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1.
Transplantation ; 104(8): 1580-1590, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732835

RESUMO

BACKGROUND: Although short-term outcomes for liver transplantation have improved, patient and graft survival are limited by infection, cancer, and other complications of immunosuppression. Rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. Tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. Since the liver is considered to be tolerogenic, we tested the hypothesis that the renal transplant transient chimerism protocol would induce liver tolerance. METHODS: Seven cynomolgus macaques received immune conditioning followed by simultaneous donor bone marrow and liver transplantation. The more extensive liver surgery required minor adaptations of the kidney protocol to decrease complications. All immunosuppression was discontinued on postoperative day (POD) 28. Peripheral blood chimerism, recipient immune reconstitution, liver function tests, and graft survival were determined. RESULTS: The level and duration of chimerism in liver recipients were comparable to those previously reported in renal transplant recipients. However, unlike in the kidney model, the liver was rejected soon after immunosuppression withdrawal. Rejection was associated with proliferation of recipient CD8 T effector cells in the periphery and liver, increased serum interleukin (IL)-6 and IL-2, but peripheral regulatory T cell (Treg) numbers did not increase. Antidonor antibody was also detected. CONCLUSIONS: These data show the transient chimerism protocol does not induce tolerance to livers, likely due to greater CD8 T cell responses than in the kidney model. Successful tolerance induction may depend on greater control or deletion of CD8 T cells in this model.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Rejeição de Enxerto/prevenção & controle , Transplante de Fígado/efeitos adversos , Quimeras de Transplante/imunologia , Condicionamento Pré-Transplante/métodos , Aloenxertos/imunologia , Animais , Medula Óssea/imunologia , Transplante de Medula Óssea/métodos , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Fígado/imunologia , Transplante de Fígado/métodos , Macaca fascicularis , Linfócitos T Citotóxicos/imunologia , Tolerância ao Transplante , Transplante Homólogo/efeitos adversos
2.
Transplantation ; 104(8): 1591-1603, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732836

RESUMO

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Preservação de Órgãos/métodos , Idoso , Aloenxertos/imunologia , Aloenxertos/provisão & distribução , Isquemia Fria/instrumentação , Isquemia Fria/métodos , Isquemia Fria/estatística & dados numéricos , Doença Hepática Terminal/complicações , Estudos de Viabilidade , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Humanos , Rim/imunologia , Transplante de Rim/ética , Transplante de Rim/métodos , Transplante de Rim/estatística & dados numéricos , Transplante de Fígado/ética , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Masculino , Futilidade Médica/ética , Pessoa de Meia-Idade , Preservação de Órgãos/instrumentação , Preservação de Órgãos/estatística & dados numéricos , Perfusão/instrumentação , Perfusão/métodos , Perfusão/estatística & dados numéricos , Insuficiência Renal/etiologia , Insuficiência Renal/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/ética , Transplante Homólogo/métodos , Resultado do Tratamento
3.
Transplantation ; 104(8): 1604-1611, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732837

RESUMO

BACKGROUND: Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts. METHODS: Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression. RESULTS: Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers. CONCLUSIONS: The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.


Assuntos
Doença Hepática Terminal/cirurgia , Fígado Gorduroso/diagnóstico , Rejeição de Enxerto/epidemiologia , Transplante de Fígado/efeitos adversos , Seleção de Pacientes , Adulto , Idoso , Aloenxertos/patologia , Aloenxertos/provisão & distribução , Modificador do Efeito Epidemiológico , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Fígado Gorduroso/patologia , Feminino , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/cirurgia , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Medição de Risco , Índice de Gravidade de Doença , Transplantados/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia
4.
Transplantation ; 104(8): 1633-1643, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732841

