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The ID10 beamline of the SESAME (Synchrotron-light for Experimental Science and Applications in the Middle East) synchrotron light source in Jordan was inaugurated in June 2023 and is now open to scientific users. The beamline, which was designed and installed within the European Horizon 2020 project BEAmline for Tomography at SESAME (BEATS), provides full-field X-ray radiography and microtomography imaging with monochromatic or polychromatic X-rays up to photon energies of 100â keV. The photon source generated by a 2.9â T wavelength shifter with variable gap, and a double-multilayer monochromator system allow versatile application for experiments requiring either an X-ray beam with high intensity and flux, and/or a partially spatial coherent beam for phase-contrast applications. Sample manipulation and X-ray detection systems are designed to allow scanning samples with different size, weight and material, providing image voxel sizes from 13â µm down to 0.33â µm. A state-of-the-art computing infrastructure for data collection, three-dimensional (3D) image reconstruction and data analysis allows the visualization and exploration of results online within a few seconds from the completion of a scan. Insights from 3D X-ray imaging are key to the investigation of specimens from archaeology and cultural heritage, biology and health sciences, materials science and engineering, earth, environmental sciences and more. Microtomography scans and preliminary results obtained at the beamline demonstrate that the new beamline ID10-BEATS expands significantly the range of scientific applications that can be targeted at SESAME.
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BACKGROUND: Immunosuppression with calcineurin inhibitors (CNIs) is reportedly associated with risk of renal impairment in liver transplant recipients. It is believed that this can be mitigated by decreasing initial exposure to CNIs or delaying CNI introduction until 3-4 d posttransplantation. The ADVAGRAF studied in combination with mycophenolate mofetil and basiliximab in liver transplantation (DIAMOND) trial evaluated different administration strategies for prolonged-release tacrolimus (PR-T). METHODS: DIAMOND was a 24-wk, open-label, phase 3b trial in de novo liver transplant recipients randomized to: PR-T 0.2 mg/kg/d (Arm 1); PR-T 0.15-0.175 mg/kg/d plus basiliximab (Arm 2); or PR-T 0.2 mg/kg/d delayed until day 5 posttransplant plus basiliximab (Arm 3). In a 5-y follow-up, patients were maintained on an immunosuppressive regimen according to standard clinical practice (NCT02057484). Primary endpoint: graft survival (Kaplan-Meier analysis). RESULTS: Follow-up study included 856 patients. Overall graft survival was 84.6% and 73.5% at 1 and 5 y post transplant, respectively. Five-year rates for Arms 1, 2, and 3 were 74.7%, 71.5%, and 74.5%, respectively. At 5 y, death-censored graft survival in the entire cohort was 74.7%. Overall graft survival in patients remaining on PR-T for ≥30 d was 79.1%. Graft survival in patients who remained on PR-T at 5 y was 87.3%. Patient survival was 86.6% at 1 y and 76.3% at 5 y, with survival rates similar in the 3 treatment arms at 5 y. Estimated glomerular filtration rate at the end of the 24-wk initial study and 5 y posttransplant was 62.1 and 61.5 mL/min/1.73 m2, respectively, and was similar between the 3 treatment arms at 5 y. Overall, 18 (2.9%) patients had ≥1 adverse drug reaction, considered possibly related to PR-T in 6 patients. CONCLUSIONS: In the DIAMOND study patient cohort, renal function, graft survival, and patient survival were similar between treatment arms at 5 y posttransplant.
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Post-transplant cytomegalovirus (CMV) infections and increased viral replication are associated with CMV-specific T-cell anergy. In the ATHENA-study, de-novo everolimus (EVR) with reduced-exposure tacrolimus (TAC) or cyclosporine (CyA) showed significant benefit in preventing CMV infections in renal transplant recipients as compared to standard TAC + mycophenolic acid (MPA). However, immunomodulatory mechanisms for this effect remain largely unknown. Ninety patients from the ATHENA-study completing the 12-month visit on-treatment (EVR + TAC n = 28; EVR + CyA n = 19; MPA + TAC n = 43) were included in a posthoc analysis. Total lymphocyte subpopulations were quantified. CMV-specific CD4 T cells were determined after stimulation with CMV-antigen, and cytokine-profiles and various T-cell anergy markers were analyzed using flow cytometry. While 25.6% of MPA + TAC-treated patients had CMV-infections, no such events were reported in EVR-treated patients. Absolute numbers of lymphocyte subpopulations were comparable between arms, whereas the percentage of regulatory T cells was significantly higher with EVR + CyA versus MPA + TAC (p = 0.019). Despite similar percentages of CMV-specific T cells, their median expression of CTLA-4 and PD-1 was lower with EVR + TAC (p < 0.05 for both) or EVR + CyA (p = 0.045 for CTLA-4) compared with MPA + TAC. Moreover, mean percentages of multifunctional CMV-specific T cells were higher with EVR + TAC (27.2%) and EVR + CyA (29.4%) than with MPA + TAC (19.0%). In conclusion, EVR-treated patients retained CMV-specific T-cell functionality, which may contribute to enhanced protection against CMV infections.
