RESUMEN
BACKGROUND: Lung transplantation outcomes are among the least favorable, with most recipients eventually developing bronchiolitis obliterans syndrome (BOS) and subsequent graft failure. The presence of human leukocyte antigen (HLA)-DR has been implicated in the pathogenesis of BOS and may play a role in these poor outcomes. METHODS: Lung transplant donor and recipient data were retrospectively gathered from the United Network for Organ Sharing database from January 2006 to June 2013. Donor and recipient characteristics, proportion of recipients treated for first year rejection, and 5-y rates of survival and freedom from BOS were determined according to HLA-DR1, -DR7, -DR13, and -DR15 status in both donor and recipient. Each HLA-DR allele was stratified by donor-recipient pair positivity status. RESULTS: A total of 7402 lung transplant recipients met the inclusion and exclusion criteria. There were significant but small differences in donor and recipient characteristics for each HLA-DR group. The recipients in the D(-)R(+) pairing for HLA-DR13 and those in the D(+)R(-) pairing for HLA-DR15 had significantly higher rates of receiving treatment for rejection within the first year after transplant (P = 0.024 and P = 0.001, respectively). There were no differences in 5-y survival or freedom from BOS for any of the four HLA-DR alleles studied. CONCLUSIONS: There are higher rates of patients treated for rejection within the first year who are either negative for the HLA-DR15 allele but received a donor-positive lung or positive for the HLA-DR13 allele but received a donor-negative lung for that allele. However, these differences do not appear to affect long-term outcomes.
Asunto(s)
Bronquiolitis Obliterante/inmunología , Rechazo de Injerto/inmunología , Subtipos Serológicos HLA-DR/metabolismo , Trasplante de Pulmón , Complicaciones Posoperatorias/inmunología , Adulto , Anciano , Biomarcadores/metabolismo , Bronquiolitis Obliterante/etiología , Femenino , Humanos , Modelos Logísticos , Trasplante de Pulmón/mortalidad , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
The abdominal aortic aneurysm (AAA) is a disease process that carries significant morbidity and mortality in the absence of early identification and treatment. While current management includes surveillance and surgical treatment of low- and high-risk aneurysms, respectively, our narrow understanding of the pathophysiology of AAAs limits our ability to more effectively manage and perhaps even prevent the occurrence of this highly morbid disease. Over the past couple of decades, there has been considerable interest in exploring the role of autoimmunity as an etiological component of AAA. This review covers the current literature pertaining to this immunological process, focusing on research that highlights the local and systemic immune components found in both human patients and murine models. A better understanding of the autoimmune mechanisms in the pathogenesis of AAAs can pave the way to novel and improved treatment strategies in this patient population.
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Aneurisma de la Aorta Abdominal/inmunología , Autoinmunidad , Animales , Aneurisma de la Aorta Abdominal/etiología , HumanosRESUMEN
Although recipient body mass index (BMI) and age are known risk factors for mortality after heart transplantation, how they interact to influence survival is unknown. Our study utilized the UNOS registry from 1997 to 2012 to define the interaction between BMI and age and its impact on survival after heart transplantation. Recipients were stratified by BMI: underweight (<18.5), normal weight (18.5-24.99), overweight (25-29.99), and either moderate (30-34.99), severe (35-39.99), or very severe (≥40) obesity. Recipients were secondarily stratified based on age: 18-40 (younger recipients), 40-65 (reference group), and ≥65 (advanced age recipients). Among younger recipients, being underweight was associated with improved adjusted survival (HR 0.902; p = 0.010) while higher mortality was seen in younger overweight recipients (HR 1.260; p = 0.005). However, no differences in adjusted survival were appreciated in underweight and overweight advanced age recipients. Obesity (BMI ≥ 30) was associated with increased adjusted mortality in normal age recipients (HR 1.152; p = 0.021) and even more so with young (HR 1.576; p < 0.001) and advanced age recipients (HR 1.292; p = 0.001). These results demonstrate that BMI and age interact to impact survival as age modifies BMI-mortality curves, particularly with younger and advanced age recipients.
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Factores de Edad , Índice de Masa Corporal , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía , Trasplante de Corazón/mortalidad , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND: Data are limited regarding the influence of donor age on outcomes after heart transplantation. We sought to determine if advanced donor age is associated with differences in survival after heart transplantation and how this compares to waitlist survival. METHODS: All adult heart transplants from 2000 to 2012 were identified using the United Network for Organ Sharing database. Donors were stratified into four age groups: 18-39 (reference group), 40-49, 50-54, and 55 and above. Propensity scoring was used to compare status IA waitlist patients who did not undergo transplantation with IA recipients who received hearts from advanced age donors. The primary outcome of interest was recipient survival and this was analyzed with multivariate Cox regression analysis and the Kaplan-Meier method. RESULTS: A total of 22,960 adult heart transplant recipients were identified. Recipients of hearts from all three older donor groups had significantly increased risk of mortality (HR, 1.187-1.426, all p < 0.001) compared to recipients from donors age 18 to 39. Additionally, propensity-matched status IA patients managed medically without transplantation had significantly worse adjusted survival than status IA recipients who received hearts from older donors age ≥55 (HR, 1.362, p < 0.001). CONCLUSIONS: Compared to donors aged 18-39, age 40 and above is associated with worse adjusted recipient survival in heart transplantation. This survival difference becomes more pronounced as age increases to above 55. However, the survival rate among status IA patients who receive hearts from advanced age donors (≥55) is significantly better compared to similar status IA patients who are managed without transplantation.
