) that use organs from this group.Between January 2011 and December 2015, 265 LTx were performed at our center. Twenty-two recipients received lungs from donors after suicidal hanging (group 1). The remaining 243 transplantations were used as a control (group 2). Analysis of recipient and donor characteristics as well as outcomes was performed.No statistically significant difference was found in the donor characteristics between analyzed groups, except for higher incidence of cardiac arrest, younger age and smoking history of hanging donors (P donor cause of death is not associated with poor mid-term survival or chronic lung allograft dysfunction following transplantation. These results encourage assessment of lungs from hanging donors, and their consideration for transplantation.

  5. No survival benefit to gaining private health insurance coverage for post-lung transplant care in adults with cystic fibrosis.

    Science.gov (United States)

    Tumin, Dmitry; Foraker, Randi E; Tobias, Joseph D; Hayes, Don

    2016-03-01

    The use of public insurance is associated with diminished survival in patients with cystic fibrosis (CF) following lung transplantation. No data exist on benefits of gaining private health insurance for post-transplant care among such patients previously using public insurance. The United Network for Organ Sharing database was used to identify first-time lung transplant recipients participating in Medicare or Medicaid, diagnosed with CF, and transplanted between 2005 and 2015. Survival outcomes were compared between recipients gaining private insurance after transplantation and those maintaining public coverage throughout follow-up. Since implementation of the lung allocation score, 575 adults with CF received lung transplantation funded by Medicare or Medicaid and contributed data on insurance status post-transplant. There were 128 (22%) patients who gained private insurance. Multivariable analysis of time-varying insurance status found no survival benefit of gaining private insurance (HR = 0.822; 95% CI = 0.525, 1.286; p = 0.390). Further analysis demonstrated that resuming public insurance coverage was detrimental, relative to gaining and keeping private insurance (HR = 2.315; 95% CI = 1.020, 5.258; p = 0.045). Survival disadvantages of lung transplant recipients with CF who have public health insurance were not ameliorated by a switch to private coverage for post-transplant care. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. CD25, CD28 and CD38 expression in peripheral blood lymphocytes as a tool to predict acute rejection after liver transplantation.

    Science.gov (United States)

    Boleslawski, Emmanuel; BenOthman, Samia; Grabar, Sophie; Correia, Leonor; Podevin, Philippe; Chouzenoux, Sandrine; Soubrane, Olivier; Calmus, Yvon; Conti, Filomena

    2008-01-01

    The aim of this study was to determine whether the expression of CD25, CD28 and CD38 (which reflects the degree of T-cell activation) by peripheral blood mononuclear cells constitutes a useful means of measuring the immune status of liver transplant recipients. Fifty-two patients enrolled in a prospective randomized study comparing cyclosporine and tacrolimus as the principal immunosuppressive drugs were monitored prospectively. The expression of CD25, CD28 and CD38 was analyzed on CD3-, CD4- and CD8-positive cells from whole blood using flow cytometry. The prognostic value of baseline and day 14 measurements regarding acute rejection was examined using Kaplan-Meier estimates for univariate analyses and the Cox model for multivariate analyses. The mean frequencies of CD28 and CD38-expressing T cells were significantly higher in patients with acute rejection (p = 0.01 and p = 0.001, respectively), whereas the frequency CD25-expressing T cells did not differ significantly. Under univariate analysis, baseline CD25 levels, the type of calcineurin inhibitor, as well as the CD28 and CD38 frequencies obtained at day 14 were associated with the subsequent development of acute rejection. Under multivariate analysis, only CD28 and CD38 frequencies obtained at day 14 were independently associated with acute rejection. The evaluation of CD28 and CD38 expression in peripheral blood lymphocytes is a simple marker that could be used routinely in clinical practice to assess the level of immunosuppression.

  7. A 47-Year-Old Man With Fever, Dry Cough, and a Lung Mass After Redo Lung Transplantation.

    Science.gov (United States)

    Chaddha, Udit; Patil, Pradnya D; Omar, Ashraf; Walia, Rajat; Panchabhai, Tanmay S

    2018-06-01

    A 47-year-old man who was a redo double lung transplant recipient (cytomegalovirus [CMV] status: donor positive/recipient positive; Epstein-Barr virus status: donor positive/recipient positive) presented to the hospital with 1 week of generalized malaise, low-grade fevers, and dry cough. His redo lung transplantation was necessitated by bronchiolitis obliterans syndrome, and his previous lung transplantation 5 years earlier was for silicosis-related progressive massive fibrosis. He denied any difficulty breathing or chest pain. There was no history of GI or urinary symptoms, and the patient had no anorexia, weight loss, night sweats, sick contacts, or history of travel. He had a history of 1 earlier episode of CMV viremia that was treated with valganciclovir. His immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisone, and his infection prophylaxis included trimethoprim-sulfamethoxazole, itraconazole, and valganciclovir. Results of a chest radiograph 8 weeks earlier were normal. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  8. Use of telehealth technology for home spirometry after lung transplantation: a randomized controlled trial.

    Science.gov (United States)

    Sengpiel, Juliane; Fuehner, Thomas; Kugler, Christiane; Avsar, Murat; Bodmann, Isabelle; Boemke, Annelies; Simon, Andre; Welte, Tobias; Gottlieb, Jens

    2010-12-01

    Complications often occur during the early phase after lung transplantation, and rapid diagnosis is vital. Home spirometry is used to detect early changes in graft function. Bluetooth-equipped cell phones are easy to use and facilitate data transfer from home spirometry. To explore use of home spirometry with Bluetooth data transfer in outpatient lung transplant recipients. Single-center prospective randomized controlled trial. Intervention-Fifty-six patients were randomized either to home spirometry with data transfer via Bluetooth-equipped cell phones or to home spirometry alone before discharge after lung transplantation. In the Bluetooth group, results were transferred to a database capable of generating alarm messages. Time from onset of symptoms to physician consultation during the first 6 months after lung transplantation was the primary end point. Adherence to home spirometry was 97.2% in the Bluetooth group and 95.3% in the home spirometry alone group (P = .73). Median time to first consultation (P = .60) and frequency of consultation (P = .06) did not differ significantly in the 2 groups. Mean scores on the Hospital Anxiety and Depression Scale were lower in patients in the Bluetooth group (1.5; range, 0.0-4.0) than in the home spirometry alone group (4.0; range, 2.0-6.0; P = .04). Home spirometry with data transfer is feasible and safe in lung transplant recipients. Compared with home spirometry alone, additional data transfer was equally effective regarding the time interval from symptom onset to consultation. Patients in the Bluetooth group reported less anxiety, which may improve emotional well-being.

  9. Vasculites e eosinófilos em biópsia endomiocárdica, como preditores de rejeição em transplante cardíaco Vasculitis y eosinófilos en biopsia endomiocárdica, como predictores de rechazo en transplante cardíaco Vasculitides and eosinophils in emdomyocardial biopsies as rejection predictors in heart transplantation

    Directory of Open Access Journals (Sweden)

    Reginaldo Cipullo

    2011-08-01

    precedieron rechazo agudo; y (2 Biopsias no predictoras: aquellas que no precedieron rechazo agudo. Comparamos la ocurrencia de los siguientes hallazgos histológicos: vasculitis, lesiones isquémicas, efecto Quilty y eosinófilos por análisis uni y multivariado entre los grupos. RESULTADOS: Después de análisis estadístico se verificó la presencia de vasculitis intensa y de eosinófilos como mayores predictores para rechazo agudo futuro, presentando respectivamente las siguientes razones de posibilidad: 10,60 (IC95%: 3,62 - 31,06. p BACKGROUND: The clinical significance of vasculitides, ischemic lesions, Quilty effect and the presence of eosinophils in endomyocardial biopsies of heart transplantation recipients with mild rejection has yet to be established. OBJECTIVE: To verify whether these histological findings observed in endomyocardial biopsies (eosinophils, vasculitides, Quilty effect and ischemic lesions are capable of predicting acute graft rejection. METHODS: A total of 1,012 consecutive endomyocardial biopsies were reevaluated; of these, 939 were classified as OR or 1R according to the Nomenclature of the International Society of Heart and Lung Transplantation of 2005 and divided in two groups: (1 Predictive biopsies: those that preceded acute rejection; and (2 Nonpredictive biopsies: those that did not precede acute rejection. We compared the occurrence of the following histological findings: vasculitides, ischemic lesions, Quilty effect and eosinophils between the groups by uni- and multivariate analyses. RESULTS: The statistical analysis showed that the presence of severe vasculitides and eosinophils were the best predictors for future acute rejection, with the following odds ratios: 10.60 (95%CI: 3.62 - 31.06. p < 0.001 and 6.26 (95%CI: 3.16 - 12.43, p < 0.001. CONCLUSION: Severe vasculitides and eosinophils in myocardial biopsies are the main predictive factors of acute graft rejection post-heart transplantation.

  10. Prevalência de refluxo gastroesofágico em pacientes com doença pulmonar avançada candidatos a transplante pulmonar Prevalence of gastroesophageal reflux in lung transplant candidates with advanced lung disease

    Directory of Open Access Journals (Sweden)

    Gustavo Almeida Fortunato

    2008-10-01

    Full Text Available OBJETIVO: Avaliar o perfil funcional do esôfago e a prevalência de refluxo gastroesofágico (RGE em pacientes candidatos a transplante pulmonar. MÉTODOS: Foram analisados prospectivamente, entre junho de 2005 e novembro de 2006, 55 pacientes candidatos a transplante pulmonar da Santa Casa de Misericórdia de Porto Alegre. Os pacientes foram submetidos a esofagomanometria estacionária e pHmetria esofágica ambulatorial de 24 h de um e dois eletrodos antes de serem submetidos ao transplante pulmonar. RESULTADOS: A esofagomanometria foi anormal em 80% dos pacientes e a pHmetria revelou RGE ácido patológico em 24%. Os sintomas digestivos apresentaram sensibilidade de 50% e especificidade de 61% para RGE. Dos pacientes com doença pulmonar obstrutiva crônica, 94% apresentaram alteração à manometria, e 80% apresentaram hipotonia do esfíncter inferior, que foi o achado mais freqüente. Pacientes com bronquiectasias apresentaram a maior prevalência de RGE (50%. CONCLUSÕES: O achado freqüente em pacientes com doença pulmonar avançada é RGE. Na população examinada, a presença de sintomas digestivos de RGE não foi preditiva de refluxo ácido patológico. A contribuição do RGE na rejeição crônica deve ser considerada e requer estudos posteriores para seu esclarecimento.OBJECTIVE: To assess the esophageal function profile and the prevalence of gastro-esophageal reflux (GER in lung transplant candidates. METHODS: From July of 2005 to November of 2006, a prospective study was conducted involving 55 candidates for lung transplantation at the Santa Casa de Misericórdia Hospital in Porto Alegre, Brazil. Prior to transplantation, patients underwent outpatient stationary esophageal manometry and 24-h esophageal pH-metry using one and two electrodes. RESULTS: Abnormal esophageal manometry was documented in 80% of the patients, and 24% of the patients presented pathological acid reflux. Digestive symptoms presented sensitivity and

  11. Early and mid-term results of lung transplantation with donors 60 years and older.

    Science.gov (United States)

    López, Iker; Zapata, Ricardo; Solé, Juan; Jaúregui, Alberto; Deu, María; Romero, Laura; Pérez, Javier; Bello, Irene; Wong, Manuel; Ribas, Montse; Masnou, Nuria; Rello, Jordi; Roman, Antonio; Canela, Mercedes

    2015-01-01

    There are doubts about the age limit for lung donors and the ideal donor has traditionally been considered to be one younger than 55 years. The objective of this study was to compare the outcomes in lung transplantation between organs from donors older and younger than 60 years. We performed a retrospective observational study comparing the group of patients receiving organs from donors 60 years or older (Group A) or younger than 60 years (Group B) between January 2007 and December 2011. Postoperative evolution and mortality rates, short-term and mid-term postoperative complications, and global survival rate were evaluated. We analysed a total of 230 lung transplants, of which 53 (23%) involved lungs from donors 60 years of age or older (Group A), and 177 (77%) were from donors younger than 60 years (Group B). Three (5.7%) patients from Group A and 14 patients (7.9%) from Group B died within 30 days (P = 0.58). The percentage of patients free from chronic lung allograft dysfunction at 1-3 years was 95.5, 74.3 and 69.3% for Group A, and 94.5, 84.8 and 73.3% for Group B, respectively (P = 0.47). There were no statistically significant differences between Groups A and B in terms of survival at 3 years, (69.4 vs 68.8%; P = 0.28). Our results support the idea that lungs from donors aged 60-70 years can be used safely for lung transplantation with comparable results to lungs from younger donors in terms of postoperative mortality and mid-term survival. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  12. Low Radiation Dose and Low Cell Dose Increase the Risk of Graft Rejection in a Canine Hematopoietic Stem Cell Transplantation Model.