RESUMO

BACKGROUND: The cellular infiltrate in protocol liver biopsies (PB) following pediatric liver transplantation remains mostly uncharacterized, yet there is increasing concern about the role of inflammation and fibrosis in long-term liver allografts. We aimed to define cell types in PB and to analyze their relationship with donor-specific antibodies (DSA) and histological phenotype. METHODS: PB were performed at least 1 year after transplantation. We identified 4 phenotypes: normal, fibrosis, inflammation, inflammation with fibrosis. Cell types were counted after immunostaining for CD3, CD4, CD8, CD68, CD20, MUM1, and FoxP3. RESULTS: Forty-four patients underwent 1 PB between 2000 and 2015. Eleven percent (5/44) of PB displayed normal histology, 13.6% (6/44) fibrosis, 34.1% (15/44) inflammation, and 40.9% (18/44) inflammation and fibrosis. The main cell types in the portal tracts and lobules were CD3+ and CD68+ cells. Frequency of de novo DSA was 63% (27/44). The presence of CD8+ cells in the lobules was associated with fibrosis. Inflammation and fibrosis in PB were associated with the presence of circulating de novo DSA, number of de novo DSA, and C1q binding activity when compared to other phenotypes. CONCLUSIONS: T cells (CD3+) and macrophages (CD68+) were the most prevalent cell-types in PB. In the presence of inflammation, portal tracts were enriched in CD3+, CD20+ but displayed fewer CD68+. This coincided with the presence and number of de novo DSA. How these cellular and humoral actors interact is unclear, but peripheral DSA may be a marker of immune cellular activity in the seemingly quiescent allograft.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/imunologia , Isoanticorpos/imunologia , Transplante de Fígado/efeitos adversos , Sistema Porta/imunologia , Adolescente , Adulto , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Biópsia , Criança , Pré-Escolar , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Feminino , Fibrose , Seguimentos , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Imunidade Celular , Lactente , Isoanticorpos/análise , Fígado/irrigação sanguínea , Fígado/imunologia , Fígado/patologia , Doadores Vivos/estatística & dados numéricos , Macrófagos/imunologia , Masculino , Sistema Porta/citologia , Índice de Gravidade de Doença , Linfócitos T/imunologia , Transplantados/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Adulto Jovem
7.
PLoS One ; 15(8): e0237503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810154

RESUMO

BACKGROUND: Intraoperative restrictive fluid management strategies might improve postoperative outcomes in liver transplantation. Effects of vasopressors within any hemodynamic management strategy are unclear. METHODS: We conducted an observational cohort study on adult liver transplant recipients between July 2008 and December 2017. We measured the effect of vasopressors infused at admission in the intensive care unit (ICU) and total intraoperative fluid balance. Our primary outcome was 48-hour acute kidney injury (AKI) and our secondary outcomes were 7-day AKI, need for postoperative renal replacement therapy (RRT), time to extubation in the ICU, time to ICU discharge and survival up to 1 year. We fitted models adjusted for confounders using generalized estimating equations or survival models using robust standard errors. We reported results with 95% confidence intervals. RESULTS: We included 532 patients. Vasopressors use was not associated with 48-hour or 7-day AKI but modified the effects of fluid balance on RRT and mortality. A higher fluid balance was associated with a higher need for RRT (OR = 1.52 [1.15, 2.01], p<0.001 for interaction) and lower survival (HR = 1.71 [1.26, 2.34], p<0.01 for interaction) only among patients without vasopressors. In patients with vasopressors, higher doses of vasopressors were associated with a higher mortality (HR = 1.29 [1.13, 1.49] per 10 µg/min of norepinephrine). CONCLUSION: The presence of any vasopressor at the end of surgery was not associated with AKI or RRT. The use of vasopressors might modify the harmful association between fluid balance and other postoperative outcomes. The liberal use of vasopressors to implement a restrictive fluid management strategy deserves further investigation.


