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1.
Rev Col Bras Cir ; 46(1): e2039, 2019.
Artigo em Português, Inglês | MEDLINE | ID: mdl-31017176

RESUMO

Avoiding deaths in the waiting list for an organ is no longer the only focus of the transplant teams attention. Research and care in clinical practice has been increasingly focused on post transplant graft survival and functioning. In the present work, we performed an integrative literature review to identify the terminology used about liver graft dysfunction and non-function, as well as to investigate the incidence and risk factors of these clinical events. We chosen articles written in Portuguese, English and Spanish between 2012 and 2016, based on CINAHL, MEDLINE, Cochrane, LILACS, BDENF, IBECS, EMBASE and Web of Science. We selected 14 studies, in which we identified the incidence of hepatic graft dysfunction ranging from 7% to 27%. The terminology used to describe this clinical event was initial malfunction, graft hypofunction, marginal function or delay in function. The primary non-function of the liver graft was found in 1.4% to 8.4% of the patients, and the terminology used to describe the event was early dysfunction or graft loss. The risk factors found are related to donor, recipient, graft and transplant logistics variables. We conclude that knowledge of the different terminologies employed in the literature, related to dysfunction and primary non- function incidence, and of their risk factors are fundamental to qualify the control of the events, aiming to improve patients' survival after liver transplantation.


Assuntos
Transplante de Fígado/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Humanos , Fígado/fisiopatologia , Transplante de Fígado/métodos , Disfunção Primária do Enxerto/fisiopatologia , Medição de Risco , Fatores de Risco , Doadores de Tecidos , Transplantados
2.
Ann Vasc Surg ; 59: 312.e7-312.e9, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31009723

RESUMO

Vascular complications such as renal artery or renal vein thrombosis and laceration and iliac artery dissection are rarely encountered after renal transplantation. Timely management of these vascular complications is important to prevent ischemic injury of a transplanted kidney. We hereby report a case of a 60-year-old male who had acute renal dysfunction due to iatrogenic left external iliac artery dissection after renal transplantation. An endovascular stenting of the dissected iliac artery resulted in a brisk flow across both iliac and transplanted renal arteries. The management issues related to this rare vascular complication is discussed in the article.


Assuntos
Aneurisma Dissecante/cirurgia , Procedimentos Endovasculares , Doença Iatrogênica , Aneurisma Ilíaco/cirurgia , Transplante de Rim/efeitos adversos , Disfunção Primária do Enxerto/etiologia , Aneurisma Dissecante/diagnóstico por imagem , Aneurisma Dissecante/etiologia , Aneurisma Dissecante/fisiopatologia , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/instrumentação , Humanos , Aneurisma Ilíaco/diagnóstico por imagem , Aneurisma Ilíaco/etiologia , Aneurisma Ilíaco/fisiopatologia , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/fisiopatologia , Stents , Resultado do Tratamento , Ultrassonografia Doppler em Cores
3.
Transplant Proc ; 50(10): 3863-3872, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577279

RESUMO

Development of chronic lung allograft dysfunction involves various alloimmune-independent insults including those mediated by Toll-like receptor (TLR) signaling, which is known to activate alloimmune responses. We hypothesized that TLR signaling may also contribute to the activation of fibroblasts and promoting allograft airway fibrosis. Mouse orthotopic tracheal transplants were conducted between major histocompatibility complex (MHC)-mismatched Balb/c donor and wild-type C3H or C3H-derived TLR4 mutant recipients (nonfunctional TLR4). Immunohistochemistry on day 21 showed significantly smaller alpha-smooth muscle actin (α-SMA)-positive areas in TLR4 mutant recipients than wild-type recipients (P = .01). No difference was found for CD3+ T-cell infiltration. Proliferation of alloreactive T cells derived from the recipient spleen showed no difference between TLR4 mutant and wild-type recipients in a mixed lymphocyte reaction. The effect of TLR4 signaling was examined in primary pulmonary fibroblast cultures both with lipopolysaccharide (LPS) and transforming growth factor (TGF)-ß1. Stimulation with LPS significantly increased expression of α-SMA mRNA in wild-type fibroblasts cultured with TGF-ß1 compared with the control without LPS (P = .001). Taken together, these findings suggest disruption of TLR signaling leads to reduced activation of fibroblasts without affecting T-cell infiltration and proliferation in this model. TLR4-mediated activation of fibroblasts may be a potentially important mechanism of allograft remodeling.