    Science.gov (United States)

    Lange, Sandra; Steder, Anne; Glass, Änne; Killian, Doreen; Wittmann, Susanne; Machka, Christoph; Werner, Juliane; Schäfer, Stephanie; Roolf, Catrin; Junghanss, Christian

    2016-04-01

    The canine hematopoietic stem cell transplantation (HSCT) model has become accepted in recent decades as a good preclinical model for the development of new transplantation strategies. Information on factors associated with outcome after allogeneic HSCT are a prerequisite for designing new risk-adapted transplantation protocols. Here we report a retrospective analysis aimed at identifying risk factors for allograft rejection in the canine HSCT model. A total of 75 dog leukocyte antigen-identical sibling HSCTs were performed since 2003 on 10 different protocols. Conditioning consisted of total body irradiation at 1.0 Gy (n = 20), 2.0 Gy (n = 40), or 4.5 Gy (n = 15). Bone marrow was infused either intravenously (n = 54) or intraosseously (n = 21). Cyclosporin A alone or different combinations of cyclosporine A, mycophenolate mofetil, and everolimus were used for immunosuppression. A median cell dose of 3.5 (range, 1.0 to 11.8) total nucleated cells (TNCs)/kg was infused. Cox analyses were used to assess the influence of age, weight, radiation dose, donor/recipient sex, type of immunosuppression, and cell dose (TNCs, CD34(+) cells) on allograft rejection. Initial engraftment occurred in all dogs. Forty-two dogs (56%) experienced graft rejection at median of 11 weeks (range, 6 to 56 weeks) after HSCT. Univariate analyses revealed radiation dose, type of immunosuppression, TNC dose, recipient weight, and recipient age as factors influencing long-term engraftment. In multivariate analysis, low radiation dose (P rejection. Peripheral blood mononuclear cell chimerism ≥30% (P = .008) and granulocyte chimerism ≥70% (P = .023) at 4 weeks after HSCT were independent predictors of stable engraftment. In summary, these data indicate that even in low-dose total body irradiation-based regimens, the irradiation dose is important for engraftment. The level of blood chimerism at 4 weeks post-HSCT was predictive of long-term engraftment in the canine HSCT

  13. Patient-reported outcome 2 years after lung transplantation: does the underlying diagnosis matter?

    Directory of Open Access Journals (Sweden)

    Ghosh S

    2012-11-01

    Full Text Available Maria Jose Santana,1 David Feeny,2 Sunita Ghosh,3 Dale C Lien41Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada; 2Kaiser Permanente Center for Health Research, Portland, OR, USA; 3Cross Cancer Center, University of Alberta, Edmonton, Alberta, Canada; 4University of Alberta Hospital, Edmonton, Alberta, CanadaPurpose: Transplantation has the potential to produce profound effects on survival and health-related quality of life (HRQL. The inclusion of the patient’s perspective may play an important role in the assessment of the effectiveness of lung transplantation. Patient perspectives are assessed by patient-reported outcome measures, including HRQL measures. We describe how patients’ HRQL among different diagnosis groups can be used by clinicians to monitor and evaluate the outcomes associated with transplantation.Methods: Consecutive lung transplant recipients attending the lung transplant outpatient clinic in a tertiary institution completed the 15-item Health Utilities Index (HUI questionnaire on a touchscreen computer. The results were available to clinicians at every patient visit. The HUI3 covers a range of severity and comorbidities in eight dimensions of health status. Overall HUI3 scores are on a scale in which dead = 0.00 and perfect health = 1.00; disability categories range from no disability = 1 to severe disability <0.70. Single-attribute and overall HUI3 scores were used to compare patients’ HRQL among different diagnosis groups. Random-effect models with time since transplant as a random variable and age, gender, underlying diagnoses, infections, and broncholitis obliterans syndrome as fixed variables were built to identify determinants of health status at 2-years posttransplantation.Results: Two hundred and fourteen lung transplant recipients of whom 61% were male with a mean age of 52 (19–75 years were included in the study. Chronic obstructive pulmonary disease and cystic fibrosis patients displayed

  14. Nosocomial legionellosis in three heart-lung transplant patients

    DEFF Research Database (Denmark)

    Bangsborg, Jette Marie; Uldum, S; Jensen, J S

    1995-01-01

    Organ transplant recipients are at high risk of contracting Legionnaires' disease in a hospital environment contaminated with legionellae. This study describes the first cases of culture-verified Legionella infections with an established link to potable hospital water in Denmark; three patients...

  15. Dimensão fractal na quantificação do grau de rejeição celular miocárdica pós-transplante cardíaco Fractal dimension in quantifying the degree of myocardial cellular rejection after cardiac transplantation

    Directory of Open Access Journals (Sweden)

    Roberto Douglas Moreira

    2011-06-01

    agreement with the "International Society for Heart and Lung Transplantation" (ISHLT 2004. The final report of the degree of rejection was confirmed and redefined after an exhaustive review of the slides by an external experienced pathologist. 658 slides were evaluated with the following distribution among the degrees of rejection (R: 335 (0R; 214 (1R; 70 (2R; 39 (3R. The data were statistically analyzed with Kruskal-Wallis tests and ROC curves being considered significant values of P < 0.05. RESULTS: There was significant statistical difference between the various degrees of rejection with the exception of R3 versus R2. The same trend was observed in applying the ROC curve. CONCLUSION: FD may contribute to the assessment of myocardial cellular rejection. Higher values are directly associated with progressively higher degrees of rejection. This may help in decision making of doubtful cases and those which contemplate the intensification of immunosuppressive medication.

  16. Outside-in HLA class I signaling regulates ICAM-1 clustering and endothelial cell-monocyte interactions via mTOR in transplant antibody-mediated rejection.

    Science.gov (United States)

    Salehi, Sahar; Sosa, Rebecca A; Jin, Yi-Ping; Kageyama, Shoichi; Fishbein, Michael C; Rozengurt, Enrique; Kupiec-Weglinski, Jerzy W; Reed, Elaine F

    2018-05-01

    Antibody-mediated rejection (AMR) resulting in transplant allograft vasculopathy (TAV) is the major obstacle for long-term survival of solid organ transplants. AMR is caused by donor-specific antibodies to HLA, which contribute to TAV by initiating outside-in signaling transduction pathways that elicit monocyte recruitment to activated endothelium. Mechanistic target of rapamycin (mTOR) inhibitors can attenuate TAV; therefore, we sought to understand the mechanistic underpinnings of mTOR signaling in HLA class I Ab-mediated endothelial cell activation and monocyte recruitment. We used an in vitro model to assess monocyte binding to HLA I Ab-activated endothelial cells and found mTOR inhibition reduced ezrin/radixin/moesin (ERM) phosphorylation, intercellular adhesion molecule 1 (ICAM-1) clustering, and monocyte firm adhesion to HLA I Ab-activated endothelium. Further, in a mouse model of AMR, in which C57BL/6. RAG1 -/- recipients of BALB/c cardiac allografts were passively transferred with donor-specific MHC I antibodies, mTOR inhibition significantly reduced vascular injury, ERM phosphorylation, and macrophage infiltration of the allograft. Taken together, these studies indicate mTOR inhibition suppresses ERM phosphorylation in endothelial cells, which impedes ICAM-1 clustering in response to HLA class I Ab and prevents macrophage infiltration into cardiac allografts. These findings indicate a novel therapeutic application for mTOR inhibitors to disrupt endothelial cell-monocyte interactions during AMR. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Delirium after lung transplantation: Association with recipient characteristics, hospital resource utilization, and mortality.

    Science.gov (United States)

    Sher, Yelizaveta; Mooney, Joshua; Dhillon, Gundeep; Lee, Roy; Maldonado, José R

    2017-05-01

    Delirium is associated with increased morbidity and mortality. The factors associated with post-lung transplant delirium and its impact on outcomes are under characterized. The medical records of 163 consecutive adult lung transplant recipients were reviewed for delirium within 5 days (early-onset) and 30 hospital days (ever-onset) post-transplantation. A multivariable logistic regression model assessed factors associated with delirium. Multivariable negative binomial regression and Cox proportional hazards models assessed the association of delirium with ventilator duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, and one-year mortality. Thirty-six percent of patients developed early-onset, and 44% developed ever-onset delirium. Obesity (OR 6.35, 95% CI 1.61-24.98) and bolused benzodiazepines within the first postoperative day (OR 2.28, 95% CI 1.07-4.89) were associated with early-onset delirium. Early-onset delirium was associated with longer adjusted mechanical ventilation duration (P=.001), ICU LOS (Pdelirium was associated with longer ICU (Pdelirium was not significantly associated with one-year mortality (early-onset HR 1.65, 95% CI 0.67-4.03; ever-onset HR 1.70, 95% CI 0.63-4.55). Delirium is common after lung transplant surgery and associated with increased hospital resources. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Patient factors associated with lung transplant referral and waitlist for patients with cystic fibrosis and pulmonary fibrosis.

    Science.gov (United States)

    Liu, Yuan; Vela, Monica; Rudakevych, Tanya; Wigfield, Christopher; Garrity, Edward; Saunders, Milda R

    2017-03-01

    Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance. Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  19. Emphysema Is Common in Lungs of Cystic Fibrosis Lung Transplantation Patients: A Histopathological and Computed Tomography Study.

    Directory of Open Access Journals (Sweden)

    Onno M Mets

    Full Text Available Lung disease in cystic fibrosis (CF involves excessive inflammation, repetitive infections and development of bronchiectasis. Recently, literature on emphysema in CF has emerged, which might become an increasingly important disease component due to the increased life expectancy. The purpose of this study was to assess the presence and extent of emphysema in endstage CF lungs.In explanted lungs of 20 CF patients emphysema was semi-quantitatively assessed on histology specimens. Also, emphysema was automatically quantified on pre-transplantation computed tomography (CT using the percentage of voxels below -950 Houndfield Units and was visually scored on CT. The relation between emphysema extent, pre-transplantation lung function and age was determined.All CF patients showed emphysema on histological examination: 3/20 (15% showed mild, 15/20 (75% moderate and 2/20 (10% severe emphysema, defined as 0-20% emphysema, 20-50% emphysema and >50% emphysema in residual lung tissue, respectively. Visually upper lobe bullous emphysema was identified in 13/20 and more diffuse non-bullous emphysema in 18/20. Histology showed a significant correlation to quantified CT emphysema (p = 0.03 and visual emphysema score (p = 0.001. CT and visual emphysema extent were positively correlated with age (p = 0.045 and p = 0.04, respectively.In conclusion, this study both pathologically and radiologically confirms that emphysema is common in end-stage CF lungs, and is age related. Emphysema might become an increasingly important disease component in the aging CF population.

  20. Prevention of ischemia-reperfusion lung injury during static cold preservation by supplementation of standard preservation solution with HEMO2life® in pig lung transplantation model.

    Science.gov (United States)

    Glorion, M; Polard, V; Favereau, F; Hauet, T; Zal, F; Fadel, E; Sage, E

    2017-10-25

    We describe the results of adding a new biological agent HEMO 2 life ® to a standard preservation solution for hypothermic static lung preservation aiming to improve early functional parameters after lung transplantation. HEMO 2 life ® is a natural oxygen carrier extracted from Arenicola marina with high oxygen affinity developed as an additive to standard organ preservation solutions. Standard preservation solution (Perfadex ® ) was compared with Perfadex ® associated with HEMO 2 life ® and with sham animals after 24 h of hypothermic preservation followed by lung transplantation. During five hours of lung reperfusion, functional parameters and biomarkers expression in serum and in bronchoalveolar lavage fluid (BALF) were measured. After five hours of reperfusion, HEMO 2 life ® group led to significant improvement in functional parameters: reduction of graft vascular resistance (p preservation improves early graft function after prolonged cold ischemia in lung transplantation.

