298 results on '"A. Haverich"'
Search Results
2. Cardiac transplantation across preformed HLA-antibody barriers
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Ius, Fabio, Haverich, Axel, and Warnecke, Gregor
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- 2018
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3. Immune-Mechanistic Insights into Improved Lung Preservation using the Organ Care System in a Porcine Transplantation Model in Comparison to the INSPIRE Trial
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Siemeni, Thierry, Salman, Jawad, BellmasSanz, Ramon, Jansson, Katharina, Knöfel, Ann-Kathrin, Ius, Fabio, Sommer, Wiebke, Höffler, Klaus, Wiegmann, Bettina, Tudorache, Igor, Haverich, Axel, Falk, Christine S, and Warnecke, Gregor
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- 2018
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- View/download PDF
4. Ex Vivo Lung Perfusion using the portable OCS Maintains Endothelial Integrity in the Context of Reduced Severe PGD Rates
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Wiegmann, Bettina, BellmasSanz, Ramon, Neudörfl, Christine, Tudorache, Igor, Kühn, Christian, Avsar, Murat, Haverich, Axel, Warnecke, Gregor, and Falk, Christine S.
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- 2018
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5. Leukocytes from Lung Transplant Recipients with Severe Primary Graft Dysfunction Adoptively Transfer Alloreactivity to Vessel Grafts Trans Vivo
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Knoefel, Ann-Katrin, Siemeni, Thierry, Madrahimov, Nodir, Sommer, Wiebke, Avsar, Murat, Ius, Fabio, Jansson, Katharina, Ahrens, Linda, Salman, Jawad, Kühn, Christian, Tudorache, Igor, Haverich, Axel, Falk, Christine, and Warnecke, Gregor
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- 2018
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- View/download PDF
6. Ischemia Reperfusion Injury Significantly Differs between Lung vs. Heart Transplantation with Respect to Lead Cytokines and Correlation to Clinical Outcome
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Wiegmann, Bettina, Ledwoch, Nadine, Iske, Jasper, Kaufeld, Tim, Ius, Fabio, Rochas, Sebastian, Avsar, Murat, Haverich, Axel, Warnecke, Gregor, and Falk, Christine S
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- 2018
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- View/download PDF
7. Technique and Outcomes of Less Invasive Lung Retransplantation
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Sommer, Wiebke, Ius, Fabio, Kühn, Christian, Avsar, Murat, Salman, Jawad, Siemeni, Thierry, Müller, Carsten, Schwerk, Nicolaus, Greer, Mark, Gottlieb, Jens, Welte, Tobias, Haverich, Axel, Tudorache, Igor, and Warnecke, Gregor
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- 2018
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8. MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy
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Neumann, Anneke, Napp, L. Christian, Kleeberger, Jan A., Benecke, Nils, Pfanne, Angelika, Haverich, Axel, Thum, Thomas, and Bara, Christoph
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- 2017
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9. Epithelial and Erythrocyte Microvesicles From Bronchoalveolar Lavage Fluid Are Elevated and Associated With Outcome in Chronic Lung Allograft Dysfunction
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Harms, Anja, Fuehner, Thomas, Warnecke, Gregor, Haverich, Axel, Gottlieb, Jens, and Trummer, Arne
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- 2015
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10. Technique and Outcomes of Less Invasive Lung Retransplantation
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Murat Avsar, Jens Gottlieb, Christian Kühn, Gregor Warnecke, Nicolaus Schwerk, Tobias Welte, Fabio Ius, Carsten Müller, Thierry Siemeni, Jawad Salman, Igor Tudorache, Axel Haverich, Mark Greer, and Wiebke Sommer
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Adult ,Male ,Reoperation ,medicine.medical_specialty ,medicine.medical_treatment ,Less invasive ,030204 cardiovascular system & hematology ,law.invention ,03 medical and health sciences ,Extracorporeal Membrane Oxygenation ,0302 clinical medicine ,law ,Extracorporeal membrane oxygenation ,Humans ,Medicine ,Retrospective Studies ,Transplantation ,Lung ,business.industry ,Patient survival ,Retrospective cohort study ,Middle Aged ,Intensive care unit ,Surgery ,medicine.anatomical_structure ,030228 respiratory system ,Cohort ,Female ,business ,Lung Transplantation - Abstract
Background Lung retransplantation is a demanding procedure with outcomes lagging primary transplantation. We implemented less invasive surgical techniques aiming at improving early outcomes. Here, we wish to describe these techniques and analyze the clinical outcomes. Methods Since April 2010, a protocol of less invasive techniques was applied to all lung retransplantations. This protocol comprises bilateral lung retransplantation via sternum-sparing anterolateral thoracotomies, off-pump surgery, and empiric administration of 2 g fibrinogen and 2 platelet concentrates. Patient charts were retrospectively reviewed starting in April 2010 until May 2016 for this study and compared with a cohort of patients undergoing lung retransplantation between January 2005 and March 2010. Results From April 2010 through March 2016, 774 total lung transplantations were performed at our center, 49 were retransplantations. In the era January 2005 to March 2010, a total of 480 lung transplantations were performed, 38 of those being retransplantations. Mean operation time in the era April 2010 to May 2016 was significantly longer as compared with the era January 2005 to March 2010, median time until extubation was significantly shorter in the era April 2010 to May 2016 (1 [1-2] days vs 11.5 [1-24] days; P = 0.0009). Similarly, median intensive care unit stay time was shorter in the era April 2010 to May 2016 (4 [2-5.5] days vs 12.5 [3-30.5] days; P = 0.003). Patient survival was significantly better in the era starting in April 2010 at 30 days (98% vs 76.3%, P = 0.002) as well as at 1 year (80.6% vs 63.2%; P = 0.01). Conclusions Less invasive retransplantation of the lung via sternum-sparing anterolateral thoracotomies and off-pump is a safe procedure with low associated morbidity and favorable midterm survival.
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- 2018
11. MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy
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Angelika Pfanne, Jan A. Kleeberger, Nils Benecke, Anneke Neumann, Thomas Thum, Christoph Bara, Axel Haverich, and L. Christian Napp
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Adult ,Genetic Markers ,Male ,Time Factors ,medicine.medical_treatment ,Pilot Projects ,Coronary Artery Disease ,030204 cardiovascular system & hematology ,030230 surgery ,Coronary artery disease ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Predictive Value of Tests ,microRNA ,Gene expression ,medicine ,Humans ,Aged ,Oligonucleotide Array Sequence Analysis ,Heart transplantation ,Transplantation ,Reverse Transcriptase Polymerase Chain Reaction ,Microarray analysis techniques ,business.industry ,Gene Expression Profiling ,Reproducibility of Results ,Middle Aged ,Allografts ,medicine.disease ,Non-coding RNA ,Up-Regulation ,Gene expression profiling ,MicroRNAs ,Treatment Outcome ,ROC Curve ,Area Under Curve ,Case-Control Studies ,cardiovascular system ,Cancer research ,Heart Transplantation ,Biomarker (medicine) ,Female ,business - Abstract
Background Cardiac allograft vasculopathy (CAV) remains the leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Because of its clinically silent progression and lack of symptoms, detection is often difficult and invasive coronary angiography is performed routinely. To date, there are no established noninvasive biomarkers available for prediction of CAV in transplanted patients.MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules that negatively regulate gene expression. As they are detectable in peripheral blood, recent studies have suggested miRNAs as biomarkers for various cardiovascular diseases. Thus, we hypothesized that circulating miRNAs may serve as noninvasive biomarkers for CAV. Methods To determine the regulation of circulating miRNAs, we performed miRNA profiling studies in plasma samples of OHT patients with confirmed high-degree CAV and a matched control group consisting of patients without any signs of CAV at least 5 years after OHT. Candidate miRNAs were verified by quantitative reverse transcriptase polymerase chain reaction. Results Microarray analysis revealed 5 candidate miRNAs (miR-34a, miR-98, miR-155, miR-204, miR-628-5p) that were differentially regulated in plasma samples of patients with CAV and therefore were selected for verification by quantitative reverse transcriptase polymerase chain reaction. In CAV patients, plasma levels of miR-628-5p and miR-155 were significantly increased (P = 0.001 and P = 0.028, respectively). A miR628-5p value above 1.336 was able to predict CAV with a sensitivity of 72% and a specificity of 83%. Conclusions For the first time, the present study identifies the circulating miRNA miR-628-5p as a novel potential biomarker of CAV in patients after OHT.