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Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Everolimo/imunologia , Imunossupressores/imunologia , Transplante de Rim/métodos , Linfócitos T/imunologia , Adulto , Ciclosporina/imunologia , Ciclosporina/uso terapêutico , Citomegalovirus/efeitos dos fármacos , Citomegalovirus/fisiologia , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Everolimo/uso terapêutico , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/imunologia , Ácido Micofenólico/uso terapêutico , Linfócitos T/metabolismo , Linfócitos T/virologia , Tacrolimo/imunologia , Tacrolimo/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND This post hoc analysis of data from the prospective OSAKA study evaluated the efficacy and safety of prolonged- and immediate-release tacrolimus in patients who received kidneys from extended-criteria (ECD) and standard-criteria (SCD) donors. MATERIAL AND METHODS Within the ECD and SCD groups, patients were randomized to one of 4 tacrolimus-based regimens (initial dose): Arm 1, immediate-release tacrolimus (0.2 mg/kg/day); Arm 2, prolonged-release tacrolimus (0.2 mg/kg/day); Arm 3, prolonged-release tacrolimus (0.3 mg/kg/day); Arm 4, prolonged-release tacrolimus (0.2 mg/kg/day) plus basiliximab. All patients received mycophenolate mofetil and bolus corticosteroids; Arms 1-3 also received tapered corticosteroids. ECDs met the definition: living/deceased donors aged ≥60 years, or 50-60 years with ≥1 other risk factor, and donation after circulatory death. Primary composite endpoint: graft loss, biopsy-confirmed acute rejection or renal dysfunction by Day 168. Outcomes were compared across treatment arms with the chi-squared or Fisher's exact test. RESULTS A total of 1198 patients were included in the analysis (ECD: n=620 [51.8%], SCD: n=578 [48.2%]). Patients with kidneys from ECDs were older versus SCDs (mean age, 55.7 vs. 44.5 years, p<0.0001). A higher proportion of patients with kidneys from ECDs versus SCDs met the primary composite endpoint (56.8% vs. 32.4%, p<0.0001). However, no statistically significant differences in clinical outcomes or the incidence of treatment-emergent adverse events were seen between treatment arms within each donor group. CONCLUSIONS Worse outcomes were experienced in patients who received kidneys from ECDs versus SCDs. Prolonged-release tacrolimus provided similar graft survival to the immediate-release formulation, with a manageable tolerability profile.
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Imunossupressores/administração & dosagem , Falência Renal Crônica/cirurgia , Transplante de Rim , Tacrolimo/administração & dosagem , Adulto , Idoso , Preparações de Ação Retardada , Seleção do Doador , Esquema de Medicação , Feminino , Sobrevivência de Enxerto , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
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.
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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 terapêuticoRESUMO
Early conversion to everolimus was assessed in kidney transplant recipients participating in the Eurotransplant Senior Program (ESP), a population in whom data are lacking. The SENATOR multicenter study enrolled 207 kidney transplant recipients undergoing steroid withdrawal at week 2 post-transplant (ClinicalTrials.gov [NCT00956293]). At week 7, patients were randomized (1:2 ratio) to continue the previous calcineurin inhibitor (CNI)-based regimen with mycophenolic acid (MPA) and cyclosporine or switch to a CNI-free regimen with MPA, everolimus (5-10 ng/mL) and basiliximab at weeks 7 and 12, then followed for 18 weeks to month 6 post-transplant. The primary endpoint was estimated GFR (eGFR). At week 7, 77/207 (37.2%) patients were randomized (53 everolimus, 24 control). At month 6, eGFR was comparable: 36.5±10.8ml/min with everolimus versus 42.0±13.0ml/min in the control group (p = 0.784). Discontinuation due to adverse events occurred in 27.8% of everolimus-treated patients and 0.0% of control patients (p = 0005). Efficacy profiles showed no difference. In conclusion, eGFR, safety and efficacy outcomes at month 6 post-transplant showed no difference between groups. The everolimus group experienced a higher rate of discontinuation due to adverse events. However, the high rate of non-randomization is highly relevant, indicating this to be a somewhat unstable patient population regardless of treatment.