  1. Removal of metallic tracheobronchial stents in lung transplantation with flexible bronchoscopy

    Directory of Open Access Journals (Sweden)

    Fruchter Oren

    2010-09-01

    Full Text Available Abstract Background Airway complications are among the most challenging problems after lung transplantation, and Self-Expandable Metallic Stents (SEMS are used to treat airway complications such as stenosis or malacia at the bronchial anastomosis sites. Several transplantation centers are reluctant to use SEMS since their removal is sometimes needed and usually requires the use of rigid bronchoscopy under general anesthesia. The objective of the current report is to describe our experience in SEMS retrieval by flexible bronchoscopy under conscious sedation. Methods A retrospective review was done of patients requiring tracheobronchial stent placement after lung transplantation in which the SEMS had to be removed. The retrieval procedure was done by flexible bronchoscopy on a day-care ambulatory basis. Results Between January 2004 and January 2010, out of 305 lung transplantation patients, 24 (7.8% underwent SEMS placement. Indications included bronchial stenosis in 20 and bronchomalacia in 4. In six patients (25% the SEMS had to be removed due to excessive granulation tissue formation and stent obstruction. The average time from SEMS placement to retrieval was 30 months (range 16-48 months. The stent was completely removed in five patients and partially removed in one patient; no major complications were encountered, and all patients were discharged within 3 hours of the procedure. In all procedures, new SEMS was successfully re-inserted thereafter. Conclusions The retrieval of SEMS in patients that underwent lung transplantation can be effectively and safely done under conscious sedation using flexible bronchoscopy on a day-care basis, this observation should encourage increasing usage of SEMS in highly selected patients.

  2. Elevated plasma angiopoietin-2 levels and primary graft dysfunction after lung transplantation.

    Directory of Open Access Journals (Sweden)

    Joshua M Diamond

    Full Text Available Primary graft dysfunction (PGD is a significant contributor to early morbidity and mortality after lung transplantation. Increased vascular permeability in the allograft has been identified as a possible mechanism leading to PGD. Angiopoietin-2 serves as a partial antagonist to the Tie-2 receptor and induces increased endothelial permeability. We hypothesized that elevated Ang2 levels would be associated with development of PGD.We performed a case-control study, nested within the multi-center Lung Transplant Outcomes Group cohort. Plasma angiopoietin-2 levels were measured pre-transplant and 6 and 24 hours post-reperfusion. The primary outcome was development of grade 3 PGD in the first 72 hours. The association of angiopoietin-2 plasma levels and PGD was evaluated using generalized estimating equations (GEE.There were 40 PGD subjects and 79 non-PGD subjects included for analysis. Twenty-four PGD subjects (40% and 47 non-PGD subjects (59% received a transplant for the diagnosis of idiopathic pulmonary fibrosis (IPF. Among all subjects, GEE modeling identified a significant change in angiopoietin-2 level over time in cases compared to controls (p = 0.03. The association between change in angiopoietin-2 level over the perioperative time period was most significant in patients with a pre-operative diagnosis of IPF (p = 0.02; there was no statistically significant correlation between angiopoietin-2 plasma levels and the development of PGD in the subset of patients transplanted for chronic obstructive pulmonary disease (COPD (p = 0.9.Angiopoietin-2 levels were significantly associated with the development of PGD after lung transplantation. Further studies examining the regulation of endothelial cell permeability in the pathogenesis of PGD are indicated.

  3. Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant.

    Science.gov (United States)

    Cantu, Edward; Diamond, Joshua M; Suzuki, Yoshikazu; Lasky, Jared; Schaufler, Christian; Lim, Brian; Shah, Rupal; Porteous, Mary; Lederer, David J; Kawut, Steven M; Palmer, Scott M; Snyder, Laurie D; Hartwig, Matthew G; Lama, Vibha N; Bhorade, Sangeeta; Bermudez, Christian; Crespo, Maria; McDyer, John; Wille, Keith; Orens, Jonathan; Shah, Pali D; Weinacker, Ann; Weill, David; Wilkes, David; Roe, David; Hage, Chadi; Ware, Lorraine B; Bellamy, Scarlett L; Christie, Jason D

    2018-01-15

    Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.

  4. Influence of Pulmonary Hypertension on Patients With Idiopathic Pulmonary Fibrosis Awaiting Lung Transplantation.

    Science.gov (United States)

    Hayes, Don; Black, Sylvester M; Tobias, Joseph D; Kirkby, Stephen; Mansour, Heidi M; Whitson, Bryan A

    2016-01-01

    The influence of varying levels of pulmonary hypertension (PH) on survival in idiopathic pulmonary fibrosis is not well defined. The United Network for Organ Sharing database was queried from 2005 to 2013 to identify first-time lung transplant candidates listed for lung transplantation who were tracked from waitlist entry date until death or censoring to determine the influence of PH on patients with advanced lung disease. Using data for right heart catheterization measurements, mild PH was defined as mean pulmonary artery pressure of 25 mm Hg or more, and severe as 35 mm Hg or more. Of 6,657 idiopathic pulmonary fibrosis patients, 6,651 were used for univariate analysis, 6,126 for Kaplan-Meier survival function, 6,013 for multivariate Cox models, and 5,186 (mild PH) and 2,014 (severe PH) for propensity score matching, respectively. Univariate Cox proportional hazards analysis found significant differences in survival for mild PH (hazard ratio [HR] 1.689, 95% confidence interval [CI]: 1.434 to 1.988, p idiopathic pulmonary fibrosis awaiting lung transplantation, so referral should be considered early in the disease course. Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  5. Heart rate variability and baroreflex sensitivity in bilateral lung transplant recipients.

    Science.gov (United States)

    Fontolliet, Timothée; Gianella, Pietro; Pichot, Vincent; Barthélémy, Jean-Claude; Gasche-Soccal, Paola; Ferretti, Guido; Lador, Frédéric

    2018-01-09

    The effects of lung afferents denervation on cardiovascular regulation can be assessed on bilateral lung transplantation patients. The high-frequency component of heart rate variability is known to be synchronous with breathing frequency. Then, if heart beat is neurally modulated by breathing frequency, we may expect disappearance of high frequency of heart rate variability in bilateral lung transplantation patients. On 11 patients and 11 matching healthy controls, we measured R-R interval (electrocardiography), blood pressure (Portapres ® ) and breathing frequency (ultrasonic device) in supine rest, during 10-min free breathing, 10-min cadenced breathing (0·25 Hz) and 5-min handgrip. We analysed heart rate variability and spontaneous variability of arterial blood pressure, by power spectral analysis, and baroreflex sensitivity, by the sequence method. Concerning heart rate variability, with respect to controls, transplant recipients had lower total power and lower low- and high-frequency power. The low-frequency/high-frequency ratio was higher. Concerning systolic, diastolic and mean arterial pressure variability, transplant recipients had lower total power (only for cadenced breathing), low frequency and low-frequency/high-frequency ratio during free and cadenced breathing. Baroreflex sensitivity was decreased. Denervated lungs induced strong heart rate variability reduction. The higher low-frequency/high-frequency ratio suggested that the total power drop was mostly due to high frequency. These results support the hypothesis that neural modulation from lung afferents contributes to the high frequency of heart rate variability. © 2018 Scandinavian Society of Clinical Physiology and Nuclear Medicine. Published by John Wiley & Sons Ltd.

  6. Aspergillus infection of the respiratory tract after lung transplantation: chest radiographic and CT findings

    International Nuclear Information System (INIS)

    Diederich, S.; Scadeng, M.; Flower, C.D.R.; Dennis, C.; Stewart, S.

    1998-01-01

    The objective of our study was to assess radiographic and CT findings in lung transplant patients with evidence of Aspergillus colonization or infection of the airways and correlate the findings with clinical, laboratory, bronchoalveolar lavage, biopsy and autopsy findings. The records of 189 patients who had undergone lung transplantation were retrospectively reviewed for evidence of Aspergillus colonization or infection of the airways. Aspergillus was demonstrated by culture or microscopy of sputum or bronchoalveolar lavage fluid or histologically from lung biopsies or postmortem studies in 44 patients (23 %). Notes and radiographs were available for analysis in 30 patients. In 12 of the 30 patients (40 %) chest radiographs remained normal. In 11 of 18 patients with abnormal radiographs pulmonary abnormalities were attributed to invasive pulmonary aspergillosis (IPA) in the absence of other causes for pulmonary abnormalities (8 patients) or because of histological demonstration of IPA (3 patients). In these 11 patients initial radiographic abnormalities were focal areas of patchy consolidation (8 patients), ill-defined pulmonary nodules (2 patients) or a combination of both (1 patient). In some of the lesions cavitation was demonstrated subsequently. At CT a ''halo'' of decreased density was demonstrated in some of the nodules and lesion morphology and location were shown more precisely. Demonstration of Aspergillus from the respiratory tract after lung transplantation does not necessarily reflect IPA but may represent colonization of the airways or semi-invasive aspergillosis. The findings in patients with IPA did not differ from those described in the literature in other immunocompromised patients, suggesting that surgical disruption of lymphatic drainage and nervous supply or effects of preservation and transport of the transplant lung do not affect the radiographic appearances. (orig.)

  7. Acute cellular rejection is a risk factor for bronchiolitis obliterans syndrome independent of post-transplant baseline FEV1

    DEFF Research Database (Denmark)

    Burton, C.M.; Iversen, M.; Carlsen, J.

    2009-01-01

    BACKGROUND: Post-transplant baseline forced expiratory volume in 1 second (FEV(1)) constitutes a systematic bias in analyses of bronchiolitis obliterans syndrome (BOS). This retrospective study evaluates risk factors for BOS adjusting for the confounding of post-transplant baseline FEV(1). METHODS......-specific hazard of BOS (hazard ratio 1.4, confidence interval 1.1 to 1.8, p = 0.009). The absolute value of baseline FEV(1) was a significant confounder in all survival and competing risk analyses of BOS (p ... an independent risk factor for the development of BOS after adjusting for the confounding of post-transplant baseline FEV(1) Udgivelsesdato: 2009/9...

  8. Intra-operative protective mechanical ventilation in lung transplantation: a randomised, controlled trial.

    Science.gov (United States)

    Verbeek, G L; Myles, P S; Westall, G P; Lin, E; Hastings, S L; Marasco, S F; Jaffar, J; Meehan, A C

    2017-08-01

    Primary graft dysfunction occurs in up to 25% of patients after lung transplantation. Contributing factors include ventilator-induced lung injury, cardiopulmonary bypass, ischaemia-reperfusion injury and excessive fluid administration. We evaluated the feasibility, safety and efficacy of an open-lung protective ventilation strategy aimed at reducing ventilator-induced lung injury. We enrolled adult patients scheduled to undergo bilateral sequential lung transplantation, and randomly assigned them to either a control group (volume-controlled ventilation with 5 cmH 2 O, positive end-expiratory pressure, low tidal volumes (two-lung ventilation 6 ml.kg -1 , one-lung ventilation 4 ml.kg -1 )) or an alveolar recruitment group (regular step-wise positive end-expiratory pressure-based alveolar recruitment manoeuvres, pressure-controlled ventilation set at 16 cmH 2 O with 10 cmH 2 O positive end-expiratory pressure). Ventilation strategies were commenced from reperfusion of the first lung allograft and continued for the duration of surgery. Regular PaO 2 /F I O 2 ratios were calculated and venous blood samples collected for inflammatory marker evaluation during the procedure and for the first 24 h of intensive care stay. The primary end-point was the PaO 2 /F I O 2 ratio at 24 h after first lung reperfusion. Thirty adult patients were studied. The primary outcome was not different between groups (mean (SD) PaO 2 /F I O 2 ratio control group 340 (111) vs. alveolar recruitment group 404 (153); adjusted p = 0.26). Patients in the control group had poorer mean (SD) PaO 2 /F I O 2 ratios at the end of the surgical procedure and a longer median (IQR [range]) time to tracheal extubation compared with the alveolar recruitment group (308 (144) vs. 402 (154) (p = 0.03) and 18 (10-27 [5-468]) h vs. 15 (11-36 [5-115]) h (p = 0.01), respectively). An open-lung protective ventilation strategy during surgery for lung transplantation is feasible, safe and achieves favourable

  9. Identification of patients at risk of acute rejection by pretransplantation and posttransplantation monitoring of soluble CD30 levels in kidney transplantation.

