RESUMEN
The role of mammalian target of rapamycin (mTOR) inhibitors in de novo immunosuppression after lung transplantation is not well defined. We compared Everolimus versus mycophenolate mofetil in an investigator-initiated single-center trial in Hannover, Germany. A total of 190 patients were randomly assigned 1:1 on day 28 posttransplantation to mycophenolate mofetil (MMF) or Everolimus combined with cyclosporine A (CsA) and steroids. Patients were followed up for 2 years. The primary endpoint was freedom from bronchiolitis obliterans syndrome (BOS). The secondary endpoints were incidence of acute rejections, infections, treatment failure and kidney function. BOS-free survival in intention-to-treat (ITT) analysis was similar in both groups (p = 0.174). The study protocol was completed by 51% of enrolled patients. The per-protocol analysis shows incidence of bronchiolitis obliterans syndrome (BOS): 1/43 in the Everolimus group and 8/54 in the MMF group (p = 0.041). Less biopsy-proven acute rejection (AR) (p = 0.005), cytomegalovirus (CMV) antigenemia (p = 0.005) and lower respiratory tract infection (p = 0.003) and no leucopenia were seen in the Everolimus group. The glomerular filtration rate (GFR) decreased in both groups about 50% within 6 months. Due to a high withdrawal rate, the study was underpowered to prove a difference in BOS-free survival. The dropout rate was more pronounced in the Everolimus group. Secondary endpoints indicate potential advantages of Everolimus-based protocols but also a potentially higher rate of drug-related serious adverse events.
Asunto(s)
Everolimus/farmacología , Rechazo de Injerto/tratamiento farmacológico , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/efectos adversos , Ácido Micofenólico/farmacología , Complicaciones Posoperatorias/tratamiento farmacológico , Adolescente , Adulto , Anciano , Antibióticos Antineoplásicos/farmacología , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Supervivencia de Injerto/efectos de los fármacos , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
The aim of this study was to assess performance of the new lung allocation system in Germany based on lung allocation score (LAS). Retrospective analysis of waitlist (WL) outflow, lung transplantation (LTx) activity and 3-month outcomes comparing 1-year pre- and post-LAS introduction on December 10, 2011 was performed. Following LAS introduction, WL registrations remained constant, while WL mortality fell by 23% (p = 0.04). Reductions in WL mortality occurred in patients with cystic fibrosis (CF; -52%), emphysema (chronic obstructive pulmonary disease [COPD]; -49%) and pulmonary hypertension (PH; -67%), but not idiopathic pulmonary fibrosis (IPF; +48%). LTx activity increased by 9% (p = 0.146). Compared to pre-LAS, more patients with IPF (32% vs. 29%) and CF (20% vs. 18%) underwent transplantation and comparatively fewer with COPD (30% vs. 39%). Median LAS among transplant recipients was highest in PH (53) and IPF (49) and lowest in COPD (34). Transplantation under invasive respiratory support increased to 13% (in CF 28%, +85%, p = 0.017). Three-month survival remained unchanged (pre: 96.1% and post: 94.9%, p = 0.94). Following LAS implementation in Germany, reductions in waiting list size and WL mortality were observed. Composition of transplant recipients changed, with fewer COPD and more IPF recipients. Transplantation under invasive respiratory support increased. Reductions in WL mortality were most pronounced among CF and PH patients.
Asunto(s)
Asignación de Recursos para la Atención de Salud , Trasplante de Pulmón , Alemania , Humanos , Enfermedades Pulmonares/cirugía , Listas de EsperaRESUMEN
We report on the use of veno-arterial extracorporeal membrane oxygenation (ECMO) as a bridging strategy to lung transplantation in awake and spontaneously breathing patients. All five patients described in this series presented with cardiopulmonary failure due to pulmonary hypertension with or without concomitant lung disease. ECMO insertion was performed under local anesthesia without sedation and resulted in immediate stabilization of hemodynamics and gas exchange as well as recovery from secondary organ dysfunction. Two patients later required endotracheal intubation because of bleeding complications and both of them eventually died. The other three patients remained awake on ECMO support for 18-35 days until the time of transplantation. These patients were able to breathe spontaneously, to eat and drink, and they received passive and active physiotherapy as well as psychological support. All of them made a full recovery after transplantation, which demonstrates the feasibility of using ECMO support in nonintubated patients with cardiopulmonary failure as a bridging strategy to lung transplantation.
