RESUMO
Data for liver transplant recipients (LTRs) regarding the benefit of care concordant with clinical practice guidelines for management of blood pressure (BP) are sparse. This paper reports on clinician adherence with BP clinical practice guideline recommendations and whether BP control is associated with mortality and cardiovascular events (CVEs) among LTRs. We conducted a longitudinal cohort study of adult LTRs who survived to hospital discharge at a large tertiary care network between 2010 and 2016. The primary exposure was a BP of <140/<90 mm Hg within year 1 of LT. Among 602 LTRs (mean age 56.7 years, 64% men), 92% had hypertension and 38% had new onset hypertension. Less than 30% of LTRs achieved a BP of <140/<90 mm Hg over a mean of 43.2 months. In multivariable models, adjusted for key confounders, BP control post-LT compared with lack of control was associated with a significantly lower hazard of mortality (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.39, 0.87) and of CVEs (HR 0.65, 95% CI 0.43, 0.97). The association between BP control of <140/<90 mm Hg with improved survival and decreased CVEs in LTRs suggests that efforts to improve clinician adherence to BP clinical practice recommendations should be intensified.
Assuntos
Doenças Cardiovasculares , Hipertensão , Transplante de Fígado , Adulto , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Hipertensão/epidemiologia , Estudos Longitudinais , Masculino , Pessoa de Meia-IdadeRESUMO
Cardiovascular disease (CVD) complications are important causes of morbidity and mortality after orthotopic liver transplantation (OLT). There is currently no preoperative risk-assessment tool that allows physicians to estimate the risk for CVD events following OLT. We sought to develop a point-based prediction model (risk score) for CVD complications after OLT, the Cardiovascular Risk in Orthotopic Liver Transplantation risk score, among a cohort of 1,024 consecutive patients aged 18-75 years who underwent first OLT in a tertiary-care teaching hospital (2002-2011). The main outcome measures were major 1-year CVD complications, defined as death from a CVD cause or hospitalization for a major CVD event (myocardial infarction, revascularization, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism, and/or stroke). The bootstrap method yielded bias-corrected 95% confidence intervals for the regression coefficients of the final model. Among 1,024 first OLT recipients, major CVD complications occurred in 329 (32.1%). Variables selected for inclusion in the model (using model optimization strategies) included preoperative recipient age, sex, race, employment status, education status, history of hepatocellular carcinoma, diabetes, heart failure, atrial fibrillation, pulmonary or systemic hypertension, and respiratory failure. The discriminative performance of the point-based score (C statistic = 0.78, bias-corrected C statistic = 0.77) was superior to other published risk models for postoperative CVD morbidity and mortality, and it had appropriate calibration (Hosmer-Lemeshow P = 0.33). CONCLUSION: The point-based risk score can identify patients at risk for CVD complications after OLT surgery (available at www.carolt.us); this score may be useful for identification of candidates for further risk stratification or other management strategies to improve CVD outcomes after OLT. (Hepatology 2017;66:1968-1979).
Assuntos
Doenças Cardiovasculares , Transplante de Fígado , Complicações Pós-Operatórias , Adulto , Idoso , Técnicas de Apoio para a Decisão , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de RiscoRESUMO
Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection. We found that MAIT cells, defined as CD3ε+Vα7.2+CD161++ or CD3ε+MR1 tetramer+ cells, were present within both healthy and tumor-afflicted hepatic tissues. Paired and grouped analyses of samples revealed the physical proximity of MAIT cells to metastatic lesions to drastically influence their functional competence. Accordingly, unlike those residing in the healthy liver compartment, tumor-infiltrating MAIT cells failed to produce IFN-γ in response to a panel of TCR and cytokine receptor ligands, and tumor-margin MAIT cells were only partially active. Furthermore, chemotherapy did not account for intratumoral MAIT cell insufficiencies. Our findings demonstrate for the first time that CRLM-penetrating MAIT cells exhibit wide-ranging functional impairments, which are dictated by their physical location but not by preoperative chemotherapy. Therefore, we propose that MAIT cells may provide an attractive therapeutic target in CRC and that their ligands may be combined with chemotherapeutic agents to treat CRLM.