    Science.gov (United States)

    Sengul, Sule; Keven, Kenan; Gormez, Ulku; Kutlay, Sim; Erturk, Sehsuvar; Erbay, Bulent

    2006-04-27

    In this study, we investigated the impact of pre- and posttransplantation sCD30 monitoring on early (acute rejection (AR) risk and analyzed the effect of different immunosuppressive regimens on posttransplantation sCD30 levels in kidney recipients. Fifty patients receiving kidney allograft and 10 healthy donors were included in this retrospective cohort study. Eight patients developed biopsy-proven AR (19%). In pretransplantation samples, patients showed a significantly higher sCD30 than healthy controls. The pretransplantation and posttransplantation (day-15) sCD30 levels were significantly elevated in rejecting patients compared to non-rejecting patients. No significant differences among immunosuppressive regimens were found in posttransplantation sCD30 levels. High pretransplantation and posttransplantation (day 15) sCD30 levels are associated with increased risk of early AR, and sCD30 can be another tool to evaluate immunological risk prior to kidney transplantation. There was no difference in immunosuppressive regimens used in this study on posttransplantation sCD30 levels at the first month.

  10. Successful Recanalization of a Complete Lobar Bronchial Stenosis in a Lung Transplant Patient Using a Combined Percutaneous and Bronchoscopic Approach

    International Nuclear Information System (INIS)

    Miraglia, Roberto; Vitulo, Patrizio; Maruzzelli, Luigi; Burgio, Gaetano; Caruso, Settimo; Bertani, Alessandro; Callari, Adriana; Luca, Angelo

    2016-01-01

    Airway stenosis is a major complication after lung transplantation that is usually managed with a combination of interventional endoscopic techniques, including endobronchial debridement, balloon dilation, and stent placement. Herein, we report a successful case of recanalization of a complete stenosis of the right middle lobe bronchus in a lung transplant patient, by using a combined percutaneous–bronchoscopic approach after the failure of endobronchial debridement

  11. Successful Recanalization of a Complete Lobar Bronchial Stenosis in a Lung Transplant Patient Using a Combined Percutaneous and Bronchoscopic Approach

    Energy Technology Data Exchange (ETDEWEB)

    Miraglia, Roberto, E-mail: rmiraglia@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy); Vitulo, Patrizio, E-mail: pvitulo@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Pulmonology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation (Italy); Maruzzelli, Luigi, E-mail: lmaruzzelli@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy); Burgio, Gaetano, E-mail: gburgio@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Operating Room Service, Department of Anesthesia and Intensive Care (Italy); Caruso, Settimo, E-mail: secaruso@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy); Bertani, Alessandro, E-mail: abertani@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Thoracic Surgery and Lung Transplantation Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation (Italy); Callari, Adriana, E-mail: acallari@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Pulmonology Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation (Italy); Luca, Angelo, E-mail: aluca@ismett.edu [Mediterranean Institute for Transplantation and Advanced Specialized Therapies (ISMETT), Radiology Service, Department of Diagnostic and Therapeutic Services (Italy)

    2016-03-15

    Airway stenosis is a major complication after lung transplantation that is usually managed with a combination of interventional endoscopic techniques, including endobronchial debridement, balloon dilation, and stent placement. Herein, we report a successful case of recanalization of a complete stenosis of the right middle lobe bronchus in a lung transplant patient, by using a combined percutaneous–bronchoscopic approach after the failure of endobronchial debridement.

  12. Review: The transcripts associated with organ allograft rejection.

    Science.gov (United States)

    Halloran, Philip F; Venner, Jeffery M; Madill-Thomsen, Katelynn S; Einecke, Gunilla; Parkes, Michael D; Hidalgo, Luis G; Famulski, Konrad S

    2018-04-01

    The molecular mechanisms operating in human organ transplant rejection are best inferred from the mRNAs expressed in biopsies because the corresponding proteins often have low expression and short half-lives, while small non-coding RNAs lack specificity. Associations should be characterized in a population that rigorously identifies T cell-mediated (TCMR) and antibody-mediated rejection (ABMR). This is best achieved in kidney transplant biopsies, but the results are generalizable to heart, lung, or liver transplants. Associations can be universal (all rejection), TCMR-selective, or ABMR-selective, with universal being strongest and ABMR-selective weakest. Top universal transcripts are IFNG-inducible (eg, CXCL11 IDO1, WARS) or shared by effector T cells (ETCs) and NK cells (eg, KLRD1, CCL4). TCMR-selective transcripts are expressed in activated ETCs (eg, CTLA4, IFNG), activated (eg, ADAMDEC1), or IFNG-induced macrophages (eg, ANKRD22). ABMR-selective transcripts are expressed in NK cells (eg, FGFBP2, GNLY) and endothelial cells (eg, ROBO4, DARC). Transcript associations are highly reproducible between biopsy sets when the same rejection definitions, case mix, algorithm, and technology are applied, but exact ranks will vary. Previously published rejection-associated transcripts resemble universal and TCMR-selective transcripts due to incomplete representation of ABMR. Rejection-associated transcripts are never completely rejection-specific because they are shared with the stereotyped response-to-injury and innate immunity. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  13. Oxygen-sensitive 3He-MRI in bronchiolitis obliterans after lung transplantation

    International Nuclear Information System (INIS)

    Gast, Klaus K.; Biedermann, Alexander; Herweling, Annette; Schreiber, Wolfgang G.; Schmiedeskamp, Joerg; Mayer, Eckhard; Heussel, Claus P.; Markstaller, Klaus; Eberle, Balthasar; Kauczor, Hans-Ulrich

    2008-01-01

    Oxygen-sensitive 3 He-MRI was studied for the detection of differences in intrapulmonary oxygen partial pressure (pO 2 ) between patients with normal lung transplants and those with bronchiolitis obliterans syndrome (BOS). Using software developed in-house, oxygen-sensitive 3 He-MRI datasets from patients with normal lung grafts (n = 8) and with BOS (n = 6) were evaluated quantitatively. Datasets were acquired on a 1.5-T system using a spoiled gradient echo pulse sequence. Underlying diseases were pulmonary emphysema (n 10 datasets) and fibrosis (n = 4). BOS status was verified by pulmonary function tests. Additionally, 3 He-MRI was assessed blindedly for ventilation defects. Median intrapulmonary pO 2 in patients with normal lung grafts was 146 mbar compared with 108 mbar in patients with BOS. Homogeneity of pO2 distribution was greater in normal grafts (standard deviation pO2 34 versus 43 mbar). Median oxygen decrease rate during breath hold was higher in unaffected patients (-1.75 mbar/s versus -0.38 mbar/s). Normal grafts showed fewer ventilation defects (5% versus 28%, medians). Oxygen-sensitive 3 He-MRI appears capable of demonstrating differences of intrapulmonary pO2 between normal lung grafts and grafts affected by BOS. Oxygen-sensitive 3 He-MRI may add helpful regional information to other diagnostic techniques for the assessment and follow-up of lung transplant recipients. (orig.)

  14. Tracking the engraftment and regenerative capabilities of transplanted lung stem cells using fluorescent nanodiamonds.

    Science.gov (United States)

    Wu, Tsai-Jung; Tzeng, Yan-Kai; Chang, Wei-Wei; Cheng, Chi-An; Kuo, Yung; Chien, Chin-Hsiang; Chang, Huan-Cheng; Yu, John

    2013-09-01

    Lung stem/progenitor cells are potentially useful for regenerative therapy, for example in repairing damaged or lost lung tissue in patients. Several optical imaging methods and probes have been used to track how stem cells incorporate and regenerate themselves in vivo over time. However, these approaches are limited by photobleaching, toxicity and interference from background tissue autofluorescence. Here we show that fluorescent nanodiamonds, in combination with fluorescence-activated cell sorting, fluorescence lifetime imaging microscopy and immunostaining, can identify transplanted CD45(-)CD54(+)CD157(+) lung stem/progenitor cells in vivo, and track their engraftment and regenerative capabilities with single-cell resolution. Fluorescent nanodiamond labelling did not eliminate the cells' properties of self-renewal and differentiation into type I and type II pneumocytes. Time-gated fluorescence imaging of tissue sections of naphthalene-injured mice indicates that the fluorescent nanodiamond-labelled lung stem/progenitor cells preferentially reside at terminal bronchioles of the lungs for 7 days after intravenous transplantation.

  15. Extracorporeal life support as a bridge to lung transplantation-experience of a high-volume transplant center.

    Science.gov (United States)

    Hoetzenecker, Konrad; Donahoe, Laura; Yeung, Jonathan C; Azad, Sassan; Fan, Eddy; Ferguson, Niall D; Del Sorbo, Lorenzo; de Perrot, Marc; Pierre, Andrew; Yasufuku, Kazuhiro; Singer, Lianne; Waddell, Thomas K; Keshavjee, Shaf; Cypel, Marcelo

    2018-03-01

    Extracorporeal life support (ECLS) is increasingly used to bridge deteriorating patients awaiting lung transplantation (LTx), however, few systematic descriptions of this practice exist. We therefore aimed to review our institutional experience over the past 10 years. In this case series, we included all adults who received ECLS with the intent to bridge to LTx. Data were retrieved from patient charts and our institutional ECLS and transplant databases. Between January 2006 and September 2016, 1111 LTx were performed in our institution. ECLS was used in 71 adults with the intention to bridge to LTx; of these, 11 (16%) were bridged to retransplantation. The median duration of ECLS before LTx was 10 days (range, 0-95). We used a single dual-lumen venous cannula in 23 patients (32%). Nine of 13 patients (69%) with pulmonary hypertension were bridged by central pulmonary artery to left atrium Novalung. Twenty-five patients (35%) were extubated while on ECLS and 26 patients (37%) were mobilized. Sixty-three patients (89%) survived to LTx. Survival by intention to treat was 66% (1 year), 58% (3 years) and 48% (5 years). Survival was significantly shorter in patients undergoing ECLS bridge to retransplantation compared with first LTx (median survival, 15 months (95% CI, 0-31) versus 60 months (95% CI, 37-83); P = .041). In our center experience, ECLS bridge to first lung transplant leads to good short-term and long-term outcomes in carefully selected patients. In contrast, our data suggest that ECLS as a bridge to retransplantation should be used with caution. Copyright © 2017 The American Association for Thoracic Surgery. All rights reserved.

  16. Evaluation of right ventricular function for lung transplantation. Role of electron flow scan

    International Nuclear Information System (INIS)

    Stern, M.; Joint-Lambert, O.; Tainturier, C.; Seigneur, F.; Caubarrere, I.; Hernigou, A.

    1994-01-01

    Several invasive or not invasive technics were used to evaluate right ventricular insufficiency associated to severe chronic pulmonary insufficiency. But none of them were very accurate and now the use of EBT appears as a real improvement. We performed a prospective study with 50 patients waiting for a lung transplantation and we compared the values of right ventricular function obtained by EBT to those obtained by nuclear medicine and catheterism. Accuracy of EBT for left ventricle evaluation has already been proved. Stroke volumes calculated by EBT in right and left ventricles are similar and this constitutes a good validation of the method for right ventricle evaluation. Correlations with hemodynamic measurements are poor and nuclear medicine technics underestimate the ejection fraction. So, EBT is recommended for right ventricular study before and after lung transplantation. (authors). 11 refs., 4 figs

  17. High emergency organ allocation rule in lung transplantation: a simulation study.

    Science.gov (United States)

    Riou, Julien; Boëlle, Pierre-Yves; Christie, Jason D; Thabut, Gabriel

    2017-10-01

    The scarcity of suitable organ donors leads to protracted waiting times and mortality in patients awaiting lung transplantation. This study aims to assess the short- and long-term effects of a high emergency organ allocation policy on the outcome of lung transplantation. We developed a simulation model of lung transplantation waiting queues under two allocation strategies, based either on waiting time only or on additional criteria to prioritise the sickest patients. The model was informed by data from the United Network for Organ Sharing. We compared the impact of these strategies on waiting time, waiting list mortality and overall survival in various situations of organ scarcity. The impact of a high emergency allocation strategy depends largely on the organ supply. When organ supply is sufficient (>95 organs per 100 patients), it may prevent a small number of early deaths (1 year survival: 93.7% against 92.4% for waiting time only) without significant impact on waiting times or long-term survival. When the organ/recipient ratio is lower, the benefits in early mortality are larger but are counterbalanced by a dramatic increase of the size of the waiting list. Consequently, we observed a progressive increase of mortality on the waiting list (although still lower than with waiting time only), a deterioration of patients' condition at transplant and a decrease of post-transplant survival times. High emergency organ allocation is an effective strategy to reduce mortality on the waiting list, but causes a disruption of the list equilibrium that may have detrimental long-term effects in situations of significant organ scarcity.