Assuntos
Fibroblastos/metabolismo , Disfunção Primária do Enxerto/metabolismo , Disfunção Primária do Enxerto/patologia , Receptor 4 Toll-Like/metabolismo , Traqueia/transplante , Aloenxertos/metabolismo , Aloenxertos/patologia , Aloenxertos/fisiopatologia , Animais , Fibrose/metabolismo , Fibrose/patologia , Transplante de Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Disfunção Primária do Enxerto/fisiopatologia , Transplante Homólogo
4.
Ann Transplant ; 23: 481-490, 2018 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-30013021

RESUMO

BACKGROUND Successful graft regeneration is important in living-donor liver transplantation (LDLT) because partial liver grafts are used. Early allograft dysfunction (EAD) is an intermediate outcome that affects the long-term postoperative course in liver transplantation. The aim of the present study was to investigate liver graft regeneration under EAD development in LDLT. MATERIAL AND METHODS The data of 226 patients who underwent LDLT from September 2010 to July 2014 were retrospectively analyzed. The patients were classified into 2 groups: one with and one without EAD. Graft regeneration, functional recovery, and long-term patient survival were compared between the 2 groups. RESULTS The grafts grew more vigorously in the EAD group than in the non-EAD group, as evidenced by the larger absolute (ALV) and relative liver volumes (RLV) of the former on postoperative days (POD) 7 and 21. The median (interquartile range) RLVs of the non-EAD group versus the EAD group were as follows: 55.2 (47.9-65.8) vs. 53.7 (46.6-64.5)% preoperatively, p>0.05; 76.1 (66.9-85.7) vs. 86.7 (73.9-96.8)% on POD 7, p<0.01; 79.6 (69.3-91.2) vs. 93.7 (79.6-101.6)%, p<0.01 on POD 21. In the early postoperative period, hepatic function, measured as total bilirubin and international normalized ratio, was higher in the EAD group; however, after EAD development, graft function recovered in these patients. In the follow-up period, overall patient survival was comparable between the 2 groups. CONCLUSIONS The liver grafts of EAD patients steadily regenerated, such that the development of EAD did not affect long-term patient survival after LDLT.


Assuntos
Sobrevivência de Enxerto/fisiologia , Regeneração Hepática/fisiologia , Transplante de Fígado , Fígado/fisiopatologia , Disfunção Primária do Enxerto/fisiopatologia , Feminino , Humanos , Fígado/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Transplant Proc ; 50(3): 815-818, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29661444

RESUMO

INTRODUCTION: The lung transplantation (LTx) program began in Ceará in 2011 and the first LTx was performed on June 11, 2011. The aim of this study was to present the initial results of the 6-year experience of our program. METHODS: We retrospectively reviewed our experience on LTx from June 2011 to August 2017. Data on recipients and transoperative and postoperative outcomes were recorded in a database. RESULTS: Twenty-two (56.4%) were single LTx, 15 (38.5%) were double, and 2 (5.1%) bilateral lobar. The mean age was 47.5 ± 15 years, and 26 (66.7%) were men. Twenty-eight (71.8%) had pulmonary fibrosis; 5 (12.8%) had pulmonary emphysema, 3 (7.7%) had bronchiectasis; 2 (5.1%) had pulmonary hypertension, and 1 (2.6%) had lymphangioleiomyomatosis. Complications occurred in 82% (32/39) and in-hospital mortality was 30.8% (single LTx = 27.8% and double LTx = 33.3%). The main complications were infection in 17 (43.5%) cases and primary graft dysfunction in 7 (17.9%). There was a significant improvement in pulmonary function in the first year of follow-up (forced expiratory volume pre-LTx = 37% ± 16% and 12 months post-LTx = 72% ± 22%, P = .001); and overall survival at 36 months was 59.0%, with no difference between single- and double-lung transplants. CONCLUSIONS: Idiopathic pulmonary fibrosis was the most common underlying disease and single LTx was the most commonly performed operation. There was a high incidence of postoperative complications and in-hospital mortality, but the 36-month follow-up showed a marked improvement in lung function and a global survival similar to the literature.


Assuntos
Fibrose Pulmonar Idiopática/cirurgia , Pneumopatias/cirurgia , Transplante de Pulmão/métodos , Complicações Pós-Operatórias/mortalidade , Disfunção Primária do Enxerto/mortalidade , Adulto , Brasil , Feminino , Volume Expiratório Forçado , Mortalidade Hospitalar , Humanos , Incidência , Pulmão/fisiopatologia , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Período Pós-Operatório , Disfunção Primária do Enxerto/fisiopatologia , Testes de Função Respiratória , Estudos Retrospectivos , Resultado do Tratamento
6.
Transplant Proc ; 50(2): 605-609, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29579865