Assuntos
Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/secundário , Células T Invariantes Associadas à Mucosa/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunidade nas Mucosas , Masculino , Pessoa de Meia-Idade , Células T Invariantes Associadas à Mucosa/patologia , Metástase Neoplásica , Microambiente TumoralRESUMO
BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is an independent risk factor for cardiovascular disease (CVD) morbidity after liver transplantation, but its impact on CVD mortality is unknown. We sought to assess the impact of NASH on CVD mortality after liver transplantation and to predict which NASH recipients are at highest risk of a CVD-related death following a liver transplant. METHODS: Using the Organ Procurement and Transplantation Network database, we examined associations between NASH and post-liver transplant CVD mortality, defined as primary cause of death from thromboembolism, arrhythmia, heart failure, myocardial infarction or stroke. A physician panel reviewed cause of death. RESULTS: Of 48 360 liver transplants (2/2002-12/2011), 5057 (10.5%) were performed for NASH cirrhosis. NASH recipients were more likely to be older, female, obese, diabetic and have history of renal failure or prior CVD vs. non-NASH (P < 0.001 for all). Although there was no difference in overall all-cause mortality (log-rank P = 0.96), both early (30-day) and long-term CVD-specific mortality was increased among NASH recipients (Odds ratio = 1.30, 95% Confidence interval (CI): 1.02-1.66; Hazard ratio = 1.42, 95% CI: 1.07-1.41 respectively). These associations were no longer significant after adjustment for pre-transplant diabetes, renal impairment or CVD. A risk score comprising age ≥55, male sex, diabetes and renal impairment was developed for prediction of post-liver transplant CVD mortality (c-statistic 0.60). CONCLUSION: NASH recipients have an increased risk of CVD mortality after liver transplantation explained by a high prevalence of comorbid cardiometabolic risk factors that in aggregate identify those at highest risk of post-transplant CVD mortality.
Assuntos
Doenças Cardiovasculares , Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/cirurgia , Complicações Pós-Operatórias , Insuficiência Renal/epidemiologia , Fatores Etários , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Causas de Morte , Comorbidade , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Obesidade/epidemiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/mortalidade , Prevalência , Medição de Risco , Fatores de Risco , Fatores Sexuais , Estados UnidosRESUMO
There are complex risk-benefit tradeoffs with different transplantation strategies for end-stage liver disease patients on renal support. Using a Markov discrete-time state transition model, we compared survival for this group with 3 strategies: simultaneous liver-kidney (SLK) transplantation, liver transplantation alone (LTA) followed by immediate kidney transplantation if renal function did not recover, and LTA followed by placement on the kidney transplant wait list. Patients were followed for 30 years from the age of 50 years. The probabilities of events were synthesized from population data and clinical trials according to Model for End-Stage Liver Disease (MELD) scores (21-30 and >30) to estimate input parameters. Sensitivity analyses tested the impact of uncertainty on survival. Overall, the highest survival rates were seen with SLK transplantation for both MELD score groups (82.8% for MELD scores of 21-30 and 82.5% for MELD scores > 30 at 1 year), albeit at the cost of using kidneys that might not be needed. Liver transplantation followed by kidney transplantation led to higher survival rates (77.3% and 76.4%, respectively, at 1 year) than placement on the kidney transplant wait list (75.1% and 74.3%, respectively, at 1 year). When uncertainty was considered, the results indicated that the waiting time and renal recovery affected conclusions about survival after SLK transplantation and liver transplantation, respectively. The subgroups with the longest durations of pretransplant renal replacement therapy and highest MELD scores had the largest absolute increases in survival with SLK transplantation versus sequential transplantation. In conclusion, the findings demonstrate the inherent tension in choices about the use of available kidneys and suggest that performing liver transplantation and using renal transplantation only for those who fail to recover their native renal function could free up available donor kidneys. These results could inform discussions about transplantation policy.