  18. Increased proximal acid reflux is associated with early readmission following lung transplantation.

    Science.gov (United States)

    Lo, W-K; Goldberg, H J; Burakoff, R; Feldman, N; Chan, W W

    2016-02-01

    Gastroesophageal reflux disease has been associated with poor outcomes following lung transplantation. However, the association between pretransplant reflux and post-transplant readmission, an indicator of early clinical outcome, has not been previously assessed. This was a retrospective cohort study of lung transplant recipients undergoing pretransplant multichannel intraluminal impedance and pH (MII-pH) study off acid suppression at a tertiary care center since 2007. Subjects with pretransplant fundoplication were excluded. Time to readmission was defined as duration from post-transplant discharge to next hospital admission for any reason. Subgroup analysis was performed to exclude elective readmissions. Time-to-event analysis was performed using Cox proportional hazards model, with appropriate censoring. Forty-three subjects (60% men, mean age: 57, median follow-up: 1.7 years) met inclusion criteria for the study. Patient demographics and pretransplant cardiopulmonary function were similar between readmission cohorts. Time to all-cause readmission was associated with increased distal acid episodes (HR: 3.15, p = 0.04) and proximal acid episodes (HR: 3.61, p = 0.008) on impedance, increased acid exposure on pH (HR: 2.22, p = 0.04), and elevated Demeester score (HR: 2.26, p = 0.03). When elective readmissions were excluded, early readmission remained significantly associated with increased proximal acid reflux episodes (HR: 2.49, p = 0.04). All findings were confirmed on Kaplan-Meier analysis. Elevated proximal acid reflux on pretransplant MII-pH testing was associated with early readmission following lung transplantation, even after excluding elective readmissions. Exposure to severe acid reflux has measurable effects on early postoperative outcomes such as readmission, and aggressive early antireflux therapy should be considered. © 2015 John Wiley & Sons Ltd.

  19. Higher tacrolimus trough levels on days 2-5 post-renal transplant are associated with reduced rates of acute rejection.

    LENUS (Irish Health Repository)

    O'Seaghdha, C M

    2011-04-06

    We analyzed the association between whole-blood trough tacrolimus (TAC) levels in the first days post-kidney transplant and acute cellular rejection (ACR) rates. Four hundred and sixty-four consecutive, deceased-donor kidney transplant recipients were included. All were treated with a combination of TAC, mycophenolate mofetil and prednisolone. Patients were analyzed in four groups based on quartiles of the mean TAC on days 2 and 5 post-transplant: Group 1: median TAC 11 ng\\/mL (n = 122, range 2-13.5 ng\\/mL), Group 2: median 17 ng\\/mL (n = 123, range 14-20 ng\\/mL), Group 3: median 24 ng\\/mL (n = 108, range 20.5-27 ng\\/mL) and Group 4: median 33.5 ng\\/mL (n = 116, range 27.5-77.5 ng\\/mL). A graded reduction in the rates of ACR was observed for each incremental days 2-5 TAC. The one-yr ACR rate was 24.03% (95% CI 17.26-32.88), 22.20% (95% CI 15.78-30.70), 13.41% (95% CI 8.15-21.63) and 8.69% (95% CI 4.77-15.55) for Groups 1-4, respectively (p = 0.003). This study suggests that higher early TACs are associated with reduced rates of ACR at one yr.

  20. Development of PET Imaging to Visualize Activated Macrophages Accumulated in the Transplanted iPSc-Derived Cardiac Myocytes of Allogeneic Origin for Detecting the Immune Rejection of Allogeneic Cell Transplants in Mice.

    Directory of Open Access Journals (Sweden)

    Noriyuki Kashiyama

    Full Text Available Allogeneic transplantation (Tx of induced pluripotent stem cells (iPSCs is a promising tissue regeneration therapy. However, this inevitably induces macrophage-mediated immune response against the graft, limiting its therapeutic efficacy. Monitoring the magnitude of the immune response using imaging tools would be useful for prolonging graft survival and increasing the therapy longevity. Minimally invasive quantitative detection of activated macrophages by medical imaging technologies such as positron emission tomography (PET imaging targets translocator protein (TSPO, which is highly expressed on mitochondrial membrane, especially in activated macrophage. N,N-diethyl-2-[4-(2-fluoroethoxy phenyl]-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-acetamide (DPA-714 is known as a TSPO ligand used in clinical settings. We herein hypothesized that immune rejection of the transplanted iPSC-derived cardiomyocytes (iPSC-CMs of allogeneic origin may be quantitated using 18F-DPA-714-PET imaging study. iPSC-CM cell-sheets of C57BL/6 mice origin were transplanted on the surface of the left ventricle (LV of C57BL/6 mice as a syngeneic cell-transplant model (syngeneic Tx group, or Balb/c mice as an allogeneic model (allogeneic Tx group. 18F-DPA-714-PET was used to determine the uptake ratio, calculated as the maximum standardized uptake value in the anterior and septal wall of the LV. The uptake ratio was significantly higher in the allogeneic Tx group than in the syngeneic group or the sham group at days 7 and day 10 after the cell transplantation. In addition, the immunochemistry showed significant presence of CD68 and CD3-positive cells at day 7 and 10 in the transplanted graft of the allogeneic Tx group. The expression of TSPO, CD68, IL-1 beta, and MCP-1 was significantly higher in the allogeneic Tx group than in the syngeneic Tx and the sham groups at day 7. The 18F-DPA-714-PET imaging study enabled quantitative visualization of the macrophages-mediated immune

  1. Thoracic organ transplantation: laboratory methods.

    Science.gov (United States)

    Patel, Jignesh K; Kobashigawa, Jon A

    2013-01-01

    Although great progress has been achieved in thoracic organ transplantation through the development of effective immunosuppression, there is still significant risk of rejection during the early post-transplant period, creating a need for routine monitoring for both acute antibody and cellular mediated rejection. The currently available multiplexed, microbead assays utilizing solubilized HLA antigens afford the capability of sensitive detection and identification of HLA and non-HLA specific antibodies. These assays are being used to assess the relative strength of donor specific antibodies; to permit performance of virtual crossmatches which can reduce the waiting time to transplantation; to monitor antibody levels during desensitization; and for heart transplants to monitor antibodies post-transplant. For cell mediated immune responses, the recent development of gene expression profiling has allowed noninvasive monitoring of heart transplant recipients yielding predictive values for acute cellular rejection. T cell immune monitoring in heart and lung transplant recipients has allowed individual tailoring of immunosuppression, particularly to minimize risk of infection. While the current antibody and cellular laboratory techniques have enhanced the ability to manage thoracic organ transplant recipients, future developments from improved understanding of microchimerism and graft tolerance may allow more refined allograft monitoring techniques.

  2. Pseudomembranous aspergillus bronchitis in a double-lung transplanted patient: unusual radiographic and CT features

    International Nuclear Information System (INIS)

    Ducreux, D.; Chevallier, P.; Raffaelli, C.; Padovani, B.; Perrin, C.; Jourdan, J.; Hofman, P.

    2000-01-01

    Pseudomembranous aspergillus bronchitis is considered as an early form of invasive pulmonary aspergillosis, a well-known airway infection in immunocompromised patients. Radiologic features concerning invasive aspergillosis of the airways have been reported. However, we describe here an unusual feature of invasive aspergillus bronchitis, never reported to date, observed in a double-lung transplanted patient. Chest radiograph and CT revealed significant peribronchial thickening without any parenchymal involvement. (orig.)

  3. Corneal Allograft Rejection: Topical Treatment Vs. Pulsed Intravenous Methylprednisolone - Ten Years' Result [rejeição De Transplantes De Córnea: Tratamento Tópico Vs. Pulsoterapia - Resultados De 10 Anos

    OpenAIRE

    Costa D.C.; de Castro R.S.; Ferraz de Camargo M.S.; Kara-Jose N.

    2008-01-01

    Purpose: To evaluate the efficacy of intravenous 500 mg methylprednisolone in addition to topical treatment with 1% prednisolone in the treatment of the first episode of corneal endothelial rejection in patients that were submitted to corneal allograft transplantation. Methods: Retrospective casecontrol study with 81 patients that presented the first episode of corneal endothelial rejection and were treated within the first 15 days of the onset of symptoms. Results: 67 patients were treated w...

  4. Alveolar and serum concentrations of imipenem in two lung transplant recipients supported with extracorporeal membrane oxygenation.

    Science.gov (United States)

    Welsch, C; Augustin, P; Allyn, J; Massias, L; Montravers, P; Allou, N

    2015-02-01

    Venovenous extracorporeal membrane oxygenation (ECMO) is increasingly used in patients with respiratory failure who fail conventional treatment. Postoperative pneumonia is the most common infection after lung transplantation (40%). Imipenem is frequently used for empirical treatment of nosocomial pneumonia in the intensive care unit. Nevertheless, few data are available on the impact of ECMO on pharmacokinetics, and no data on imipenem dosing during ECMO. Currently, no guidelines exist for antibiotic dosing during ECMO support. We report the cases of 2 patients supported with venovenous ECMO for refractory acute respiratory distress syndrome following single lung transplantation for pulmonary fibrosis, treated empirically with 1 g of imipenem intravenously every 6 h. Enterobacter cloacae was isolated from the respiratory sample of Patient 1 and Klebsiella pneumoniae was isolated from the respiratory sample of Patient 2. Minimum inhibitory concentrations of the 2 isolated strains were 0.125 and 0.25 mg/L, respectively. Both patients were still alive on day 28. This is the first report, to our knowledge, of imipenem concentrations in lung transplantation patients supported with ECMO. This study confirms high variability in imipenem trough concentrations in patients on ECMO and with preserved renal function. An elevated dosing regimen (4 g/24 h) is more likely to optimize drug exposure, and therapeutic drug monitoring is recommended, where available. Population pharmacokinetic studies are indicated to develop evidence-based dosing guidelines for ECMO patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  5. Influence of early neurological complications on clinical outcome following lung transplant.

    Science.gov (United States)

    Gamez, Josep; Salvado, Maria; Martinez-de La Ossa, Alejandro; Deu, Maria; Romero, Laura; Roman, Antonio; Sacanell, Judith; Laborda, Cesar; Rochera, Isabel; Nadal, Miriam; Carmona, Francesc; Santamarina, Estevo; Raguer, Nuria; Canela, Merce; Solé, Joan

    2017-01-01

    Neurological complications after lung transplantation are common. The full spectrum of neurological complications and their impact on clinical outcomes has not been extensively studied. We investigated the neurological incidence of complications, categorized according to whether they affected the central, peripheral or autonomic nervous systems, in a series of 109 patients undergoing lung transplantation at our center between January 1 2013 and December 31 2014. Fifty-one patients (46.8%) presented at least one neurological complication. Critical illness polyneuropathy-myopathy (31 cases) and phrenic nerve injury (26 cases) were the two most prevalent complications. These two neuromuscular complications lengthened hospital stays by a median period of 35.5 and 32.5 days respectively. However, neurological complications did not affect patients' survival. The real incidence of neurological complications among lung transplant recipients is probably underestimated. They usually appear in the first two months after surgery. Despite not affecting mortality, they do affect the mean length of hospital stay, and especially the time spent in the Intensive Care Unit. We found no risk factor for neurological complications except for long operating times, ischemic time and need for transfusion. It is necessary to develop programs for the prevention and early recognition of these complications, and the prevention of their precipitant and risk factors.

  6. Diagnosis of human metapneumovirus infection in immunosuppressed lung transplant recipients and children evaluated for pertussis.

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St; Wadowsky, Robert M; Paterson, David L; McCurry, Kenneth R; Reinhart, Todd A; Husain, Shahid; Rinaldo, Charles R

    2007-02-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses.

  7. Diagnosis of Human Metapneumovirus Infection in Immunosuppressed Lung Transplant Recipients and Children Evaluated for Pertussis▿

    Science.gov (United States)

    Dare, Ryan; Sanghavi, Sonali; Bullotta, Arlene; Keightley, Maria-Cristina; George, Kirsten St.; Wadowsky, Robert M.; Paterson, David L.; McCurry, Kenneth R.; Reinhart, Todd A.; Husain, Shahid; Rinaldo, Charles R.