Assuntos
Lesão Renal Aguda , Hemodinâmica/fisiologia , Cuidados Intraoperatórios/métodos , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias , Lesão Renal Aguda/epidemiologia , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/prevenção & controle , Adulto , Idoso , Estudos de Coortes , Feminino , Hidratação/métodos , Humanos , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Quebeque/epidemiologia , Terapia de Substituição Renal/estatística & dados numéricos , Fatores de Risco , Resultado do Tratamento , Equilíbrio Hidroeletrolítico/fisiologia
8.
Transplantation ; 104(9): 1929-1942, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32769628

RESUMO

BACKGROUND: Liver graft viability assessment has long been considered a limit of hypothermic oxygenated machine perfusion (HOPE). Aim of this study was assessing correlations of easily available perfusate parameters (PP) (aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, glucose, lactate, and pH) with graft features and outcome. METHODS: In the period October 2018-February 2020, perfusate samples were obtained every 30 minutes during 50 dual-HOPE (D-HOPE) procedures. Correlations of PP with graft factors, 90-day graft loss, early allograft dysfunction (EAD), L-GrAFT score, acute kidney injury, and comprehensive complication index were analyzed using Pearson coefficient, receiver-operating characteristics analysis and by univariable and multivariable regression. RESULTS: Median D-HOPE time was 122 minutes. All parameters were normalized to liver weight. Only macrovesicular steatosis (MaS) significantly impacted PP levels and slope. Grafts with ≥30% MaS exhibited significantly different PP values and slope. Graft loss and EAD rate were 2% (n = 1) and 26% (n = 13). All PP except lactate correlated with EAD, 90-minute alanine aminotransferase showing the highest area under the receiver-operating characteristics curve (0.84). However, at multivariable analysis, the only factor independently associated with EAD was MaS (odds ratio, 5.44; confidence interval, 1.05-28.21; P = 0.04). Ninety minutes lactate dehydrogenase had the strongest correlation with L-GrAFT (R = 0.70; P < 0.001). PP correlated poorly with comprehensive complication index and grades 2-3 acute kidney injury rate. CONCLUSIONS: PP were predictive of graft function after transplant, but their association with graft survival and clinical outcomes requires further evaluation. MaS influenced levels of PP and was the only independent predictor of EAD.


Assuntos
Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos , Alanina Transaminase/análise , Aspartato Aminotransferases/análise , Temperatura Baixa , Feminino , Sobrevivência de Enxerto , Humanos , Concentração de Íons de Hidrogênio , L-Lactato Desidrogenase/análise , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Front Immunol ; 11: 1392, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612614

RESUMO

Since December 2019, the ongoing coronavirus disease 2019 (COVID-19) pandemic has significantly affected solid organ transplantation (SOT) worldwide and has become a threat to the lives of SOT recipients. Here, we have reviewed, condensed, and organized the available information on COVID-19 to provide recommendations to transplant healthcare workers. Our review of reported cases shows that the symptoms of SOT patients with COVID-19 are similar to those of the normal population, but their severity and outcomes are worse. Thus far, there is no evidence that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) directly causes permanent damage to kidney, liver, or heart allografts.


Assuntos
Infecções por Coronavirus/patologia , Transplante de Coração/efeitos adversos , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Pneumonia Viral/patologia , Adulto , Idoso , Betacoronavirus , Infecções por Coronavirus/transmissão , Feminino , Coração/virologia , Humanos , Rim/patologia , Rim/virologia , Fígado/patologia , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Miocárdio/patologia , Pandemias , Pneumonia Viral/transmissão , Transplantados/estatística & dados numéricos
10.
Int J Nanomedicine ; 15: 4125-4138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606668

