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1.
Transpl Int ; 34(5): 844-854, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33606319

RESUMO

Paradoxically, higher serum levels of osteoprotegerin (OPG: a vascular calcification inhibitor) have been associated with increased arterial stiffness, risk of cardiovascular disease and all-cause mortality. A few studies reported that post-transplant OPG levels are associated with mortality in kidney transplant (KT) recipients. In this study, this association was assessed in a cohort of prevalent KT recipients, adjusting for previously untested potential confounders, including fibroblast growth factor 23 (FGF23) and interleukin 6 (IL-6). Socio-demographic and clinical parameters, medical and transplant history, and laboratory data were collected from 982 prevalent KT recipients. The association between serum OPG and all-cause mortality over a 6-year follow-up period was examined using Kaplan-Meier survival curves and multivariable-adjusted Cox regression models. Participants with high serum OPG were more likely female, older, deceased donor KT recipients and have more comorbidity, lower eGFR, higher FGF23, higher IL-6, and longer dialysis vintage. Each 1 pmol/l higher serum OPG level was associated with a 49% higher risk of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.49 [1.40-1.61]). This association persisted after adjusting for confounders (HR [95% CI]: 1.20 [1.10-1.30]). In conclusion, serum OPG was associated with all-cause mortality independent of several novel confounders in prevalent KT recipients.


Assuntos
Transplante de Rim , Osteoprotegerina , Biomarcadores/sangue , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Transplante de Rim/mortalidade , Masculino , Osteoprotegerina/sangue , Estudos Prospectivos , Fatores de Risco , Transplantados
2.
Transpl Int ; 33(2): 161-173, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31536654

RESUMO

The objectives of this study were to assess long-term graft survival, patient survival, renal function, and acute rejections in de novo kidney transplant recipients, treated with once-daily prolonged-release tacrolimus-based therapy. The study was a 5-year non-interventional prospective follow-up of patients from the ADHERE study, a Phase IV 12-month open-label assessment of patients randomized to receive prolonged-release tacrolimus in combination with mycophenolate mofetil (MMF) (Arm 1) or sirolimus (Arm 2). From 838 patients in the randomized study, 587 were included in the long-term follow-up, of whom 510 completed the study at year 5. At 1 year post-transplant, graft and patient survival rates were 93.0% and 97.8%, respectively, and at 5 years were 84.0% and 90.8%, respectively. Cox proportional hazards analysis showed no association between graft loss, initial randomized treatment arm, donor age, donor type, or sex. The 5-year acute rejection-free survival rate was 77.4%, and biopsy-confirmed acute rejection-free survival rate was 86.0%. Renal function remained stable over the follow-up period: mean ± SD eGFR 4-variable modification diet in renal disease formula (MDRD4) was 52.3 ± 21.6 ml/min/1.73 m2 at 6 months and 52.5 ± 23.0 ml/min/1.73 m2 at 5 years post-transplant. These findings support the role of long-term once-daily prolonged-release tacrolimus-based immunosuppression, in combination with sirolimus or MMF, for renal transplant recipients in routine clinical practice.


Assuntos
Imunossupressores/uso terapêutico , Transplante de Rim , Tacrolimo/uso terapêutico , Preparações de Ação Retardada/uso terapêutico , Seguimentos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Sirolimo/uso terapêutico
3.
J Ren Nutr ; 29(3): 188-195, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30819599

RESUMO

OBJECTIVE(S): Prealbumin, a transport protein mostly synthesized in the liver, is a marker of nutrition. Although decreased prealbumin levels are associated with increased mortality in end-stage kidney disease patients, its association with mortality in kidney transplant recipients remains unknown. We evaluated the association between prealbumin levels and outcomes in kidney transplant recipients. DESIGN: This was a prospective prevalent cohort study. This study included 991 kidney transplant recipients enrolled from December 31, 2006, to December 31, 2007, and followed over a 6-year period. Sociodemographic, past medical history, clinical, and laboratory data were collected at the study entry. Associations between prealbumin levels and death with functioning graft, all-cause mortality, and graft loss were examined using survival models. RESULTS: Serum prealbumin levels showed significant negative correlation with estimated glomerular filtration rate (R = -0.28; P < .001) and high-sensitive C-reactive protein (R = -0.24; P < .001). Each 5 mg/dL lower serum prealbumin level was associated with 20% higher risk of death with functioning graft (subdistribution hazard ratio [95% confidence interval]: 1.20 [1.08-1.35]; P = .001), which persisted after multivariable adjustments (subdistribution hazard ratio [95% confidence interval]: 1.13 [1.00-1.28]; P = .039). Qualitatively similar trend was observed in all-cause mortality; however, there was no association between prealbumin levels and graft loss. CONCLUSION(S): Lower serum prealbumin level is associated with increased risk of death with functioning graft in prevalent kidney transplant recipients.