    2007-01-01

    Human metapneumovirus (hMPV) is a recently discovered paramyxovirus that is known to cause respiratory tract infections in children and immunocompromised individuals. Given the difficulties of identifying hMPV by conventional culture, molecular techniques could improve the detection of this virus in clinical specimens. In this study, we developed a real-time reverse transcription-PCR (RT-PCR) assay designed to detect the four genetic lineages of hMPV. This assay and a commercial real-time nucleic acid sequence-based amplification (NASBA) assay (bioMérieux, Durham, NC) were used to determine the prevalence of hMPV in 114 immunosuppressed asymptomatic and symptomatic lung transplant recipients and 232 pediatric patients who were being evaluated for pertussis. hMPV was detected in 4.3% of the immunosuppressed lung transplant recipients and in 9.9% of children evaluated for pertussis. Both RT-PCR and NASBA assays were efficient in detection of hMPV infection in respiratory specimens. Even though hMPV was detected in a small number of the lung transplant recipients, it was still the most prevalent etiologic agent detected in patients with respiratory symptoms. In both of these diverse patient populations, hMPV infection was the most frequent viral respiratory tract infection identified. Given our findings, infection with hMPV infection should be determined as part of the differential diagnosis of respiratory illnesses. PMID:17065270

  8. A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death.

    Science.gov (United States)

    van Suylen, V; Luijk, B; Hoek, R A S; van de Graaf, E A; Verschuuren, E A; Van De Wauwer, C; Bekkers, J A; Meijer, R C A; van der Bij, W; Erasmus, M E

    2017-10-01

    The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one-to-one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long-term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  9. High variation of individual soluble serum CD30 levels of pre-transplantation patients: sCD30 a feasible marker for prediction of kidney allograft rejection?

    Science.gov (United States)

    Altermann, Wolfgang; Schlaf, Gerald; Rothhoff, Anita; Seliger, Barbara

    2007-10-01

    Previous studies have suggested that the pre-transplant levels of the soluble CD30 molecule (sCD30) represent a non-invasive tool which can be used as a biomarker for the prediction of kidney allograft rejections. In order to evaluate the feasibility of sCD30 for pre-transplantation monitoring the sera of potential kidney recipients (n = 652) were collected four times in a 3 months interval. Serum from healthy blood donors (n = 203) served as controls. The sCD30 concentrations of all samples were determined using a commercially available ELISA. This strategy allowed the detection of possible variations of individual sCD30 levels over time. Heterogeneous sCD30 concentrations were found in the samples obtained from individual putative kidney transplant recipients when quarterly measured over 1 year. Total 95% of serum samples obtained from healthy controls exhibited sCD30 values 30 U/ml). Total 524 patients (80.4%) constantly exhibited serum concentrations of sCD30 values >100 U/ml was significantly lower than that previously reported. The high degree of variation does not allow the stratification of patients into high and low immunological risk groups based on a single sCD30 value > 100 U/ml. Due to the heterogeneity of sCD30 levels during time course and the high values of SD, its implementation as a pre-transplant marker cannot be justified to generate special provisions for the organ allocation to patients with single sCD30 values > 100 U/ml.

  10. Successful lung transplantation for talcosis secondary to intravenous abuse of oral drug

    Directory of Open Access Journals (Sweden)

    Dekel Shlomi

    2008-06-01

    Full Text Available Dekel Shlomi1, David Shitrit1, Daniele Bendayan1, Gidon Sahar2, Yitshak Shechtman3, Mordechai R Kramer11Pulmonary Institute, Departments of 2Cardiothoracic Surgery and 3Pathology, Rabin Medical Center, Beilinson Campus, Petah Tiqwa, and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAbstract: Talcosis due to intravenous injection of oral drugs can cause severe pulmonary disease with progressive dyspnea even when drug use is discontinued. We describe a 54-yearold woman with severe emphysema who underwent left lung transplantation. The patient had a remote history of intravenous injection of crushed methylphenidate (Ritalin tablets. Chest computed tomography showed severe emphysematous changes, more prominent in the lower lobes. Microscopic examination of the extracted lung demonstrated multinucleated giant cells with birefringent crystals, compatible with talcosis. At follow-up, daily symptoms were completely alleviated and lung function was good. We recommend that lung transplantation be considered as a viable option in the treatment of talcosis.Keywords: methylphenidate (Ritalin, emphysema

  11. 3He-MRI in follow-up of lung transplant recipients

    International Nuclear Information System (INIS)

    Gast, Klaus Kurt; Zaporozhan, Julia; Ley, Sebastian; Biedermann, Alexander; Knitz, Frank; Eberle, Balthasar; Schmiedeskamp, Joerg; Heussel, Claus-Peter; Mayer, Eckhard; Schreiber, Wolfgang Guenter; Thelen, Manfred; Kauczor, Hans-Ulrich

    2004-01-01

    The aim of this study was to evaluate the possible contribution of 3 He-MRI to detect obliterative bronchiolitis (OB) in the follow-up of lung transplant recipients. Nine single- and double-lung transplanted patients were studied by an initial and a follow-up 3 He-MRI study. Images were evaluated subjectively by estimation of ventilation defect area and quantitatively by individually adapted threshold segmentation and subsequent calculation of ventilated lung volume. Bronchiolitis obliterans syndrome (BOS) was diagnosed using pulmonary function tests. At 3 He-MRI, OB was suspected if ventilated lung volume had decreased by 10% or more at the follow-up MRI study compared with the initial study. General accordance between pulmonary function testing and 3 He-MRI was good, although subjective evaluation of 3 He-MRI underestimated improvement in ventilation as obtained by pulmonary function tests. The 3 He-MRI indicated OB in 6 cases. According to pulmonary function tests, BOS was diagnosed in 5 cases. All diagnoses of BOS were also detected by 3 He-MRI. In 2 of these 5 cases, 3 He-MRI indicated OB earlier than pulmonary function tests. The results support the hypothesis that 3 He-MRI may be sensitive for early detection of OB and emphasize the need for larger prospective follow-up studies. (orig.)

  12. Treatment of intractable interstitial lung injury with alemtuzumab after lung transplantation

    DEFF Research Database (Denmark)

    Kohno, M; Perch, M; Andersen, E

    2011-01-01

    of acute rejection, worsened within 2 weeks, despite high-dose steroids, change of calcineurin inhibitor, and plasmapheresis. Within a few days after a single, 10-mg, intravenous dose of alemtuzumab, the patient's health improved markedly. She has remained stable for 4 months on a standard, ambulatory...

  13. Chest computed tomography scores are predictive of survival in patients with cystic fibrosis awaiting lung transplantation

    DEFF Research Database (Denmark)

    Loeve, Martine; Hop, Wim C. J.; de Bruijne, Marleen

    2012-01-01

    Rationale: Up to a third of cystic fibrosis (CF) patients awaiting lung transplantation (LTX) die while waiting. Inclusion of computed tomography (CT) scores may improve survival prediction models such as the lung allocation score (LAS). Objectives: This study investigated the association between...... CT and survival in CF patients screened for LTX. Methods: Clinical data and chest CTs of 411 CF patients screened for LTX between 1990 and 2005 were collected from 17 centers. CTs were scored with the Severe Advanced Lung Disease (SALD) 4-category scoring system, including the components "infection....../inflammation" (INF), air trapping/hypoperfusion (AT), normal/hyperperfusion (NOR) and bulla/cysts (BUL). The volume of each component was computed using semi-automated software. Survival analysis included Kaplan-Meier curves, and Cox-regression models. Measurements and main results: 366 (186 males) out of 411...

  14. False Elevation of the Blood Tacrolimus Concentration, as Assessed by an Affinity Column-mediated Immunoassay (ACMIA), Led to Acute T Cell-mediated Rejection after Kidney Transplantation.

    Science.gov (United States)

    Kono, Momoko; Hasegawa, Jumpei; Ogawa, Hina; Yoshikawa, Kanae; Ishiwatari, Ayumi; Wakai, Sachiko; Tanabe, Kazunari; Shirakawa, Hiroki

    2018-05-01

    Tacrolimus is the most commonly used immunosuppressant. Because of its narrow therapeutic range, it is necessary to frequently monitor its concentration. We report the case of a 25-year-old man who underwent kidney transplantation whose tacrolimus concentrations, as measured by an affinity column-mediated immunoassay, were falsely elevated. As we reduced the dose of tacrolimus, the recipient developed T cell-mediated rejection. Using the same blood samples, an enzyme-multiplied immunoassay technique showed that the patient's levels of tacrolimus were extremely low. A further examination indicated that the false increase in the tacrolimus concentration was likely due to an unknown interfering substance. We administered methylprednisolone and antithymocyte-globulin. The patient's serum creatinine level decreased and remained stable after these treatments.

  15. Abbreviated AUC monitoring of cyclosporine more adequately identified patients at risk for acute rejection during induction of immunosuppressive therapy after kidney transplantation than recommended C2 concentration values.

    Science.gov (United States)

    Troncoso, P; Ortiz, A M; Jara, A; Vilches, S

    2009-01-01

    Monitoring of cyclosporine (CsA) is critical during the induction of immunosuppressive therapy. Although most centers have incorporated C2 levels, our unit still uses an abbreviated AUC model which includes concentrations at C1, C2, and C6 post-dose (AUC(1-6)). The objective of this study was to compare both strategies of CsA monitoring during the first 30 days after kidney transplantation. The study included 89 recipients induced with CsA microemulsion and steroids. AUC(1-6) profiles were performed around days 3, 10, and 30 after transplantation with a target of 5500 to 6000 ng*h/mL considered therapeutic. For comparison purposes, a value of C2 >/= 1500 ng/mL was also considered therapeutic. Mean C2 and AUC(1-6) values were low dated with biopsy-proven acute rejection episodes (BPAR) during the study period. Twenty patients received living donor kidneys and overall there were 46 females. During this period, 253 AUC(1-6) were performed including 44 (17.4%) below the therapeutic range. When the analysis included only C2, 171 (67.6%) were below the therapeutic target (P AUC(1-6) at day 10 discriminated rejectors versus nonrejectors (5645 +/- 1390 and 8221 +/- 2502, respectively; P = .008). C2 was not significantly different at any time in either group. In this study, abbreviated AUC monitoring more adequately identified patients at risk for acute rejection than C2. Recommended C2 concentration levels need to be redefined in our patients.

  16. Dietary vitamin K2 supplement improves bone status after lung and heart transplantation.

    Science.gov (United States)

    Forli, Liv; Bollerslev, Jens; Simonsen, Svein; Isaksen, Gunhild A; Kvamsdal, Kari E; Godang, Kristin; Gadeholt, Gaut; Pripp, Are H; Bjortuft, Oystein

    2010-02-27

    Osteoporosis is a problem after transplantation. Studies since the last year indicate that vitamin K plays a role in optimal bone health. The aim of this randomized, double blind, prospective longitudinal study was to investigate the effect of a dietary supplement with vitamin K2 (180 microg menakinon-7) on bone mass, the first year after lung and heart transplantation. After preoperative baseline investigation of bone mass and bone-related biochemistry, 35 lung and 59 heart recipients were postoperatively randomized to vitamin K2 or placebo and reinvestigated the following year. In all recipients, 1 year after solid organ transplantation, the difference between vitamin K2 and placebo for the lumbar spine (L2-L4) bone mineral density (BMD) was 0.028 (SE 0.014) g/cm(2), P=0.055 and for L2 to L4 bone mineral content was 1.33 (SE 1.91) g/cm(2) (P=0.5). In lung recipients separately, the difference for bone mineral content was 3.39 g (SE 1.65), P=0.048 and in heart recipients 0.45 (SE 0.02) g, P=0.9 after controlling for baseline measures. In a forward stepwise linear regression analysis fitted to model differences in the L2 to L4 BMD, controlled for possible confounding variables (including use of bisphosphonate), and the only significant predictors were organ (B=-0.065 g/cm(2), P<0.001) and vitamin K2 (B=0.034 g/cm(2), P=0.019). Insufficient vitamin D status was common, and the parathyroid hormone was highest in the K2 group indicating a higher need for vitamin D. One year of vitamin K2 supplement suggest a favorable effect on lumbar spine BMD with different response in lung and heart recipients. Vitamin D status should receive more attention.

  17. A computer simulation model of the cost-effectiveness of routine Staphylococcus aureus screening and decolonization among lung and heart-lung transplant recipients.

