Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 35
Filtrar
1.
Nat Commun ; 14(1): 4643, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37607932

RESUMO

Recent temperature extremes have shattered previously observed records, reaching intensities that were inconceivable before the events. Could the possibility of an event with such unprecedented intensity as the 2021 Pacific Northwest heatwave have been foreseen, based on climate model information available before the event? Could the scientific community have quantified its potential intensity based on the current generation of climate models? Here, we demonstrate how an ensemble boosting approach can be used to generate physically plausible storylines of a heatwave hotter than observed in the Pacific Northwest. We also show that heatwaves of much greater intensities than ever observed are possible in other locations like the Greater Chicago and Paris regions. In order to establish confidence in storylines of 'black swan'-type events, different lines of evidence need to be combined along with process understanding to make this information robust and actionable for stakeholders.

2.
Transplant Proc ; 49(9): 2040-2049, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29149958

RESUMO

BACKGROUND: Two large, prospective studies (12-03; OSAKA) compared the efficacy and tolerability of prolonged-release versus immediate-release tacrolimus in kidney transplant patients also receiving mycophenolate mofetil and low-dose corticosteroids (without induction therapy). METHODS: Data were combined into one database to compare results over 24 weeks using 3 alternative endpoints: biopsy-confirmed acute rejection (BCAR); the Food and Drug Administration composite endpoint (graft loss, BCAR, and loss to follow-up), and the European Medicines Agency composite endpoint (graft loss, BCAR, and graft dysfunction). The 95% confidence intervals were calculated (10% noninferiority margin). RESULTS: Overall, 633 patients received prolonged-release tacrolimus (12-03, n = 331; OSAKA, n = 302) and 645 received immediate-release tacrolimus (n = 336; n = 309). Baseline characteristics were comparable. Proportionately more patients receiving prolonged-release tacrolimus had trough levels of 5-15 ng/mL on day 1 (60.8%) and 2 (56.6%) versus immediate-release tacrolimus (42.5% and 43.9%, respectively, both P < .001). Efficacy of prolonged-release and immediate-release tacrolimus were similar as assessed by BCAR (13.9% vs 14.1%, respectively), European Medicines Agency composite endpoint (40.3% vs 38.3%) and US Food and Drug Administration composite endpoint (21.5% vs 19.8%). CONCLUSIONS: Novel efficacy endpoints as required by the European Medicines Agency and US Food and Drug Administration demonstrate noninferiority of prolonged-release versus immediate-release tacrolimus. Significantly more patients treated with prolonged-release tacrolimus versus immediate-release tacrolimus achieved trough levels of 5 to 15 ng/mL early after transplantation. ClinicalTrials.govNCT00189839; NCT00717470.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim , Tacrolimo/administração & dosagem , Corticosteroides/administração & dosagem , Adulto , Bases de Dados Factuais , Preparações de Ação Retardada , Quimioterapia Combinada , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Falha de Tratamento
3.
Int J Surg Case Rep ; 39: 140-144, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28841541

RESUMO

INTRODUCTION: The presence of liver cirrhosis goes along with a higher chance for the need of liver resection. As established laboratory parameters often underestimate the degree of cirrhosis this is associated with an increased risk for postoperative liver failure due to the preoperatively impaired liver function. Known liver function tests are unlikely to be performed in daily use because of high cost or expenditure of time. Liver maximum function capacity test (LiMAx) provides a novel tool for measurement of liver function and references for the safety of liver resection. PRESENTATION OF CASE: A 63-year old patient presented at our hospital with a large, solitary liver metastasis from hypopharyngeal cancer in segments VII/VIII with infiltration of the diaphragm. Liver resection was unsuccessful in a peripheral hospital 10 months before due to considerable macroscopic liver cirrhosis (CHILD B). Upon presentation conventional laboratory parameters revealed sufficient liver function. LiMAx was performed and showed regular liver function (354µg/kg/h; at norm >315µg/kg/h). Consequently, atypical liver resection (R0) was performed resulting in a postoperative LiMAx value of 281µg/h/kg (>150µg/kg/h). The patient was discharged from hospital 37days after surgery without any signs of postoperative liver failure. CONCLUSION: The LiMAx-test enables determination of liver function at a so far unavailable level (metabolism via cytochrome P450 1A2) and hence might provide crucial additional diagnostic information to allow for safe liver resection even in cirrhotic patients.