Assuntos
Sobrevivência de Enxerto/fisiologia , Transplante de Rim , Pré-Albumina/análise , Adulto , Idoso , Proteína C-Reativa/análise , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/epidemiologia , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
4.
Transpl Int ; 31(5): 554-565, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29405487

RESUMO

History of psychosis or mania, if uncontrolled, both represent relative contraindications for kidney transplantation. We examined 3680 US veterans who underwent kidney transplantation. The diagnosis of history of psychosis/mania was based on a validated algorithm. Measured confounders were used to create a propensity score-matched cohort (n = 442). Associations between pretransplantation psychosis/mania and death with functioning graft, all-cause death, graft loss, and rejection were examined in survival models and logistic regression models. Post-transplant medication nonadherence was assessed using proportion of days covered (PDC) for tacrolimus and mycophenolic acid in both groups. The mean ± SD age of the cohort at baseline was 61 ± 11 years, 92% were male, and 66% and 27% of patients were white and African-American, respectively. Compared to patients without history of psychosis/mania, patients with a history of psychosis/mania had similar risk of death with functioning graft [subhazard ratio (SHR) (95% confidence interval (CI)): 0.94(0.42-2.09)], all-cause death [hazard ratio (95% CI): 1.04 (0.51-2.14)], graft loss [SHR (95% CI): 1.07 (0.45-2.57)], and rejection [odds ratio(95% CI): 1.23(0.60-2.53)]. Moreover, there was no difference in immunosuppressive drug PDC in patients with and without history of psychosis/mania (PDC: 76 ± 21% vs. 78 ± 19%, P = 0.529 for tacrolimus; PDC: 78 ± 17% vs. 79 ± 18%, P = 0.666 for mycophenolic acid). After careful selection, pretransplantation psychosis/mania is not associated with adverse outcomes in kidney transplant recipients.


Assuntos
Transtorno Bipolar/tratamento farmacológico , Transplante de Rim/mortalidade , Transtornos Psicóticos/tratamento farmacológico , Idoso , Transtorno Bipolar/complicações , Causas de Morte , Feminino , Rejeição de Enxerto/etiologia , Humanos , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Transtornos Psicóticos/complicações , Estudos Retrospectivos
5.
Orv Hetil ; 159(46): 1882-1890, 2018 11.
Artigo em Húngaro | MEDLINE | ID: mdl-30450928

RESUMO

Machine perfusion of marginal grafts might be a possible solution to organ shortage and a promising tool for reducing waiting list morbidity and mortality. In recent years, optimizing the circumstances of organ preservation prior to implantation via machine perfusion has become a hot topic of research. Machine perfusion offers a platform for organ reconditioning, assessment of cell viability and function, pharmacological preconditioning, prolongation of preservation time (ischemia time) and finally reducing graft injury. The objective of the new technology is to increase the pool of transplantable organs safely. Multicentric prospective studies have been evaluating the short and long term outcomes of different methods, however, several questions still remain unanswered. This review summarizes the recent advances in the field of machine perfusion, focusing on preclinical and clinical results. Machine perfusion seems to be a new milestone in the modern era of solid organ transplantation. Orv Hetil. 2018; 159(46): 1882-1890.