    Science.gov (United States)

    Clancy, C J; Bartsch, S M; Nguyen, M H; Stuckey, D R; Shields, R K; Lee, B Y

    2014-06-01

    Our objective was to model the cost-effectiveness and economic value of routine peri-operative Staphylococcus aureus screening and decolonization of lung and heart-lung transplant recipients from hospital and third-party payer perspectives. We used clinical data from 596 lung and heart-lung transplant recipients to develop a model in TreeAge Pro 2009 (Williamsport, MA, USA). Sensitivity analyses varied S. aureus colonization rate (5-15 %), probability of infection if colonized (10-30 %), and decolonization efficacy (25-90 %). Data were collected from the Cardiothoracic Transplant Program at the University of Pittsburgh Medical Center. Consecutive lung and heart-lung transplant recipients from January 2006 to December 2010 were enrolled retrospectively. Baseline rates of S. aureus colonization, infection and decolonization efficacy were 9.6 %, 36.7 %, and 31.9 %, respectively. Screening and decolonization was economically dominant for all scenarios tested, providing more cost savings and health benefits than no screening. Savings per case averted (2012 $US) ranged from $73,567 to $133,157 (hospital perspective) and $10,748 to $16,723 (third party payer perspective), varying with the probability of colonization, infection, and decolonization efficacy. Using our clinical data, screening and decolonization led to cost savings per case averted of $240,602 (hospital perspective) and averted 6.7 S. aureus infections (4.3 MRSA and 2.4 MSSA); 89 patients needed to be screened to prevent one S. aureus infection. Our data support routine S. aureus screening and decolonization of lung and heart-lung transplant patients. The economic value of screening and decolonization was greater than in previous models of other surgical populations.

  18. HEart trAnsplantation Registry of piTie-Salpetriere University Hospital

    Science.gov (United States)

    2018-01-08

    Cardiac Transplant Disorder; Cardiac Death; Heart Failure; Acute Cellular Graft Rejection; Antibody-Mediated Graft Rejection; Cardiac Allograft Vasculopathy; Heart Transplant Rejection; Immune Tolerance

  19. Characteristics and outcomes among patients with need for early dialysis after lung transplantation surgery.

    Science.gov (United States)

    Banga, Amit; Mohanka, Manish; Mullins, Jessica; Bollineni, Srinivas; Kaza, Vaidehi; Tanriover, Bekir; Torres, Fernando

    2017-11-01

    With the introduction of lung allocation score (LAS), increasingly sicker patients are undergoing lung transplantation (LT). This study was conducted to determine the time trends in need for dialysis after LT, identify variables independently associated with need for dialysis, and evaluate its association with 1- and 5-year mortality. We queried the United Network of Organ Sharing database for adult patients undergoing LT between 1994 and 2014. We excluded patients with simultaneous dual organ transplantation and where data regarding the need for dialysis were not available. Time trends in the yearly incidence of the need for dialysis showed a gradual increase (P = .012). In the post-LAS era, ethnicity, underlying diagnosis, estimated GFR 35 mm Hg, ventilator or extracorporeal membrane oxygenation support at LT, and >20% increase in serum creatinine between listing and match were independently associated with the need for dialysis. Patients with need for dialysis had significantly increased hazard of 1-year (n = 13 849; adjusted hazard ratio, 95% CI:7.23, 6.2-8.4, P need for early dialysis after LT, and these patients have significantly worse early and late survival. Several pre-transplant recipient characteristics are independently associated with the need for dialysis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

    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.

  1. Use of tacrolimus in rescue therapy of acute and chronic rejection in liver transplantation Uso de tacrolimus na terapia de resgate de rejeições agudas e crônicas no transplante de fígado

    Directory of Open Access Journals (Sweden)

    Fabricio Ferreira Coelho

    2003-01-01

    Full Text Available PURPOSE: To study the indications and results of tacrolimus as rescue therapy for acute cellular or chronic rejection in liver transplantation. PATIENTS AND METHODS: Eighteen liver transplant recipients who underwent rescue therapy with tacrolimus between March 1995 and August 1999 were retrospectively studied. The treatment indication, patients, and graft situation were recorded as of October 31st, 1999. The response to tacrolimus was defined as patient survival with a functional graft and histological reversal of acute cellular, or for chronic rejection, bilirubin serum levels decreasing to up to twice the upper normal limit. RESULTS: Fourteen cases (77.8% presented a good response. The response rate for the different indications was: (1 acute cellular + sepsis - 0/1 case; (2 recurrent acute cellular - 1/1 case; (3 OKT3-resistant acute cellular - 2/2 cases; (4 steroid-resistant acute cellular + active viral infection - 3/3 cases; (5 chronic rejection - 8/11 cases (72.7% response rate. The 4 patients who did not respond died. CONCLUSION: Tacrolimus rescue therapy was successful in most cases of acute cellular and chronic rejection in liver transplantation.OBJETIVO: Estudar os critérios de indicação e o resultado do uso de tacrolimus na terapia de resgate de rejeições agudas ou crônicas no transplante de fígado. CASUÍSTICA E MÉTODO: Foram estudados 18 pacientes transplantados de fígado, submetidos a terapia de resgate com tacrolimus entre março de 1995 e agosto de 1999. Foram registradas a indicação do tratamento e a situação de pacientes e enxertos em 31/10/1999. Considerou-se "respondendores" pacientes vivos, com enxerto funcionante e regressão histológica da terapia de resgate de rejeições agudas, ou com bilirrubina até 2 vezes o valor normal, no caso de terapia de resgate de rejeições crônicas. RESULTADO: Observou-se resposta em 14 casos (77,8%. A taxa de resposta nas diferentes indicações foi: (1 terapia de resgate

  2. Annual literature review of donor-specific HLA antibodies after organ transplantation.

    Science.gov (United States)

    Kaneku, Hugo

    2011-01-01

    The literature review of post-transplant DSA published in 2011 shows: Observations after kidney and lung transplant in non-sensitized transplant recipients show that monitoring post-transplant HLA antibodies offers limited benefit in predicting acute rejection episodes. It remains to be seen if a different monitoring schedule and/ or studying other organs may show otherwise. Nevertheless, others have shown that monitoring post-transplant antibodies does identify patients at higher risk for chronic rejection. Studies in kidney, heart, and liver patients transplanted in the presence of preformed DSA show that detecting these antibodies early after transplant identifies a group of patients with greater risk for allograft dysfunction. New and larger studies using bortezomib and eculizumab to treat acute antibody-mediated rejection confirm earlier observations that these two therapies are effective in treating and preventing rejections. In general, identification of HLAantibodies and DSA after transplant is associated with higher rates of rejection and poor allograft survival in all organs examined. IgM antibodies appear to play an important role after lung transplants.

  3. Heart and lung organ offer acceptance practices of transplant programs are associated with waitlist mortality and organ yield.

    Science.gov (United States)

    Wey, Andrew; Valapour, Maryam; Skeans, Melissa A; Salkowski, Nicholas; Colvin, Monica; Kasiske, Bertram L; Israni, Ajay K; Snyder, Jon J

    2018-04-19

    Variation in heart and lung offer acceptance practices may affect numbers of transplanted organs and create variability in waitlist mortality. To investigate these issues, offer acceptance ratios, or adjusted odds ratios, for heart and lung transplant programs individually and for all programs within donation service areas (DSAs) were estimated using offers from donors recovered July 1, 2016-June 30, 2017. Logistic regressions estimated the association of DSA-level offer acceptance ratios with donor yield and local placement of organs recovered in the DSA. Competing risk methodology estimated the association of program-level offer acceptance ratios with incidence and rate of waitlist removals due to death or becoming too sick to undergo transplant. Higher DSA-level offer acceptance was associated with higher yield (odds ratios [ORs]: lung, 1.04 1.11 1.19 ; heart, 1.09 1.21 1.35 ) and more local placement of transplanted organs (ORs: lung, 1.01 1.12 1.24 ; heart, 1.47 1.69 1.93 ). Higher program-level offer acceptance was associated with lower incidence of waitlist removal due to death or becoming too sick to undergo transplant (hazard ratios [HRs]: heart, 0.80 0.86 0.93 ; lung, 0.67 0.75 0.83 ), but not with rate of waitlist removal (HRs: heart, 0.91 0.98 1.06 ; lung, 0.89 0.99 1.10 ). Heart and lung offer acceptance practices affected numbers of transplanted organs and contributed to program-level variability in the probability of waitlist mortality. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  4. Contemporary Outcomes of Extracorporeal Membrane Oxygenation Used as Bridge to Lung Transplantation.

    Science.gov (United States)

    Hakim, Ali H; Ahmad, Usman; McCurry, Kenneth R; Johnston, Douglas R; Pettersson, Gosta B; Budev, Marie; Murthy, Sudish; Blackstone, Eugene H; Tong, Michael Z

    2018-07-01

    Extracorporeal membrane oxygenation (ECMO), when used as bridge to lung transplantation, (BTT) identifies high-risk candidates. Recent advances in cannula design and patient selection fosters "awake ambulatory ECMO" as a viable option for critically ill candidates in an attempt to retard deconditioning while awaiting allografts. From 2012 to 2015, 30 patients underwent ECMO as BTT. Candidacy for ECMO was determined before listing for transplant. A dual-lumen single cannula was used first in 13 of 30 patients (43%). Of the remaining 30 patients, 6 (20%) were supported with venoarterial ECMO and 11 (37%) with venovenous ECMO, with double-site cannulation in 11 (37%), and 6 of 11 converted to a dual-lumen single cannula. All ECMO patients were managed in a dedicated heart/lung failure intensive care unit, and early aggressive physical therapy, ambulation, and spontaneous breathing trials were emphasized. BTT was successful in 26 patients (87%). In the 19 patients with dual-lumen single cannula, 5 (26%) were successfully ambulated, and 6 (32%) achieved spontaneous ventilation. Median (25th, 75th percentile) lengths of stay in the intensive care unit and hospital were 33 days (20, 46 days) and 56 days (28, 78 days), respectively, and were 20 and 31 days, respectively, in patients successfully ambulated (intensive care unit: p = 0.5; hospital: p = 0.4). Among all patients who received a transplant, 30-day, 1-year, and 3-year survival were 92%, 85%, and 80%, respectively. Among patients undergoing primary transplants, 3-year survival was 91%. ECMO as BTT has led to encouraging perioperative outcomes and early survival. Careful patient selection and early use of ECMO seems to allow for preservation of vitality while these critically ill candidates await donor organs, which may improve outcomes. Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  5. HDR brachytherapy. An option for preventing nonmalignant obstruction in patients after lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Meyer, A.; Karstens, J.H.; Christiansen, H. [Medical School Hannover (Germany). Dept. of Radiation Oncology; Warszawski-Baumann, A.; Baumann, R. [Medical School Hannover (Germany). Dept. of Radiation Oncology; Medical Practice for Radiotherapy and Radiation Oncology, Hannover (Germany); Gottlieb, J.; Welte, T. [Medical School Hannover (Germany). Dept. of Respiratory Medicine

    2012-12-15

    Purpose: Interventional bronchoscopy is the main treatment modality in managing benign airway obstructions following lung transplantation. We analyzed the effect of intraluminal brachytherapy on preventing recurrence of hyperplastic tissue. Patients and methods: From September 2002 to September 2004, a total of 24 intraluminal brachytherapy applications were carried out on 12 lung transplant patients in 15 different locations. A single dose of 3 Gy was calculated at a 5-mm distance from the catheter surface; the target volume included a stenosis plus safety interval of 0.5-1.0 cm. Results: All patients had a mean 10.6 local interventions (Argon plasma coagulation, balloon dilatations, stenting) over 4.4 months before the first application of endobronchial brachytherapy, with a mean amount of 2.4 applications per month. The mean forced expiratory volume in 1 s (FEV1) was 2,219 ml in the 3 months before application of brachytherapy. After endobronchial brachytherapy, all patients experienced improvement in clinical status and respiratory function. The mean level of FEV1 in the 3 months after application was 2,435 ml (p = 0.02), and the number of invasive interventions dropped to a mean rate of 5.2 interventions in the 5.1 months after the first intervention, with an amount of 1 application per month. No treatment-related complications were seen. Four patients were treated twice, 1 patient three times, and 1 patient four times at the same localization. Conclusions: Recurrent symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal high-dose-rate brachytherapy with a dose of 3 Gy at a 5-mm distance from the catheter surface and a longitudinal safety margin of 1 cm. (orig.)

  6. HDR brachytherapy. An option for preventing nonmalignant obstruction in patients after lung transplantation

    International Nuclear Information System (INIS)

    Meyer, A.; Karstens, J.H.; Christiansen, H.; Gottlieb, J.; Welte, T.