4.
Zentralbl Chir ; 142(2): 180-188, 2017 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-26562501

RESUMO

In cases of chronic renal insufficiency, successful kidney transplantation is the method of choice to restore patients' health, well-being and physical fitness. The interdisciplinary collaboration of nephrologists and transplant surgeons has always been a prerequisite for the successful pre-, peri- and post-transplant care of renal transplant patients. The same holds true for liver transplant patients. Here the nephrologist is often involved in cases requiring pre- or post-transplant dialysis as well as in decision making for combined liver-kidney transplantation. This review focuses on nephrological aspects in patient care before and after kidney and liver transplantation.


Assuntos
Comunicação Interdisciplinar , Colaboração Intersetorial , Transplante de Rim , Transplante de Fígado , Equipe de Assistência ao Paciente , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Humanos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/terapia , Disfunção Primária do Enxerto/diagnóstico , Disfunção Primária do Enxerto/terapia
5.
Biomater Sci ; 4(11): 1562-1573, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27709146

RESUMO

The typical foreign body response (FBR) to synthetic implants is characterized by local inflammation and tissue fibrosis. Silicone implants have been associated with the development of adverse capsular contraction (ACC); a form of excessive FBR to the material that often requires the replacement of the implant. It has been shown that surface roughening of silicone can reduce the prevalence of ACC, but the mechanisms remain poorly understood. Macrophages are key cells in FBR. They exert their control mainly by polarizing into pro-inflammatory (M1) or pro-healing (M2) cells. It is postulated that surface topography can reduce M1 polarization by limiting cell spreading and cytoskeleton organization. To test this hypothesis, we used KrF Excimer laser ablation with half-tone masks to produce convex and concave topographies with controlled surface dimensional parameters. Cells in convex and concave topographies were compared to cells in planar surfaces, with or without chemical polarization. We show that chemical polarization induced specific changes in the cell shape on planar substrates. Macrophage shape and size was different in concave and convex surfaces, but no correlation was found with the cell polarization state. The results highlight that chemical polarization of macrophages is associated with changes in the cell shape; however, topography-induced changes in macrophage shape could not be linked with a shift in macrophage polarization. Thus, the sole manipulation of cell shape does not seem to be the mechanism by which macrophage function could be controlled.


Assuntos
Forma Celular/fisiologia , Macrófagos/citologia , Silicones/química , Polaridade Celular , Humanos , Inflamação , Macrófagos/química , Macrófagos/imunologia , Próteses e Implantes , Cicatrização
6.
Transpl Infect Dis ; 17(3): 406-10, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25704879

RESUMO

Hydatid disease is a systemic disorder affecting especially the liver and lungs. Although it is not endemic in Europe, it can be seen sporadically, particularly because of travel and immigration. Severe, multiple organ involvement is quite rare. A 39-year-old Kurdish male patient presented with the previous diagnosis of hydatid disease and disseminated cysts in the liver, lung, and left kidney, leading to renal failure and the need for hemodialysis. Following multiple operations, complete eradication of infectious cysts was achieved, and kidney transplantation was performed. After 4 years of follow-up, the patient is in good condition, especially with normal renal function and no sign of recurrent hydatid disease.


Assuntos
Equinococose/complicações , Transplante de Rim , Insuficiência Renal/etiologia , Adulto , Animais , Cistos , Equinococose/diagnóstico por imagem , Equinococose/patologia , Equinococose/cirurgia , Humanos , Rim/parasitologia , Rim/cirurgia , Fígado/parasitologia , Fígado/cirurgia , Pulmão/parasitologia , Pulmão/cirurgia , Masculino , Diálise Renal , Insuficiência Renal/cirurgia , Tomografia Computadorizada por Raios X
7.
Am J Transplant ; 15(1): 119-28, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25521535