Assuntos
Transplante de Órgãos/métodos , Transplante de Órgãos/tendências , Perfusão/métodos , Perfusão/tendências , Transplante de Coração/métodos , Transplante de Coração/tendências , Humanos , Transplante de Rim/métodos , Transplante de Rim/tendências , Transplante de Fígado/métodos , Transplante de Fígado/tendências , Transplante de Pulmão/métodos , Transplante de Pulmão/tendências , Preservação de Órgãos , Transplante de Pâncreas/métodos , Transplante de Pâncreas/tendências
6.
Magy Onkol ; 62(1): 37-44, 2018 Mar 23.
Artigo em Húngaro | MEDLINE | ID: mdl-29570185

RESUMO

More than 9000 laparoscopic liver resections (LLR) are performed worldwide for benign lesions, malignancy (mainly for hepatocellular carcinoma and colorectal cancer liver metastasis), and living donor hepatectomy. Although there is no absolute size criterion, smaller, peripheral lesions (<5 cm) of the anteriolateral segments, that lie far from major vessels and anticipated transection planes are most amenable to LLR, but nowadays lesions of the less ideal posterosuperior segments are feasible for LLR too. Centers with extensive experience in hepatobiliary surgery and laparoscopy have performed laparoscopic major hepatic resections with satisfactory outcomes. Patient benefits from LLR include less intraoperative blood loss, less postoperative pain and painkiller requirement, early mobilization and shorter length of hospital stay, with comparable postoperative morbidity and mortality to open liver resection. Comparison studies between open resection and LLR have revealed no differences in width of resection margins or overall survival after resection for hepatocellular cancer or colorectal cancer liver metastases. Other advantages of LLR for HCC are avoidance of collateral vessel ligation, decreased postoperative hepatic insufficiency and fewer postoperative adhesions, all of them facilitates a possible subsequent liver transplantation.


Assuntos
Laparoscopia , Neoplasias Hepáticas/cirurgia , Fígado/cirurgia , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/cirurgia , Neoplasias Colorretais/complicações , Neoplasias Colorretais/cirurgia , Humanos , Tempo de Internação , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/secundário , Complicações Pós-Operatórias/prevenção & controle
7.
Magy Onkol ; 62(1): 26-28, 2018 Mar 23.
Artigo em Húngaro | MEDLINE | ID: mdl-29570183

RESUMO

The indications for liver transplantation have become generally accepted over the last decades. However, in the last ten years, this indication area changes, it seems to be enlarged. Increasingly, previously classified as contraindications have become indications like cholangiocarcinoma or colorectal cancer liver metastases in selected cases. We have reviewed the old and new oncologic indications, whose survival rates do not differ from liver transplants due to other indications.


Assuntos
Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Neoplasias Hepáticas/secundário , Metástase Neoplásica/terapia , Resultado do Tratamento
8.
Magy Onkol ; 62(1): 29-36, 2018 Mar 23.
Artigo em Húngaro | MEDLINE | ID: mdl-29570184

RESUMO

Surgical treatment of liver metastases, under certain conditions, can be a step of a multidisciplinary treatment strategy for advanced malignant disease. Nevertheless, it is not the same if metachronous or synchronous metastases are planned to be treated. Indications for surgery are the most clearly defined and accepted in cases of colorectal and neuroendocrine liver metastases. At the same time, the steps of the traditional oncotherapy has changed in the management of synchronous colorectal metastases: the novel concept of the treatment strategy is removing the liver metastases before the colorectal primary. The role of surgery is less clear and defined in the management of metastases from other, non-colorectal and non-neuroendocrine primaries. The main purpose is to evaluate which kind of criteria should be fulfilled to indicate the resection of liver metastases, which are the conditions that, when present, may provide a benefit to a patient from surgery, improving survival. These criteria have not been clarified precisely yet; randomized prospective trials are needed. Consensus recommendations in such cases could be determined based on the results of the mentioned trials.