Assuntos
Doença Hepática Terminal/cirurgia , Nefropatias/terapia , Transplante de Rim/métodos , Transplante de Fígado/métodos , Pesquisa Comparativa da Efetividade , Simulação por Computador , Doença Hepática Terminal/complicações , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Feminino , Humanos , Nefropatias/complicações , Nefropatias/diagnóstico , Nefropatias/mortalidade , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Tempo para o Tratamento , Doadores de Tecidos/provisão & distribuição , Resultado do Tratamento , Listas de EsperaRESUMO
Cardiovascular disease (CVD) contributes to excessive long-term mortality after liver transplantation (LT); however, little is known about early postoperative CVD mortality in the current era. In addition, there is no model for predicting early postoperative CVD mortality across centers. We analyzed adult recipients of primary LT in the Organ Procurement and Transplantation Network (OPTN) database between February 2002 and December 2012 to assess the prevalence and predictors of early (30-day) CVD mortality, which was defined as death from arrhythmia, heart failure, myocardial infarction, cardiac arrest, thromboembolism, and/or stroke. We performed logistic regression with stepwise selection to develop a predictive model of early CVD mortality. Sex and center volume were forced into the final model, which was validated with bootstrapping techniques. Among 54,697 LT recipients, there were 1576 deaths (2.9%) within 30 days. CVD death was the leading cause of 30-day mortality (40.2%), and it was followed by infection (27.9%) and graft failure (12.2%). In a multivariate analysis, 9 significant covariates (6 recipient covariates, 2 donor covariates, and 1 operative covariate) were identified: age, preoperative hospitalization, intensive care unit status, ventilator status, calculated Model for End-Stage Liver Disease score, portal vein thrombosis, national organ sharing, donor body mass index, and cold ischemia time. The model showed moderate discrimination (C statistic = 0.66, 95% confidence interval = 0.63-0.68). In conclusion, we provide the first multicenter prognostic model for the prediction of early post-LT CVD death, the most common cause of early post-LT mortality in the current transplant era. However, evaluations of additional CVD-related variables not collected by the OPTN are needed in order to improve the model's accuracy and potential clinical utility.
Assuntos
Doenças Cardiovasculares/mortalidade , Transplante de Fígado , Complicações Pós-Operatórias/mortalidade , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Medição de Risco , Estados Unidos/epidemiologiaRESUMO
PURPOSE OF REVIEW: Measuring and monitoring transplant center performance is vital to ongoing quality assessment and performance improvement initiatives geared toward ensuring optimal care for patients with end-stage organ failure. The impact of regulatory oversight on transplant center behavior and programmatic decision-making is complex. RECENT FINDINGS: Program-specific reports (PSRs) are published by the Scientific Registry for Transplant Recipients (SRTR) and are publically available for use by a variety of stakeholders, including patients, regulators, insurers, and care providers. PSRs have been both groundbreaking and controversial. The principal areas of concern relate to potential unintended consequences of PSRs, limitations in both the data collected by the registry and the currently used statistical methodology employed by the SRTR for risk adjustment, and the subsequent impact on transplant program behavior. SUMMARY: PSRs, which serve the purposes of fueling ongoing performance improvement initiatives and informing consumers and payers by fostering transparency in the communication of risk, also involve trade-offs because of their unintended use for regulatory oversight and subsequent impact on transplant center behavior. Future research is necessary to improve data integrity and risk-adjustment methodologies which will enhance regulation and preserve access to transplantation among vulnerable patient populations.