RESUMO

ZEUS study was an open-label, 12-month, multicenter study in which 300 de novo kidney transplant recipients were randomized to continue receiving cyclosporine (CsA) or convert to everolimus at 4.5 months posttransplant. Five-year follow-up data were available for 245/269 patients (91.1%) who completed the core 12-month study (123 everolimus, 109 CsA). At 5 years, adjusted estimated GFR was 66.2 mL/min/1.73 m(2) with everolimus versus 60.9 mL/min/1.73 m(2) with CsA; the mean difference was 5.3 mL/min/1.73 m(2) in favor of everolimus (95% CI 2.4, 8.3; p < 0.001 [intent-to-treat population]). In a post hoc analysis of patients remaining on study drug at 5 years (everolimus 77, CsA 86), mean difference was 8.2 mL/min/1.73 m(2) (95% CI 4.3, 12.1; p < 0.001) in favor of everolimus. The cumulative incidence of biopsy-proven acute rejection postrandomization was 13.6% with everolimus versus 7.5% with CsA (p = 0.095), largely accounted for by grade I rejection (16/21 patients and 7/11 patients, respectively). Postrandomization, graft loss, mortality, serious adverse events and neoplasms were similar in both arms. In conclusion, conversion of kidney transplant patients to everolimus at 4.5 months posttransplant is associated with a significant improvement in renal function that is maintained to at least 5 years. The increase in early mild acute rejection did not affect long-term graft function.


Assuntos
Ciclosporina/uso terapêutico , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Falência Renal Crônica/cirurgia , Transplante de Rim , Sirolimo/análogos & derivados , Adolescente , Adulto , Idoso , Everolimo , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Falência Renal Crônica/complicações , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Projetos de Pesquisa , Fatores de Risco , Sirolimo/uso terapêutico , Transplantados , Adulto Jovem
8.
Transpl Infect Dis ; 16(6): 958-67, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25393916

RESUMO

BACKGROUND: Hepatitis C is the leading indication for liver transplantation. Differentiation between recurrent graft hepatitis C (RGH-C) and graft rejection (GR) is challenging. Liver biopsy is standard to diagnose both conditions; however, little information is available regarding this procedure in hepatitis C virus (HCV)-infected liver transplant recipients. METHODS: Liver biopsies (n = 211) from all consecutive patients (n = 138) transplanted for hepatitis C at Hannover Medical School between January 2000 and October 2011 were screened, and a final cohort of 96 patients with 196 biopsies was included. Indications, histopathological findings, and biopsy-related complications were documented. Modifications in the treatment based on the biopsy result and the biochemical outcome were analyzed. RESULTS: Most biopsies (196/211, 93%) were representative. Five patients (2.5%) developed non-fatal biopsy-related complications. Biopsy results were GR (35%), RGH-C (31%), and other diagnoses (34%). GR was independently associated with lower albumin (P = 0.025) and higher bilirubin levels (P = 0.011). Treatment was modified based on the biopsy result in 25% of cases. Alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and bilirubin levels improved in 41%, 25%, and 31% of cases 4 weeks post biopsy respectively. ALT improvements were more significant in patients with GR than in those with RGH-C. CONCLUSION: Liver biopsy in HCV-infected liver transplant recipients is safe and representative in >90% of cases. GR is independently associated with lower albumin and higher bilirubin levels.


Assuntos
Hepatite C/complicações , Falência Hepática/etiologia , Falência Hepática/patologia , Transplante de Fígado , Fígado/patologia , Adulto , Idoso , Biópsia/efeitos adversos , Biópsia/métodos , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/patologia , Hepatite C/diagnóstico , Humanos , Falência Hepática/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
9.
Langenbecks Arch Surg ; 399(6): 789-93, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24722781

RESUMO

BACKGROUND: Abdominal complications after thoracic transplantation (Tx) are potentially associated with an increased risk of mortality. We recently reported about the severe outcome after bowel perforation in patients following lung transplantation (LuTx). The aim of the present study was to likewise identify the risk factors with an impact on patient survival following heart transplantation (HTx). METHODS: A retrospective analysis for the frequency and outcome of abdominal interventions following HTx was performed in 342 patients, and these data thereafter compared to a re-evaluated pool of 1,074 patients following LuTx. All patients were transplanted at Hanover Medical School, Germany, between January 2000 and October 2011. RESULTS: The incidence for abdominal surgery was comparable between patients following HTx (n = 33; 9.6 %) and LuTx (n = 90; 8.4 %). Elective operations were more frequently performed in patients after HTx (8.5 vs. 5.1 %). In contrast, the incidence of emergency interventions was higher after LuTx (5.3 %) than that following HTx (2.3 %). Herewith associated was the mortality observed in these transplant recipients (15.3 and 9.9 % for LuTx and HTx, respectively). Leading diagnosis for emergency surgery was bowel perforation (n = 18, regarding all cases). In 11 of these patients, perforation occurred within the first 6 months after Tx and eight of them died in the course of this complication (one patient after HTx and seven patients after LuTx). CONCLUSIONS: Abdominal complications after HTx are less frequently than after LuTx but equally correlate with a high mortality rate. In finding or even reasonable suspicion of an acute abdomen after thoracic Tx, a broad practice for extended diagnostics and a low barrier for an early explorative laparotomy thus are recommended.


