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1.
Ann Pharmacother ; 56(4): 387-392, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34323121

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a potential option for the management of severe acute respiratory failure secondary to COVID-19. Conflicting the use of this therapy is the known coagulopathy within COVID-19, leading to an incidence of venous thrombotic events of 25% to 49%. To date, limited guidance is available on optimal anticoagulation strategies in this population. OBJECTIVE: The purpose of this study was to evaluate the utilization of a pharmacist-driven bivalirudin dosing protocol for anticoagulation in the setting of ECMO for COVID-19-associated respiratory failure. METHODS: This was a single-center retrospective chart review over a 9-month period of patients receiving bivalirudin while on ECMO. All patients with acute respiratory failure requiring ECMO with a positive SARS-CoV-2 polymerase chain reaction were included. Bivalirudin was dosed via aPTT monitoring after a starting dose of 0.2 or 0.3 mg/kg/h. RESULTS: There were 33 patients included in this study, all receiving mechanical ventilation. The most common starting dose of bivalirudin was 0.2 mg/kg/h, with an average time to therapeutic range of 20 hours. Compared to previous reports, rates of bleeding were low at 15.1%, and 6.1% of patients developed a new venous thromboembolic event while on ECMO. ECMO survival was 51.5%, with an ICU mortality rate of 48.5%. CONCLUSION AND RELEVANCE: In the first published report of its use within this population, bivalirudin was found to be a viable choice for anticoagulation in those patients on ECMO for severe respiratory failure secondary to COVID-19.


Assuntos
COVID-19 , Oxigenação por Membrana Extracorpórea , Insuficiência Respiratória , Anticoagulantes/efeitos adversos , COVID-19/complicações , COVID-19/terapia , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Hirudinas , Humanos , Fragmentos de Peptídeos , Proteínas Recombinantes , Insuficiência Respiratória/terapia , Estudos Retrospectivos , SARS-CoV-2
2.
Cureus ; 13(8): e17152, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34548969

RESUMO

Coronavirus disease 2019 (COVID-19) is currently a significant cause of acute respiratory failure worldwide, leading to irreversible fibrotic lung disease. In patients with persistent respiratory failure after acute COVID-19 infection, lung transplant is an emerging option. Here, we have presented a case where the patient required venovenous extracorporeal membrane oxygenation (VV-ECMO) support for 33 days until a bilateral lung transplant was performed on day 71 after the initial COVID-19 infection. The early outcomes have been favorable. Currently, no guidelines exist for an acceptable time period after initial COVID-19 infection, duration of negative COVID polymerase chain reaction (PCR) testing, or negative Vero cell culture in the setting of persistent positive COVID PCR testing before listing for a lung transplant. Due to a lack of standardized guidelines, this patient was not listed for a lung transplant until the COVID-19 PCRs came negative on days 47 and 49 after the infection.

3.
Transpl Infect Dis ; 20(6): e12986, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30171789

RESUMO

BACKGROUND: Patient outcomes post-lung transplant remain inferior to other types of solid organ transplantation. We investigated whether the presence of potentially pathogenic bacteria (PPB) in donor lung bronchial cultures was associated with adverse outcomes postoperatively. METHODS: All patients who underwent lung transplantation between August 2015 and April 2017 at the University of Kentucky Medical Center were retrospectively reviewed. Retransplants, patients with bronchiectasis (including cystic fibrosis), and individuals who received organs from donation after cardiac death (DCD) donors were excluded. The remaining subjects were separated into two groups: individuals whose donor bronchial cultures grew PPB, and those whose cultures either returned negative for PPB or were sterile. 30-day mortality rates as well as the incidence of grade 3 primary graft dysfunction (PGD) and acute kidney injury (AKI) at both 24 and 72 hours post-transplant were calculated. The duration of mechanical ventilation postoperatively was also recorded. RESULTS: Thirty two subjects comprised the study population. 20 patients (63%) had growth of PPB on donor cultures, while 12 (37%) did not. Patients with PPB had a significantly greater number of days on the ventilator postoperatively compared to those with no PPB (mean = 11.3 and median = 5.0 vs mean = 5.8 and median = 3.0, respectively, P = 0.0232). Subsequent regression analysis revealed this association to not be influenced by recipient lung allocation score (LAS), donor age, donor smoking history, recipient mean pulmonary artery pressure (mPAP) value, and/or use of cardiopulmonary bypass at the time of transplantation. Neither 30-day survival nor incidence of Grade 3 PGD and AKI at 24 or 72 hours post-transplant differed between the two groups (P > 0.05). CONCLUSION: The recovery of PPB in donor lung cultures was associated with a longer duration of mechanical ventilation postoperatively in lung transplant recipients.