Assuntos
Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Neoplasias Hepáticas/patologia
9.
J Ren Nutr ; 27(1): 53-61, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27666945

RESUMO

OBJECTIVE: Leptin is a hormone made by adipocytes and associated with hypertension, inflammation, and coronary artery disease. Low serum leptin level was associated with higher risk of death in patients with advanced chronic kidney disease. Little is known about the association of serum leptin with outcomes in kidney transplant recipients. DESIGN: Prospective prevalent cohort. SETTING AND SUBJECT: We collected sociodemographic and clinical parameters, medical and transplant history, and laboratory data of 979 prevalent kidney transplant recipients. Associations between serum leptin level and death with a functioning graft, all-cause death, and death-censored graft loss over a 6-year follow-up period were examined in survival models. RESULTS: Serum leptin levels showed moderate negative correlation with eGFR (R = -0.21, P < .001) and positive correlations with BMI (R = 0.48, P < .001) and C-reactive protein (R = 0.20, P < .001). Each 10 ng/mL higher serum leptin level was associated with 7% lower risk of death with functioning graft (hazard ratio [HR] (95% confidence interval [CI]), 0.93 (0.87-0.99)), and this association persisted after adjustment for confounders: HR (95% CI), 0.90 (0.82-0.99). Similar associations were found with all-cause death as outcome. The association between serum leptin level and risk of graft loss was nonlinear, and only low serum leptin level was associated with higher risk of graft loss. CONCLUSIONS: In prevalent kidney transplant recipients, lower serum leptin was an independent predictor of death.


Assuntos
Inflamação/sangue , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Transplante de Rim/efeitos adversos , Leptina/sangue , Adulto , Idoso , Índice de Massa Corporal , Proteína C-Reativa/análise , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores Socioeconômicos , Resultado do Tratamento
10.
Transpl Int ; 29(3): 352-61, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26639524

RESUMO

Resistin is an adipocytokine that is associated with inflammation, coronary artery disease, and other types of cardiovascular disease among patients with normal kidney function. However, little is known about the association of resistin with outcomes in kidney transplant recipients. We collected socio-demographic and clinical parameters, medical and transplant history, and laboratory data from 988 prevalent kidney transplant recipients enrolled in the Malnutrition-Inflammation in Transplant-Hungary Study (MINIT-HU study). Serum resistin levels were measured at baseline. Associations between serum resistin level and death with a functioning graft over a 6-year follow-up period were examined in unadjusted and adjusted models. The mean±SD age of the study population was 51 ± 13 years, among whom 57% were men and 21% were diabetics. Median serum resistin concentrations were significantly higher in patients who died with a functioning graft as compared to those who did not die during the follow-up period (median [IQR]: 22[15-26] vs. 19[14-22] ng/ml, respectively; P < 0.001). Higher serum resistin level was associated with higher mortality risk in both unadjusted and fully adjusted models: HRs (95% CI): 1.33(1.16-1.54) and 1.21(1.01-1.46), respectively. In prevalent kidney transplant recipients, serum resistin was an independent predictor of death with a functioning graft.


Assuntos
Transplante de Rim/mortalidade , Resistina/sangue , Adulto , Proteína C-Reativa/metabolismo , Estudos de Coortes , Feminino , Sobrevivência de Enxerto , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade
11.
J Ren Nutr ; 26(5): 325-33, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27038807

RESUMO

OBJECTIVE: Increased abdominal circumference is a marker of obesity, and it is associated with increased mortality in renal transplant recipients. Recent findings suggest that increased visceral fat deposition is a modifier of inflammation. However, little is known about the association of inflammation with abdominal circumference in kidney transplant recipients. DESIGN: Cross-sectional. SUBJECT: We collected sociodemographic and clinical parameters, medical and transplant history, and laboratory data from 985 prevalent kidney transplant recipients. Abdominal circumference, body mass index (BMI), and inflammatory markers were measured at baseline. Associations of inflammatory markers with abdominal circumference and BMI were examined in unadjusted and adjusted regression models. RESULTS: Mean ± standard deviation age was a 51 ± 13 years, 57% were men, and 21% were diabetics. Patients with abdominal circumference above the median had higher BMI and were older (mean ± standard deviation: 23.9 ± 3.6 vs. 30.1 ± 3.9 kg/m(2), P < .001; and 48 ± 14 vs. 54 ± 11 years, P < .001). Furthermore, patients with higher abdominal circumference had higher inflammatory parameters: median (interquartile range) C-reactive protein (mg/L): 2.3 (3.9) versus 4.1 (6.2), P < .001; and IL-6 (pg/mL): 1.9 (2.2) versus 2.3 (2.4), P < .001. In multivariable-adjusted linear regression models, higher abdominal circumference showed significant linear associations with inflammatory markers (standardized regression coefficients (ß) of abdominal circumference for lnCRP: ßabdominal circumference = 0.29, P < .001; and for lnIL-6: ßabdominal circumference = 0.09, P = .018). Moreover, in multivariable-adjusted linear regression models, higher BMI showed significant linear associations with inflammatory markers (standardized regression coefficients (ß) of BMI for lnCRP: ßBMI = 0.24, P < .001; and for white blood cells: ßBMI = 0.07, P = .041). CONCLUSIONS: Abdominal circumference and BMI are independently associated with inflammatory markers in prevalent kidney transplant recipients.