RESUMO

Purpose: To investigate the effect and mechanism of macrophage membrane-coated nanoparticles (M-NPs) on hepatic ischemia-reperfusion injury (I/RI) caused by orthotopic liver transplantation. In addition, the advantages of TLR4+/M-NPs compared to M-NPs are discussed. Materials and Methods: We prepared biomimetic M-NPs and identified their characteristics. M-NPs were injected into an SD rat model of orthotopic liver transplantation, and the anti-inflammatory and anti-I/RI activities of M-NPs were studied in vivo and in vitro. In addition, we overexpressed macrophage membrane Toll-like receptor 4 (TLR4) in vitro and prepared TLR4+/M-NPs. Then, we assessed the characteristics and advantages of TLR4+/M-NPs. Results: The M-NPs neutralized endotoxin, inhibited the overactivation of Kupffer cells (KCs) and suppressed the secretion of inflammatory factors by inhibiting the endotoxin-mediated TLR4/MyD88/IRAK1/NF-κB signaling pathway. In an orthotopic liver transplantation model in SD rats, M-NPs showed significant therapeutic efficacy by neutralizing endotoxin and suppressing the secretion of inflammatory factors. Moreover, overexpression of TLR4 on the macrophage membrane by using a TLR4+-plasmid in vitro effectively reduced the amount of M-NPs needed to neutralize an equivalent dose of endotoxin, reducing the potential risks of NP overuse. Conclusion: This study indicates that M-NPs can effectively alleviate I/RI induced by liver transplantation.


Assuntos
Membrana Celular/metabolismo , Endotoxinas/metabolismo , Transplante de Fígado/efeitos adversos , Fígado/irrigação sanguínea , Macrófagos/metabolismo , Nanopartículas/química , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/terapia , Animais , Anti-Inflamatórios/farmacologia , Fluorescência , Lipopolissacarídeos/farmacologia , Fígado/efeitos dos fármacos , Fígado/patologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Nanopartículas/ultraestrutura , Células RAW 264.7 , Ratos Sprague-Dawley , Receptor 4 Toll-Like/metabolismo
11.
Lancet HIV ; 7(9): e611-e619, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32730756

RESUMO

BACKGROUND: One of the primary risks of HIV-positive to HIV-positive organ transplantation is loss of virological control because of donor-derived HIV superinfection, which occurs when an HIV-positive individual becomes infected with a new distinct HIV strain. In this study, as part of the larger HIV Organ Policy Equity pilot study, HIV-positive to HIV-positive kidney and liver transplant recipients in the USA were examined for evidence of sustained donor-derived HIV superinfection. METHODS: In this multicentre, prospective, observational study, HIV-positive to HIV-positive kidney and liver transplant recipients were followed in three hospitals in the USA. Candidates with well controlled HIV infection on ART, no active opportunistic infections, and minimum CD4 T-cell counts (>100 cells per µL for liver and >200 cells per µL for kidney per federal guidelines) were eligible to receive a kidney or liver from deceased HIV-positive donors without active infections or neoplasm. Peripheral blood mononuclear cells were collected from donor-recipient pairs at the time of transplantation, and from recipients at several timepoints up to 3 years after transplantation. Donor samples were assessed for HIV RNA viral load, CD4 cell count, and antiretroviral drug-resistant mutations. Donor and recipient HIV proviral DNA, and viral RNA from the viraemic timepoint were sequenced using a site-directed next-generation sequencing assay for the reverse transcriptase and gp41 genes. Neighbour-joining phylogenetic trees and direct sequence comparison were used to detect the presence of HIV superinfection. This study is registered with ClinicalTrials.gov, NCT02602262. FINDINGS: 14 HIV-positive to HIV-positive kidney and eight liver transplant recipients were followed from March, 2016, to July, 2019. 17 recipients had adequate viral sequences allowing for HIV superinfection assessment. Eight donors were suppressed (viral load <400 copies per mL), and none had multiclass drug-resistant mutations detected. None of the recipients examined had evidence of HIV superinfection. One recipient had a viraemic episode (viral load of 2 080 000 copies per mL) 3 years after transplantation as a result of non-adherence to ART. Only recipient viral sequences were detected during the viraemic episode, suggesting that the donor virus, if present, was not reactivated despite temporary withdrawal of ART. INTERPRETATION: These findings suggest that loss of HIV suppression due to donor-derived HIV superinfection might not be a significant clinical concern in carefully monitored ART suppressed HIV-positive organ recipients. FUNDING: US National Institute of Allergy and Infectious Diseases and National Cancer Institute.