Assuntos
Lesão Pulmonar Aguda/epidemiologia , Aloenxertos/microbiologia , Bactérias/isolamento & purificação , Rejeição de Enxerto/epidemiologia , Transplante de Pulmão/efeitos adversos , Pulmão/microbiologia , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/microbiologia , Adulto , Idoso , Antibacterianos/uso terapêutico , Feminino , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/microbiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mortalidade , Período Pós-Operatório , Respiração Artificial/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Tempo , Doadores de Tecidos/estatística & dados numéricos , Resultado do Tratamento
5.
Ann Thorac Surg ; 103(4): 1076-1083, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28017335

RESUMO

BACKGROUND: Lung retransplantation (ReTx) comprises an increasing share of lung transplants and recently has shown improved outcomes. The aim of this study was to identify risk factors affecting overall survival after pulmonary ReTx. METHODS: The United Network for Organ Sharing database was used to identify patients undergoing lung transplantation at our institution from 1995 to 2014. Of the total 542 lung transplants performed, 87 (16.1%) were ReTxs. The primary outcome was overall survival. Multivariate Cox regression models were used to assess the effect of recipient and donor characteristics on survival. RESULTS: Of the patients who underwent ReTx, median survival was 2 years. Predictors of worse survival include recipient age between 50 and 60 years (relative risk, 4.3; p = 0.02) or older than 60 years (relative risk, 10.2; p < 0.001), and time to ReTx of less than 2 years (relative risk, 3.8; p = 0.01). ReTx for bronchiolitis obliterans syndrome had longer median survival than for restrictive chronic lung allograft dysfunction (2.7 years vs 0.9 years; p = 0.055). Overall survival of ReTx patients after initiation of the lung allocation score was not significantly different (p = 0.21). CONCLUSIONS: Lung ReTx outcomes are significantly worse than for primary transplantation but may be appropriate in well-selected patients with certain diagnoses. Lung ReTx in patients older than 50 years or within 2 years of primary lung transplantation was associated with decreased survival. Further work is warranted to identify patients who benefit most from ReTx.


Assuntos
Transplante de Pulmão/mortalidade , Reoperação/mortalidade , Adolescente , Adulto , Fatores Etários , Bronquiolite Obliterante/cirurgia , Feminino , Volume Expiratório Forçado , Rejeição de Enxerto , Humanos , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Transplante Homólogo , Adulto Jovem
6.
Transplantation ; 99(10): 2190-5, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25769073

RESUMO

BACKGROUND: Acute cellular rejection (ACR) is a major early complication after lung transplantation (LT) and is a risk factor for chronic rejection. Induction immunosuppression has been used as a strategy to reduce early ACR. Recently, our LT program changed our primary induction protocol from basiliximab with standard maintenance immunosuppression to alemtuzumab induction with reduced dose maintenance immunosuppression. The objective of this study was to compare incidence of ACR after this change in the first 6 months after transplantation. METHODS: A retrospective, cohort review of patients 18 years or older, which received their first LT between January 2010 and September 2012. RESULTS: The primary outcome was comparison of average lung biopsy scores at 6 months. Secondary outcomes included development of grade A2 or higher rejection, infectious outcomes, overall graft and patient survival. At 6 months, the average biopsy score was significantly lower in the alemtuzumab group than the basiliximab group (0.12 ± 0.29 vs 0.74 ± 0.67; P < 0.0001) (Table 2). Grade 2 or higher rejection was significantly higher in the basiliximab group (P < 0.0001). CONCLUSIONS: Alemtuzumab provided superior outcomes in regard to average biopsy score and lower incidence of grade 2 or higher rejection at 6 months. There were no differences in infectious complications or overall graft or patient survival between the 2 groups.