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- 2017
12. IgM-Enriched Human Intravenous Immunoglobulin-Based Treatment of Patients With Early Donor Specific Anti-HLA Antibodies After Lung Transplantation
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Fabio Ius, Daniela Kieneke, Nicolaus Schwerk, Murielle Verboom, Rainer Blasczyk, Christian Kühn, Michael Hallensleben, Tobias Welte, Thierry Siemeni, Jan T. Kielstein, Carolin Erdfelder, Igor Tudorache, Andreas Tecklenburg, Jens Gottlieb, Murat Avsar, Axel Haverich, Jawad Salman, Wiebke Sommer, Gregor Warnecke, and Mark Greer
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Adult ,Male ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,030230 surgery ,Group A ,Gastroenterology ,Group B ,03 medical and health sciences ,0302 clinical medicine ,HLA Antigens ,Internal medicine ,medicine ,Lung transplantation ,Humans ,Retrospective Studies ,Transplantation ,Lung ,biology ,Plasma Exchange ,business.industry ,Graft Survival ,Immunoglobulins, Intravenous ,Retrospective cohort study ,Original Clinical Science—General ,Middle Aged ,Tissue Donors ,body regions ,medicine.anatomical_structure ,Treatment Outcome ,Immunoglobulin M ,biology.protein ,030211 gastroenterology & hepatology ,Graft survival ,Rituximab ,Female ,Antibody ,business ,medicine.drug ,Lung Transplantation - Abstract
Background At our institution, until April 2013, patients who showed early donor specific anti-HLA antibodies (DSA) after lung transplantation were preemptively treated with therapeutic plasma exchange (tPE) and a single dose of Rituximab. In April 2013, we moved to a therapy based on IgM-enriched human immunoglobulins (IVIG), repeated every 4 weeks, and a single dose of Rituximab. Methods This observational study was designed to evaluate the short-term patient and graft survival in patients who underwent IVIG-based DSA treatment (group A, n = 57) versus contemporary patients transplanted between April 2013 and January 2015 without DSA (group C, n = 180), as well as to evaluate DSA clearance in IVIG-treated patients versus historic patients who had undergone tPE-based treatment (group B, n = 56). Patient records were retrospectively reviewed. Follow-up ended on April 1, 2015. Results At 6 months and 1 year of follow-up, group A had a survival similar to group C (P = 0.81) but better than group B (P = 0.008). Group A showed statistically nonsignificant trends toward improved freedom from pulsed-steroid therapy and biopsy-confirmed rejection over groups B and C. The DSA clearance was better in group A than group B at treatment end (92% vs 64%; P = 0.002) and last DSA control (90% vs 75%; P = 0.04). Conclusions Patients with new early DSA but without graft dysfunction that are treated with IVIG and Rituximab have similarly good early survival as contemporary lung transplant recipients without early DSA. The IVIG yielded increased DSA clearance compared with historic tPE-based treatment, yet spontaneous clearance of new DSA also remains common., Combination treatment of IgM enriched human immunoglobulins (IVIG) and a single dose of rituximab significantly reduced the incidence of de novo DSA production after lung transplantation compared to historical therapeutic plasma exchange and a single dose of rituximab. Supplemental digital content is available in the text.
- Published
- 2016
13. Cardiac Transplantation Across Preformed HLA-antibody Barriers
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Gregor Warnecke, Axel Haverich, and Fabio Ius
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Heart transplantation ,Transplantation ,biology ,business.industry ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,030230 surgery ,Antibodies ,03 medical and health sciences ,0302 clinical medicine ,Immunology ,medicine ,biology.protein ,Heart Transplantation ,Hla antibodies ,Antibody ,business - Published
- 2018
14. CARDIAC TRANSPLANTATION IS ACCOMPANIED BY MAJOR CHANGES IN THE T AND NK CELL SUBSET COMPOSITION IMMEDIATELY AFTER TRANSPLANTATION
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Kristina Ludwig, Jenny F. Kuehne, N. Ledwoch, Fabio Ius, Jawad Salman, Christine S. Falk, Axel Haverich, Ann-Kathrin Knoefel, Jasper Iske, Bettina Wiegmann, Evgeny Chichelnitskiy, Thierry Siemeni, and Gregor Warnecke
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Transplantation ,business.industry ,Immunology ,T cell subset ,Medicine ,Composition (combinatorics) ,business - Published
- 2020
15. Cardiac Transplantation Across Preformed HLA-antibody Barriers
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Ius, Fabio, primary, Haverich, Axel, additional, and Warnecke, Gregor, additional
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- 2019
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16. Allogeneic CD4+CD25high T Cells Regulate Obliterative Bronchiolitis of Heterotopic Bronchus Allografts in Both Porcinized and Humanized Mouse Models
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Gustavo Salguero, Nodir Madrahimov, Murat Avsar, Danny Jonigk, Tobias Welte, K. Dreckmann, Ulrich A. Maus, Jawad Salman, Wiebke Sommer, Ann-Kathrin Knöfel, Katharina Jansson, Axel Haverich, and Gregor Warnecke
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CD4-Positive T-Lymphocytes ,Pathology ,medicine.medical_specialty ,Swine ,Bronchiolitis obliterans ,Bronchi ,Cell Separation ,Major histocompatibility complex ,T-Lymphocytes, Regulatory ,Peripheral blood mononuclear cell ,Major Histocompatibility Complex ,Mice ,Mice, Inbred NOD ,In vivo ,Animals ,Humans ,Medicine ,IL-2 receptor ,Bronchiolitis Obliterans ,Mice, Knockout ,Transplantation ,Bronchus ,Lung ,biology ,business.industry ,Interleukin-2 Receptor alpha Subunit ,hemic and immune systems ,Allografts ,medicine.disease ,Tissue Donors ,Disease Models, Animal ,Phenotype ,medicine.anatomical_structure ,Humanized mouse ,Immunology ,Leukocytes, Mononuclear ,biology.protein ,Swine, Miniature ,Female ,business - Abstract
Background Bronchiolitis obliterans syndrome is caused by a fibroproliferative process in lung allografts resulting in irreversible damage. In this study, we induced obliterative bronchiolitis and studied the contribution of regulatory T cells to its development in immune-deficient mice receiving heterotopic porcine bronchus transplants, and major histocompatibility complex-mismatched porcine peripheral blood mononuclear cell. Furthermore, we aimed to corroborate our findings in a humanized mouse model. Methods Heterotopic bronchus transplantation was performed in 33 NOD.rag(−/−)γc(−/−) mice, using miniature pigs as tissue donors.The recipient mice then either received saline (negative control), unsorted MHC-mismatched PBMC (positive control), PBMC enriched with CD4(+)CD25(high) cells or PBMC depleted of CD4(+)CD25(high) cells for reconstitution. The results were validated in 28 NOD.rag(−/−)γc(−/−) mice undergoing heterotopic human bronchus transplantation and reconstitution with allogeneic human PBMC. Results Histological lesions similar to those typical for obliterative bronchiolitis developed in vivo after reconstitution with allogeneic PBMC and were more severe in animals engrafted with PBMC depleted of CD4(+)CD25(high) cells. In contrast, the group reconstituted with PBMC enriched with CD4(+)CD25(high) cells showed well-preserved histology. The results of the humanized model confirmed those obtained in the porcinized model. Conclusions In conclusion, both porcinized and humanized mouse models of heterotopic subcutaneous bronchus transplantation imitate the in vivo development of bronchiolitis obliterans syndrome-like lesions and reveal its sensitivity to T-cell regulation.
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- 2015
17. Lung Transplantation for Severe Pulmonary Hypertension—Awake Extracorporeal Membrane Oxygenation for Postoperative Left Ventricular Remodelling
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Jens Gottlieb, Axel Haverich, Johannes Hadem, Igor Tudorache, Thomas Fühner, Gregor Warnecke, Christoph Bara, Fabio Ius, Tobias Welte, Murat Avsar, Dietmar Böthig, Olaf Wiesner, Marius M. Hoeper, Christian Kühn, Wiebke Sommer, and Nicolaus Schwerk
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Adult ,Male ,Time Factors ,Adolescent ,Hypertension, Pulmonary ,medicine.medical_treatment ,Hemodynamics ,Kaplan-Meier Estimate ,Airway Extubation ,Severity of Illness Index ,Ventricular Function, Left ,Ventricular Dysfunction, Left ,Young Adult ,Extracorporeal Membrane Oxygenation ,Risk Factors ,Severity of illness ,Extracorporeal membrane oxygenation ,Humans ,Medicine ,Lung transplantation ,Wakefulness ,Child ,Ventricular remodeling ,Transplantation ,Ventilator weaning ,Ventricular Remodeling ,business.industry ,Middle Aged ,medicine.disease ,Pulmonary hypertension ,Treatment Outcome ,Case-Control Studies ,Anesthesia ,Female ,business ,Ventilator Weaning ,Lung Transplantation - Abstract
Bilateral lung transplantation (BLTx) is an established treatment for end-stage pulmonary hypertension (PH). Ventilator weaning failure and death are more common as in BLTx for other indications. We hypothesized that left ventricular (LV) dysfunction is the main cause of early postoperative morbidity or mortality and investigated a weaning strategy using awake venoarterial extracorporeal membrane oxygenation (ECMO).In 23 BLTx for severe PH, ECMO used during BLTx was continued for a minimum of 5 days (BLTx-ECMO group). Echocardiography, left atrial (LA) and Swan-Ganz catheters were used for monitoring. Early extubation after transplantation was attempted under continued ECMO.Preoperatively, all patients had severely reduced cardiac index (mean, 2.1 L/min/m2). On postoperative day 2, reduction of ECMO flow resulted in increasing LA and decreasing systemic blood pressures. On the day of ECMO explantation (median, postoperative day 8), LV diameter had increased; LA and blood pressures remained stable. Survival rates at 3 and 12 months were 100% and 96%, respectively. Data were compared to two historic control groups of BLTx without ECMO (BLTx ventilation) or combined heart-lung transplantation for severe PH.Early after BLTx for severe PH, the LV may be unable to handle normalized LV preload. This can be effectively bridged with awake venoarterial ECMO.