Assuntos
Soropositividade para HIV/epidemiologia , Transplante de Rim , Transplante de Fígado , Superinfecção/epidemiologia , Superinfecção/etiologia , Idoso , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Feminino , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/imunologia , Soropositividade para HIV/virologia , Humanos , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Filogenia , Estudos Prospectivos , Análise de Sequência de DNA , Superinfecção/diagnóstico , Carga Viral , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
12.
Transplantation ; 104(9): 1943-1951, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32639402

RESUMO

BACKGROUND: Liver transplantation (LT) from controlled donation after circulatory death (cDCD) was initiated in France in 2015 under a protocol based on the use of normothermic regional perfusion (NRP) before organ procurement. The aim was to compare outcomes following cDCD LT with NRP and donation after brain death (DBD) LT. METHODS: This is a multicenter retrospective study comparing cDCD LT with NRP and DBD LT. A case-matched study (1:2) was performed using the variables such as recipient and donor age, indication of LT. RESULTS: A total of 50 patients from the cDCD group were matched to 100 patients from the DBD group. From postoperative days 1-4, serum transaminase release was significantly lower in the cDCD group compared to the DBD group (P < 0.05). Early allograft dysfunction (cDCD: 18% versus DBD: 32%; P = 0.11), acute kidney injury (26% versus 33%; P = 0.49), 90-d graft loss (2% versus 5%; P = 0.66), and arterial (4% versus 12%; P = 0.19) and biliary (16% versus 17%; P = 0.94) complications were similar between the 2 groups. The 2-y graft survival was 88% for cDCD group and 85% for DBD group (P = 0.91). The 2-y patient survival was 90% for cDCD group and 88% for DBD group (P = 0.68). CONCLUSIONS: This study provides evidence that cDCD LT following postmortem NRP can be safely and effectively performed in selected recipients with similar graft and patient survival outcomes, without increased rates of biliary complications and early graft dysfunction compared to DBD LT.


Assuntos
Morte Encefálica , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Perfusão/métodos , Doadores de Tecidos , Adulto , Doenças Biliares/epidemiologia , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
13.
Med. intensiva (Madr., Ed. impr.) ; 44(5): 275-282, jun.-jul. 2020. graf, tab
Artigo em Inglês | IBECS | ID: ibc-193187

RESUMO

OBJECTIVE: To explore the behavior of C-reactive protein (CRP) after orthotopic liver transplantation (OLT) during the first postoperative days, and its usefulness as a marker of severe early allograft dysfunction (EAD). DESIGN: A prospective, single-center cohort study was carried out. SETTING: The Intensive Care Unit (ICU) of a regional hospital with a liver transplant program since 1997. PATIENTS: The study comprised a total of 183 patients admitted to our ICU immediately after liver transplantation between 2009 and 2015. VARIABLES OF INTEREST: C-reactive protein levels upon ICU admission and after 24 and 48h, severe EAD and hospital mortality. RESULTS: The CRP levels after OLT were: upon ICU admission 57.5 (51.6-63.3) mg/L, after 24h 80.1 (72.9-87.3)mg/L and after 48h 69.9 (62.5-77.4) mg/L. Severe EAD patients (14.2%) had higher mortality (23.1 vs 2.5; OR 11.48: 2.98-44.19) and lower CRP upon ICU admission (39.3 [29.8-48.7] mg/L) than the patients without EAD (0.5 [53.9-67.0]; p < 0.05] - the best cut-off point being 68mg/L (sensitivity 92.3%; specificity 40.1%; Youden index 0.33). Lower CRP upon ICU admission was correlated to higher mortality (24.5 [9.2-39.7] vs 59.4 [53.4-65.4]; p < 0.01, AUC 0.79 [0.65-0.92]). CONCLUSIÓN: Liver transplant is a strong inflammatory stimulus accompanied by high levels of C-reactive protein. A blunted rise in CRP on the first postoperative day after OLT may be a marker of poor allograft function and is related to hospital mortality