Asunto(s)
Oxigenación por Membrana Extracorpórea , Insuficiencia Cardíaca/etiología , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/cirugía , Trasplante de Pulmón/métodos , Cuidados Preoperatorios , Insuficiencia Respiratoria/etiología , Adulto , Epistaxis/etiología , Epistaxis/mortalidad , Epistaxis/terapia , Oxigenación por Membrana Extracorpórea/efectos adversos , Femenino , Insuficiencia Cardíaca/fisiopatología , Hemodinámica , Hemorragia/etiología , Hemorragia/mortalidad , Hemorragia/terapia , Humanos , Hipertensión Pulmonar/fisiopatología , Intubación Intratraqueal , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/mortalidad , Enfermedades Pulmonares/terapia , Masculino , Persona de Mediana Edad , Intercambio Gaseoso Pulmonar , Recuperación de la Función , Insuficiencia Respiratoria/fisiopatología , Terapias en InvestigaciónRESUMEN
We describe a novel technique of pumpless extracorporeal life support in four patients with cardiogenic shock due to end-stage pulmonary hypertension (PH) including patients with veno-occlusive disease (PVOD) using a pumpless lung assist device (LAD). The device was connected via the pulmonary arterial main trunk and the left atrium, thereby creating a septostomy-like shunt with the unique addition of gas exchange abilities in parallel to the lung. Using this approach, all four patients were successfully bridged to bilateral lung transplantation and combined heart-lung transplantation, respectively. Although all patients presented in cardiogenic shock, hemodynamic unloading of the right ventricle using the low-resistance LAD stabilized the hemodynamic situation immediately so that no pump support was subsequently required.
Asunto(s)
Circulación Asistida/métodos , Corazón Auxiliar , Trasplante de Corazón-Pulmón/fisiología , Hipertensión Pulmonar/cirugía , Sistemas de Manutención de la Vida/instrumentación , Trasplante de Pulmón/fisiología , Adulto , Diseño de Equipo , Femenino , Insuficiencia Cardíaca/cirugía , Hemodinámica , Humanos , Masculino , Resultado del Tratamiento , Adulto JovenRESUMEN
Bronchiolitis obliterans syndrome (BOS) represents the leading cause of late mortality after lung transplantation (LTx). Cystic fibrosis (CF) patients frequently show airway colonization with gram-negative bacteria (GNB) both before and after LTx. Graft colonization with GNB and its relevance towards BOS development were investigated in a CF population after LTx. Adult CF patients receiving LTx and surviving at least 6 months were included in this prospective observational study between 1/1/2002 and 30/6/2006 in a single center and followed until 31/3/2007. Pre- and post-LTx respiratory culture samples were compared for the presence of identical GNB. BOS-free survival was compared in colonized and non-colonized patients. Fifty-nine adult CF patients with a median age at LTx of 25.5 (18-49) years were included and had a median follow-up of 966 (128-1889) days. Seven patients (15%) demonstrated immediate eradication of GNB in lower respiratory tract samples. A further 18 patients (34%) demonstrated transient colonization. Thirty-four recipients had further positive samples after LTx. Eighteen patients (31%) developed BOS >or=stage 1, 508 (114-1167) days after LTx. Freedom of graft colonization with pseudomonads was independently associated with less frequent development of BOS (p=0.006). Persistent graft colonization with pseudomonads increases the prevalence of BOS after LTx in CF patients. A significant proportion of post-LTx CF patients demonstrates subsequent GNB eradication during later follow-up and this may have a protective role against development of BOS. Strategies to eradicate airway colonization or reduce bacterial load may prevent BOS in CF patients after LTx.
Asunto(s)
Bronquiolitis Obliterante/microbiología , Líquido del Lavado Bronquioalveolar/microbiología , Fibrosis Quística/microbiología , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/microbiología , Trasplante de Pulmón/efectos adversos , Adolescente , Adulto , Fibrosis Quística/cirugía , Supervivencia sin Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Absidia corymbifera is a rare cause of pulmonary tract infection. There exist only 5 case reports predominantly diagnosed in bone marrow transplant patients. Lung transplant patients are at high risk for invasive fungal infections. Due to A. corymbifera as pathogen, known to be voriconazole resistant, a fatal invasive pulmonary mycosis occurred. In the present case voriconazole prophylaxis failed. A second patient showed a transient colonization of the bronchi. To prevent airborne transmitted invasive pulmonary mycosis in the first postoperative period of lung transplantation the patient should be situated in a room ventilated by HEPA-filtered air. The specific treatment should start very early when first suspicion arises. A review of the literature on pulmonary tract infections induced by Absidia corymbifera is provided.