Assuntos
Índice de Massa Corporal , Inflamação , Transplante de Rim , Circunferência da Cintura , Adulto , Idoso , Biomarcadores/sangue , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
12.
Gut ; 64(5): 791-9, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25134788

RESUMO

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is closely linked to obesity and constitutes part of the metabolic syndrome, which have been associated with low serum vitamin D (VD). Due to known crosstalk between VD and transforming growth factor (TGF)-ß signalling, VD has been proposed as an antifibrotic treatment. DESIGN: We evaluated the association between VD, the vitamin D receptor (VDR) and liver fibrosis in primary human hepatic stellate cells (phHSC) and 106 morbidly obese patients with NAFLD. RESULTS: Treating phHSC with VD ameliorated TGF-ß-induced fibrogenesis via both VDR-dependent and VDR-independent mechanisms. Reduction of fibrogenic response was abolished in cells homozygous for GG at the A1012G single nucleotide polymorphisms within the VDR gene. Compared with healthy livers, NAFLD livers expressed higher levels of VDR mRNA and VDR fragments. VDR mRNA was lower in patients homozygous for GG at A1012G and expression of pro-fibrogenic genes was higher in patients carrying the G allele. CONCLUSIONS: VD may be an antifibrotic treatment option early in the onset of fibrosis in specific genotypes for VDR. Known polymorphisms of the VDR may influence the response to VD treatment.


Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de Calcitriol/fisiologia , Fator de Crescimento Transformador beta/antagonistas & inibidores , Vitamina D/farmacologia , Adulto , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Feminino , Regulação da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes/métodos , Células Estreladas do Fígado/fisiologia , Humanos , Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade Mórbida/complicações , Obesidade Mórbida/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/genética , Receptores de Calcitriol/genética , Receptores de Calcitriol/metabolismo , Transdução de Sinais/fisiologia , Proteína Smad2/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Fator de Crescimento Transformador beta/fisiologia , Vitamina D/sangue , Adulto Jovem
13.
Liver Int ; 35(6): 1756-63, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25522767

RESUMO

BACKGROUND & AIMS: Cardiac arrest (CA) in deceased organ donors can potentially be associated with ischaemic organ injury, resulting in allograft dysfunction after liver transplantation (LT). The aim of this study was to analyse the influence of cardiac arrest in liver donors. METHODS: We evaluated 884 consecutive adult patients undergoing LT at our Institution from September 2003 to December 2011. Uni- and multivariable analyses was performed to identify predictive factors of outcome and survival for organs from donors with (CA donor) and without (no CA donor) a history of cardiac arrest. RESULTS: We identified 77 (8.7%) CA donors. Median resuscitation time was 16.5 (1-150) minutes. Allografts from CA donors had prolonged CIT (p = 0.016), were obtained from younger individuals (p < 0.001), and had higher terminal preprocurement AST and ALT (p < 0.001) than those of no CA donors. 3-month, 1-year and 5-year survival for recipients of CA donor grafts was 79%, 76% and 57% and 72.1%, 65.1% and 53% for no CA donor grafts (log rank p = 0.435). Peak AST after LT was significantly lower in CA donor organs than in no CA donor ones (886U/l vs 1321U/l; p = 0.031). Multivariable analysis identified CIT as a risk factor for both patient and graft survival in CA donors. CONCLUSION: This analysis represents the largest cohort of liver donors with a history of cardiac arrest. Reasonable selection of these donors constitutes a safe approach to the expansion of the donor pool. Rapid allocation and implantation with diminution of CIT may further improve the outcomes of livers from CA donors.