Assuntos
Estudos de Avaliação como Assunto , Transplante de Órgãos/normas , Avaliação de Programas e Projetos de Saúde , Relatório de Pesquisa , Centros Cirúrgicos/normas , Humanos , Garantia da Qualidade dos Cuidados de Saúde , Sistema de Registros , Medição de RiscoRESUMO
Due to organ scarcity and wait-list mortality, transplantation of donation after cardiac death (DCD) livers has increased. However, the group of patients benefiting from DCD liver transplantation is unknown. We studied the comparative effectiveness of DCD versus donation after brain death (DBD) liver transplantation. A Markov model was constructed to compare undergoing DCD transplantation with remaining on the wait-list until death or DBD liver transplantation. Differences in life years, quality-adjusted life years (QALYs), and costs according to candidate Model for End-Stage Liver Disease (MELD) score were considered. A separate model for hepatocellular carcinoma (HCC) patients with and without MELD exception points was constructed. For patients with a MELD score <15, DCD transplantation resulted in greater costs and reduced effectiveness. Patients with a MELD score of 15 to 20 experienced an improvement in effectiveness (0.07 QALYs) with DCD liver transplantation, but the incremental cost-effectiveness ratio (ICER) was >$2,000,000/QALY. Patients with MELD scores of 21 to 30 (0.25 QALYs) and >30 (0.83 QALYs) also benefited from DCD transplantation with ICERs of $478,222/QALY and $120,144/QALY, respectively. Sensitivity analyses demonstrated stable results for MELD scores <15 and >20, but the preferred strategy for the MELD 15 to 20 category was uncertain. DCD transplantation was associated with increased costs and reduced survival for HCC patients with exception points but led to improved survival (0.26 QALYs) at a cost of $392,067/QALY for patients without exception points. In conclusion, DCD liver transplantation results in inferior survival for patients with a MELD score <15 and HCC patients receiving MELD exception points, but provides a survival benefit to patients with a MELD score >20 and to HCC patients without MELD exception points.
Assuntos
Morte Encefálica , Morte , Transplante de Fígado/mortalidade , Modelos Estatísticos , Doadores de Tecidos/estatística & dados numéricos , Análise Custo-Benefício , Árvores de Decisões , Humanos , Transplante de Fígado/economia , Masculino , Cadeias de Markov , Pessoa de Meia-Idade , Seleção de Pacientes , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/mortalidade , Fatores de Risco , Obtenção de Tecidos e Órgãos/economia , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Estados Unidos/epidemiologiaRESUMO
PURPOSE OF REVIEW: In this review, we briefly summarize three fruitful, emerging areas in liver transplantation research, quality of life; risk assessment; and patient safety. Our goal is to highlight recent findings in these areas, with a call for increased integration of social scientists and transplant clinicians to address how best to shape policy and improve outcomes. RECENT FINDINGS: After liver transplantation, recipients generally experience clinically significant, sustained improvement in their physical, social and emotional well being. However, a sizeable minority of patients do experience excess morbidity that may benefit from ongoing surveillance and/or intervention. There is growing body of research that describes risks associated with liver transplantation, which can be useful aids to better inform decision making by patients, clinicians, payers, and policy makers. In contrast, there has been a relative lack of empirical data on transplant patient safety vulnerabilities, placing the field of surgery in stark contrast to other high-risk industries, wherein such assessments inform continuous process improvement. SUMMARY: Health services and outcomes research has grown in importance in the liver transplantation literature, but several important questions remain unanswered that merit programmatic, interdisciplinary research.