Assuntos
Dor Abdominal/epidemiologia , Cardiopatias/cirurgia , Transplante de Coração/efeitos adversos , Perfuração Intestinal/epidemiologia , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Dor Abdominal/diagnóstico , Dor Abdominal/cirurgia , Procedimentos Cirúrgicos Eletivos , Emergências , Feminino , Cardiopatias/mortalidade , Cardiopatias/patologia , Humanos , Perfuração Intestinal/diagnóstico , Perfuração Intestinal/cirurgia , Laparotomia , Pneumopatias/mortalidade , Pneumopatias/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
10.
Am J Transplant ; 14(3): 701-10, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24502384

RESUMO

The feasibility of de novo everolimus without calcineurin inhibitor (CNI) therapy following liver transplantation was assessed in a multicenter, prospective, open-label trial. Liver transplant patients were randomized at 4 weeks to start everolimus and discontinue CNI, or continue their current CNI-based regimen. The primary endpoint was adjusted estimated GFR (eGFR; Cockcroft-Gault) at month 11 post randomization. A 24-month extension phase followed 81/114 (71.1%) of eligible patients to month 35 post randomization. The adjusted mean eGFR benefit from randomization to month 35 was 10.1 mL/min (95% confidence interval [CI] -1.3, 21.5 mL/min, p = 0.082) in favor of CNI-free versus CNI using Cockcroft-Gault, 9.4 mL/min/1.73 m(2) (95% CI -0.4, 18.9, p = 0.053) with Modification of Diet in Renal Disease (four-variable) and 9.5 mL/min/1.73 m(2) (95% CI -1.1, 17.9, p = 0.028) using Nankivell. The difference in favor of the CNI-free regimen increased gradually over time due to a small progressive decline in eGFR in the CNI cohort despite a reduction in CNI exposure. Biopsy-proven acute rejection, graft loss and death were similar between groups. Adverse events led to study drug discontinuation in five CNI-free patients and five CNI patients (12.2% vs. 12.5%, p = 1.000) during the extension phase. Everolimus-based CNI-free immunosuppression is feasible following liver transplantation and patients benefit from sustained preservation of renal function versus patients on CNI for at least 3 years.


Assuntos
Inibidores de Calcineurina , Ciclosporina/administração & dosagem , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/administração & dosagem , Hepatopatias/cirurgia , Transplante de Fígado , Sirolimo/análogos & derivados , Adolescente , Adulto , Idoso , Ciclosporina/efeitos adversos , Everolimo , Estudos de Viabilidade , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sirolimo/administração & dosagem , Fatores de Tempo , Suspensão de Tratamento , Adulto Jovem
11.
J Viral Hepat ; 21(11): 769-79, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24251818

RESUMO

HCV RNA levels correlate with the long-term outcome of hepatitis C in liver transplant recipients. Nucleic acid testing (NAT) is usually used to confirm HCV reinfection and to examine viral loads after liver transplantation. HCV core antigen (HCVcoreAg) testing could be an alternative to NAT with some potential advantages including very low intra- and interassay variabilities and lower costs. The performance of HCVcoreAg testing in organ transplant recipients is unknown. We prospectively studied 1011 sera for HCV RNA and HCVcoreAg in a routine real-world setting including 222 samples obtained from patients after liver or kidney transplantation. HCV RNA and HCVcoreAg test results showed a consistency of 98% with a very good correlation in transplanted patients (r > 0.85). The correlation between HCV RNA and HCVcoreAg was higher in sera with high viral loads and in samples from patients with low biochemical disease. Patients treated with tacrolimus showed a better correlation between both parameters than individuals receiving cyclosporine A. HCV RNA/HCVcoreAg ratios did not differ between transplanted and nontransplanted patients, and HCV RNA and HCVcoreAg kinetics were almost identical during the first days after liver transplantation. HCVcoreAg testing can be used to monitor HCV viral loads in patients after organ transplantation. However, the assay is not recommended to monitor antiviral therapies.