Assuntos
Sobrevivência de Enxerto , Parada Cardíaca/fisiopatologia , Transplante de Fígado/métodos , Doadores de Tecidos/classificação , Coleta de Tecidos e Órgãos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Morte Encefálica , Criança , Pré-Escolar , Isquemia Fria , Seleção do Doador , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Transplantados , Resultado do Tratamento , Isquemia Quente , Adulto Jovem
14.
Liver Int ; 35(1): 156-63, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24351095

RESUMO

BACKGROUND & AIMS: Poor initial graft function was recently newly defined as early allograft dysfunction (EAD) [Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010; 16: 943]. Aim of this analysis was to evaluate predictive donor information for development of EAD. METHODS: Six hundred and seventy-eight consecutive adult patients (mean age 51.6 years; 60.3% men) who received a primary liver transplantation (LT) (09/2003-12/2011) were included. Standard donor data were correlated with EAD and outcome by univariable/multivariable logistic regression and Cox proportional hazards to identify prognostic donor factors after adjustment for recipient confounders. Estimates of relevant factors were utilized for construction of a new continuous risk index to develop EAD. RESULTS: 38.7% patients developed EAD. 30-day survival of grafts with and without EAD was 59.8% and 89.7% (P < 0.0001). 30-day survival of patients with and without EAD was 68.5% and 93.1% (P < 0.0001) respectively. Donor body mass index (P = 0.0112), gGT (P = 0.0471), macrosteatosis (P = 0.0006) and cold ischaemia time (CIT) (P = 0.0031) were predictors of EAD. Internal cross validation showed a high predictive value (c-index = 0.622). CONCLUSIONS: Early allograft dysfunction correlates with early results of LT and can be predicted by donor data only. The newly introduced risk index potentially optimizes individual decisions to accept/decline high risk organs. Outcome of these organs might be improved by shortening CIT.


Assuntos
Aloenxertos/fisiopatologia , Transplante de Fígado/efeitos adversos , Escores de Disfunção Orgânica , Doadores de Tecidos/estatística & dados numéricos , Adulto , Fatores Etários , Bilirrubina/sangue , Índice de Massa Corporal , Feminino , Humanos , Estimativa de Kaplan-Meier , Transplante de Fígado/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Risco , Fatores Sexuais
15.
Liver Int ; 35(11): 2448-57, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25818805

RESUMO

BACKGROUND & AIMS: Cholangiocarcinomas (CCA) paradoxically express the death ligand TRAIL and thus, are dependent on effective survival signals to circumvent apoptosis. Hedgehog signalling exerts major survival signals in CCA by regulating serine/threonine kinase polo-like kinase (PLK)2. We here aimed to examine the role of PLK1/2/3 expression for CCA tumour biology. METHODS: We employed CCA samples from 73 patients and human HUCCT-1/Mz-CHA1/KMCH-1 CCA cells. Immunohistochemistry for PLK1/2/3 was performed using tissue microarrays from representative tumour areas. RESULTS: PLK1/2/3-immunoreactive cancer cells were present in most of the CCA samples. However, only PLK1 and especially PLK3 were expressed in higher amounts within CCA cells as compared to normal liver. Given that fibroblast growth factor (FGF) can induce PLK3 expression and also is present in CCA, we examined the effect of FGF on PLK3 in vitro. Indeed, rhFGF rapidly increased PLK3 mRNA expression all three CCA cell lines giving an explanation for the abundant PLK3 presence in the tissue samples. Clinicopathologically, PLK3 expression was associated with decreased tumour cell migration and lymph/blood vessel infiltration whereas higher levels of PLK1 were correlated with larger tumour sizes. Moreover, strong PLK3 expression was associated with prolonged overall survival. CONCLUSIONS: The results suggest that PLK3 predominantly is expressed in CCA cells and that high PLK3 expression correlates with prolonged overall survival. These observations might have implications for prognosis prediction of human CCA as well as the potential therapeutic use of polo-like kinase inhibitors (i.e., PLK1/2 specifity).