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- 2015
18. Spirometric Obstructive Lung Function Pattern Early After Lung Transplantation
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Hendrik, Suhling, Sabine, Dettmer, Jessica, Rademacher, Mark, Greer, Greer, Mark, Hoen-Oh, Shin, Igor, Tudorache, Christian, Kühn, Axel, Haverich, Tobias, Welte, Gregor, Warnecke, and Jens, Gottlieb
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Adult ,Male ,Spirometry ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,Vital Capacity ,Bronchiolitis obliterans ,Lung injury ,Pulmonary function testing ,Forced Expiratory Volume ,Internal medicine ,medicine ,Humans ,Lung transplantation ,Lung volumes ,Lung Diseases, Obstructive ,Bronchiolitis Obliterans ,Transplantation ,Lung ,medicine.diagnostic_test ,business.industry ,Middle Aged ,medicine.disease ,Tissue Donors ,medicine.anatomical_structure ,Cardiology ,Female ,business ,Follow-Up Studies ,Lung Transplantation - Abstract
BACKGROUND An obstructive pattern in pulmonary function test is common after lung transplantation (LTx) and may be caused by multiple disorders. In this study, the impact and outcome of an obstructive spirometric pattern identified in transplant recipients early posttransplantation were investigated. METHODS Analyzing all patients undergoing double LTx between September 1, 2007, and October 1, 2009, we separated patients with an obstructive (forced expiratory volume in 1 sec [FEV(1)]: vital capacity [VC]
- Published
- 2012
19. Epithelial and Erythrocyte Microvesicles From Bronchoalveolar Lavage Fluid Are Elevated and Associated With Outcome in Chronic Lung Allograft Dysfunction
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Arne Trummer, Jens Gottlieb, Axel Haverich, Gregor Warnecke, Thomas Fuehner, and Anja Harms
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Adult ,Lung Diseases ,Male ,Pathology ,medicine.medical_specialty ,Erythrocytes ,Time Factors ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Disease-Free Survival ,Flow cytometry ,Cell-Derived Microparticles ,Risk Factors ,Medicine ,Lung transplantation ,Humans ,Endothelial dysfunction ,Proportional Hazards Models ,Retrospective Studies ,Transplantation ,Lung ,medicine.diagnostic_test ,business.industry ,Microangiopathy ,Epithelial Cells ,respiratory system ,Middle Aged ,medicine.disease ,Allografts ,Flow Cytometry ,Microvesicles ,respiratory tract diseases ,Bronchoalveolar lavage ,medicine.anatomical_structure ,Treatment Outcome ,Chronic Disease ,Female ,Complication ,business ,Bronchoalveolar Lavage Fluid ,Biomarkers ,Lung Transplantation - Abstract
BACKGROUND Chronic lung allograft dysfunction (CLAD) is the major outcome limitation for lung transplant recipients (LTR) after the first year, and therapies targeting immunological pathways show only limited success. Because microvesicles (MV) are biomarkers of endothelial dysfunction and coagulation but are also involved in immunological responses, we hypothesized that MV, found in bronchoalveolar lavage (BAL) fluids (BALF) of LTR at CLAD diagnosis, are elevated and potential prognostic biomarkers. METHODS The BALF was collected from 37 LTR at time point of CLAD diagnosis and 37 LTR without any complication at routinely performed BAL. The MV concentration and origin were determined by flow cytometry by detection of different antigens. Patient- and transplant-related risk factors were included in a retrospective statistical analysis. RESULTS The BALF-MV levels of epithelial and red blood cell (RBC) origin were significantly higher in CLAD patients (mean: 1533/μL and 158/μL) compared to controls (436/μL, 57/μL). The LTR with high levels of epithelial MV >580/μL showed a significantly shorter overall survival at 4 years after BAL (39.5%) compared to patients with low MV (66.4%) and this proofed to be an independent prognostic factor in multivariate Cox analysis (hazards ratio = 3.05). Furthermore, LTR with high levels of RBC MV ≥225/μL were also associated with worse disease-specific survival, with probabilities at 4 years after BAL of 85.8% vs. 36.0%. CONCLUSIONS Epithelial and RBC BALF-MV are elevated at CLAD diagnosis, have a potential as biomarkers, and support the hypothesis of a pathway, including activation of coagulation and complement, endothelial barrier dysfunction, and microangiopathy.
- Published
- 2015
20. Proteomic Bronchiolitis Obliterans Syndrome Risk Monitoring in Lung Transplant Recipients
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Andreas Pich, Marc Zapatka, Roland Eils, Brigitte Schlegelberger, Benedikt Brors, Thomas Wolf, Nils von Neuhoff, Jens Gottlieb, Tonio Oumeraci, Tobias Welte, and Axel Haverich
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Adult ,Male ,Proteomics ,alpha-Defensins ,Proteome ,medicine.medical_treatment ,Bronchiolitis obliterans ,Enzyme-Linked Immunosorbent Assay ,Histatins ,Predictive Value of Tests ,Risk Factors ,medicine ,Humans ,Uteroglobin ,Lung transplantation ,Calgranulin A ,Clinical significance ,Bronchiolitis Obliterans ,Transplantation ,Lung ,medicine.diagnostic_test ,business.industry ,Surrogate endpoint ,Syndrome ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Bronchoalveolar lavage ,Bronchiolitis ,Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ,Immunology ,Female ,business ,Bronchoalveolar Lavage Fluid ,Lung Transplantation - Abstract
BACKGROUND Obliterative bronchiolitis poses a primary obstacle for long-term survival of lung transplant recipients and manifests clinically as bronchiolitis obliterans syndrome (BOS). Establishing a molecular level screening method to detect BOS-related proteome changes before its diagnosis by forced expiratory volume surrogate marker criteria was the main objective of this study. METHODS Bronchoalveolar lavage was performed in 82 lung transplant recipients (48/34 with/without known BOS development) at different time points between 12 and 48 months after lung transplantation. A mass spectrometry-based method was devised to generate bronchoalveolar lavage fluid proteome profiles that were screened for BOS-specific alterations. Statistically significant marker peptides and proteins were identified and validated by in-gel digestion, tandem mass spectrometric sequencing, and quantitative immunoassays. RESULTS Among the panel of statistically significant markers were Clara cell protein, calgranulin A, human neutrophil peptides, and the antimicrobial agent histatin. To assess their clinical relevance, a highly sensitive and specific classifier model was developed. Positive BOS classification by monitoring of seven polypeptides correlated strongly with a significant decrease in BOS-free time. Thus, it was possible to detect high-risk patients early on in the pathogenetic process. CONCLUSIONS Monitoring the bronchoalveolar lavage fluid levels of seven polypeptides detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry allows a reliable prediction of early BOS using a Random Forest decision tree-based classifier model. The high accuracy of this robust model and its synergistic potential in combination with established forced expiratory volume-based diagnostics could make it an effective tool to supplement the current diagnostic regime after multicentric validation.