RESUMO

INTRODUCTION: The current imbalance between available donors and potential recipients for orthotopic liver transplantation (OLT) has led to a liberalization of organ acceptance criteria, increasing the risk of post-transplant complications such as early allograft dysfunction (EAD). Consequently, we need accurate criteria to detect patients with early poor graft function to guide the strategies of management. We evaluated the usefulness of two frequently used criteria: the definition from Olthoff et al and the Model for Early Allograft Function (MEAF) scoring. PATIENTS AND METHODS: Unicentric cohort study of patients undergoing OLT between January 1, 2010, and November 20, 2016. We performed a univariate study to detect donor, recipient, and transplant factors favoring EAD, defined both by Olthoff criteria and a MEAF score higher than 7. Finally, we developed a comparative survival analysis for cases having or not EAD. RESULTS: In all, 201 transplants met inclusion criteria. According to the stated cutoff for MEAF score, the frequency of EAD was 9.3%, with a significant association to low recipient body mass index and prolonged total graft ischemia time, resulting in lower patient 3-month postoperative survival. According to Olthoff criteria, EAD incidence was 22.1% and was associated with younger donor and recipient ages and higher Model for End-stage Liver Disease and Child-Pugh recipient scores. Its development resulted in lower graft and recipient survival at 3 months after OLT. CONCLUSION: MEAF score and Olthoff criteria are useful tools for detection of EAD. The latter could select more appropriately patients at risk, but its calculation cannot be done until the seventh day after OLT, unlike MEAF score, available on third day.


Assuntos
Sobrevivência de Enxerto/fisiologia , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/epidemiologia , Índice de Gravidade de Doença , Adulto , Aloenxertos/fisiopatologia , Estudos de Coortes , Feminino , Humanos , Incidência , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/fisiopatologia , Fatores de Risco , Fatores de Tempo , Doadores de Tecidos , Transplante Homólogo/efeitos adversos
7.
Ann Am Thorac Soc ; 14(Supplement_3): S242-S246, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28945471

RESUMO

Lung transplantation is now considered to be a therapeutic option for patients with advanced-stage lung diseases. Unfortunately, due to post-transplant complications, both infectious and noninfectious, it is only a treatment and not a cure. Infections (e.g., bacterial, viral, and fungal) in the immunosuppressed lung transplant recipient are a common cause of mortality post transplant. Infections have more recently been explored as factors contributing to the risk of chronic lung allograft dysfunction (CLAD). Each major class of infection-(1) bacterial (Staphylococcus aureus and Pseudomonas aeruginosa); (2) viral (cytomegalovirus and community-acquired respiratory viruses); and (3) fungal (Aspergillus)-has been associated with the development of CLAD. Mechanistically, the microbe seems to be interacting with the allograft cells, stimulating the induction of chemokines, which recruit recipient leukocytes to the graft. The recipient leukocyte interactions with the microbe further up-regulate chemokines, amplifying the influx of allograft-infiltrating mononuclear cells. These events can promote recipient leukocytes to interact with the allograft, triggering an alloresponse and graft dysfunction. Overall, interactions between the microbe-allograft-host immune system alters chemokine production, which, in part, plays a role in the pathobiology of CLAD and mortality due to CLAD.


Assuntos
Interações Hospedeiro-Patógeno/fisiologia , Transplante de Pulmão , Infecções Oportunistas/fisiopatologia , Disfunção Primária do Enxerto/fisiopatologia , Aloenxertos , Quimiocinas/metabolismo , Humanos
8.
Comput Biol Med ; 89: 275-281, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28850899

RESUMO

BACKGROUND: To assess how quantitative CT (qCT) metrics compare to pulmonary function testing (PFT) and semi-quantitative image scores (SQS) to diagnose bronchiolitis obliterans syndrome (BOS), manifestation of chronic lung allograft dysfunction after lung transplantation (LTx), according to the type of LTx (unilateral or bilateral). METHODS: Paired inspiratory-expiratory CT scans and PFTs of 176 LTx patients were analyzed retrospectively, and separated into BOS (78) and non-BOS (98) cohorts. SQS were assessed by 2 radiologists and graded (0-3) for features including mosaic attenuation and bronchiectasis. qCT metrics included lung volumes and air trapping volumes. Multivariate logistic regression (MVLR) and support vector machines (SVM) were used for the classification task. RESULTS: MVLR and SVM models using PFT metrics demonstrated highest accuracy for bilateral LTx (max AUC 0.771), whereas models using qCT metrics-only outperformed models using SQS or PFTs in unilateral LTx (max AUC 0.817), to diagnose BOS. Adding PC (principal components) from qCT on top of PFT improved model diagnostic accuracy for all transplant types. CONCLUSIONS: Combinations of qCT metrics augment the diagnostic performance of PFTs, are superior to SQS to predict BOS status, and outperform PFTs in the unilateral LTx group. This suggests that latent information on paired volumetric CT may allow early diagnosis of BOS in LTx patients, particularly in unilateral LTx.