Assuntos
Hepatopatias/cirurgia , Transplante de Fígado , Erros Médicos , Segurança do Paciente , Qualidade de Vida , Pesquisa Biomédica , Humanos , Transplante de Fígado/psicologia , Transplante de Fígado/estatística & dados numéricos , Erros Médicos/economia , Erros Médicos/prevenção & controle , Morbidade , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida/psicologia , Medição de RiscoRESUMO
INTRODUCTION: Despite use of operative and non-operative interventions to reduce blood loss during liver resection, 20%-40% of patients receive a perioperative blood transfusion. Extensive intraoperative blood loss is a major risk factor for postoperative morbidity and mortality and receipt of blood transfusion is associated with serious risks including an association with long-term cancer recurrence and overall survival. In addition, blood products are scarce and associated with appreciable expense; decreasing blood transfusion requirements would therefore have health system benefits. Tranexamic acid (TXA), an antifibrinolytic, has been shown to reduce the probability of receiving a blood transfusion by one-third for patients undergoing cardiac or orthopaedic surgery. However, its applicability in liver resection has not been widely researched. METHODS AND ANALYSIS: This protocol describes a prospective, blinded, randomised controlled trial being conducted at 10 sites in Canada and 1 in the USA. 1230 eligible and consenting participants will be randomised to one of two parallel groups: experimental (2 g of intravenous TXA) or placebo (saline) administered intraoperatively. The primary endpoint is receipt of blood transfusion within 7 days of surgery. Secondary outcomes include blood loss, postoperative complications, quality of life and 5-year disease-free and overall survival. ETHICS AND DISSEMINATION: This trial has been approved by the research ethics boards at participating centres and Health Canada (parent control number 177992) and is currently enrolling participants. All participants will provide written informed consent. Results will be distributed widely through local and international meetings, presentation, publication and ClinicalTrials.gov. TRIAL REGISTRATION NUMBER: NCT02261415.
Assuntos
Antifibrinolíticos , Ácido Tranexâmico , Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Humanos , Fígado , Estudos Prospectivos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Ácido Tranexâmico/uso terapêuticoRESUMO
BACKGROUND & AIMS: Organ scarcity has resulted in increased utilization of donation after cardiac death (DCD) donors. Prior analysis of patient survival following DCD liver transplantation has been restricted to single institution cohorts and a limited national experience. We compared the current national experience with DCD and DBD livers to better understand survival after transplantation. METHODS: We compared 1113 DCD and 42,254 DBD recipients from the Scientific Registry of Transplant Recipients database between 1996 and 2007. Patient survival was analyzed using the Kaplan-Meier methodology and Cox regression. RESULTS: DCD recipients experienced worse patient survival compared to DBD recipients (p<0.001). One and 3 year survival was 82% and 71% for DCD compared to 86% and 77% for DBD recipients. Moreover, DCD recipients required re-transplantation more frequently (DCD 14.7% vs. DBD 6.8%, p<0.001), and re-transplantation survival was markedly inferior to survival after primary transplant irrespective of graft type. Amplification of mortality risk was observed when DCD was combined with cold ischemia time >12h (HR = 1.81), shared organs (HR = 1.69), recipient hepatocellular carcinoma (HR=1.80), recipient age >60 years (HR = 1.92), and recipient renal insufficiency (HR = 1.82). CONCLUSIONS: DCD recipients experience significantly worse patient survival after transplantation. This increased risk of mortality is comparable in magnitude to, but often exacerbated by other well-established risk predictors. Utilization decisions should carefully consider DCD graft risks in combination with these other factors.