- Published
- 2011
21. Health-Related Quality of Life in Long-Term Survivors After Heart and Lung Transplantation: A Prospective Cohort Study
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D. Malehsa, Jens Gottlieb, Christoph Bara, Uwe Tegtbur, Axel Haverich, Christiane Kugler, Andre Simon, and Martin Dierich
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Adult ,Male ,Pediatrics ,medicine.medical_specialty ,Skin Neoplasms ,Time Factors ,Heart-Lung Transplantation ,medicine.medical_treatment ,Bronchiolitis obliterans ,Cohort Studies ,Quality of life ,Neoplasms ,Humans ,Medicine ,Lung transplantation ,Prospective Studies ,Social Behavior ,Prospective cohort study ,Transplantation ,business.industry ,Incidence (epidemiology) ,Middle Aged ,medicine.disease ,humanities ,Mental Health ,Quality of Life ,Female ,business ,Psychosocial ,Follow-Up Studies ,Cohort study - Abstract
Background. Health-related quality of life (HRQoL) represents an important outcome measure to assess the success of transplantation in the long term. This study evaluated HRQoL in heart (HTx) and lung (LTx) transplant survivors, and assessed potential outcome-related predictors from before to 5 years after transplantation. Methods. Study participants (n= 170) were prospectively followed up from before to 5 years after HTx (n=82) or LTx (n=88), including HRQoL assessments (pretransplantation, 6, 12, and yearly between 24 and 60 months) using the Short Form-36, employment status index, and monitoring of adverse events. Results. Patient groups (HTx vs. LTx) differed with respect to gender (men 74% vs. 48%; P
- Published
- 2010
22. Immune-Mechanistic Insights into Improved Lung Preservation using the Organ Care System in a Porcine Transplantation Model in Comparison to the INSPIRE Trial
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Wiebke Sommer, Bettina Wiegmann, Ann-Kathrin Knöfel, Fabio Ius, Katharina Jansson, Igor Tudorache, Gregor Warnecke, Thierry Siemeni, Axel Haverich, Klaus Höffler, Jawad Salman, R. Bellmas-Sanz, and Christine S. Falk
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Transplantation ,Immune system ,business.industry ,Lung preservation ,Medicine ,Bioinformatics ,business - Published
- 2018
23. Ischemia Reperfusion Injury Significantly Differs between Lung vs. Heart Transplantation with Respect to Lead Cytokines and Correlation to Clinical Outcome
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Fabio Ius, Bettina Wiegmann, N. Ledwoch, Christine S. Falk, Axel Haverich, Jasper Iske, Sebastian Rochas, Tim Kaufeld, Murat Avsar, and Gregor Warnecke
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Heart transplantation ,Transplantation ,medicine.medical_specialty ,Lung ,business.industry ,medicine.medical_treatment ,Ischemia ,medicine.disease ,medicine.anatomical_structure ,Internal medicine ,medicine ,Cardiology ,Lead (electronics) ,business ,Reperfusion injury - Published
- 2018
24. Indications for and Outcomes After Combined Lung and Liver Transplantation: A Single-Center Experience on 13 Consecutive Cases
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Axel Haverich, Jens Gottlieb, Marius M. Hoeper, Martin Strueber, Michael Neipp, Björn Nashan, Christian P. Strassburg, R. Lück, Thomas Becker, Jürgen Klempnauer, Gerrit Grannas, Michael P. Manns, Tobias Welte, and Andre R. Simon
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Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Heart-Lung Transplantation ,Hypertension, Pulmonary ,medicine.medical_treatment ,Liver transplantation ,Infections ,Single Center ,Liver disease ,Postoperative Complications ,medicine ,Humans ,Retrospective Studies ,Transplantation ,Portopulmonary hypertension ,business.industry ,Liver Diseases ,Graft Survival ,Immunosuppression ,Retrospective cohort study ,Perioperative ,Middle Aged ,medicine.disease ,Survival Analysis ,Liver Transplantation ,Surgery ,Regimen ,Female ,business ,Lung Transplantation - Abstract
Background Combined lung and liver transplantation (Lu-LTx) is a therapeutic option for selected patients with coexisting lung and liver disease. For several reasons, Lu-LTx is performed in few centers and information about the technical issues, posttransplant management and long-term outcomes associated with this procedure is limited. Methods We analyzed data from 13 consecutive patients who underwent combined Lu-LTx at Hannover Medical School (Hannover, Germany) between April 1999 and December 2003. The main indications were cystic fibrosis, alpha1-proteinase inhibitor deficiency and portopulmonary hypertension. All patients had advanced cirrhosis and severe pulmonary disease manifestation. Results Ten patients received a sequential double Lu-LTx, one patient received a single Lu-LTx, one received a double lung and split liver transplantation, and one received an en-bloc heart-lung and liver transplantation. Immunosuppression was based on cyclosporine in a triple/quadruple regimen. Postoperative surgical complications occurred in eight patients. There were two perioperative deaths; two patients died during the first year on day 67 and 354, respectively, and one patient died at month 53. The overall patient survival rates at 1, 3, and 5 years were 69%, 62%, and 49%, respectively. Conclusion Combined Lu-LTx is a therapeutic option for highly selected patients with end-stage lung and liver disease with acceptable long-term outcome.
- Published
- 2008
25. IgM-Enriched Human Intravenous Immunoglobulin-Based Treatment of Patients With Early Donor Specific Anti-HLA Antibodies After Lung Transplantation
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Ius, Fabio, primary, Sommer, Wiebke, additional, Kieneke, Daniela, additional, Tudorache, Igor, additional, Kühn, Christian, additional, Avsar, Murat, additional, Siemeni, Thierry, additional, Salman, Jawad, additional, Erdfelder, Carolin, additional, Verboom, Murielle, additional, Kielstein, Jan, additional, Tecklenburg, Andreas, additional, Greer, Mark, additional, Hallensleben, Michael, additional, Blasczyk, Rainer, additional, Schwerk, Nicolaus, additional, Gottlieb, Jens, additional, Welte, Tobias, additional, Haverich, Axel, additional, and Warnecke, Gregor, additional
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- 2016
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26. Lung Preservation With Perfadex or Celsior in Clinical Transplantation: A Retrospective Single-Center Analysis of Outcomes
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Christian Hagl, A. Niehaus, Jens Gottlieb, Axel Haverich, Stefan Fischer, Andre R. Simon, Bernhard Gohrbandt, Martin Strueber, Gregor Warnecke, and Tobias Welte
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Organ Preservation Solutions ,Bronchiolitis obliterans ,Kaplan-Meier Estimate ,Single Center ,Disaccharides ,Disease-Free Survival ,law.invention ,Electrolytes ,Glutamates ,law ,Risk Factors ,Germany ,medicine ,Humans ,Histidine ,Mannitol ,Citrates ,Proportional Hazards Models ,Retrospective Studies ,Transplantation ,Lung ,Proportional hazards model ,business.industry ,Retrospective cohort study ,Organ Preservation ,Length of Stay ,Middle Aged ,medicine.disease ,Intensive care unit ,Glutathione ,Respiration, Artificial ,Surgery ,Intensive Care Units ,medicine.anatomical_structure ,Treatment Outcome ,Cohort ,Bronchiolitis ,Female ,Primary Graft Dysfunction ,business ,Lung Transplantation - Abstract
BACKGROUND Despite improvement of lung preservation by the introduction of low-potassium dextran (LPD) solution, ischemia-reperfusion injury remains a major contributor to early post-lung transplant graft dysfunction and mortality. After favorable experimental data, Celsior solution was used in our clinical lung transplant program. Data were compared with our historic LPD cohort. METHODS Between January 2002 and January 2005, 209 consecutive lung transplantations were performed with LPD. These were compared to 208 transplants between February 2005 and September 2007 with Celsior. Endpoints included posttransplant PaO2/FiO2 ratio at different timepoints after intensive care unit (ICU) admission, posttransplant ventilation time, ICU stay and 30-day mortality, follow-up survival, and bronchiolitis obliterans syndrome-free survival. RESULTS Ratios of sex, urgency status, type of procedure, length of posttransplant ICU stay, and age did not show significant differences between the 2 groups. Mean ischemia times were significantly longer in the Celsior group (LPD, 355 ± 105 minutes vs Celsior, 436 ± 139 minutes, P < 0.001). Overall 3-year-survival (LPD, 66.5% vs Celsior, 72.0%; P = 0.25) was nonsignificantly improved in the Celsior cohort. CONCLUSIONS A trend toward better survival (P = 0.09) and increased freedom from bronchiolitis obliterans syndrome (P = 0.03) was observed in the Celsior group despite prolonged ischemic times compared with LPD. Lung preservation with Celsior is safe and effective and may carry advantages.
- Published
- 2015
27. Potential of an Injectable Polymer to Prevent Hyperacute Rejection of Ex Vivo Perfused Porcine Lungs
- Author
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K Wiebe, Jochen Pöling, Mehmet Oezkur, and Axel Haverich
- Subjects
Graft Rejection ,Pulmonary Circulation ,Pathology ,medicine.medical_specialty ,Swine ,medicine.medical_treatment ,medicine ,Animals ,Lung transplantation ,Respiratory system ,Transplantation ,Lung ,biology ,business.industry ,Graft Survival ,Pulmonary edema ,medicine.disease ,Oxygen ,medicine.anatomical_structure ,Immunoglobulin M ,Immunoglobulin G ,Acute Disease ,Models, Animal ,Vascular resistance ,biology.protein ,Vascular Resistance ,Antibody ,business ,Trisaccharides ,Perfusion ,Ex vivo ,Lung Transplantation - Abstract
BACKGROUND Removal of xenoreactive antibodies in pig-to-human lung transplantation by columns or organ perfusions proofed to be unsatisfactory and associated with adverse effects. In an ex-vivo lung perfusion model, we evaluated the potential of a soluble trisaccharide polymer (GAS914) to bind alpha-Gal antibodies and to protect a pulmonary xenograft from hyperacute rejection (HAR) and pulmonary xenograft dysfunction. METHODS Porcine lungs were perfused with fresh human blood for 240 min. In the GAS914 treated group (n=6) the polymer was applied in three different concentrations. The control group (n=6) received no GAS914. Survival and function of perfused xenografts were monitored, and alpha-Gal antibodies as well as cytolytic anti-porcine antibodies analyzed. RESULTS In the GAS-treated group survival of lungs was significantly prolonged, pulmonary vascular resistance reduced, pulmonary edema prevented, and oxygenation improved. On histopathological evaluation application of GAS resulted in minimal graft injury and significantly less deposition of the terminal complement complex C5b-9. Following application of GAS914, up to 89.8% of IgG alpha-Gal, 79.5% of IgM and 73.6% of anti-porcine antibodies in the human blood were bound by the polymer. Subsequent perfusion of porcine lungs resulted in absorption of only 3% of the baseline IgG alpha-Gal antibodies in the GAS914 group, compared to 87% in the controls. CONCLUSIONS In this ex-vivo lung perfusion model, a trisaccharide polymer prevented immediate HAR, due to effective removal of alpha-Gal antibodies. In combination with additional strategies GAS914 may be a valuable tool in overcoming HAR and dysfunction of pulmonary xenografts.