Assuntos
Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais/administração & dosagem , Imunossupressores/administração & dosagem , Transplante de Pulmão , Proteínas Recombinantes de Fusão/administração & dosagem , Adulto , Idoso , Alemtuzumab , Basiliximab , Biópsia , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Transplantados , Resultado do Tratamento
7.
J Heart Lung Transplant ; 34(1): 65-74, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25447585

RESUMO

BACKGROUND: Long-term outcomes after lung transplantation are limited due to chronic lung allograft dysfunction (CLAD). Bronchiolitis obliterans syndrome (BOS) is the most common form of obstructive CLAD and its definition derives from spirometric measurements. Given the importance of this diagnosis, both the accuracy and reliability of the definition of CLAD are crucial in understanding the pathophysiology of this disease to develop therapeutic options and influence outcome after lung transplantation. METHODS: A web-based survey was designed and distributed to members of the Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) to better understand the accuracy and reliability of pulmonary function criteria in diagnosing BOS. Spirometric data from five patient scenarios that were discordant among reviewers regarding BOS determination from the Assessment of Immunosuppressive Regimen in Suppressing Acute and Chronic Rejection (AIRSAC) trial were randomly selected and summarized in this survey. Survey questions included the respondent's general understanding of the BOS definition, the determination of BOS, and difficulties with the current BOS definition. RESULTS: Eighty-seven respondents from the Pulmonary Council of the ISHLT responded to this survey. There was an overall 70% interobserver agreement regarding the presence or absence of BOS. Among those who agreed upon the presence of BOS, there was a 41% interobserver agreement regarding its time of onset. Despite this variability, the majority of respondents were not only familiar and agreed with the BOS criteria, they also felt confident in applying these criteria. CONCLUSIONS: Our survey identified potential limitations with the current criteria for diagnosing BOS. With recognition of the various CLAD phenotypes, further refinements of these diagnostic criteria will allow for an improved ability to identify and characterize patients who develop or are at risk for BOS, prognosticate outcomes, and, most importantly, marshal in future strategies directed at treating and preventing chronic lung dysfunction after lung transplantation.


Assuntos
Bronquiolite Obliterante/diagnóstico , Volume Expiratório Forçado/fisiologia , Transplante de Pulmão , Complicações Pós-Operatórias/diagnóstico , Inquéritos e Questionários , Bronquiolite Obliterante/epidemiologia , Bronquiolite Obliterante/fisiopatologia , Seguimentos , Humanos , Incidência , Complicações Pós-Operatórias/epidemiologia , Curva ROC , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Espirometria/métodos , Taxa de Sobrevida/tendências , Fatores de Tempo , Estados Unidos/epidemiologia
8.
J Heart Lung Transplant ; 32(7): 701-6, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23664526

RESUMO

BACKGROUND: Cytomegalovirus (CMV) is the most common opportunistic infection in lung transplantation. A recent multicenter, randomized trial (the AIRSAC study) comparing sirolimus to azathioprine in lung transplant recipients showed a decreased incidence of CMV events in the sirolimus cohort. To better characterize this relationship of decreased incidence of CMV events with sirolimus, we examined known risk factors and characteristics of CMV events from the AIRSAC database. METHODS: The AIRSAC database included 181 lung transplant patients from 8 U.S.-based lung transplant centers that were randomized to sirolimus or azathioprine at 3 months post-transplantation. CMV incidence, prophylaxis, diagnosis and treatment data were all prospectively collected. Prophylaxis and treatment of CMV were at the discretion of each institution. RESULTS: The overall incidence of any CMV event was decreased in the sirolimus arm when compared with the azathioprine arm at 1 year after lung transplantation (relative risk [RR] = 0.67, confidence interval [CI] 0.55 to 0.82, p < 0.01). This decreased incidence of CMV events with sirolimus remained significant after adjusting for confounding factors of CMV serostatus and CMV prophylaxis. CONCLUSIONS: These data support results from other solid-organ transplantation studies and suggest further investigation of this agent in the treatment of lung transplant recipients at high risk for CMV events.