    2012-01-01

    Purpose: Interventional bronchoscopy is the main treatment modality in managing benign airway obstructions following lung transplantation. We analyzed the effect of intraluminal brachytherapy on preventing recurrence of hyperplastic tissue. Patients and methods: From September 2002 to September 2004, a total of 24 intraluminal brachytherapy applications were carried out on 12 lung transplant patients in 15 different locations. A single dose of 3 Gy was calculated at a 5-mm distance from the catheter surface; the target volume included a stenosis plus safety interval of 0.5-1.0 cm. Results: All patients had a mean 10.6 local interventions (Argon plasma coagulation, balloon dilatations, stenting) over 4.4 months before the first application of endobronchial brachytherapy, with a mean amount of 2.4 applications per month. The mean forced expiratory volume in 1 s (FEV1) was 2,219 ml in the 3 months before application of brachytherapy. After endobronchial brachytherapy, all patients experienced improvement in clinical status and respiratory function. The mean level of FEV1 in the 3 months after application was 2,435 ml (p = 0.02), and the number of invasive interventions dropped to a mean rate of 5.2 interventions in the 5.1 months after the first intervention, with an amount of 1 application per month. No treatment-related complications were seen. Four patients were treated twice, 1 patient three times, and 1 patient four times at the same localization. Conclusions: Recurrent symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal high-dose-rate brachytherapy with a dose of 3 Gy at a 5-mm distance from the catheter surface and a longitudinal safety margin of 1 cm. (orig.)

  7. Nocturnal weakly acidic reflux promotes aspiration of bile acids in lung transplant recipients.

    Science.gov (United States)

    Blondeau, Kathleen; Mertens, Veerle; Vanaudenaerde, Bart A; Verleden, Geert M; Van Raemdonck, Dirk E; Sifrim, Daniel; Dupont, Lieven J

    2009-02-01

    Gastroesophageal reflux (GER) and aspiration of bile acids have been implicated as non-alloimmune risk factors for the development of bronchiolitis obliterans syndrome (BOS) after lung transplantation. The aim of our study was to investigate the association between GER and gastric aspiration of bile acids and to establish which reflux characteristics may promote aspiration of bile acids into the lungs and may feature as a potential diagnostic tool in identifying lung transplantation (LTx) patients at risk for aspiration. Twenty-four stable LTx recipients were studied 1 year after transplantation. All patients underwent 24-hour ambulatory impedance-pH recording for the detection of acid (pH acidic (pH 4 to 7) reflux. On the same day, bronchoalveolar lavage fluid (BALF) was collected and then analyzed for the presence of bile acids (Bioquant enzymatic assay). Increased GER was detected in 13 patients, of whom 9 had increased acid reflux and 4 had exclusively increased weakly acidic reflux. Sixteen patients had detectable bile acids in the BALF (0.6 [0.4 to 1.5] micromol/liter). The 24-hour esophageal volume exposure was significantly increased in patients with bile acids compared to patients without bile acids in the BALF. Acid exposure and the number of reflux events (total, acid and weakly acidic) were unrelated to the presence of bile acids in the BALF. However, both nocturnal volume exposure and the number of nocturnal weakly acidic reflux events were significantly higher in patients with bile acids in the BALF. Weakly acidic reflux events, especially during the night, are associated with the aspiration of bile acids in LTx recipients and may therefore feature as a potential risk factor for the development of BOS.

  8. Performance of long-term CT monitoring in diagnosing bronchiolitis obliterans after lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Berstad, Audun E. [Department of Radiology, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo (Norway)]. E-mail: a.e.berstad@medisin.uio.no; Aalokken, Trond Mogens [Department of Radiology, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo (Norway); Kolbenstvedt, Alf [Department of Radiology, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo (Norway); Bjortuft, Oystein [Department of Thoracic Medicine, Rikshospitalet University Hospital, Sognsvannsveien 20, N-0027 Oslo (Norway)

    2006-04-15

    Aim: The purpose of the study was to evaluate the ability of CT, including expiratory scans with minimum intensity projection in predicting the development of bronchiolitis obliterans syndrome after lung transplantation. Materials and methods: Forty consecutive patients, 29 bilateral and 11 single lung transplanted, were followed-up with regular scans for a median of 36 months. Air trapping was evaluated on expiratory scans constructed from two short spiral scans with minimum intensity projection-technique, one at the level of the carina and the other midway between the right diaphragm and the carina. Air trapping was scored on a 16-point scale. Bronchiolitis obliterans syndrome was diagnosed according to established clinical criteria and quantified spirometrically. Results: Bronchiolitis obliterans syndrome developed in 17 patients (43%) after a median of 12 months. Air trapping and bronchiectasis was seen before the diagnosis of bronchiolitis obliterans syndrome in only two and one patient, respectively. Interobserver agreement for air trapping score was good (kappa = 0.65). Air trapping scores performed significantly better than that achieved by chance alone in determining the presence of bronchiolitis obliterans syndrome (P = 0.0025). An air trapping score of 4 or more provided the best results with regard to sensitivity and specificity in diagnosing bronchiolitis obliterans syndrome. The sensitivity, specificity, positive and negative predictive values of an air trapping of 4 or more in the diagnosis of bronchiolitis obliterans syndrome were 77, 74, 68 and 81%, respectively. Conclusion: Expiratory CT scans with minimum intensity projection-reconstruction did not predict the development of bronchiolitis obliterans syndrome in most patients. The findings seriously limit the clinical usefulness of long-term CT monitoring for diagnosing bronchiolitis obliterans syndrome after lung transplantation.

  9. Aminoglycoside exposure and renal function before lung transplantation in adult cystic fibrosis patients.

    Science.gov (United States)

    Novel-Catin, Etienne; Pelletier, Solenne; Reynaud, Quitterie; Nove-Josserand, Raphaele; Durupt, Stephane; Dubourg, Laurence; Durieu, Isabelle; Fouque, Denis

    2018-04-18

    Patients with cystic fibrosis (CF) are at risk of kidney injury even before undergoing lung transplantation, because of prolonged exposure to aminoglycosides (AGs), chronic dehydration and complications of diabetes mellitus. The usual equations estimating the glomerular filtration rate (GFR), such as Cockcroft-Gault and Modification of Diet in Renal Disease, are not adapted to the CF population due to patients' low body weight and reduced muscle mass. The aim of this study was to precisely measure GFR in adult CF patients and to see whether repeated AG treatment would impair renal function before lung transplantation. Inulin or iohexol clearances were performed in 25 adult CF patients when they entered the lung transplant waiting list. No patient was treated with AGs at the time of GFR measurement. Body mass index (BMI), history of diabetes mellitus and blood pressure were recorded. Exposure to intravenous (IV) AGs within 5 years prior to the GFR measurement was obtained from the patient's medical files. Urine samples were collected to check for albuminuria and proteinuria. The population was predominantly female (67%). The mean age was 32 years, the mean BMI was 19 kg/m2 and 28% had CF-related diabetes. Median exposure to IV AG within 5 years before GFR measurement was 155 days with a mean dosage of 7.7mg/kg/day. The mean measured GFR was 106 mL/min/1.73 m2 and the mean estimated GFR according to the Chronic Kidney Disease Epidemiology Collaboration formula was 124 mL/min/1.73 m2. Despite prolonged exposure to high-dose IV AG, no decline in GFR was observed in these patients.

  10. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Hammer, Mark M.; Sheybani, Elizabeth F. [Washington University School of Medicine, Mallinckrodt Institute of Radiology, 510 S. Kingshighway Blvd., Campus Box 8131, St. Louis, MO (United States); Zhang, Lingxin [Washington University School of Medicine, Department of Pathology, St. Louis, MO (United States); Stoll, Janis M. [Washington University School of Medicine, Division of Gastroenterology, Hepatology and Nutrition, St. Louis, MO (United States)

    2016-04-15

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. (orig.)

  11. A Multiphase Non-Linear Mixed Effects Model: An Application to Spirometry after Lung Transplantation

    Science.gov (United States)

    Rajeswaran, Jeevanantham; Blackstone, Eugene H.

    2014-01-01

    In medical sciences, we often encounter longitudinal temporal relationships that are non-linear in nature. The influence of risk factors may also change across longitudinal follow-up. A system of multiphase non-linear mixed effects model is presented to model temporal patterns of longitudinal continuous measurements, with temporal decomposition to identify the phases and risk factors within each phase. Application of this model is illustrated using spirometry data after lung transplantation using readily available statistical software. This application illustrates the usefulness of our flexible model when dealing with complex non-linear patterns and time varying coefficients. PMID:24919830

  12. Low pretransplant IgA level is associated with early post-lung transplant seromucous infection.

    Science.gov (United States)

    Murthy, Sudish C; Avery, Robin K; Budev, Marie; Gupta, Sandeep; Pettersson, Gösta B; Nowicki, Edward R; Mehta, Atul; Chapman, Jeffrey T; Rajeswaran, Jeevanantham; Blackstone, Eugene H

    2018-04-13

    Infection is an important cause of morbidity and mortality after lung transplantation. Immunoglobulins are part of both seromucous (IgA) and serum (IgG) infection defense mechanisms. We therefore hypothesized that lower pretransplant IgA levels would be associated with more early post-lung transplant seromucous infections and greater mortality independent of IgG. From January 2000 to July 2010, 538 patients undergoing primary lung transplantation had pretransplant IgA (n = 429) and IgG (n = 488) measured as a clinical routine. Median IgA was 200 mg·dL -1 (2% < 70 mg·dL -1 , lower limit of normal); median IgG was 970 mg·dL -1 (5% < 600 mg·dL -1 ). Intensive microbiology review was used to categorize infections and their causative organisms within the first posttransplant year. In total, 397 seromucous infections were observed in 247 patients, most bacterial. Although IgA and IgG were moderately correlated (r = 0.5, P < .0001), low pretransplant IgA was a strong risk factor (P = .01) for seromucous infections, but pretransplant IgG was not (P ≥ .6). As pretransplant IgA levels fell below 200 mg·dL -1 , the risk of these posttransplant infections rose nearly linearly. Lower pretransplant levels of IgA were associated with greater posttransplant mortality to end of follow-up (P = .004), but pretransplant IgG was not (P ≥ .3). Low levels of preoperative IgA, an important immunoglobulin involved in mucosal immunologic defense, but not IgG, are associated with seromucous infections in the year after lung transplantation and increased follow-up mortality. It would appear prudent to identify patients with relative IgA deficiency at listing and to increase vigilance of monitoring for, and prophylaxis against, seromucous infection in this high-risk population. Copyright © 2018. Published by Elsevier Inc.

  13. Candida albicans pancreatitis in a child with cystic fibrosis post lung transplantation

    International Nuclear Information System (INIS)

    Hammer, Mark M.; Sheybani, Elizabeth F.; Zhang, Lingxin; Stoll, Janis M.

    2016-01-01

    We present a case of Candida albicans infection of a previously intact pancreas in a child with cystic fibrosis status post lung transplantation. Although Candida superinfection in necrotizing pancreatitis is not uncommon, this is a unique case of Candida infection of non-necrotic pancreatic parenchyma. This case presented a diagnostic dilemma for radiologists because it appeared virtually identical to acute interstitial edematous pancreatitis on imaging. Ultimately, endoscopic US-based biopsy was pursued for diagnosis. Although difficult to treat and compounded by the immunocompromised status of the child, the pancreatic infection improved with antifungal therapy. (orig.)

  14. Influence of thorax irradiation on the survival of mice with spontaneous or artificial lung metastases from a transplantable mammary adenocarcinoma

    International Nuclear Information System (INIS)

    Wondergem, J.; Haveman, J.; van der Schueren, E.

    1985-01-01

    The effect of thorax irradiation on lung metastases, either occurring spontaneously from a primary mammary adenocarcinoma (M8013X) transplanted on the leg or artificially induced by intravenous injection of tumor cells was studied. Increasing the interval between the moment at which lung metastases are supposed to originate and the thorax irradiation resulted in a rapid decrease of the effectiveness of this treatment in preventing the development of lung metastases. Increasing the radiation dose led to an increased number of cures; however, an increased number of mice dying of lethal lung damage was also observed. Irradiation of the lungs of mice with 5 or 10 Gy, 24 hours, 7 days or 14 days prior to i.v. injection with tumor cells, did not significantly increase the number of mice with lung metastases. Immunological resistance against the tumor played a role in our experiments with both spontaneous and artificial lung metastases

  15. Utilization of the organ care system for bilateral lung transplantation: preliminary results of a comparative study.

    Science.gov (United States)

    Zeriouh, Mohamed; Sabashnikov, Anton; Mohite, Prashant N; Zych, Bartlomiej; Patil, Nikhil P; García-Sáez, Diana; Koch, Achim; Weymann, Alexander; Soresi, Simona; Wippermann, Jens; Wahlers, Thorsten; De Robertis, Fabio;