Assuntos
Morte Súbita Cardíaca/epidemiologia , Transplante de Fígado/mortalidade , Sistema de Registros/estatística & dados numéricos , Doadores de Tecidos/estatística & dados numéricos , Adulto , Distribuição por Idade , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , Hepatite C Crônica/mortalidade , Hepatite C Crônica/cirurgia , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/mortalidade , Reoperação/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Análise de Sobrevida , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To conduct a meta-analysis to enhance understanding of the risks of biliary complications, particularly ischemic cholangiopathy (IC), after donation after cardiac death (DCD) compared with donation after brain death (DBD) liver transplantation. BACKGROUND: Biliary complications after liver transplantation have profound health and economic implications which merit further investigation. METHODS: The MEDLINE (19502009), EMBASE, and Cochrane Library databases were searched and supplemented by review of conference proceedings and publication bibliographies. All original single institution studies reporting outcomes for DCD and DBD liver transplant recipients were considered. Odds ratios (OR) and 95% confidence intervals (CI) based on random effects models were calculated. RESULTS: Eleven publications, all retrospective cohort studies, involving 489 DCD and 4455 DBD recipients, were included. Donation after cardiac death recipients had a 2.4 times increased odds of biliary complications (95% CI= 1.83.4) and a 10.8 times increased odds of IC (95% CI = 4.824.2).Ischemic cholangiopathy was present in 16% of DCD compared with 3% of DBD recipients. Donation after cardiac death recipients also experienced higher odds of 1-year patient mortality (OR = 1.6, 95% CI = 1.042.5) and graft failure (OR = 2.1, 95% CI = 1.52.8). CONCLUSIONS: Donation after cardiac death liver transplantation is marred by inferior outcomes including higher rates of biliary complications and IC as well as increased mortality and graft failure. Despite current federal mandates to increase DCD donation, these serious complications translate into poor outcomes for individuals and increased healthcare costs. These risks should be considered in decisions regarding the utilization of these grafts.
Assuntos
Doenças dos Ductos Biliares/etiologia , Transplante de Fígado/efeitos adversos , Doadores de Tecidos , Doenças Biliares/etiologia , Morte Encefálica , Causas de Morte , Rejeição de Enxerto , Humanos , Isquemia/etiologia , Disfunção Primária do EnxertoRESUMO
BACKGROUND: Ischemia-reperfusion injury (IRI) is the major cause of primary graft dysfunction in organ transplantation. The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) signaling pathway plays a crucial role in cell physiological and pathological processes including IRI. This study aims to investigate whether inhibition of ERK signaling with U0126 can prevent prolonged cold IRI in heart transplantation. METHODS: Rat cardiac cell line H9c2 cells were treated with U0126 before exposure to hypothermic hypoxia/reoxygenation (H/R) conditions. The effect of U0126 on H9c2 cells in response to H/R stress was determined by measuring cell death, reactive oxygen species production, mitochondrial membrane potential, and ERK signaling activation. Mouse syngeneic heterotopic heart transplantation was conducted, where a donor heart was preserved in the University of Wisconsin (UW) solution supplemented with U0126 for 24 hours at 4°C before transplantation. Heart graft function, histopathologic changes, apoptosis, and fibrosis were measured to assess IRI. RESULTS: Phosphorylated ERK was increased in both in vitro H/R-injured H9c2 cells and in vivo heart grafts with IRI. Pretreatment with U0126 inhibited ERK phosphorylation and prevented H9c2 cells from cell death, reactive oxygen species generation, and mitochondrial membrane potential loss in response to H/R. Preservation of donor hearts with U0126-supplemented solution improved graft function and reduced IRI by reductions in cell apoptosis/death, neutrophil infiltration, and fibrosis of the graft. CONCLUSIONS: Addition of U0126 to UW solution reduces ERK signal activation and attenuates prolonged cold IRI in a heart transplantation model. ERK inhibition with U0126 may be a useful strategy to minimize IRI in organ transplantation.