Assuntos
Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/prevenção & controle , Imunossupressores/uso terapêutico , Transplante de Pulmão , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Sirolimo/uso terapêutico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
9.
Chest ; 143(6): 1717-1724, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23370547

RESUMO

BACKGROUND: Acute rejection remains a major source of morbidity after lung transplantation. Given the importance of this diagnosis, an international grading system was developed to standardize the diagnosis of acute lung-allograft rejection. The reliability of this grading system has not been adequately assessed by previous studies. METHODS: We examined the level of agreement in grading transbronchial biopsy specimens obtained from a large multicenter study (AIRSAC [Comparison of a Tacrolimus/Sirolimus/Prednisone Regimen vs Tacrolimus/Azathioprine/Prednisone Immunosuppressive Regimen in Lung Transplantation] trial). Biopsy specimens were initially graded for acute rejection and lymphocytic bronchiolitis by the site pathologist and subsequently graded by a central pathologist. Reliability of interobserver grading was evaluated using Cohen κ coefficients. RESULTS: A total of 481 transbronchial biopsy specimens were graded by both the site and central pathologists. The overall concordance rates were 74% and 89% for grade A and grade B biopsy specimens, respectively. When samples from biopsies performed at different time points after transplantation were assessed, there was a higher level of agreement early (≤ 6 weeks) after transplant compared with later time points for acute rejection. However, there was still only moderate agreement for both grade A (κ score 0.479; 95% CI, 0.29-0.67) and grade B (κ score 0.465; 95% CI, 0.08-0.85) rejection. CONCLUSIONS: These results expand upon previous reports of interobserver variability in grading transbronchial biopsy specimens after lung transplantation. Given the variability in grading these specimens, we advocate further education of the histopathologic findings in lung transplant biopsy specimens, as well as revisiting the current criteria for grading transbronchial biopsy specimens to improve concordance among lung transplant pathologists. TRIAL REGISTRY: ClinicalTrials.gov; No. NCT00321906; URL: www.clinicaltrials.gov.


Assuntos
Biópsia/métodos , Rejeição de Enxerto/diagnóstico , Transplante de Pulmão/patologia , Pulmão/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Broncoscopia , Feminino , Rejeição de Enxerto/patologia , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Prospectivos , Estados Unidos
10.
J Surg Res ; 171(1): e107-11, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21872270

RESUMO

BACKGROUND: Since the advent of ex vivo lung perfusion (EVLP), there has been increased focus on swine models of lung transplantation; however, the anatomic differences between human and swine lungs and the technical challenges in performing porcine lung transplantation are not well described in the surgical literature. METHODS: Surgically important anatomic variations are described, and the technical measures taken to address them during harvest and transplantation are introduced. RESULTS: There are three surgically important anatomic variations in pigs. First, the right cranial lobe bronchus arises directly from the trachea, which makes right lung transplantation technically challenging if not prohibitive. Second, the left hemi-azygos vein is fully developed and courses upward through the posterior mediastinum, where it crosses the left pulmonary hilum and drains directly into the coronary sinus. During transplantation, this vein is ligated and dissected away to expose the underlying left pulmonary hilar structures. Third, the right inferior pulmonary vein crosses the midline to drain into the left atrium immediately adjacent to the left inferior pulmonary vein. During donor lung preparation, the right inferior pulmonary vein is ligated distally from the left atrium, which leaves an adequate atrial cuff around the left sided pulmonary veins for later anastomosis. CONCLUSION: Experimental porcine lung transplantation is technically demanding. We have found recognition of the above described anatomical differences and technical nuances facilitate transplantation and provide reproducible results.


Assuntos
Transplante de Pulmão/métodos , Pulmão/anatomia & histologia , Pulmão/cirurgia , Modelos Animais , Suínos/anatomia & histologia , Animais , Humanos , Especificidade da Espécie , Coleta de Tecidos e Órgãos/métodos , Imunologia de Transplantes
11.
J Heart Lung Transplant ; 30(2): 175-81, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20947384