Assuntos
Bronquiolite Obliterante , Transplante de Pulmão , Modelos Biológicos , Disfunção Primária do Enxerto , Tomografia Computadorizada por Raios X , Adulto , Idoso , Aloenxertos , Bronquiolite Obliterante/diagnóstico , Bronquiolite Obliterante/diagnóstico por imagem , Bronquiolite Obliterante/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/diagnóstico por imagem , Disfunção Primária do Enxerto/fisiopatologia , Testes de Função Respiratória , Síndrome
9.
J Heart Lung Transplant ; 36(9): 921-933, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28662986

RESUMO

BACKGROUND: Long-term success of lung transplantation is limited by the development of chronic lung allograft dysfunction (CLAD), of which bronchiolitis obliterans syndrome (BOS) is the most common form. This systematic review sought to identify the current evidence base for CLAD-BOS therapies after initial immunosuppressive treatment strategies. METHODS: The MEDLINE, Embase, and Cochrane Library databases from inception to May 3, 2016, were searched using keywords relating to CLAD-BOS, study designs, and treatments of interest, including extracorporeal photopheresis (ECP), aerosolized cyclosporine, total lymphoid irradiation (TLI), alemtuzumab, and montelukast. Titles, abstracts, and full texts were screened by 2 independent reviewers to identify studies of CLAD-BOS second-line therapy in adult lung transplant patients. Quality was assessed according to the Downs and Black checklist. RESULTS: Of the 936 individual citations identified, 47 reports of 40 studies met inclusion criteria, including 17 full publications, 11 recent (2015-2016), and 12 older (pre-2015) congress proceedings. Most of the full publications and recent abstracts investigated ECP (n = 11), TLI (n = 5), alemtuzumab (n = 4), and montelukast (n = 2). Most studies were uncontrolled and retrospective. Compared with standard therapy alone, improved lung function and survival was reported for ECP in 2 studies without randomization, with lower-quality evidence for improved lung function for TLI, montelukast, and aerosolized cyclosporine. CONCLUSIONS: Because most identified studies were of retrospective and uncontrolled design, comparison of treatment effects was limited. Available evidence suggests stabilized lung function after ECP in combination with established immunosuppressive regimens in late-line CLAD-BOS treatment, with fewer data for TLI, montelukast, and aerosolized cyclosporine.


Assuntos
Bronquiolite Obliterante/terapia , Transplante de Pulmão/efeitos adversos , Irradiação Linfática/métodos , Fotoferese/métodos , Disfunção Primária do Enxerto/terapia , Aloenxertos , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/etiologia , Feminino , Rejeição de Enxerto , Humanos , Imunossupressores/administração & dosagem , Incidência , Transplante de Pulmão/métodos , Masculino , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/fisiopatologia , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Medição de Risco , Síndrome , Imunologia de Transplantes , Resultado do Tratamento
10.
J Heart Lung Transplant ; 36(9): 1004-1012, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28624139

RESUMO

BACKGROUND: Use of new genomic techniques in clinical settings requires that such methods are rigorous and reproducible. Previous studies have shown that quantitation of donor-derived cell-free DNA (%ddcfDNA) by unbiased shotgun sequencing is a sensitive, non-invasive marker of acute rejection after heart transplantation. The primary goal of this study was to assess the reproducibility of %ddcfDNA measurements across technical replicates, manual vs automated platforms, and rejection phenotypes in distinct patient cohorts. METHODS: After developing and validating the %ddcfDNA assay, we subjected the method to a rigorous test of its reproducibility. We measured %ddcfDNA in technical replicates performed by 2 independent laboratories and verified the reproducibility of %ddcfDNA patterns of 2 rejection phenotypes: acute cellular rejection and antibody-mediated rejection in distinct patient cohorts. RESULTS: We observed strong concordance of technical-replicate %ddcfDNA measurements across 2 independent laboratories (slope = 1.02, R2 > 0.99, p < 10-6), as well as across manual and automated platforms (slope = 0.80, R2 = 0.92, p < 0.001). The %ddcfDNA measurements in distinct heart transplant cohorts had similar baselines and error rates. The %ddcfDNA temporal patterns associated with rejection phenotypes were similar in both patient cohorts; however, the quantity of ddcfDNA was significantly higher in samples with severe vs mild histologic rejection grade (2.73% vs 0.14%, respectively; p < 0.001). CONCLUSIONS: The %ddcfDNA assay is precise and reproducible across laboratories and in samples from 2 distinct types of heart transplant rejection. These findings pave the way for larger studies to assess the clinical utility of %ddcfDNA as a marker of acute rejection after heart transplantation.


Assuntos
Ácidos Nucleicos Livres/análise , Rejeição de Enxerto/sangue , Transplante de Coração/efeitos adversos , Disfunção Primária do Enxerto/sangue , Doadores de Tecidos , Doença Aguda , Adulto , Biomarcadores/sangue , Feminino , Transplante de Coração/métodos , Humanos , Modelos Lineares , Masculino , Disfunção Primária do Enxerto/fisiopatologia , Reprodutibilidade dos Testes , Estatísticas não Paramétricas
11.
Eur J Radiol ; 94: 78-84, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28647206