Assuntos
Butadienos/farmacologia , Isquemia Fria , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Transplante de Coração/efeitos adversos , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Nitrilas/farmacologia , Soluções para Preservação de Órgãos/farmacologia , Preservação de Órgãos , Inibidores de Proteínas Quinases/farmacologia , Adenosina/farmacologia , Alopurinol/farmacologia , Animais , Apoptose/efeitos dos fármacos , Hipóxia Celular , Linhagem Celular , Isquemia Fria/efeitos adversos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibrose , Glutationa/farmacologia , Insulina/farmacologia , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/fisiopatologia , Miócitos Cardíacos/enzimologia , Miócitos Cardíacos/patologia , Preservação de Órgãos/efeitos adversos , Estresse Oxidativo/efeitos dos fármacos , Fosforilação , Rafinose/farmacologia , Ratos , Transdução de Sinais , Função Ventricular Esquerda/efeitos dos fármacosRESUMO
The deleterious effects of psychological stress on mainstream T lymphocytes are well documented. However, how stress impacts innate-like T cells is unclear. We report that long-term stress surprisingly abrogates both T helper 1 (TH1)- and TH2-type responses orchestrated by invariant natural killer T (iNKT) cells. This is not due to iNKT cell death because these cells are unusually refractory to stress-inflicted apoptosis. Activated iNKT cells in stressed mice exhibit a "split" inflammatory signature and trigger sudden serum interleukin-10 (IL-10), IL-23, and IL-27 spikes. iNKT cell dysregulation is mediated by cell-autonomous glucocorticoid receptor signaling and corrected upon habituation to predictable stressors. Importantly, under stress, iNKT cells fail to potentiate cytotoxicity against lymphoma or to reduce the burden of metastatic melanoma. Finally, stress physically spares mouse mucosa-associated invariant T (MAIT) cells but hinders their TH1-/TH2-type responses. The above findings are corroborated in human peripheral blood and hepatic iNKT/MAIT cell cultures. Our work uncovers a mechanism of stress-induced immunosuppression.
Assuntos
Neoplasias Hepáticas/imunologia , Linfoma/imunologia , Células T Invariantes Associadas à Mucosa/imunologia , Células T Matadoras Naturais/imunologia , Estresse Psicológico/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Linhagem Celular Tumoral , Doença Crônica , Corticosterona/farmacologia , Citotoxicidade Imunológica , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imobilização , Imunidade Inata , Interleucina-10/genética , Interleucina-10/imunologia , Interleucina-23/genética , Interleucina-23/imunologia , Interleucinas/genética , Interleucinas/imunologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Linfoma/genética , Linfoma/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Transgênicos , Células T Invariantes Associadas à Mucosa/efeitos dos fármacos , Células T Invariantes Associadas à Mucosa/patologia , Células T Matadoras Naturais/efeitos dos fármacos , Células T Matadoras Naturais/patologia , Metástase Neoplásica , Oxidopamina/farmacologia , Transdução de Sinais , Estresse Psicológico/genética , Estresse Psicológico/patologia , Linfócitos T Auxiliares-Indutores/efeitos dos fármacos , Linfócitos T Auxiliares-Indutores/patologia , Equilíbrio Th1-Th2RESUMO
OBJECTIVE: To determine the effect of donation after cardiac death (DCD) livers on post-transplantation costs. BACKGROUND: DCD livers are increasingly being used to expand the donor pool despite higher complication rates. Although complications after liver transplantation have profound financial implications, the effect of DCD livers on post-transplantation costs has not been studied. METHODS: We estimated direct medical care costs based on inpatient and outpatient hospital costs for 28 DCD and 198 donation after brain death (DBD) liver recipients. Organ acquisition and physician costs were excluded. RESULTS: Donor and recipient demographics were comparable for DCD and DBD transplants. One-year, post-transplantation costs were higher for DCD recipients (124.9% of DBD costs, P = 0.04). DCD costs remained higher (125.2% of DBD costs, P = 0.009) after adjusting for recipient characteristics. Furthermore, DCD post-transplantation costs were 30% higher than DBD costs after adjusting for pre-transplantation costs (P = 0.02). Biliary complications (DCD 58% vs. DBD 21%; P < 0.001) and, specifically, ischemic cholangiopathy (DCD 44% vs. DBD 1.6%; P < 0.001) occurred more frequently after DCD transplantation. Moreover, DCD recipients underwent retransplantation more often (DCD 21% vs. DBD 7.1%, P = 0.02). One-year costs were increased for recipients with ischemic cholangiopathy or retransplantation by 53% (P = 0.01) and 107% (P < 0.001), respectively. However, DCD costs continued to be higher when retransplanted patients were excluded (120% of DBD costs, P = 0.02). CONCLUSIONS: Higher rates of graft failure and biliary complications translate into markedly increased direct medical care costs for DCD recipients. These important financial implications should be considered in decisions regarding the use of DCD livers.