RESUMO

BACKGROUND: Sirolimus (rapamycin) is a potent anti-proliferative agent with immunosuppressive properties that is increasingly being used in solid-organ and hematopoietic stem cell transplantation. In addition, this drug is being investigated for treatment of a broad range of disorders, including cardiovascular disease, malignancies, tuberous sclerosis, and lymphangeioleiomyomatosis. In this study, we found an increased risk of venous thromboembolism (VTE) in lung transplant recipients treated with a sirolimus (SIR)-based immunosuppressive regimen. METHODS: One hundred eighty-one lung transplant recipients were enrolled in a prospective, multicenter, randomized, open-label trial comparing a tacrolimus (TAC)/SIR/prednisone immunosuppression regimen with a TAC/azathioprine (AZA)/prednisone immunosuppressive regimen. The differences in rates of VTE were examined. RESULTS: There was a significantly higher occurrence of VTE in the SIR cohort [15 of 87 (17.2%)] compared with the AZA cohort [3 of 94 (3.2%)] (stratified log-rank statistic = 7.44, p < 0.01). When adjusted for pre-transplant diagnosis and stratified by transplant center, this difference remained essentially unchanged (hazard ratio for SIR vs AZA = 5.2, 95% confidence interval 1.4 to 19.5, p = 0.01). CONCLUSION: Clinicians prescribing SIR should maintain a high level of vigilance for VTE, particularly among patients with other risk factors for this complication.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/efeitos adversos , Transplante de Pulmão/imunologia , Sirolimo/efeitos adversos , Tromboembolia Venosa/epidemiologia , Azatioprina/uso terapêutico , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Estudos Prospectivos , Fatores de Risco , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico
12.
Am J Respir Crit Care Med ; 183(3): 379-87, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20833822

RESUMO

RATIONALE: Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of chronic rejection. Sirolimus is beneficial in preventing cardiac rejection and may decrease rejection after lung transplantation. OBJECTIVES: To determine the potential benefit versus risk of sirolimus in lung transplantation. METHODS: We conducted a multicenter randomized, open label controlled trial comparing sirolimus (SIR) with azathioprine (AZA) in a tacrolimus-based immunosuppressive regimen in lung transplantation. The primary end point was the incidence of acute rejection at 1 year after transplantation between the two study groups. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-one patients were randomized to be included in this study. At 1 year after transplantation, there was no significant difference in the incidence of grade A acute rejection between the two study groups. Similarly, the incidence of chronic rejection and graft survival was no different between the two study groups. Cytomegalovirus infection was decreased in the SIR arm compared with the AZA arm (relative risk, 0.67 [95% confidence interval, 0.55, 0.82]; P < 0.01). There was a higher rate of adverse events leading to early discontinuation of SIR (64%) compared with AZA (49%) during the course of this study. CONCLUSIONS: Sirolimus, an mTOR inhibitor, did not decrease the incidence of acute rejection at 1 year compared with azathioprine in lung transplantation. These results differ from previous results in cardiac and renal transplantation and emphasize the need for multicenter randomized controlled trials in lung transplantation. Clinical trial registered with www.clinicaltrials.gov (NCT 00321906).


Assuntos
Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Pulmão , Sirolimo/uso terapêutico , Tacrolimo/uso terapêutico , Azatioprina/efeitos adversos , Bronquiolite Obliterante/etiologia , Quimioterapia Combinada , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Sirolimo/efeitos adversos , Fatores de Tempo
13.
J Heart Lung Transplant ; 29(8): 865-72, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20466565

RESUMO

BACKGROUND: Limited information is available about the prevalence of pulmonary hypertension diagnosed by right heart catheterization (RHC) in patients with cystic fibrosis being evaluated for lung transplantation. It is unclear whether there are factors that can predict the presence of pulmonary hypertension and whether the presence of pulmonary hypertension influences patient outcomes. METHODS: The study included 57 unique and consecutive adult patients (33 women) with cystic fibrosis who underwent lung transplant evaluation at the University of Florida. RESULTS: The average age at evaluation was 31.8 +/- 10 years. All patients were in New York Heart Association class III. The median (interquartile range) of mean pulmonary artery pressure (PAP) was 26 (24-30) mm Hg. Thirty-six patients (63.2%) had pulmonary hypertension (mean PAP >or= 25 mm Hg) and had a significantly higher degree of hypoxemia and oxygen requirements. Echocardiography evidenced limitations for the diagnosis of pulmonary hypertension. The 5-year mortality rate was similar in patients with or without pulmonary hypertension; however, it was higher in 7 patients identified by cluster analysis and in patients with a left ventricular ejection fraction < 55%. CONCLUSIONS: More than half of our patients with cystic fibrosis and advanced lung disease have elevation of PAP, usually of mild degree. A lower left ventricular ejection fraction, but not the presence of pulmonary hypertension, was associated with worse outcomes.