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Trasplante de Corazón/mortalidad , Sistema de Registros , Donantes de Tejidos/estadística & datos numéricos , Obtención de Tejidos y Órganos/organización & administración , Obtención de Tejidos y Órganos/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Bases de Datos Factuales , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Riesgo , Tasa de Supervivencia , Adulto JovenRESUMEN
BACKGROUND: Vascular surgical patients have a high rate of readmission, and the cost of readmission for these patients has not been described. Herein, we characterize and compare institutional index hospitalization and 30-day readmission cost following open and endovascular vascular procedures. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was used to identify inpatient open and endovascular procedures at a single institution, from January 2011 through June 2012. Variable and fixed costs for index hospitalization and unplanned 30-day readmissions were obtained using SAP BusinessObjects. Patient characteristics and outcome variables were analyzed using Student t tests or Wilcoxon rank-sum nonparametric tests for continuous variables and Fisher exact tests for categorical variables. RESULTS: One thousand twenty-six inpatient procedures were included in the analysis. There were 605 (59%) open and 421 (41%) endovascular procedures with a 30-day unplanned readmission rate of 16.9% and 17.8%, respectively (P = .679). The mean index hospitalization costs for open and endovascular procedures were US$27 653 and US$23 999, respectively (P = .146). The mean costs for 30-day unplanned readmission for open and endovascular procedures were US$19 117 and US$17 887, respectively (P = .635). Among open procedures, the mean cost for patients not readmitted was US$28 321 compared to US$31 115 for those readmitted (P = .003). Among endovascular procedures, the mean cost for patients not readmitted was US$26 908 compared to US$32 262 for those readmitted (P = .028). CONCLUSION: The cost of index hospitalization and 30-day unplanned readmission are similar for open and endovascular procedures. Readmitted patients had a higher mean index hospitalization cost irrespective of open or endovascular procedure.
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Implantación de Prótesis Vascular/economía , Procedimientos Endovasculares/economía , Costos de Hospital , Readmisión del Paciente/economía , Anciano , Anciano de 80 o más Años , Implantación de Prótesis Vascular/efectos adversos , Bases de Datos Factuales , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Económicos , Modelos Estadísticos , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
Despite significant medical advances since the advent of lung transplantation, improvements in long-term survival have been largely unrealized. Chronic lung allograft dysfunction, in particular obliterative bronchiolitis, is the primary limiting factor. The predominant etiology of obliterative bronchiolitis involves the recipient's innate and adaptive immune response to the transplanted allograft. Current therapeutic strategies have failed to provide a definitive treatment paradigm to improve long-term outcomes. Inducing immune tolerance is an emerging therapeutic strategy that abrogates allograft rejection, avoids immunosuppression, and improves long-term graft function. The aim of this review is to discuss the key immunologic components of obliterative bronchiolitis, describe the state of establishing immune tolerance in transplantation, and highlight those strategies being evaluated in lung transplantation.
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Bronquiolitis Obliterante/prevención & control , Rechazo de Injerto/prevención & control , Isoantígenos/administración & dosificación , Trasplante de Pulmón , Tolerancia al Trasplante/efectos de los fármacos , Inmunidad Adaptativa , Administración Oral , Células Presentadoras de Antígenos/efectos de los fármacos , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/patología , Bronquiolitis Obliterante/inmunología , Bronquiolitis Obliterante/patología , Complejo CD3/genética , Complejo CD3/inmunología , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , Humanos , Inmunidad Innata , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/patología , Receptores de Antígenos de Linfocitos T/antagonistas & inhibidores , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/inmunología , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/patología , Quimera por Trasplante , Trasplante HomólogoRESUMEN
Traumatic brain injury (TBI) results in systemic inflammatory responses that affect the lung. This is especially critical in the setting of lung transplantation, where more than half of donor allografts are obtained postmortem from individuals with TBI. The mechanism by which TBI causes pulmonary dysfunction remains unclear but may involve the interaction of high-mobility group box-1 (HMGB1) protein with the receptor for advanced glycation end products (RAGE). To investigate the role of HMGB1 and RAGE in TBI-induced lung dysfunction, RAGE-sufficient (wild-type) or RAGE-deficient (RAGE(-/-)) C57BL/6 mice were subjected to TBI through controlled cortical impact and studied for cardiopulmonary injury. Compared to control animals, TBI induced systemic hypoxia, acute lung injury, pulmonary neutrophilia, and decreased compliance (a measure of the lungs' ability to expand), all of which were attenuated in RAGE(-/-) mice. Neutralizing systemic HMGB1 induced by TBI reversed hypoxia and improved lung compliance. Compared to wild-type donors, lungs from RAGE(-/-) TBI donors did not develop acute lung injury after transplantation. In a study of clinical transplantation, elevated systemic HMGB1 in donors correlated with impaired systemic oxygenation of the donor lung before transplantation and predicted impaired oxygenation after transplantation. These data suggest that the HMGB1-RAGE axis plays a role in the mechanism by which TBI induces lung dysfunction and that targeting this pathway before transplant may improve recipient outcomes after lung transplantation.