RESUMO

PURPOSE: To describe early signs for restrictive subtype of chronic lung allograft dysfunction (CLAD) after lung transplantation in computed tomography (CT) and to evaluate the predictive value for disease progression and survival. MATERIAL AND METHODS: 52 CT examinations in lung transplant patients at CLAD onset were scored for CT features referring to airways disease, parenchymal or pleural abnormality. Patients with and without later development of restrictive CLAD (TLC≤80%) were compared. A radiological score for inflammation including pleural effusion, central and peripheral ground glass opacities and consolidations was calculated and used for survival analysis. RESULTS: CT of patients with later development of restrictive CLAD showed significantly more often abnormalities at CLAD onset, in particular consolidations (57% vs. 4%; p<0.001) and ground glass attenuations (71% vs. 7%; p<0.001) than those of patients without the restrictive phenotype. CT score for inflammation was significantly higher in patients with than without later restrictive CLAD (3.4 vs. 0.6; p<0.001). Survival of patients with a high score (>2) for inflammation in CT at CLAD onset was significantly lower than of those with a low score (443 vs. 2415 days; p=0.019). CONCLUSIONS: CT at CLAD onset differs in patients with/without later development of the restrictive phenotype. It is therefore an indicator for future development of restrictive CLAD and predictor for survival. It should be implemented in the diagnostic work-up at diagnosis of CLAD.


Assuntos
Pneumopatias/diagnóstico por imagem , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , Progressão da Doença , Feminino , Seguimentos , Humanos , Pneumopatias/mortalidade , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Valor Preditivo dos Testes , Disfunção Primária do Enxerto/mortalidade , Disfunção Primária do Enxerto/fisiopatologia , Estudos Retrospectivos , Análise de Sobrevida , Tomografia Computadorizada por Raios X/métodos
12.
J Heart Lung Transplant ; 36(9): 980-984, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28651906

RESUMO

BACKGROUND: The principal obstacle to long-term survival after lung transplant is chronic lung allograft dysfunction (CLAD), which primarily affects the small airways. After transplant, patients are monitored with spirometry, which is a generally insensitive detector of small airways obstruction. The lung clearance index (LCI) is a measure obtained during multiple breath washout (MBW) maneuvers. We hypothesized that among lung allograft recipients, LCI would detect small airways disease not detected with spirometry. METHODS: This study enrolled 15 patients, 5 of whom already had a diagnosis of CLAD. We added MBW as an additional index of peripheral airway function to the established post-transplant routine care protocol. RESULTS: Of trials, 87.9% yielded valid measurements, and single maneuvers were 2-8 minutes. LCI did not yield any false-negative findings-no patients were considered obstructed by forced expiratory volume in 1 second (FEV1) but normal by LCI. At enrollment, 6 patients without CLAD had an elevated LCI, and 4 progressed to CLAD. Only 2 of these 4 patients would have been identified by a decrease in FEV1. CONCLUSIONS: LCI identified lung allograft dysfunction in more patients than the use of standardized spirometric measures, including patients with abnormal FEV1. These data suggest that LCI from MBW may be a more sensitive means to detect allograft peripheral airway disease than standard methods for measurement of small airways function.


Assuntos
Bronquíolos/fisiopatologia , Broncospirometria/métodos , Volume Expiratório Forçado/fisiologia , Transplante de Pulmão/efeitos adversos , Transplantados , Adolescente , Aloenxertos , Criança , Pré-Escolar , Estudos de Coortes , Fibrose Cística/diagnóstico , Fibrose Cística/cirurgia , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/cirurgia , Modelos Lineares , Transplante de Pulmão/métodos , Masculino , Pediatria , Valor Preditivo dos Testes , Disfunção Primária do Enxerto/mortalidade , Disfunção Primária do Enxerto/fisiopatologia , Prognóstico , Estudos Prospectivos , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
13.
J Cardiovasc Pharmacol Ther ; 22(4): 330-336, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28395520

RESUMO

Ischemia-reperfusion injury is a composite of the injury sustained during a period of reduced or absent blood flow to a tissue or organ and the additional insult sustained on reperfusion, which limits the amount of tissue that can be salvaged. Ischemia-reperfusion injury is the predominant insult during kidney transplantation, contributing to graft dysfunction, increased rates of acute rejection, and reduced rejection-free graft survival. In this review, we discuss the potential therapeutic benefits of a cost-effective and low-risk intervention, ischemic preconditioning, and its potential for improving kidney function following transplantation.