Assuntos
Fibrose Cística/complicações , Fibrose Cística/cirurgia , Hipertensão Pulmonar/epidemiologia , Hipertensão Pulmonar/mortalidade , Transplante de Pulmão , Adulto , Pressão Sanguínea/fisiologia , Cateterismo Cardíaco , Ecocardiografia Doppler , Feminino , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Prevalência , Prognóstico , Estudos Retrospectivos , Volume Sistólico/fisiologia , Taxa de Sobrevida
14.
Clin Transplant ; 24(5): 610-4, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19925469

RESUMO

We sought to investigate the role of autopsy diagnoses in lung transplantation by comparing the clinically derived cause of death with autopsy deduced cause of death in a cohort of lung transplant recipients. We retrospectively reviewed all consecutive autopsy findings on lung transplant recipients transplanted between March 1994 and March 2007. We reviewed medical records and our lung transplant database to determine the clinical diagnosis of cause of death based on the clinical assessment and discharge summary at the time of death. Our study showed that 21% of the autopsies performed on lung transplant recipients at our institution revealed findings unsuspected at the time of death. Myocardial infarction, pulmonary embolism, high grade acute cellular rejection and infections were the most frequently missed diagnoses. The autopsy remains a useful tool in confirming diagnostic accuracy in lung transplant recipients.


Assuntos
Transplante de Pulmão/mortalidade , Adulto , Autopsia , Causas de Morte , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Adulto Jovem
15.
Prog Transplant ; 19(3): 267-71, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19813490

RESUMO

OBJECTIVE: To observe the effect of naloxone on the lung function of potential lung transplant donors with neurogenic pulmonary edema. DESIGN AND INTERVENTIONS: Donors aged 16 to 55 years without any factors to contraindicate lung donation (pneumonia, pulmonary contusion, etc) were included. Ventilator settings were standardized to a tidal volume of 10 to 12 mL/kg, an FIO2 of 0.40, and a respiratory rate that kept PCO2 between 35 and 45 mm Hg. Chest physiotherapy, nebulizer treatments, and frequent suctioning were undertaken. Baseline arterial blood gas analysis and an oxygen challenge were performed. The patients were then given 8 to 10 mg of naloxone. Oxygen challenges and arterial blood gas analyses were repeated every 4 to 6 hours. The data were analyzed by using a paired t test, and each patient served as his or her own control. SETTING: These interventions were performed on the 19 LifeQuest donors who met the set criteria from July 2002 to July 2004. RESULTS: The PaO2 on the oxygen challenge immediately after administration of naloxone increased from 329 (SD 177) to 363 (SD 191) mm Hg, although the increase from baseline was not significant. The PaO2 from the second oxygen challenge (median time, 7 hours after administration of naloxone) increased to 413 (SD 177) mm Hg (P<.01).


Assuntos
Morte Encefálica , Transplante de Pulmão , Naloxona/administração & dosagem , Antagonistas de Entorpecentes/administração & dosagem , Troca Gasosa Pulmonar/efeitos dos fármacos , Doadores de Tecidos , Adolescente , Adulto , Gasometria , Morte Encefálica/metabolismo , Morte Encefálica/fisiopatologia , Seleção do Doador , Humanos , Infusões Intravenosas , Transplante de Pulmão/estatística & dados numéricos , Pessoa de Meia-Idade , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Oxigênio/sangue , Respiração com Pressão Positiva/métodos , Taxa Respiratória , Terapia Respiratória , Estudos Retrospectivos , Volume de Ventilação Pulmonar , Obtenção de Tecidos e Órgãos/métodos
16.
Am J Physiol Lung Cell Mol Physiol ; 297(1): L115-24, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19411308