Assuntos
Apoptose/genética , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/mortalidade , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Idoso , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Supressoras de Tumor
16.
Nephrol Dial Transplant ; 30(11): 1825-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25473123

RESUMO

Transplant glomerulopathy (TG) is generally accepted to result from repeated episodes of endothelial activation, injury and repair, leading to pathological abnormalities of double contouring or multi-layering of the glomerular basement membrane. TG is a major sequel of chronic active antibody-mediated rejection (cABMR), from pre-existing or de novo anti-HLA antibodies. Hepatitis C infection, thrombotic microangiopathy or other factors may also contribute to TG development. TG prevalence is 5-20% in most series, reaching 55%, in some high-risk cohorts, and is associated with worse allograft outcomes. Despite its prevalence and clinical significance, few well-studied treatment options have been proposed. Similar to desensitization protocols, plasmapheresis with or without immunoabsorption, high-dose intravenous immunoglobulin, rituximab, bortezomib and eculizumab have been proposed in the treatment of TG due to cABMR individually or in various combinations. Robust clinical trials are urgently needed to address this major cause of allograft loss. This review summarizes the current knowledge of the epidemiology, etiology, pathology, and the preventive and treatment options for TG secondary to cABMR.


Assuntos
Glomerulonefrite/etiologia , Rejeição de Enxerto/etiologia , Isoanticorpos/efeitos adversos , Glomérulos Renais/patologia , Transplante de Rim/efeitos adversos , Glomerulonefrite/metabolismo , Humanos , Nefropatias/cirurgia
17.
Transpl Int ; 28(10): 1216-26, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26152659

RESUMO

The purpose of our study was to investigate the anatomical variations of the extrahepatic arterial structures of the liver with particular attention to rare variations and their potential impact on liver surgery. A total of 50 human abdominal organ complexes were used to prepare corrosion casts. A multicomponent resin mixture was injected into the abdominal aorta. The portal vein was injected with a different colored resin in 16 cases. Digestion of soft tissues was achieved using cc. KOH solution at 60-65 °C. Extrahepatic arterial variations were classified according to Michels. All specimens underwent 3D volumetric CT reconstruction. Normal anatomy was seen in 42% of cases, and variants were seen in the other 58%. No Michels type VI or X variations were present; however, in 18% of cases the extrahepatic arterial anatomy did not fit into Michels' classification. We report four new extrahepatic arterial variations. In contrast to the available data, normal anatomy was found much less frequently, whereas the prevalence of unclassified arterial variations was higher. We detected four previously unknown variations. Our data may contribute to the reduction of complications during surgical and radiological interventions in the upper abdomen.


Assuntos
Artérias/anormalidades , Fígado/irrigação sanguínea , Angiografia , Aorta Abdominal/anatomia & histologia , Classificação , Anormalidades Congênitas/epidemiologia , Molde por Corrosão , Artéria Hepática/anormalidades , Artéria Hepática/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Fígado/cirurgia , Artéria Mesentérica Superior/anormalidades , Artéria Mesentérica Superior/diagnóstico por imagem , Veia Porta/anatomia & histologia , Prevalência , Tomografia Computadorizada por Raios X
18.
Orv Hetil ; 156(34): 1366-82, 2015 Aug 23.
Artigo em Húngaro | MEDLINE | ID: mdl-26278482

RESUMO

INTRODUCTION: The authors reviewed the prevalence of postoperative infections, the results of bacterium cultures, and the incidence of multidrug resistance in their liver transplanted patients during a period between 2003 and 2012. AIM: The aim of this study was to analyse risk factors and colonisations of bacterial infections. METHOD: The files of 408 patients (281 bacterium cultures) were reviewed. RESULTS: Of the 408 patients 70 had a postoperative infection (17%); 58 patients (14.2%) had positive and 12 patients (2.9%) negative bacterial culture results. Cholangitis was found in 7 cases (12.1%), abdominal infection in 17 cases (29.3%), and pulmonary infection in 28 cases (48.3%). Postoperative infection was more frequent in patients with initial poor graft function, acute renal insufficiency, biliary complication, and in those with intraabdominal bleeding. The 1-, 3- and 5-year cumulative survival of patients who had infection was 70%, 56% and 56%, respectively, whereas the cumulative survival data of patients without infection was 94%, 87% and 85%, respectively (p<0.001). Multidrug resistance was found in 56% of the positive cultures, however, the one-year survival was not different in patients who had multidrug resistance positive and negative bacterial infection (both 70.2%). CONCLUSIONS: Infection control must target the management of multidrug resistance microbes through encouraging prevention, hygienic, and isolation rules, improving the operative, transfusion, and antimicrobial policy in a teamwork setting.