Assuntos
Precondicionamento Isquêmico/métodos , Transplante de Rim/efeitos adversos , Traumatismo por Reperfusão/prevenção & controle , Animais , Intervalo Livre de Doença , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/fisiopatologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Disfunção Primária do Enxerto/etiologia , Disfunção Primária do Enxerto/patologia , Disfunção Primária do Enxerto/fisiopatologia , Disfunção Primária do Enxerto/prevenção & controle , Fluxo Sanguíneo Regional , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
Eur Respir J ; 49(4)2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28404648

RESUMO

Identification of disease phenotypes might improve the understanding of patients with chronic lung allograft dysfunction (CLAD). The aim of the study was to assess the impact of pulmonary restriction and air trapping by lung volume measurements at the onset of CLAD.A total of 396 bilateral lung transplant recipients were analysed. At onset, CLAD was further categorised based on plethysmography. A restrictive CLAD (R-CLAD) was defined as a loss of total lung capacity from baseline. CLAD with air trapping (AT-CLAD) was defined as an increased ratio of residual volume to total lung capacity. Outcome was survival after CLAD onset. Patients with insufficient clinical information were excluded (n=95).Of 301 lung transplant recipients, 94 (31.2%) developed CLAD. Patients with R-CLAD (n=20) and AT-CLAD (n=21), respectively, had a significantly worse survival (p<0.001) than patients with non-R/AT-CLAD. Both R-CLAD and AT-CLAD were associated with increased mortality when controlling for multiple confounding variables (hazard ratio (HR) 3.57, 95% CI 1.39-9.18; p=0.008; and HR 2.65, 95% CI 1.05-6.68; p=0.039). Furthermore, measurement of lung volumes was useful to identify patients with combined phenotypes.Measurement of lung volumes in the long-term follow-up of lung transplant recipients allows the identification of patients who are at risk for worse outcome and warrant special consideration.


Assuntos
Bronquiolite Obliterante/fisiopatologia , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/mortalidade , Disfunção Primária do Enxerto/fisiopatologia , Adulto , Azitromicina/uso terapêutico , Bronquiolite Obliterante/tratamento farmacológico , Doença Crônica , Feminino , Alemanha , Humanos , Pulmão/fisiopatologia , Pulmão/cirurgia , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/etiologia , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Volume de Ventilação Pulmonar , Transplante Homólogo
15.
J Heart Lung Transplant ; 36(8): 897-905, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28365177

RESUMO

BACKGROUND: Vitamin D may have innate immunomodulatory functions with potentially beneficial therapeutic effects in lung transplant recipients. METHODS: This was a single-center, double blind, randomized, placebo-controlled, prevention trial of once-monthly oral vitamin D (cholecalciferol; 100,000 IU, n = 44) vs placebo (n = 43) during 2 years in adult lung transplant recipients enrolled from October 2010 to August 2013. Primary outcome was prevalence of chronic lung allograft dysfunction (CLAD) 3 years after transplantation. Secondary outcomes included overall survival, prevalence of acute rejection, lymphocytic bronchiolitis and infection, lung function, pulmonary and systemic inflammation, and bone mineral density. RESULTS: All included patients underwent bilateral lung transplantation and were mostly middle-aged men with prior smoking-related emphysema. Levels of 25-hydroxy vitamin D after 1 year (p < .001) and 2 years (p < .001) were significantly higher in the vitamin D group compared with the placebo group. No difference was observed for CLAD prevalence (p = 0.7) or CLAD-free survival between both groups (p = 0.7). Secondary outcomes were overall comparable between both groups (all p > 0.05). CONCLUSIONS: Once-monthly oral vitamin D supplementation after lung transplantation fails to demonstrate a significant difference in CLAD prevalence, innate immunomodulatory, or a beneficial clinical effect compared with placebo.


Assuntos
Suplementos Nutricionais , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/prevenção & controle , Vitamina D/administração & dosagem , Administração Oral , Bélgica/epidemiologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/fisiopatologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Fatores de Tempo , Resultado do Tratamento , Vitaminas/administração & dosagem
16.
Exp Clin Transplant ; 15(Suppl 1): 53-56, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28260433

RESUMO

OBJECTIVES: To analyze how graft-weight-to-bodyweight ratio in pediatric liver transplant affects intraoperative and early postoperative hemodynamic and metabolic parameters. MATERIALS AND METHODS: We reviewed data from 130 children who underwent liver transplant between 2005 and 2015. Recipients were divided into 2 groups: those with a graft weight to body weight ratio > 4% (large for size) and those with a ratio ≤ 4% (normal for size). Data included demographics, preoperative laboratory findings, intraoperative metabolic and hemodynamic parameters, and intensive care follow-up parameters. RESULTS: Patients in the large-graft-for-size group (>4%) received more colloid solution (57.7 ± 20.1 mL/kg vs 45.1 ± 21.9 mL/kg; P = .08) and higher doses of furosemide (0.7 ± 0.6 mg/kg vs 0.4 ± 0.7 mg/kg; P = .018). They had lower mean pH (7.1 ± 0.1 vs 7.2 ± 0.1; P = .004) and PO2 (115.4 ± 44.6 mm Hg vs 147.6 ± 49.3 mm Hg; P = .004) values, higher blood glucose values (352.8 ± 96.9 mg/dL vs 262.8 ± 88.2 mg/dL; P < .001), and lower mean body temperature (34.8 ± 0.7°C vs 35.2 ± 0.6°C; P = .016) during the neohepatic phase. They received more blood transfusions during both the anhepatic (30.3 ± 24.3 mL/kg vs 18.8 ± 21.8 mL/kg; P = .013) and neohepatic (17.7 ± 20.4 mL/kg vs 10.3 ± 15.5 mL/kg; P = .031) phases and more fresh frozen plasma (13.6 ± 17.6 mL/kg vs 6.2 ± 10.2 mL/kg; P = .012) during the neohepatic phase. They also were more likely to be hypotensive (P < .05) and to receive norepinephrine infusion more often (44% vs 22%; P < .05) intraoperatively. More patients in this group were mechanically ventilated in the intensive care unit (56% vs 31%; P = .035). There were no significant differences between the groups in postoperative acute renal dysfunction, graft rejection or loss, infections, length of intensive care stay, and mortality (P > .05). CONCLUSIONS: High graft weight-to-body-weight ratio is associated with adverse metabolic and hemodynamic changes during the intraoperative and early postoperative periods. These results emphasize the importance of using an appropriately sized graft in liver transplant.