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a disease of unknown etiology characterized by the development of subpleural foci of myofibroblasts that contribute to the exuberant fibrosis noted in the pulmonary parenchyma. Pleural mesothelial cells (PMC) are metabolically dynamic cells that cover the lung and chest wall as a monolayer and are in intimate proximity to the underlying lung parenchyma. The precise role of PMC in the pathogenesis of pulmonary parenchymal fibrosis remains to be identified. Transforming growth factor (TGF)-beta1, a cytokine known for its capacity to induce proliferative and transformative changes in lung cells, is found in significantly higher quantities in the lungs of patients with IPF. High levels of TGF-beta1 in the subpleural milieu may play a key role in the transition of normal PMC to myofibroblasts. Here we demonstrate that PMC activated by TGF-beta1 undergo epithelial-mesenchymal transition (EMT) and respond with haptotactic migration to a gradient of TGF-beta1 and that the transition of PMC to myofibroblasts is dependent on smad-2 signaling. The EMT of PMC was marked by upregulation of alpha-smooth muscle actin (alpha-SMA), fibroblast specific protein-1 (FSP-1), and collagen type I expression. Cytokeratin-8 and E-cadherin expression decreased whereas vimentin remained unchanged over time in transforming PMC. Knockdown of smad-2 gene by silencing small interfering RNA significantly suppressed the transition of PMC to myofibroblasts and significantly inhibited the PMC haptotaxis. We conclude that PMC undergo EMT when exposed to TGF-beta1, involving smad-2 signaling, and PMC may be a possible source of myofibroblasts in IPF.


Assuntos
Movimento Celular/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Pleura/citologia , Fator de Crescimento Transformador beta1/farmacologia , Biomarcadores/metabolismo , Caderinas/metabolismo , Linhagem Celular Transformada , Colágeno Tipo I/biossíntese , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Inativação Gênica/efeitos dos fármacos , Humanos , Mesoderma/citologia , Mesoderma/efeitos dos fármacos , Especificidade de Órgãos/efeitos dos fármacos , Fenótipo , Fosforilação/efeitos dos fármacos , RNA Interferente Pequeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad4/metabolismo
17.
Biomarkers ; 13(5): 486-95, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18979641

RESUMO

Primary graft dysfunction and rejection are common complications in lung transplant recipients. Increased expression of thioredoxin-1 (Trx), a 12-kDa redox-regulatory protein, has been reported in multiple lung pathophysiological conditions involving oxidative and inflammatory mediated injury including graft rejection in canine and rat models of lung transplantation. Our objective was to determine whether increased Trx expression is associated with progression of rejection pathophysiology in human lung transplant recipients. Bronchoalveolar lavage (BAL) fluid and transbronchial biopsy samples were collected as a routine part of post-transplant clinical care from 18 lung transplant patients from our adult lung transplant programme. Lung transplant recipient profile included age/sex, ethnic background, days on ventilator, total ischaemic time, and cytomegalovirus (CMV) status. Based on histopathological grading criteria, patients were divided into two groups, rejecting (A1/A2 or B1) and non-rejecting (A0/B0). Rejecting and non-rejecting group total BAL cell counts and differential cell counts for neutrophils, macrophages, lymphocytes and eosinophils as well as total BAL cell Trx levels were analysed. Total BAL cell counts were significantly (p <0.05) elevated in graft rejecting versus non-rejecting patients. Differential BAL macrophage counts were comparable in rejection and non-rejection groups, whereas there were significant increases in neutrophils and lymphocytes but not eosinophils in patients with rejection versus non-rejection pathology (p <0.05). Total ischaemic time and days on ventilator in rejection and non-rejection groups were comparable. However, Trx levels were significantly elevated in BAL cells from graft-rejecting patients compared with non-rejecting patients (p <0.05). These data suggest that surveillance monitoring of BAL Trx levels after lung transplantation can serve as a biomarker to assess severity of graft rejection.


Assuntos
Biomarcadores/análise , Líquido da Lavagem Broncoalveolar , Rejeição de Enxerto , Transplante de Pulmão , Tiorredoxinas/análise , Adulto , Idoso , Diferenciação Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Referência
18.
JSLS ; 12(3): 303-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18765058

RESUMO

BACKGROUND: Gastroparesis following lung transplantation can complicate medical management leading to malnutrition, weight loss, and erratic absorption of immunosuppressive medications, which are all important factors in the success of grafts. Gastric electrical stimulation has been shown to reduce the frequency of nausea and vomiting and lead to weight gain in patients with gastroparesis refractory to standard medical treatment; however, it has not yet been reported as being used for the treatment of gastroparesis in lung transplant recipients. METHODS: We report the case of a female bilateral lung transplant recipient suffering from severe gastric reflux and severe gastroparesis, who was successfully treated with simultaneous creation of a laparoscopic Nissen fundoplication and placement of a gastric stimulator. RESULTS: The patient noted an immediate and sustained decrease in her symptoms of nausea and vomiting, and an increased appetite, and less variability in the serum levels of her immunosuppressive medication. CONCLUSION: Lung transplant recipients with severe gastroparesis and reflux may benefit from Nissen fundoplication and gastric electrical stimulation.