OBJETIVO: Explorar el comportamiento de la proteína C reactiva (PCR) en el postoperatorio inmediato de trasplante hepático y su utilidad como marcador de disfunción grave del injerto hepático. DISEÑO: Estudio de cohortes prospectivo, unicéntrico. ÁMBITO: Unidad de cuidados intensivos (UCI) de un hospital regional. PACIENTES: Ciento ochenta y tres pacientes ingresados en nuestra UCI inmediatamente después del trasplante hepático entre 2009-2015. VARIABLES DE INTERÉS: Niveles de PCR al ingreso en UCI, 24 y 48h, disfunción grave del injerto hepático, mortalidad intrahospitalaria. RESULTADOS: Los niveles de PCR en el postoperatorio inmediato de trasplante fueron: al ingreso en UCI 57,5 (51,6-63,3) mg/L, a las 24h 80,1 (72,9-87,3) mg/L y a las 48h 69,9 (62,5-77,4) mg/L. Los pacientes con disfunción grave del injerto (14,2%) tuvieron una mayor mortalidad (23,1 vs. 2,5; OR 11,48: 2,98-44,19) y PCR más baja al ingreso en UCI (39,3 [29,8-48,7]mg/L) que los pacientes sin disfunción grave (0,5 [53,9-67]; p < 0,05), siendo el mejor punto de corte para la PCR de 68mg/L (sensibilidad 92,3%; especificidad 40,1%; índice de Youden 0,33). La PCR baja al ingreso tuvo correlación directa con la mortalidad (24,5 [9,2-39,7] vs. 59,4 [53,4-65,4]; p < 0,01, AUC 0,79 [0,65-0,92]). CONCLUSIÓN: El trasplante hepático es un estímulo inflamatorio intenso que se acompaña de niveles elevados de PCR. Un ascenso truncado de la PCR, en el primer día del postoperatorio de trasplante hepático, puede ser un marcador de funcionamiento inadecuado del injerto hepático y está relacionado con la mortalidad intrahospitalaria


Assuntos
Humanos , Proteína C-Reativa/análise , Estudos de Coortes , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Disfunção Primária do Enxerto/complicações , Mortalidade Hospitalar , Unidades de Terapia Intensiva , Estudos Prospectivos , Transplante de Fígado/mortalidade , Transplante de Fígado/métodos , Sensibilidade e Especificidade , Biomarcadores/análise , Testes de Função Hepática
14.
Clinics (Sao Paulo) ; 75: e1983, 2020.
Artigo em Inglês | MEDLINE | ID: covidwho-596461

RESUMO

Coronavirus disease (COVID-19) rapidly progresses to severe acute respiratory syndrome. This review aimed at collating available data on COVID-19 infection in solid organ transplantation (SOT) patients. We performed a systematic review of SOT patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The MEDLINE and PubMed databases were electronically searched and updated until April 20, 2020. The MeSH terms used were "COVID-19" AND "Transplant." Thirty-nine COVID-19 cases were reported among SOT patients. The median interval for developing SARS-CoV-2 infection was 4 years since transplantation, and the fatality rate was 25.64% (10/39). Sixteen cases were described in liver transplant (LT) patients, and the median interval since transplantation was 5 years. The fatality rate among LT patients was 37.5% (6/16), with death occurring more than 3 years after LT. The youngest patient who died was 59 years old; there were no deaths among children. Twenty-three cases were described in kidney transplant (KT) patients. The median interval since transplantation was 4 years, and the fatality rate was 17.4% (4/23). The youngest patient who died was 71 years old. Among all transplant patients, COVID-19 had the highest fatality rate in patients older than 60 years : LT, 62.5% vs 12.5% (p=0.006); KT 44.44% vs 0 (p=0.039); and SOT, 52.94% vs 4.54% (p=0.001). This study presents a novel description of COVID-19 in abdominal SOT recipients. Furthermore, we alert medical professionals to the higher fatality risk in patients older than 60 years. (PROSPERO, registration number=CRD42020181299).