- Published
- 2006
28. Inhibition of aortic allograft vasculopathy by local delivery of platelet-derived growth factor receptor tyrosine-kinase blocker AG-12951
- Author
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Klaus Pethig, Michael Mengel, Michael Hestermann, Ilia Fishbein, Axel Haverich, Matthias Karck, Shmuel Banai, Gershon Golomb, Michael Chorny, Rolf R Meliss, and Alexander Levitzki
- Subjects
Transplantation ,medicine.medical_specialty ,Aorta ,Platelet-derived growth factor ,biology ,Growth factor ,medicine.medical_treatment ,Tyrosine phosphorylation ,Pharmacology ,chemistry.chemical_compound ,surgical procedures, operative ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Internal medicine ,medicine.artery ,medicine ,biology.protein ,Tyrosine kinase ,Platelet-derived growth factor receptor ,Blood vessel - Abstract
BACKGROUND Signal transduction through the platelet-derived growth factor (PDGF)/PDGF-receptor (PDGFR) system has been linked to vascular smooth muscle cell migration and proliferation leading to allograft vasculopathy. This study describes the effect of the tyrphostin AG-1295, a specific PDGFR tyrosine-kinase inhibitor, on neointimal formation in this disease. METHODS AND RESULTS Rat aortic allografts transplanted from dark agouti (RT1 ) donors to Wistar-Furth (RT1 ) recipients were assessed in a new treatment model for local drug delivery from polymeric carrier matrices precoated with AG-1295. Matrices were wrapped around the graft immediately after transplantation. The recipients received no background immunosuppression. At day 80 posttransplantation, intimal thickness in AG-1295-treated grafts was reduced when compared to controls (11.8+/-9.1% intimal thickness vs. 23.7+/-6.4% intimal thickness; P=0.042). This finding corresponded to inhibition of intimal PDGFR-beta expression in AG-1295-treated grafts at day 20 posttransplantation (P =0.029 vs. allogeneic controls). CONCLUSIONS The tyrphostin AG-1295 reduces neointimal formation in aortic allograft vasculopathy by inhibition of PDGFR-beta-triggered tyrosine phosphorylation. Local drug release of specific tyrosine-kinase inhibitors from perivascularly co-implanted polymeric carrier matrices is effective in the prophylaxis of allograft vasculopathy under selected experimental conditions.
- Published
- 2002
29. C1-esterase-inhibitor for primary graft dysfunction in lung transplantation
- Author
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Axel Haverich, Fabio Ius, Murat Avsar, Petra Weber, Wiebke Sommer, Christian Kühn, Jens Gottlieb, Jawad Salman, Gregor Warnecke, Igor Tudorache, Clemens Gras, and Tobias Welte
- Subjects
Adult ,Lung Diseases ,Male ,medicine.medical_specialty ,Adolescent ,Early signs ,medicine.medical_treatment ,Primary Graft Dysfunction ,Gastroenterology ,Cohort Studies ,Young Adult ,Internal medicine ,medicine ,Lung transplantation ,Humans ,Icu stay ,Postoperative Period ,Prospective Studies ,Aged ,Retrospective Studies ,Transplantation ,business.industry ,Incidence (epidemiology) ,Incidence ,Graft Survival ,Off-Label Use ,respiratory system ,Middle Aged ,bacterial infections and mycoses ,respiratory tract diseases ,C1 esterase ,Intensive Care Units ,Complement Inactivating Agents ,Treatment Outcome ,Cohort ,Female ,business ,Complement C1 Inhibitor Protein ,Lung Transplantation - Abstract
BACKGROUND Primary graft dysfunction (PGD) is the most important cause of early morbidity and mortality in lung transplantation (LTX) with an incidence of 8% to 20%. We hypothesized that application of C1-esterase-inhibitor (C1-INH) in LTX-recipients showing early signs of severe PGD would attenuate the condition. METHODS Starting as of May 2010, all recipients showing a PaO2/FiO2 ratio of less than 100 as early sign of PGD at first measurement in the OR were immediately treated with C1-INH. Postoperative courses of C1-INH-treated recipients were compared with a subgroup of recipients that developed severe PGD (PGD3-group) within 72 hours after LTX but did not receive C1-INH. Additionally, a third group consisting of all remaining recipients was assembled. RESULTS A total of 275 LTX were performed between May 2010 and September 2012 at our center. Among these, 24 patients (8.7%) revealed a first PaO2/FiO2 ratio less than 100 and were treated with C1-INH (C1-INH-group). The PGD3-group consisted of 14 patients; the control cohort consisted of 237 patients. PGD scores were significantly higher in the C1-INH-group and PGD3-group as compared with the control group at all times postoperatively. ICU stay was longest in the PGD3 cohort and prolonged in C1-INH patients compared with the control group (29 [2-70] vs. 9 [2-83] vs. 3 [1-166] days, P=0.002). One-year survival in the PGD3-cohort was 71.4%, the C1-INH-treated-group had a one-year-survival of 82.5%, the control group had the best outcome (95%) (P=0.001). CONCLUSION Treatment of PGD with C1-INH led to acceptable outcome. Although survival in the C1-INH treated patients was lower than in the remaining collective, it was as good or better, compared with the PGD3 group and as what is internationally regarded as reasonable after LTX.
- Published
- 2014
30. COMBINED EXOGENOUS SURFACTANT AND INHALED NITRIC OXIDE THERAPY FOR LUNG ISCHEMIA-REPERFUSION INJURY IN MINIPIGS1
- Author
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Gregor Warnecke, Martin Strüber, Fraud S, Axel Haverich, and Jens M. Hohlfeld
- Subjects
Transplantation ,Neutrophil extravasation ,Lung ,medicine.diagnostic_test ,business.industry ,respiratory system ,Pharmacology ,Pulmonary compliance ,medicine.disease ,respiratory tract diseases ,Nitric oxide ,chemistry.chemical_compound ,Bronchoalveolar lavage ,medicine.anatomical_structure ,chemistry ,Pulmonary surfactant ,Anesthesia ,medicine ,Respiratory system ,business ,Reperfusion injury - Abstract
BACKGROUND The combined application of exogenous surfactant and inhaled nitric oxide was evaluated for prevention of ischemia-reperfusion injury of the lung. METHODS Left lungs were selectively perfused in 18 minipigs in situ with cold preservation solution. After 90 min of warm ischemia, the lungs were reperfused and the right pulmonary artery and bronchus were ligated (control group, n=6). Exogenous surfactant was instilled via bronchoscopy during ischemia (surfactant group, n=6). In a third group, surfactant was applied, followed by administration of inhaled nitric oxide (surfactant+NO group, n=6). Hemodynamic and respiratory parameters were recorded for 7 hr, and bronchoalveolar lavage fluid (BALF) was obtained before and after reperfusion for measurement of surface tension, small aggregate/large aggregate ratio, protein and phospholipid contents, and a differential cell count. RESULTS Control group animals survived for 3.7+/-1.4 hr. In both surfactant-treated groups, five out of six animals survived the observation period (P
- Published
- 2001
31. AZATHIOPRINE WITHDRAWAL IN STABLE LUNG AND HEART/LUNG RECIPIENTS RECEIVING CYCLOSPORINE-BASED IMMUNOSUPPRESSION
- Author
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Spiekerkötter E, Jost Niedermeyer, Helmut Fabel, Marius M. Hoeper, Frank Hoffmeyer, Axel Haverich, and Wolfgang Harringer
- Subjects
Adult ,Graft Rejection ,Male ,medicine.medical_specialty ,Heart-Lung Transplantation ,medicine.medical_treatment ,Azathioprine ,Gastroenterology ,Internal medicine ,medicine ,Humans ,Lung transplantation ,Prospective Studies ,Bronchiolitis Obliterans ,Transplantation ,Chemotherapy ,Lung ,business.industry ,Immunosuppression ,Middle Aged ,respiratory system ,Ciclosporin ,Lymphoproliferative Disorders ,Respiratory Function Tests ,Surgery ,Regimen ,surgical procedures, operative ,medicine.anatomical_structure ,Acute Disease ,Cytomegalovirus Infections ,Cyclosporine ,Drug Therapy, Combination ,Female ,Safety ,business ,Immunosuppressive Agents ,Lung Transplantation ,medicine.drug - Abstract
Chronic rejection is the leading cause of graft failure after (heart-) lung transplantation. Therefore, many centers maintain a triple immunosuppressive cyclosporine-based regimen including azathioprine (AZA) during the long-term course after lung transplantation. However, an increased risk of malignancies has been attributed to prolonged immunosuppression, and there is evidence that less intensive immunosuppressive regimens are feasible in the long-term course after other solid organ transplantation. Therefore, we investigated the effects of AZA withdrawal in stable lung transplant recipients.A prospective study was performed to assess the effects of AZA withdrawal in patients who received a lung transplant more than 4 years ago with stable graft function defined by absence of rejection episodes for at least 2 years and no evidence of bronchiolitis obliterans.A total of 24 patients qualified for the study and 7 discontinued AZA. Despite the small number of patients, termination of the study became necessary after 12 months because significantly more grafts showed deteriorating function after withdrawing AZA (4 of 7) compared to recipients continuing a triple therapy (1 of 17; P0.05). In recipients with deteriorating graft function conventional treatment with high-dose corticosteroids and reinstitution of AZA failed to stop the development of obliterative bronchiolitis.Our data reinforce the importance of a potent immunosuppressive regimen for the maintenance of stable graft function after lung transplantation.