Assuntos
Custos de Cuidados de Saúde , Parada Cardíaca , Transplante de Fígado/economia , Morte Encefálica , Feminino , Recursos em Saúde/estatística & dados numéricos , Custos Hospitalares , Humanos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Doadores de Tecidos , Coleta de Tecidos e ÓrgãosAssuntos
Técnicas de Apoio para a Decisão , Equidade em Saúde/organização & administração , Acessibilidade aos Serviços de Saúde/organização & administração , Disparidades em Assistência à Saúde , Transplante de Fígado/métodos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/organização & administração , Feminino , Humanos , MasculinoRESUMO
With improvements in patient and graft survival after liver transplantation, recipient quality of life (QOL) has become an important focus of patient care and clinical outcomes research. To provide a better understanding of the instruments used to assess QOL in the adult liver transplant population, we conducted a systematic review of the MEDLINE database and Cochrane library. Our review identified 128 relevant articles utilizing more than 50 different QOL instruments. Generic health status instruments are the most commonly used, and among them the Medical Outcomes Study Short Form-36 (SF-36), the Hospital Anxiety and Depression Scale (HADS), and the Beck Depression Inventory (BDI) are the most prevalent. Few studies (16%) included targeted, disease-specific instruments. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Quality of Life questionnaire, the Liver Disease Quality of Life questionnaire, and the Chronic Liver Disease questionnaire are the most frequently employed targeted instruments; however, these instruments have been designed to assess QOL in patients with chronic liver disease rather than patients after liver transplantation. The present review focuses on the psychometric properties of the existing QOL instruments and discusses their individual strengths and limitations in evaluating liver transplantation recipients. The lack of a gold-standard QOL instrument for liver transplant recipients is an impediment to cross-study comparisons. We conclude that the development of a QOL instrument specifically for liver transplant recipients will improve QOL assessment in this population leading to a more nuanced understanding of the factors that influence transplant recipients' well-being.
Assuntos
Transplante de Fígado/fisiologia , Transplante de Fígado/psicologia , Qualidade de Vida , Adulto , Indicadores Básicos de Saúde , Humanos , Psicometria , Inquéritos e QuestionáriosRESUMO
INTRODUCTION: Real-world data with extended-release tacrolimus (ER-T) are lacking in the USA. This study examined clinical outcomes and healthcare resource utilization in kidney transplant patients receiving ER-T in clinical practice. METHODS: This was a retrospective, single-center analysis (February-June 2016) using data from Northwestern University's Enterprise Data Warehouse. Adult patients receiving a kidney transplant in the preceding 4 years, treated de novo or converted to ER-T from immediate-release tacrolimus (IR-T) within 10 days post-transplantation, and maintained on ER-T (at least 3 months) were included. Patients were matched for demographic and clinical characteristics with IR-T-treated control patients. Endpoints included clinical outcomes and healthcare resource utilization up to 1 year post-transplantation. RESULTS: A total of 19 ER-T-treated patients were matched with 55 IR-T-treated patients. No ER-T-treated patients experienced biopsy-confirmed acute rejection (BCAR) or graft failure versus 3 (5.5%) and 3 (5.5%) IR-T-treated patients, respectively. Mean estimated glomerular filtration rate (eGFR), the number of all-cause outpatient visits, readmissions, and all-cause hospitalization days were comparable between groups. Tacrolimus trough levels, days to target level (6-10 ng/mL), and number of required dose adjustments were also similar. CONCLUSION: Real-world clinical outcomes and healthcare resource utilization were similar with ER-T and IR-T. Larger studies will need to investigate the trend toward fewer BCAR events, and increased graft survival with ER-T. FUNDING: Astellas Pharma Global Development, Inc. Plain language summary available for this article.