Assuntos
Betacoronavirus , Infecções por Coronavirus/mortalidade , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Pneumonia Viral/mortalidade , Adulto , Idoso , Criança , Feminino , Humanos , Lactente , Transplante de Rim/mortalidade , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Pandemias
15.
Exp Clin Transplant ; 18(3): 270-274, 2020 06.
Artigo em Inglês | MEDLINE | ID: covidwho-594580

RESUMO

OBJECTIVES: The novel 2019 coronavirus (COVID-19) was first described in December 2019 in Wuhan, China and subsequently announced as a pandemic on March 12, 2020. In several studies, solid-organ transplant recipients were reported to have higher risk for COVID-19. Here, we aimed to determine the frequency of COVID-19 in our kidney and liver transplant patients. MATERIALS AND METHODS: Our study included 583 transplant patients who were admitted to our outpatient transplant clinics and emergency departments between March 1 and May 1, 2020. Seventy-four of them were liver transplant recipients (46 male, 28 female, of which 14 were pediatric and 60 were adult patients) and 509 of them were kidney transplant recipients (347 male, 162 female, of which 16 were pediatric and 493 were adult patients). We retrospectively evaluated demographic characteristics, currently used immunosuppressant treatment, present complaints, treatment and diagnosis of comorbid diseases, and results of COVID-19 tests. RESULTS: Of 583 transplant recipients, 538 were seen in our outpatient transplant clinics and 45 were seen in our emergency departments. Of these, 18 patients who had had cough and fever were evaluated by respiratory clinic doctors, and nasopharyngeal swab samples were taken. One kidney transplant recipient had a positive COVID-19 test; he was followed with home isolation. He received treatment with hydroxychloroquine (400 mg/day). The other 17 patients had negative tests. There were no mortalities due to COVID-19. CONCLUSIONS: Transplant patients also got affected during the COVID-19 pandemic. According to the data of our centers, this effect is not much more different from the normal population. We recommend that transplant recipients should be warned in terms of personal hygiene and should be closely monitored by organ transplant centers. If there is an indication for hospitalization, they should be followed in an isolated unit, with no aggressive changes made to immunosuppressive doses unless necessary.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/epidemiologia , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Infecções Oportunistas/epidemiologia , Pneumonia Viral/epidemiologia , Betacoronavirus/imunologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Quimioterapia Combinada , Feminino , Interações Hospedeiro-Patógeno , Humanos , Imunossupressores/efeitos adversos , Masculino , Infecções Oportunistas/diagnóstico , Infecções Oportunistas/imunologia , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Turquia/epidemiologia
17.
PLoS One ; 15(6): e0235359, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32589654

RESUMO

BACKGROUND: Liver cirrhosis has been known to be associated with increased intestinal permeability (IP); however, little is known about the modification of IP after liver transplantation (LT). The present study was aimed to assess IP after LT and evaluated its association with laboratory tests and clinical parameters, as well as with the development of infections. METHODS: LT recipients were consecutively enrolled and compared with an equal number of patients with liver cirrhosis and healthy subjects. IP was assessed by urinary excretion of chromium-51 ethylenediaminetetraacetic acid (51Cr-EDTA). RESULTS: The median 51Cr-EDTA excretion was found to be higher in 35 LT recipients as compared with that in the healthy controls [4.77% (2.79-6.03) vs. 2.07% (1.57-2.42), p<0.0001], and comparable to that in the cirrhotic patients [3.69% (2.34-6.57), p = 0.445]. 51Cr-EDTA excretion was not associated with clinical variables, the type of immunosuppressive therapy, donor-related factors, comorbidities and incidence of infections [infection/no infection: 4.97% (3.14-7.03) vs 4.62% (2.79-5.82), p = 0.938]. CONCLUSION: LT recipients show an increased IP, similar to that in patients with liver cirrhosis. However, it is not associated with a high risk of infections. Further investigations into the pathogenesis of this persistent impairment of the intestinal barrier are warranted.