- Published
- 2000
32. CARDIAC ALLOGRAFT VASCULAR DISEASE AFTER ORTHOTOPIC HEART TRANSPLANTATION
- Author
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Axel Haverich, Klaus Pethig, Andrea Hoffmann, Bernd Heublein, Gerhard Gross, and Adine Timke
- Subjects
Heart transplantation ,Transplantation ,medicine.medical_specialty ,Homocysteine ,biology ,Vascular disease ,business.industry ,medicine.medical_treatment ,medicine.disease ,Gastroenterology ,Pathogenesis ,chemistry.chemical_compound ,Endocrinology ,chemistry ,Internal medicine ,Methylenetetrahydrofolate reductase ,Genotype ,Cohort ,medicine ,biology.protein ,business - Abstract
BACKGROUND Recently, homocysteine (HCY) levels have been suggested to be a risk factor in cardiac allograft vascular disease (CAVD). As plasma levels are partially under genetic control, we investigated the influence of the methylenetetrahydrofolate reductase (MTHFR) polymorphism on HCY levels and development of CAVD in heart transplant (HTX) recipients. METHODS Genotyping and assessment of fasting HCY levels were performed in a cohort of 146 HTX recipients and correlated to the onset and progression of CAVD, assessed by serial angiography. RESULTS Actuarial freedom from CAVD did not differ significantly between the genotypes. However, patients positive for CAVD presented with higher HCY levels than CAVD-negative individuals (21.0+/-9.4 vs. 18.2+/-6.6 micromol/L, P=0.046). CONCLUSIONS There is some evidence that plasma HCY might be involved in development of CAVD. However, polymorphism of the MTHFR gene could not be shown to be related to severity of allograft vascular disease.
- Published
- 2000
33. FAMCICLOVIR TREATMENT OF CHRONIC HEPATITIS B IN HEART TRANSPLANT RECIPIENTS: A PROSPECTIVE TRIAL1,2
- Author
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Axel Haverich, J. Vollmar, Klaus Pethig, D. R. Petzold, Heiner Wedemeyer, Michael P. Manns, E. Goldmann, Klaus H.W. Böker, Hans L. Tillmann, P. Flemming, M. Bastürk, and K. E. Griffin
- Subjects
Hepatitis B virus ,Transplantation ,medicine.medical_specialty ,Nucleoside analogue ,business.industry ,medicine.medical_treatment ,Famciclovir ,Immunosuppression ,Hepatitis B ,medicine.disease ,medicine.disease_cause ,Gastroenterology ,Surgery ,HBeAg ,Internal medicine ,medicine ,Prospective cohort study ,business ,medicine.drug - Abstract
Hepatitis B may take a rapid and aggressive course in patients under immunosuppression. Nucleoside analogues have been shown to suppress viral replication effectively. To investigate the effect of famciclovir in immunosuppressed patients, 21 heart transplant recipients with chronic hepatitis B infection were included in a prospective study. Patients and methods. Patients have been treated with Famciclovir for a median of 14 months. Hepatitis B virus replication and biochemical parameters were regularly tested and liver biopsies were taken before treatment and after a median time of 7 months. HBV-polymerase was sequenced in all patients before therapy and in those patients who experienced virological breakthrough. Results. Nineteen patients were treated for at least 6 months. Hepatitis B virus-DNA levels declined in all patients and became negative in 8 patients. Mean hepatitis B virus-DNA levels decreased from 199±269 to 34±53 pg/ml after 24 weeks (P=0.003). During treatment HBeAg became negative in five patients. Mean alanine aminotransferase decreased from 42±26 to 24±10 U/L (P=0.006). Histological analysis revealed improved inflammatory activity according to the Ishak-score in 11/16 (69%) patients. Total inflammatory activity scores decreased from 8 to 6 (median, NS), but interface hepatitis score (P=0.02) and lobular inflammation score (P=0.006) improved significantly. Median fibrosis scores fell from 5 to 3 (P=0.002). Three patients developed virological breakthrough on famciclovir after 7, 8, and 26 months of treatment showing HBV-polymerase amino acid changes L528 M, S567A, and I581K, respectively. Conclusions. Famciclovir improves not only biochemical and virological features but also hepatic inflammation and liver fibrosis in patients with chronic hepatitis B under heavy immunosuppression. Virological breakthrough may develop and requires close monitoring.
- Published
- 1999
34. ATTITUDES OF PATIENTS BEFORE AND AFTER TRANSPLANTATION TOWARDS VARIOUS ALLOGRAFTS1
- Author
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Axel Haverich, B. Nashan, Hartmut Schmidt, Reinhard Brunkhorst, Rudolf Raab, and Hans J. Schlitt
- Subjects
Transplantation ,Allogeneic graft ,medicine.medical_specialty ,Coping (psychology) ,surgical procedures, operative ,business.industry ,MEDLINE ,Medicine ,Transplant patient ,business ,Organ transplantation ,Surgery - Abstract
Background.The presence of an allogeneic graft inside the body may have psychological impact on transplant patients. It was the aim of this study to evaluate the attitude of patients before and after different types of organ transplantation towards organ allografts.Methods.A total of 1,049 patients
- Published
- 1999
35. LONG-TERM OUTCOME OF CHRONIC HEPATITIS B IN HEART TRANSPLANT RECIPIENTS
- Author
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Heiner Wedemeyer, Axel Haverich, Peer Flemming, Michael P. Manns, Klaus Pethig, Doris Wagner, P. Oppelt, Dieter R. Petzold, and Klaus H.W. Boeker
- Subjects
Adult ,Liver Cirrhosis ,Male ,Hepatitis B virus ,HBsAg ,medicine.medical_specialty ,Cirrhosis ,Biopsy ,medicine.medical_treatment ,medicine.disease_cause ,Chronic liver disease ,Gastroenterology ,Organ transplantation ,Hepatitis B, Chronic ,Internal medicine ,medicine ,Humans ,Retrospective Studies ,Heart transplantation ,Transplantation ,Hepatitis B Surface Antigens ,business.industry ,Alanine Transaminase ,Bilirubin ,Middle Aged ,Hepatitis B ,medicine.disease ,Surgery ,Liver ,DNA, Viral ,Heart Transplantation ,Female ,business ,Follow-Up Studies - Abstract
Background Hepatitis B is common in organ transplant recipients. It adversely affects the prognosis after liver and kidney transplantation. The long-term outcome of hepatitis B virus (HBV) infection in heart transplant recipients has not been studied before. Methods Between July 1984 and June 1993, 436 patients underwent heart transplantation at the Hannover Medical School. A total of 345 patients survived for more than 1 year and were included in this study. Of these, 74 were found to be hepatitis B surface antigen (HBsAg)-positive during follow-up; 69 acquired HBV infection at known time points 25+/-17 months after transplantation, and 5 had already been infected before heart transplantation. Mean follow-up was 105 (range, 25-157) months. Results Patients developed significant alanine aminotransferase (ALT) elevations after HBV infection, which peaked and then remained above normal. Preinfection levels of ALT were 15.4+/-6.4 U/L, peak values were 71.2+/-47.2 U/L, and mean values after HBV infection were 28.9+/-14.6 U/L. All patients remained HBsAg-positive. Thirteen patients (18%) became HBeAg-negative during follow-up, 10 with negative quantitative HBV-DNA assays. Mean HBV-DNA levels in the remaining patients were 292+/-267 (range, 0-978) pg/ml. Thirty-four patients died during follow-up (45.9%) compared to 78/271 (28.8%) in the control group (P=0.008). Six of the HBsAg-positive patients (17.1%) died of liver failure 6.2-10.6 years (mean, 8.6) after transplantation. Histology of 25 HBsAg-positive patients more than 5 years after infection revealed severe fibrosis or cirrhosis in 14 (56%), mild fibrosis in 9 (36%), and chronic hepatitis without fibroproliferation in 2 (8%). Conclusions Hepatitis B infection after heart transplantation leads to chronic liver disease in the majority of the affected patients, causing cirrhosis in more than 55% within the first decade after transplantation. Liver failure is a common cause of death in the infected group of patients. Active HBV vaccination is mandatory for all organ transplant candidates, in particular before heart transplantation.