Assuntos
Hepatite C/diagnóstico , Transplantados , Proteínas do Core Viral/sangue , Carga Viral/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imunoensaio/métodos , Transplante de Rim , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Adulto Jovem
12.
Z Gastroenterol ; 51(11): 1269-326, 2013 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-24243572

RESUMO

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Oncologia/normas , Guias de Prática Clínica como Assunto , Alemanha , Humanos
13.
Br J Surg ; 100(7): 926-32, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23640669

RESUMO

BACKGROUND: Following resection of colorectal liver metastases (CLMs) up to 75 per cent of patients develop recurrent liver metastases. Although repeat resection remains the only curative therapy, data evaluating the outcome are deficient. This study analysed postoperative morbidity, mortality and independent predictors of survival following repeat resection of CLMs. METHODS: Data on surgical treatment of primary and recurrent CLMs between 1994 and 2010 were collected retrospectively, and compared with those for single hepatic resections carried out during the same period. Independent predictors of survival were evaluated by means of univariable and multivariable Cox regression models. RESULTS: In this interval 1026 primary resections of CLMs were performed and 94 patients underwent repeat CLM excision. Overall postoperative morbidity and mortality rates were low (15·8 and 1·3 per cent respectively), with no statistical difference in patients undergoing repeat surgery (P = 0·072). Compared with single liver resections, overall survival was improved in repeat resections (P = 0·003). Multivariable analysis revealed that size of primary CLM over 50 mm was an independent predictor of survival (hazard ratio (HR) 2·61; P = 0·008). Only major hepatic resection was associated with poorer outcome following repeat surgery (HR 2·62; P = 0·009). International Union Against Cancer stage, number of CLMs, age at surgery and need for intraoperative transfusion had no impact on survival after repeat resection. CONCLUSION: Recurrent CLM surgery is feasible with similar morbidity and mortality rates to those of initial or single CLM resections.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Transfusão de Sangue/estatística & dados numéricos , Estudos de Viabilidade , Feminino , Hepatectomia/estatística & dados numéricos , Humanos , Neoplasias Hepáticas/secundário , Masculino , Metastasectomia/estatística & dados numéricos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Duração da Cirurgia , Complicações Pós-Operatórias/cirurgia , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
14.
Z Gastroenterol ; 51(3): 296-8, 2013 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-23487359

RESUMO

We report on a 25-year-old female patient who presented with recurrent cholestasis following liver transplantation due to primary sclerosing cholangitis. Abdominal ultrasound and computed tomography showed intrahepatic bile duct dilatation and stenosis of the common hepatic artery with flow acceleration and decreased resistance index. The patient developed a severe secondary sclerosing cholangitis (SSC) with biliary casts - despite interventional stent placement of the common hepatic artery - thus requiring retransplantation. After prolonged intensive care unit treatment the patient was discharged in a good general condition. This case report describes SSC as a rare cause for graft failure. In unclear cholestasis after liver transplantation SSC has to be considered as the underlying cause.


Assuntos
Colangite Esclerosante/diagnóstico , Colangite Esclerosante/etiologia , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/etiologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Radiografia
15.
Am J Transplant ; 12(12): 3425-36, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22994589

RESUMO

Acute cellular rejection (ACR) occurs frequently after liver transplantation and can usually be controlled. Triggering of allospecific immune responses and lack of immunoregulation are currently suggested as a cause of ACR, but there are no investigations of intrahepatic immune responses during ACR. Therefore we prospectively analyzed the intrahepatic T cell infiltration pattern in correlation to the severity of ACR in a cohort of patients with graft hepatitis (n = 151). While CD4(+) cells dominated the portal infiltrates in mild-moderate ACR, CD8(+) cells prevailed in severe ACR. Furthermore portal CD8(+) and not CD4(+) infiltration correlated with serum transaminases and with the likelihood of subsequent ACRs. Surprisingly, the rise of portal effector T cells density during ACR was surpassed by the increase in portal infiltration of regulatory T cells by a factor of two. Thus ACRs rather showed an increase and not a lack of regulation, as was suggested by analysis of peripheral blood mononuclear cells. Despite the pattern of enhanced immunoregulation, patients with severe ACR had a higher risk for subsequent rejections and showed a trend to a reduced survival. Thus, patients with severe rejections might need a modification of their immunosuppression to improve prognosis.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/imunologia , Leucócitos Mononucleares/imunologia , Transplante de Fígado/imunologia , Linfócitos T Reguladores/imunologia , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Transplante Homólogo
16.
Chirurg ; 83(11): 980-8, 2012 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-22810545