Assuntos
Infecções/etiologia , Mucosa Intestinal/metabolismo , Transplante de Fígado/efeitos adversos , Idoso , Feminino , Humanos , Infecções/metabolismo , Masculino , Pessoa de Meia-Idade , Permeabilidade , Resultado do Tratamento
18.
Gene ; 754: 144887, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32534059

RESUMO

BACKGROUND: Liver transplantation (LTX)is a lifesaving- effective protocol for patients suffering end stage liver disease (ESLD) and its complications post HCV infection. Recurrence of disease is a frequent clinical complication that is observed in patients undergoing LTX. Cytokines play a central role in the immunological events occurring after the surgery. METHODS: Using Allelic Discrimination PCR, the allelic variation G174C of IL-6 gene was investigated. The abundance of IL6- mRNA and plasma IL6 cytokine levels were evaluated by using qRT-PCR in peripheral blood mononuclear cells (PBMCs) and enzyme-linked immunosorbent assay (ELISA) respectively in 76 liver transplant recipients recruited from Al Sahel teaching hospital, Ministry of Health and Population Cairo Egypt within the period between June 2015 and October 2017. RESULTS: The frequencies of IL-6 GG genotype and the G allele were significantly detected more in LTX recipients who experienced HCV recurrence versus those who did not suffer recurrence when compared to healthy controls (P = 0.001) and (P = 0.006), respectively. On the contrary, levels of IL-6 related transcripts in PBMC's of recurrent patients were indifferent from non-recurrent patients and healthy controls (P ≥ 0.124). Interestingly, the circulating IL-6 protein in plasma was significantly elevated in recurrent as compared to the non-recurrent recipients (P = 0.002). CONCLUSION: HCV recurrence post liver transplantation occur more frequently in patients with -174 G/G IL-6 genotype and elevated plasma IL-6 levels.


Assuntos
Hepacivirus/fisiologia , Hepatite C/sangue , Interleucina-6/sangue , Interleucina-6/genética , Leucócitos Mononucleares/metabolismo , Transplante de Fígado/efeitos adversos , Polimorfismo de Nucleotídeo Único , Feminino , Hepatite C/cirurgia , Hepatite C/virologia , Humanos , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Recidiva , Transplantados
19.
Transplantation ; 104(7): 1305-1307, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32568998
20.
Transplant Proc ; 52(5): 1354-1359, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32507486

RESUMO

OBJECTIVE: The objective of this study is to analyze the liver transplant complications in a reference transplant hospital in southern Brazil. METHODS: The researchers used a cross-sectional, quantitative, exploratory, and descriptive study, conducted using 103 medical records of patients who underwent liver transplantation from 2011 to 2018. Data were analyzed through median, mean, and standard deviation, and the Kruskal-Wallis test was used. RESULTS: There was a higher proportion of men (70.9%), with a mean age of 53.3 years, who had hepatitis C (43.7%). The indication for the procedure was hepatocellular carcinoma (34%). The most frequent complications included pulmonary (26.7%), graft-related complications such as rejection (21.1%), and viral infections (14.4%). In addition, infectious complications, such as pneumonia (45%) and septicemia (29%), occurred. The main causes of death were septic shock (15.6%) and multiple organ failure (21.9%). There was statistical significance between the recipient's age and the Model for End-Stage Liver Disease value at the time of transplantation for the development of complications. CONCLUSIONS: The data from the present study provide important information about liver transplant. These data may enable the team to propose strategies for practice improvements, which will certainly offer better living conditions and transplant survival.


Assuntos
Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Brasil , Estudos Transversais , Feminino , Hospitais de Ensino , Humanos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade
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