Assuntos
Terapia por Estimulação Elétrica , Fundoplicatura/métodos , Esvaziamento Gástrico , Refluxo Gastroesofágico/etiologia , Refluxo Gastroesofágico/terapia , Gastroparesia/etiologia , Gastroparesia/terapia , Laparoscopia/métodos , Transplante de Pulmão , Feminino , Humanos , Pessoa de Meia-Idade
19.
Clin Transplant ; 21(6): 722-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17988265

RESUMO

BACKGROUND: The emotional and physical well-being of lung transplant patients is enhanced by the availability and stability of a primary caregiver. METHODS: We describe the quality of life (QOL), mood, caregiving strain and benefits, and social intimacy of 73 lung transplant caregivers who completed the QOL Inventory, SF-36 Health Survey, Profile of Mood States, Caregiver Strain Index, Caregiver Benefit Index, and Miller Social Intimacy Scale. RESULTS: Clinically low QOL was reported by 17.8-35.6% of spouses. Relative to a normative sample, spouses reported significantly lower physical (z = 4.01, p < 0.001) and emotional (z = 7.01, p < 0.001) QOL. Over half (56.2%) had clinically elevated caregiving strain. Heightened physical strain (80.8%), inconvenience (79.5%), feeling confined (72.6%), feeling upset that patient has changed so much (69.9%) contributed most to caregiver strain, while discovering inner strength (60.3%), support from others (53.4%), and realizing what is important in life (42.5%) were noted caregiving benefits. Higher caregiving strain was associated with more mood disturbance (r = 0.42, p < 0.001), lower emotional QOL (r = -0.39, p < 0.002), lower social intimacy (r = -0.37, p < 0.002), and longer disease duration (r = 0.55, p < 0.001). CONCLUSION: Spouses of patients awaiting lung transplantation may experience QOL deficits and high caregiver strain. Interventions to improve QOL and reduce caregiver strain are needed.


Assuntos
Afeto/fisiologia , Cuidadores/ética , Relações Familiares , Transplante de Pulmão/psicologia , Relações Médico-Paciente/ética , Qualidade de Vida/psicologia , Listas de Espera , Feminino , Inquéritos Epidemiológicos , Humanos , Relações Interpessoais , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
J Heart Lung Transplant ; 26(10): 1072-4, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17919631

RESUMO

We describe a young man with cystic fibrosis who underwent bilateral sequential lung transplantation (BSLT) and a subsequent right single-lung re-transplant for bronchiolitis obliterans syndrome (BOS). Destruction of the retained left lung with recurrent pneumonia, worsening bronchiectasis and abscess formation was treated with a left lower lobectomy and a subsequent complete pneumonectomy. The patient tolerated the procedures and is alive and well 18 months after left pneumonectomy. In the setting of BOS, allograft pneumonectomy can be performed safely to remove non-functioning infected tissue.


Assuntos
Infecções por Bactérias Gram-Negativas/etiologia , Infecções por Bactérias Gram-Negativas/cirurgia , Pneumopatias/etiologia , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Pneumonectomia , Abscesso/diagnóstico por imagem , Abscesso/etiologia , Abscesso/cirurgia , Adulto , Bronquiectasia/etiologia , Bronquiectasia/cirurgia , Bronquiolite Obliterante/etiologia , Bronquiolite Obliterante/cirurgia , Doença Crônica , Fibrose Cística/cirurgia , Infecções por Bactérias Gram-Negativas/diagnóstico por imagem , Humanos , Pneumopatias/diagnóstico por imagem , Masculino , Pneumonia/etiologia , Pneumonia/cirurgia , Radiografia Torácica , Retratamento , Tomografia Computadorizada por Raios X , Transplante Homólogo , Resultado do Tratamento
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