Asunto(s)
Absidia , Profilaxis Antibiótica , Antifúngicos/uso terapéutico , Enfermedades Pulmonares Fúngicas/prevención & control , Trasplante de Pulmón/efectos adversos , Mucormicosis/prevención & control , Pirimidinas/uso terapéutico , Triazoles/uso terapéutico , Antifúngicos/administración & dosificación , Bronquios/microbiología , Resultado Fatal , Femenino , Humanos , Enfermedades Pulmonares Fúngicas/microbiología , Masculino , Persona de Mediana Edad , Mucormicosis/microbiología , Pirimidinas/administración & dosificación , Triazoles/administración & dosificación , VoriconazolRESUMEN
Experience with lung transplantation for bronchogenic carcinoma is limited. In our experience, 3 of 6 patients died of recurrent carcinoma within 5 to 35 months after transplantation. Hence, we currently do not support lung transplantation for patients with pre-transplant diagnosis of bronchogenic carcinoma, with the exception of bronchioloalveolar carcinoma (BAC) confined to the lung. Patients with BAC should be staged thoroughly with chest and abdominal computerized tomography, brain magnetic resonance imaging, and bone scan repeated every 3 months while on the waiting list, and should undergo mediastinoscopy at the time of transplantation, with a plan for a backup recipient if metastatic lymph nodes are detected. Proposal for lung transplantation for patients with bronchogenic carcinoma, with the exception of BAC, probably should be performed in the setting of a clinical trial developed with input from the lung transplant community.
Asunto(s)
Carcinoma Broncogénico/cirugía , Neoplasias Pulmonares/cirugía , Trasplante de Pulmón , Carcinoma Broncogénico/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/mortalidad , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: With evolving medical techniques and post-operative care, the quality of life after cardiac transplantation is improving over the recent years. However, the need for continuous immunosuppressive therapy may result in restrictions from some social and recreational activities, including traveling. The aim of this study was to analyze traveling activities and complications in a large cohort of heart transplant recipients, with the intention to develop adequate safety and behavioral guidelines. METHODS: Using a standardized questionnaire, 103 consecutive patients (pts) were asked to report about time and destination of their traveling activities, predominant activities, as well as potential travel-related complications. Documented rejection episodes as well as laboratory data are listed. RESULTS: Feedback was 97% (of 103 pts asked). Out of 100 pts who responded, [82 males, 18 females, mean age 52.3 +/- 12.4 yr, 6.9 +/- 3.8 yr post-heart transplantation (HTX)] 95 reported on traveling activities (95%). Concomitant disease was present in form of diabetes (n=8), renal insufficiency (n=5) and cardiac allograft vasculopathy (n=12). Mean cumulative traveling time was 120 +/- 125 d (3-560 d). Except from domestic journeys, 79 pts chose destinations within Europe, and 29 to overseas countries. Complications were reported by 15 of 95 pts (15.8%), being mostly small accidents and febrile episodes. Rejection episodes or other life threatening events were not observed. There was no significant correlation between observed complications and gender, age, time post-HTX, immunosuppression or comorbidities. CONCLUSIONS: Traveling after HTX appears to be safe and favorably improves quality of life, if certain precautions are met.
Asunto(s)
Trasplante de Corazón , Viaje , Adulto , Estudios de Cohortes , Comorbilidad , Femenino , Trasplante de Corazón/efectos adversos , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , Factores de Tiempo , Viaje/estadística & datos numéricosRESUMEN
Thoracic organ transplantation has evolved from an experimental to a standard treatment modality for patients suffering from end-stage heart and lung failure. Based on our experience after 1,033 heart, lung, and heart-lung transplantation procedures performed at the Hannover Thoracic Organ Transplant Program, we report: 1. Survival rates following thoracic organ transplants were similar and ranged from 76-81% after one year. 2. The one-, 5-, 10- and 15-year survival rates for heart transplant recipients were 81%, 70%, 52% and 33%, respectively. 3. The 9-year survival rate for bilateral-lung transplant recipients (56%) was significantly better than that for single-lung recipients (36%, p < 0.05). 4. Heart-lung recipients had the poorest long-term survival rate in our program--18% surviving after 9 years. 5. Retransplantation has been an effective treatment for chronic graft dysfunction in lung transplant recipients, but was less successful when used to treat acute graft failure. The one-year regraft survival rate was 74% among 15 patients retransplanted for chronic graft failure compared with only 50% for 4 patients retransplanted for acute failure.