Assuntos
Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana Múltipla , Controle de Infecções/métodos , Transplante de Fígado , Adulto , Idoso , Infecções Bacterianas/etiologia , Infecções Bacterianas/mortalidade , Transfusão de Sangue/normas , Colangite/complicações , Colangite/epidemiologia , Feminino , Trato Gastrointestinal/microbiologia , Sobrevivência de Enxerto , Humanos , Hungria/epidemiologia , Incidência , Transplante de Fígado/efeitos adversos , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Pneumonia/complicações , Pneumonia/microbiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida
19.
Transpl Int ; 27(12): 1285-93, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25082387

RESUMO

Perioperative liver graft injury is associated with elevation of aminotransferases after orthotopic liver transplantation (OLT). Values above 5000 U/l usually are regarded as extreme liver graft injury (ELGI). Some patients and organs recover from this critical condition. The aim of the study was to evaluate factors contributing to graft and patient survival after ELGI. From chart review we identified 64 of 917 OLT adult patients (median age 54.2 years; 68.8% males) transplanted between 11/2003 and 02/2012, who presented ELGI after OLT. Donor and recipient factors were analyzed and correlated with the outcome by univariable and multivariable methods. Multivariable cox proportional hazards showed that recipient's BMI (P = 0.01), model for end stage liver disease (MELD) score before OLT (P = 0.02) and laboratory MELD score 24 h after OLT (P = 0.01) were independently associated with patient survival. 30-days and 12-months survival in patients with a postoperative laboratory MELD higher than 31 was 21.4%, while patients with a postoperative laboratory MELD lower than 31 displayed 30-days and 12-months survival rates of 80% and 71.8%, respectively (P < 0.001). Retransplantation in the setting of ELGI after OLT should be based on all available data. Utilization of the postoperative labMELD enables the transplant physician within 24 h after transplantation to identify necessity of retransplantation objectively.


Assuntos
Aspartato Aminotransferases/sangue , Transplante de Fígado/estatística & dados numéricos , Complicações Pós-Operatórias/sangue , Índice de Gravidade de Doença , Adulto , Idoso , Alanina Transaminase/sangue , Aloenxertos , Doença Hepática Terminal/sangue , Feminino , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Modelos de Riscos Proporcionais , Reoperação , Resultado do Tratamento , Adulto Jovem
20.
Semin Dial ; 26(6): 667-74, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24016076

RESUMO

In the last decade, the number of patients starting dialysis after a failed kidney transplant has increased substantially. These patients appear to be different from their transplant-naïve counterparts, and so may be the timing of dialysis therapy initiation. An increasing number of studies suggest that in transplant-naïve patients, later dialysis initiation is associated with better outcomes. Very few data are available on timing of dialysis reinitiation in failed transplant recipients, and they suggest that an earlier return to dialysis therapy tended to be associated with worse survival, especially among healthier and younger patients and women. Failed transplant patients may also have unique issues such as continuation of immunosuppression versus withdrawal or the need for remnant allograft nephrectomy with regard to dialysis reinitiation. These patients may have a different predialysis preparation work-up, worse blood pressure control, higher or lower serum phosphorus levels, lower serum bicarbonate concentration, and worse anemia management. The choice of dialysis modality may also represent an important question for these patients, even though there appears to be no difference in mortality between patients starting peritoneal versus hemodialysis. Finally, failed transplant patients returning to dialysis appear to have a higher mortality rate compared with transplant-naïve incident dialysis patients, especially in the first several months of dialysis therapy. In this review, we will summarize the available data related to the timing of dialysis initiation and outcomes in failed kidney transplant patients after returning to dialysis.


Assuntos
Falência Renal Crônica/terapia , Transplante de Rim , Diálise Renal , Taxa de Filtração Glomerular , Humanos , Terapia de Imunossupressão , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Nefrectomia , Seleção de Pacientes , Fatores de Risco , Fatores de Tempo , Falha de Tratamento
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