Assuntos
Rejeição de Enxerto/etiologia , Hemodinâmica , Falência Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Fígado/cirurgia , Disfunção Primária do Enxerto/etiologia , Adolescente , Fatores Etários , Biomarcadores/sangue , Transfusão de Sangue , Peso Corporal , Fármacos Cardiovasculares/uso terapêutico , Criança , Pré-Escolar , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/fisiopatologia , Rejeição de Enxerto/terapia , Sobrevivência de Enxerto , Hemodinâmica/efeitos dos fármacos , Mortalidade Hospitalar , Humanos , Lactente , Fígado/metabolismo , Fígado/patologia , Falência Hepática/diagnóstico , Falência Hepática/mortalidade , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Masculino , Tamanho do Órgão , Seleção de Pacientes , Disfunção Primária do Enxerto/sangue , Disfunção Primária do Enxerto/fisiopatologia , Disfunção Primária do Enxerto/terapia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
17.
Liver Transpl ; 23(4): 527-536, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28073175

RESUMO

Despite the growing data supporting the role of microcirculation in regulating liver function, little of this knowledge has been translated into clinical practice. The aim of this study is to quantify hepatic microcirculation in vivo using sidestream dark field (SDF) imaging and correlate these findings with hepatic blood flow, hemodynamic parameters, and soluble mediators. Postreperfusion hepatic microcirculation was assessed using SDF imaging. Hepatic microcirculation measurements included functional sinusoidal density (cm/cm2 ), sinusoidal diameter (µm), red blood cell velocity (µm/second), volumetric blood flow (pl/second), and flow heterogeneity (FH) index. The serum concentrations of endothelin 1 (ET-1) and other inflammatory markers were analyzed with Luminex technology. Portal venous and hepatic artery flows were measured using a flowmeter. Twenty-eight patients undergoing cadaveric liver transplantations have been included in this study. Early allograft dysfunction (EAD) occurred in 7 (25%) patients and was associated with microcirculatory dysfunction. Low arterial and portal flow, high dose of inotropes, cold ischemia time, steatosis, and high ET-1 levels were all associated with impaired microcirculation. The time interval between portal venous and hepatic arterial reperfusion significantly correlated with the changes of the liver grafts' microcirculation. EAD patients tended to have higher serum levels of ET-1 on postoperative days 1, 2, 5, and 7 (all P < 0.01). Serum levels of ET-1 correlated significantly with microcirculation parameters. In conclusion, postreperfusion hepatic microcirculation is a determinant of organ dysfunction after liver reperfusion and could be used to identify very early patients at risk of EAD. Liver Transplantation 23 527-536 2017 AASLD.


Assuntos
Diagnóstico por Imagem/métodos , Doença Hepática Terminal/cirurgia , Hemodinâmica , Circulação Hepática , Transplante de Fígado/efeitos adversos , Microcirculação , Disfunção Primária do Enxerto/fisiopatologia , Adulto , Idoso , Aloenxertos/irrigação sanguínea , Biomarcadores/sangue , Velocidade do Fluxo Sanguíneo , Endotelina-1/sangue , Feminino , Artéria Hepática/fisiopatologia , Humanos , Fígado/irrigação sanguínea , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Veia Porta/fisiopatologia , Disfunção Primária do Enxerto/sangue , Disfunção Primária do Enxerto/epidemiologia , Disfunção Primária do Enxerto/etiologia , Reperfusão/efeitos adversos , Índice de Gravidade de Doença
18.
Transplant Proc ; 49(1): 49-52, 2017 Jan - Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28104157