RESUMO

INTRODUCTION: Expansion of the donor pool by the use of grafts with extended donor criteria reduces waiting list mortality with an increased risk for graft and patient survival after liver transplantation. The ability of the number of fulfilled extended donor criteria as currently defined by the German Medical Association (BÄK-Score) to predict early outcome is unclear. PATIENTS: A total of 291 consecutive adult liver transplantations (01.01.2007-31.12.2010) in 257 adult recipients were analyzed. METHODS: Primary study endpoints were 30 day mortality, 3 month mortality, 3 month patient and graft survival and the necessity of acute retransplantation within 30 days. For primary study endpoints a ROC curve analysis was performed to calculate sensitivity, specificity and overall model correctness of the BÄK score as a predictive model. Further methods included Kaplan-Meier estimates, log-rank tests, Cox regression analysis, logistic regression analysis and χ(2)-tests. RESULTS: The number of extended donor criteria fulfilled had no statistically significant influence on the primary study endpoints (p > 0.05) or on patient survival (p > 0.05). ROC curve analysis revealed areas under the curve ≤ 0.561 for the prediction of primary study endpoints (overall model correctness < 58%, sensitivity < 52%). CONCLUSIONS: The number of fulfilled extended donor criteria as currently defined by the German Medical Association is unable to predict early outcome after liver transplantation.


Assuntos
Seleção do Doador/tendências , Transplante de Fígado/mortalidade , Programas Nacionais de Saúde/tendências , Sobrevivência de Tecidos , Obtenção de Tecidos e Órgãos/tendências , Idoso , Seguimentos , Alemanha , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/cirurgia , Prognóstico , Reoperação/tendências , Taxa de Sobrevida , Resultado do Tratamento , Listas de Espera/mortalidade
17.
Am J Transplant ; 12(7): 1691-9, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22676355

RESUMO

After transplantation of solid organs or hematopoietic stem cells, a significant acute decrease in renal function occurs in the majority of patients. Depending on the degree of kidney injury, a large number of patients develop chronic kidney disease (CKD) and some develop end-stage renal disease requiring renal replacement therapy. The incidence varies depending on the transplanted organ, but important risk factors for the development of CKD are preexisting renal disease, hepatitis C, diabetes, hypertension, age, sex, posttransplant acute kidney injury and thrombotic microangiopathy. This review article focuses on the risk factors of posttransplant chronic kidney disease after organ transplantation, considering the current literature and integrates the incidence and the associated mortality rates of acute and chronic kidney disease. Furthermore, we introduce the RECAST (REnal Comorbidity After Solid organ and hematopoietic stem cell Transplantation) registry.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Nefropatias/etiologia , Transplante de Órgãos/efeitos adversos , Humanos
18.
Am J Transplant ; 12(6): 1528-40, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22642473

RESUMO

The long-term effect of conversion from calcineurin inhibitor (CNI) therapy to an mTOR inhibitor requires clarification. Following completion of the 12-month, open-label, multicenter ZEUS study, in which 300 kidney transplant recipients were randomized to continue cyclosporine (CsA) or convert to everolimus at 4.5 months posttransplant, outcomes were assessed at month 36 (n = 284; 94.7%). CNI therapy was reintroduced in 28.4% of everolimus patients by month 36. The primary efficacy endpoint, estimated glomerular filtration rate (Nankivell, ANCOVA) was significantly higher with everolimus versus the CsA group at month 24 (7.6 mL/min/1.73 m(2) , 95%CI 4.3, 11.0 mL/min/1.73 m(2) ; p < 0.001) and month 36 (7.5 mL/min/1.73 m(2) , 95%CI 3.6, 11.4 mL/min/1.73 m(2) ; p < 0.001). The incidence of biopsy-proven acute rejection from randomization to month 36 was 13.0% in the everolimus arm and 4.8% in the CsA arm (p = 0.015). Patient and graft survival, as well as incidences of malignancy, severe infections and hospitalization, were similar between groups. Kidney transplant patients who are converted from CsA to everolimus at month 4.5 and who remain on everolimus thereafter may achieve a significant improvement in renal function that is maintained to 3 years. There was a significantly higher rate of rejection in the everolimus arm but this did not exert a deleterious effect by 3 years posttransplant.