- Published
- 1998
36. Health-related quality of life after solid organ transplantation: a prospective, multiorgan cohort study
- Author
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Jens Gottlieb, Axel Haverich, Christiane Kugler, Christoph Bara, Karin Weissenborn, Ina Einhorn, Gregor Warnecke, Hannelore Barg-Hock, Anke Schwarz, and Hermann Haller
- Subjects
Adult ,Male ,Transplantation ,medicine.medical_specialty ,business.industry ,Organ Transplantation ,Middle Aged ,Organ transplantation ,Confidence interval ,Cohort Studies ,Distress ,Quality of life ,Internal medicine ,medicine ,Quality of Life ,Humans ,Female ,Prospective Studies ,Intensive care medicine ,Prospective cohort study ,business ,Psychosocial ,Cohort study ,Aged - Abstract
Background Short-term posttransplantation survival and health-related quality of life (HRQoL) is exceptionally high for all patients after organ transplantation; however, predictors of the HRQoL outcome are not well understood. Trajectories of patients' perceived benefit/burden ratio associated with the transplant procedure may differ when taking the organ type for transplantation into account. Methods A prospective, single-center cohort study assessed the trajectories of 354 patients after kidney (n=165), liver (n=53), heart (n=24), and lung (n=112) transplantation at 2, 6, 12, and 24 months with respect to psychosocial outcomes (HRQoL, anxiety, depression, social support, and work performance). Results Mean age was 50±13 years, and 61.6% were male in the overall sample. Demographics differed with respect to organ type. HRQoL measured by the mean SF-36 Physical Component Scale was 36.8 (95% confidence interval, 35.7-37.8) and 48.9 (95% confidence interval, 47.2-49.7) for the Psychosocial Component Scale for the entire sample at 2 months and showed a marginal decrease until 24 months after transplantation. Overall, HRQoL increased for all organ types with differing trajectories. Liver patients reported the lowest HRQoL benefit for the majority of the physical (P≤0.01) and psychosocial (P≤0.01) SF-36 subscales. Anxiety (17.4%) and depression (13.8%) were prevalent in the overall sample. Depression symptoms impaired HRQoL outcomes in both SF-36 components and unemployment impacted the SF-36 psychosocial outcomes. Conclusions HRQoL improved after transplantation for all four types of transplant, but the trajectories were different. Regular screening for depression symptoms may diminish psychologic disorders and distress after transplantation and thus may further improve outcomes.
- Published
- 2013
37. Low exercise tolerance correlates with reduced inspiratory capacity and respiratory muscle function in recipients with advanced chronic lung allograft dysfunction
- Author
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Annelies Boemke, Sabine Dettmer, Axel Haverich, Mark Greer, Hendrik Suhling, Gregor Warnecke, Jens Gottlieb, Tobias Welte, Jessica Rademacher, and Claudia de Wall
- Subjects
Adult ,medicine.medical_specialty ,medicine.medical_treatment ,Walking ,Inspiratory Capacity ,Internal medicine ,Forced Expiratory Volume ,Respiratory muscle ,Outpatient clinic ,Medicine ,Lung transplantation ,Humans ,Prospective Studies ,Respiratory system ,Prospective cohort study ,Work of Breathing ,Transplantation ,Lung ,Exercise Tolerance ,business.industry ,Hazard ratio ,Middle Aged ,Respiratory Muscles ,medicine.anatomical_structure ,Cross-Sectional Studies ,Cardiology ,Physical therapy ,Exercise Test ,Quality of Life ,business ,Lung Transplantation - Abstract
BACKGROUND Advanced chronic lung allograft dysfunction limits survival after lung transplantation. We hypothesize that patients with chronic lung allograft dysfunction can be subdivided by exercise tolerance in two groups, and quality of life (QOL) and survival differ between the groups. METHODS A single-center, cross-sectional, partly prospective, study was performed in our outpatient clinic between July and November 2011, including all patients with a forced expiratory volume in 1 s
- Published
- 2013
38. ISCHEMIC PRECONDITIONING ENHANCES DONOR HEART PRESERVATION1
- Author
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Axel Haverich, Parwis B. Rahmanian, and Matthias Karck
- Subjects
Heart transplantation ,Cardioprotection ,Transplantation ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Ischemia ,Hypothermia ,medicine.disease ,Anesthesia ,Internal medicine ,Ventricular pressure ,medicine ,Cardiology ,Ischemic preconditioning ,Viaspan ,medicine.symptom ,business - Abstract
Ischemic preconditioning has not been assessed in an experimental model for myocardial preservation during heart transplantation. Using isolated working rat hearts, ischemic preconditioning was investigated as an adjunct to isolated hypothermic (group 1), crystalloid (group 2: University of Wisconsin solution; group 3: St. Thomas' Hospital cardioplegic solution II; group 4: Bretschneiders' cardioplegic solution), and noncrystalloid (group 5: cold blood cardioplegia) preservation during a 10-hr period of global ischemia at 4 degrees C. After acquisition of functional baseline data, ischemic preconditioning was induced with one cycle of 5 min of normothermic ischemia and 5 min of reperfusion before induction of global hypothermic ischemia (n= 10/group). Nonpreconditioned hearts (n= 10/group) were assessed for control. Ischemic preconditioning improved postischemic: functional recovery. Thus, aortic flow after 60 min of reperfusion recovered to 0%, 8%, 0%, 1% and 0% in control groups 1 to 5 without ischemic preconditioning and 21%, 25%, 10%, 8%, and 3% in groups 1 to 5 with ischemic preconditioning. The same pattern of recovery was observed in regard to postischemic maximum developed left ventricular pressure, which recovered to 21%, 56%, 30%, 36%, and 19% in groups 1 to 5 without preconditioning and 46%, 75%, 49%, 40%, and 47% in the corresponding groups with ischemic preconditioning. High-energy phosphate contents were not significantly different between preconditioned hearts and corresponding nonpreconditioned control hearts. Creatine kinase leakage during early reperfusion was found to be reduced with ischemic preconditioning. Thus, we have demonstrated that ischemic preconditioning can improve contractile function after global hypothermic ischemia in the isolated rat heart and we have shown that this protection is additive to that of hypothermia-induced protection during global ischemia at 4 degrees C. This endogenous mechanism of cardioprotection was effective regardless of whether preservation was accomplished using cardioplegic solution or topical hypothermia alone. This may have clinical implications in myocardial preservation for heart transplantation.
- Published
- 1996
39. ENHANCEMENT OF CYTOMEGALOVIRUS INFECTION AND ACUTE REJECTION AFTER ALLOGENEIC LUNG TRANSPLANTATION IN THE RAT
- Author
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M L Lohmann-Matthes, Cathrien A. Bruggeman, D Bauer, X.-M. You, Gustav Steinhoff, Haverich A, and C. Steinmüller
- Subjects
Transplantation ,Pathology ,medicine.medical_specialty ,Allogeneic transplantation ,Lung ,Cell adhesion molecule ,medicine.medical_treatment ,Immunosuppression ,Biology ,biology.organism_classification ,Pathogenesis ,medicine.anatomical_structure ,Betaherpesvirinae ,Immunology ,medicine ,Lung transplantation - Abstract
A possible mechanism of the induction of lung transplant rejection by cytomegalovirus (CMV) infection is the inflammatory upregulation of adhesion ligand molecules on transplant endothelia by the viral infection leading to leukocyte activation. To study this question a rat model of rat cytomegalovirus (RCMV) infection and acute lung transplant rejection was established to study: (1) the influence of RCMV infection on the course of rejection, (2) the influence of rejection on the course of RCMV infection, and (3) the influence of RCMV on adhesion molecule expression and leukocyte infiltration. For this Lew (RT1l) rats received either syngenic (n=25) or allogeneic (BN, RT1n; n=38) left lateral lung transplants. Postoperatively, CsA 25mg/kg was given on days 1-3 and triple drug (CsA, Aza, Pred) immunosuppression was given from days 4-10 to induce systemic RCMV infection and acute rejection developed from postoperative day (POD) 15-25 in allogeneic transplants. In RCMV-positive animals the rejection grade was gradually increased at POD 15 and 18. Furthermore, after allogeneic transplantation an enhanced viral infection of the lung transplant as early as POD 11 was found and increased salivary gland PFU titers on days 20 and 25. In the absence of rejection infiltration a maximal induction of ICAM-1 adhesion molecules was found on lung endothelia in RCMV+ allogeneic animals as compared with noninfected controls. This induction was found to lesser degree for VCAM-1 and MHC class II adhesion ligand molecules. This was accompanied by a significantly increased CD11a+ and CD49d+ leukocyte infiltration into the alveolar interstitium on day 11 and 15 in infected transplants. The results show an enhancement of RCMV infection after allogeneic lung transplantation leading to endothelial activation and recruitment of CD11a/CD49d+ leukocytes. This mechanism may strongly influence transplant inflammation and the long-term course of lung transplant rejection.