RESUMO

BACKGROUND: Chronic allograft dysfunction (CAD) is a main cause of graft failure in kidney transplantation. METHODS: We retrospectively analyzed 279 kidney transplant recipients who survived with a functioning graft for at least 2 years. CAD was defined as chronic graft deterioration, excluding other specific causes. We defined the pattern of decline in estimated glomerular filtration rate (eGFR), as follows: (1) "plateau" was defined as decline in eGFR ≤2 mL/min/1.73 m2/year; "long plateaus" were those lasting more than 5 years; (2) "rapid decline" was a decrease in eGFR ≥20 mL/min/1.73 m2/year. Patients diagnosed with CAD were categorized according to the occurrence of rapid decline and/or long plateau as follows: group 1, neither rapid decline nor long plateau; group 2, rapid decline only; group 3, long plateau only; and group 4, both rapid decline and long plateau. RESULTS: From a total of 81 graft losses, 51 (63%) failed because of CAD, with a median of 9.4 years. Sixteen patients belonged to group 1, 14 to group 2, 12 to group 3, and nine to group 4. Mean graft survival times in the four groups were 7.7 ± 1.1, 6.1 ± 3.1, 16.2 ± 2.5, and 10.8 ± 3.6 years, respectively (P < .001). There were significant differences among groups in donor age, year of transplantation, mean eGFR at baseline, and acute rejection rate after transplantation. CONCLUSIONS: The results indicate that this cohort of kidney transplant recipients who had CAD comprised subgroups with different clinical courses.


Assuntos
Aloenxertos/fisiopatologia , Rejeição de Enxerto/fisiopatologia , Falência Renal Crônica/fisiopatologia , Transplante de Rim/efeitos adversos , Disfunção Primária do Enxerto/fisiopatologia , Adulto , Fatores Etários , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Rim/fisiopatologia , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Disfunção Primária do Enxerto/complicações , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
19.
Eur Respir J ; 49(1)2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28100545

RESUMO

An irreversible loss in lung function limits the long-term success in lung transplantation. We evaluated the role of chronic exposure to ambient air pollution on lung function levels in lung transplant recipients (LTRs).The lung function of 520 LTRs from the Cohort in Lung Transplantation (COLT) study was measured every 6 months. The levels of air pollutants (nitrogen dioxide (NO2), particulate matter with an aerodynamic cut-off diameter of x µm (PMx) and ozone (O3)) at the patients' home address were averaged in the 12 months before each spirometry test. The effects of air pollutants on forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) in % predicted were estimated using mixed linear regressions. We assessed the effect modification of macrolide antibiotics in this relationship.Increased 12-month levels of pollutants were associated with lower levels of FVC % pred (-2.56%, 95% CI -3.86--1.25 for 5 µg·m-3 of PM10; -0.75%, 95% CI -1.38--0.12 for 2 µg·m-3 of PM2.5 and -2.58%, 95% CI -4.63--0.53 for 10 µg·m-3 of NO2). In patients not taking macrolides, the deleterious association between PM and FVC tended to be stronger and PM10 was associated with lower FEV1Our study suggests a deleterious effect of chronic exposure to air pollutants on lung function levels in LTRs, which might be modified with macrolides.


Assuntos
Poluição do Ar/efeitos adversos , Transplante de Pulmão , Pulmão/fisiopatologia , Material Particulado/análise , Disfunção Primária do Enxerto/fisiopatologia , Adolescente , Adulto , Idoso , Aloenxertos , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/fisiopatologia , Doença Crônica , Exposição Ambiental , Feminino , Volume Expiratório Forçado , França , Humanos , Modelos Lineares , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Dióxido de Nitrogênio/análise , Ozônio/análise , Espirometria , Capacidade Vital , Adulto Jovem
20.
Expert Rev Respir Med ; 11(2): 119-128, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28074663

RESUMO

INTRODUCTION: Primary graft dysfunction (PGD) is a common complication of lung transplantation characterized by acute pulmonary edema associated with bilateral pulmonary infiltrates and hypoxemia in the first 3 post-operative days. Development of PGD is a predictor of poor short- and long-term outcomes after lung transplantation, but there are currently limited tools to prevent its occurrence. Areas covered: Several potentially modifiable donor, recipient, and operative risk factors for PGD have been identified. In addition, basic and translational studies in animals and ex vivo lung perfusion systems have identified several biomarkers and mechanisms of injury in PGD. In this review, we outline the clinical and genetic risk factors for PGD and summarize experimental data exploring PGD mechanisms, with a focus on strategies to reduce PGD risk and on potential novel molecular targets for PGD prevention. Expert commentary: Because of the clinical importance of PGD, development of new therapies for prevention and treatment is critically important. Improved understanding of the pathophysiology of clinical PGD provides a framework to explore novel agents to prevent or reverse PGD. Ex vivo lung perfusion provides a new opportunity for rapid development of therapeutics that target this devastating complication of lung transplantation.


Assuntos
Transplante de Pulmão/efeitos adversos , Pulmão/fisiopatologia , Disfunção Primária do Enxerto/prevenção & controle , Animais , Feminino , Humanos , Masculino , Disfunção Primária do Enxerto/fisiopatologia , Fatores de Risco , Doadores de Tecidos
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