Assuntos
Ciclosporina/administração & dosagem , Imunossupressores/administração & dosagem , Sirolimo/análogos & derivados , Adolescente , Adulto , Idoso , Análise de Variância , Everolimo , Humanos , Transplante de Rim , Pessoa de Meia-Idade , Sirolimo/administração & dosagem , Adulto Jovem
19.
Am J Transplant ; 12(7): 1855-65, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22494671

RESUMO

Posttransplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function, while mTor inhibitors such as everolimus may provide a renal-sparing alternative. In this randomized 1-year study in patients with liver transplantation (LTx), we sought to assess the effects of everolimus on glomerular filtration rate (GFR) after conversion from CNIs compared to continued CNI treatment. Eligible study patients received basiliximab induction, CNI with/without corticosteroids for 4 weeks post-LTx, and were then randomized (if GFR > 50 mL/min) to continued CNIs (N = 102) or subsequent conversion to EVR (N = 101). Mean calculated GFR 11 months postrandomization (ITT population) revealed no significant difference between treatments using the Cockcroft-Gault formula (-2.9 mL/min in favor of EVR, 95%-CI: [-10.659; 4.814], p = 0.46), whereas use of the MDRD formula showed superiority for EVR (-7.8 mL/min, 95%-CI: [-14.366; -1.191], p = 0.021). Rates of mortality (EVR: 4.2% vs. CNI: 4.1%), biopsy-proven acute rejection (17.7% vs. 15.3%), and efficacy failure (20.8% vs. 20.4%) were similar. Infections, leukocytopenia, hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group. No hepatic artery thrombosis and no excess of wound healing impairment were noted. Conversion from CNI-based to EVR-based immunosuppression proved to be a safe alternative post-LTx that deserves further investigation in terms of nephroprotection.


Assuntos
Inibidores de Calcineurina , Imunossupressores/administração & dosagem , Transplante de Fígado , Sirolimo/análogos & derivados , Adulto , Everolimo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sirolimo/administração & dosagem
20.
Transplant Proc ; 43(10): 3584-7, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22172809

RESUMO

OBJECTIVE: The aim of this study was to evaluate the health-related quality of life of living liver donors after living-donor liver transplantation (LDLT). METHODS: Health-related quality of life (HRQOL) in 55 living liver donors operated on at our center between 2002 and 2009 was assessed using the German Version of the 36-Item Health Survey (SF-36). RESULTS: Donors after full right-lobe hepatectomy (n=18) scored similarly to and without statistically significant difference from the German reference population, whereas donors after left lateral segmentectomy (n=37) revealed statistically significant higher average score values (P<.005) in the categories of physical functioning, bodily pain, and general health compared with the German reference population. In the analysis between donors after full right-lobe hepatectomy and donors after left lateral segmentectomy no statistically significant difference was observed in any of the SF-36 categories. Postoperative complications of the donors and postoperative recipient mortality were particularly revealing regarding HRQOL. Donors who developed postoperative complications presented a lower HRQOL, especially in the categories of role physical, bodily pain, and social functioning, where statistically significant differences (P<.005) were observed. Similarly, postoperative recipient mortality correlated with lower mean score values in all SF-36 categories, but a statistically significant difference (P<.005) was reached only in the categories of role emotional and mental health. CONCLUSIONS: Donors did not regret their decision to donate, because HRQOL was not negatively affected by the donation procedure. Living liver donors scored as well as or even better than the German reference population, but it was clearly shown that the development of postoperative donor complications and the postoperative recipient mortality had a negative effect on the HRQOL of donors.


Assuntos
Hepatectomia/efeitos adversos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Qualidade de Vida , Adulto , Emoções , Feminino , Alemanha , Nível de Saúde , Humanos , Transplante de Fígado/mortalidade , Doadores Vivos/psicologia , Masculino , Saúde Mental , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/psicologia , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...