- Published
- 1996
40. Graft-protective effects of the HMG-CoA reductase inhibitor pravastatin after lung transplantation--a propensity score analysis with 23 years of follow-up
- Author
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Axel Haverich, Andre R. Simon, Jens Gottlieb, Christian Kuehn, Donghui Ma, Martin Strueber, Y. Li, Georg Warnecke, and Tobias Welte
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Vital Capacity ,Bronchiolitis obliterans ,Kaplan-Meier Estimate ,Gastroenterology ,Internal medicine ,Medicine ,Lung transplantation ,Humans ,Bronchiolitis Obliterans ,Pravastatin ,Proportional Hazards Models ,Retrospective Studies ,Transplantation ,Lung ,biology ,business.industry ,Proportional hazards model ,Graft Survival ,Retrospective cohort study ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,HMG-CoA reductase ,biology.protein ,Female ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,medicine.drug ,Follow-Up Studies ,Lung Transplantation - Abstract
Background To determine whether the hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin has a graft-protective effect, we retrospectively analyzed 502 patients who had undergone lung transplantation in Hannover. Methods Propensity scores have been calculated for each patient and compared between two groups. Cox Hazard analyses were performed for different parameters (e.g., basic parameters of patients, underlying diagnoses, different operations, and important organ functions after lung transplantation). Lung function after transplantation was monitored using repeated measurement analyses. Additionally, conditional Kaplan-Meier survival analyses were used to explore the impact of different diagnoses, the severity of bronchiolitis obliterans, the type of transplantation, and different immunosuppressant regimes on patient survival. Results The results indicate a strong association between the postoperative administration of statins and the improvement of survival, maintenance of graft (lung) function, and slowing of the onset of bronchiolitis obliterans. Conclusion These findings suggest a new postoperative therapeutic focus for maintaining graft function.
- Published
- 2011
41. MicroRNA 628-5p as a Novel Biomarker for Cardiac Allograft Vasculopathy (CAV)
- Author
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Jan A. Kleeberger, A. Holzmann, Christoph Bara, A. Neumann, Axel Haverich, Thomas Thum, Nils Benecke, and B. Przybylek
- Subjects
Transplantation ,business.industry ,microRNA ,Cancer research ,Biomarker (medicine) ,Medicine ,Cardiac allograft vasculopathy ,business - Published
- 2014
42. Lung Preservation With Perfadex or Celsior in Clinical Transplantation
- Author
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Gohrbandt, Bernhard, primary, Simon, Andre R., additional, Warnecke, Gregor, additional, Fischer, Stefan, additional, Hagl, Christian, additional, Niehaus, Adelheid, additional, Gottlieb, Jens, additional, Welte, Tobias, additional, Haverich, Axel, additional, and Strueber, Martin, additional
- Published
- 2015
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43. Allogeneic CD4+CD25high T Cells Regulate Obliterative Bronchiolitis of Heterotopic Bronchus Allografts in Both Porcinized and Humanized Mouse Models
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Sommer, Wiebke, primary, Knöfel, Ann-Kathrin, additional, Madrahimov, Nodir, additional, Avsar, Murat, additional, Jonigk, Danny, additional, Salman, Jawad, additional, Dreckmann, Karla, additional, Jansson, Katharina, additional, Salguero, Gustavo, additional, Maus, Ulrich A., additional, Welte, Tobias, additional, Haverich, Axel, additional, and Warnecke, Gregor, additional
- Published
- 2015
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44. Lung Transplantation for Severe Pulmonary Hypertension—Awake Extracorporeal Membrane Oxygenation for Postoperative Left Ventricular Remodelling
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Tudorache, Igor, primary, Sommer, Wiebke, additional, Kühn, Christian, additional, Wiesner, Olaf, additional, Hadem, Johannes, additional, Fühner, Thomas, additional, Ius, Fabio, additional, Avsar, Murat, additional, Schwerk, Nicolaus, additional, Böthig, Dietmar, additional, Gottlieb, Jens, additional, Welte, Tobias, additional, Bara, Christoph, additional, Haverich, Axel, additional, Hoeper, Marius M., additional, and Warnecke, Gregor, additional
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- 2015
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45. IMPACT OF CHRONIC INFECTION WITH CHLAMYDIA PNEUMONIAE ON INCIDENCE OF CARDIAC ALLOGRAFT VASCULOPATHY
- Author
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Bernd Heublein, Omke E. Teebken, Klaus Pethig, Thorsten Wittwer, Thorsten Wahlers, Axel Haverich, and Wolfgang Harringer
- Subjects
Adult ,Male ,medicine.medical_specialty ,medicine.medical_treatment ,Coronary Disease ,Gastroenterology ,Serology ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Risk factor ,Aged ,Retrospective Studies ,Heart transplantation ,Transplantation ,Chlamydia ,business.industry ,Incidence ,Incidence (epidemiology) ,Chlamydia Infections ,Chlamydophila pneumoniae ,Middle Aged ,medicine.disease ,Antibodies, Bacterial ,Immunoglobulin A ,Chronic infection ,Immunoglobulin G ,Chronic Disease ,Immunology ,cardiovascular system ,Heart Transplantation ,Female ,business ,Complication - Abstract
Chronic infection with Chlamydia pneumoniae (CP) is associated with development of coronary disease. However, little information exists concerning CP infection and impact on posttransplant cardiac allograft vasculopathy (CAV). A total of 202 patients were investigated 5.5+/-3.1 years after cardiac transplantation (46.5+/-11.0 years; 169 male, 33 female). Assessment of CAV was performed by annual coronary angiograms. Chlamydia serology (IgG/IgA) was performed using micro-immunofluorescence. Statistics comprised analysis of variance and Kaplan-Meier analysis. A total of 152 patients were CAV positive. Elevated titers were present in 45% (IgG) and 72.8% (IgA) of patients. Generally, serostatus was not associated with development of CAV when evaluated over the total postoperative interval. However, after month 14 there was a significant trend toward lower actuarial freedom from CAV in patients with elevated IgA titers. CP seems not to play a significant role in the development of CAV early after heart transplantation but might be a predicting risk factor after the first postoperative year.
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- 2000
46. Effect of adherence to home spirometry on bronchiolitis obliterans and graft survival after lung transplantation
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Axel Haverich, Tobias Welte, Andre R. Simon, Claudia DeWall, Martin Dierich, Jens Gottlieb, Christiane Kugler, and Thomas Fuehner
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Spirometry ,Adult ,Graft Rejection ,Male ,Reoperation ,medicine.medical_specialty ,Time Factors ,Adolescent ,medicine.medical_treatment ,Bronchiolitis obliterans ,Kaplan-Meier Estimate ,Risk Assessment ,Young Adult ,Predictive Value of Tests ,Internal medicine ,medicine ,Lung transplantation ,Humans ,Prospective Studies ,Prospective cohort study ,Bronchiolitis Obliterans ,Aged ,Proportional Hazards Models ,Transplantation ,medicine.diagnostic_test ,Proportional hazards model ,business.industry ,Mortality rate ,Graft Survival ,Middle Aged ,medicine.disease ,humanities ,Surgery ,Log-rank test ,Self Care ,Early Diagnosis ,Patient Compliance ,Female ,business ,Lung Transplantation - Abstract
Background. Patient-controlled home spirometry (HS) after lung transplantation has been shown to be valid and reliable to detect the presence of graft infection and rejection at its earliest onset. Effects of nonadherence to HS on detection of the bronchiolitis obliterans syndrome (BOS) and on graft survival are unknown. Methods. A 7-year prospective cohort study assessed nonadherence longitudinally using electronic spirometry for 24 months. During follow-up, BOS, retransplantation, and survival were stratified by adherence groups. Results. Electronic monitoring of 226 patients confirmed that 123,487 measures were performed. Period prevalence was 0.76 measures per patient day and decreased significantly over time (P
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- 2009
47. In a Fully Allogeneic Mouse Aorta Transplantation Model Physical Exercise Reduces Transplant Arteriosclerosis.
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Knoefel, A., primary, Sommer, W., additional, Madrahimov, N., additional, Salman, J., additional, Jansson, K., additional, Ziehme, P., additional, Avsar, M., additional, Warnecke, G., additional, and Haverich, A., additional
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- 2014
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48. Modulation of Immune-Mediators From Donor Lungs Using the Organ Care System® - A Potential Mechanism for Improved Outcome.
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Wiegmann, B., primary, Falk, C., additional, Mueller, B., additional, Neudoerfl, C., additional, Akhdar, A., additional, Kuehn, C., additional, Tudorache, I., additional, Avsar, M., additional, Haverich, A., additional, and Warnecke, G., additional
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- 2014
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49. The INSPIRE International Lung Trial With the Organ Care System Technology (OCSTM) - Interim Report.
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Warnecke, G., primary, Haverich, A., additional, van Raemdonck, D., additional, Massard, G., additional, Santelmo, N., additional, Falcoz, P., additional, Olland, A., additional, Leseche, G., additional, Mal, H., additional, Thomas, P., additional, Rea, F., additional, Nicotra, S., additional, Schiavon, M., additional, Marulli, G., additional, Knosalla, C., additional, Hetzer, R., additional, Simon, A., additional, Tsui, S., additional, Kukreja, J., additional, Bermudez, C., additional, Moradiellos, F., additional, Varela, A., additional, Dhital, K., additional, Nagendran, J., additional, McCurry, K., additional, and Ardehali, A., additional
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- 2014
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50. Differential Outcomes for Long Term Ex Vivo Lung Perfusion in a Porcine Model -With or Without Red Cells?
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Sommer, W., primary, Avsar, M., additional, Salman, J., additional, Jansson, K., additional, Kuehn, C., additional, Tudorache, I., additional, Haverich, A., additional, and Warnecke, G., additional
- Published
- 2014
- Full Text
- View/download PDF
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