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Everolimo/administração & dosagem , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/diagnóstico , Transplante de Rim/métodos , Idoso , Basiliximab/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Ciclosporina/administração & dosagem , Everolimo/efeitos adversos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Ácido Micofenólico/administração & dosagem , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Estudos Prospectivos , Fatores de TempoRESUMO
BACKGROUND AND STUDY AIMS: Patients undergoing therapeutic endoscopic retrograde cholangiography (ERC) may require different amounts of sedative agents depending on demographic characteristics, indication of ERC, and/or endoscopic intervention. PATIENTS AND METHODS: We retrospectively analyzed all patients undergoing therapeutic ERC from 2008 - 2014 who received deep sedation with propofol ± midazolam. RESULTS: A total of 2448 ERC procedures were performed in 781 patients. The cumulative per procedure propofol dose in the different groups was as follows: PSC 479 mg (±256), bile duct stones 356 mg (±187), benign stenosis/cholestasis 395 mg (±228), malignant stenosis 401 mg (±283), and postliver transplant complications 391 mg (±223) (p < 0.05). Multivariable analysis showed that dilatation therapy (p = 0.001), age (p = 0.001), duration of the intervention (p = 0.001), BMI (p = 0.001), gender (p = 0.001), platelet count (p = 0.003), and bilirubin (p = 0.043) influence independently the propofol consumption. CONCLUSIONS: Demographic characteristics and endoscopic interventions have a distinct influence on the amount of sedation required for therapeutic ERC. Although the sedation-associated complication rate is low optimization of sedative regimens is a prime goal to further reduce adverse events of therapeutic ERC.
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Only few centers have reported their observations on patients with very long-term kidney graft survival of more than 25 years. Eighty-six subjects were identified in our center with graft survival of >25 years. Donor age was 31.3 ± 18.5 years. Mean duration of transplantation was 30.3 ± 3.6 years. At last follow-up, the cystatin C clearance was 47 ± 23 ml/min. Transplant biopsies for cause were performed in 30 subjects at a median of 28.4 years (19.1-40.3) after transplantation. Acute or chronic active T cell-mediated rejection was present in five cases and histological characteristics of acute or chronic active humoral rejection in eight cases. More than 80% of biopsies had inflammatory infiltrates in nonatrophic or atrophic cortical areas. The number of HLA mismatches were higher in biopsied subjects (3.0 ± 1.8 vs. 2.2 ± 1.7 without biopsy). Immunosuppressive therapy was adapted in most biopsied subjects; impaired graft function and proteinuria was unchanged at last follow-up. Sixty percent of all subjects had hyperparathyroidism (iPTH of the whole group: 132 ± 157 pg/ml), which was predominantly secondary, as judged by serum calcium and graft function. Young donor age was certainly a prerequisite of longterm graft survival. Nonetheless, inflammation or rejection in most biopsied patients suggests an important role of alloreactivity even in this late course.
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Sobrevivência de Enxerto , Transplante de Rim , Rim/patologia , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Adulto JovemRESUMO
Selection and prioritization of patients with HCC for LT are based on pretransplant imaging diagnostic, taking the risk of incorrect diagnosis. According to the German waitlist guidelines, imaging has to be reported to the allocation organization (Eurotransplant) and pathology reports have to be submitted thereafter. In order to assess current procedures we performed a retrospective multicenter analysis in all German transplant centers with focus on accuracy of imaging diagnostic and tumor classification. 1168 primary LT for HCC were conducted between 2007 and 2013 in Germany. Patients inside the Milan, UCSF, and up-to-seven criteria were misclassified with definitive histologic results in 18%, 15%, and 11%, respectively. Patients pretransplant outside the Milan, UCSF, and up-to-seven criteria were otherwise misclassified in 34%, 43%, and 41%. Recurrence-free survival correlated with classification by posttransplant histological report, but not pretransplant imaging diagnostic. Univariate analysis revealed tumor size, vascular invasion, and grading as significant parameters for outcome, while tumor grading was the only parameter persisting by multivariate testing. Conclusion. There was a relevant percentage (15-40%) of patients misclassified by imaging diagnosis at a time prior to LI-RADS and guidelines to improve imaging of HCC. Outcome analysis showed a good correlation to histological, in contrast poor correlation to imaging diagnosis, suggesting an adjustment of the LT selection and prioritization criteria.
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Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Transplante de Fígado/métodos , Seleção de Pacientes , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Intervalo Livre de Doença , Feminino , Alemanha , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Guias de Prática Clínica como Assunto , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVE: The long-term psychosocial outcome of young adults after paediatric liver transplantation (LT) was investigated with the focus on day-to-day living. We aimed to capture patients' subjective perceptions of well-being and autonomy based on key physical outcome parameters. METHODS: All patients following paediatric LT at Hannover Medical School born before 2002 with a post-transplant follow-up of at least four years were included in this study. This retrospective observational study compared psychosocial parameters obtained from a self-designed 77-item questionnaire with standard clinical outcome variables. RESULTS: Eighty-two patients (male: 57%) aged 13-41 years were included in the survey within a three-month period (response rate: 41%). With an adherence rate of 33%, all but two patients were immunosuppressed. In total, 53 patients had transitioned to adult care largely without problems. Eighty-three percent (n = 68) evaluated their current health status as "(very) good". Sixty-seven patients (82%) did not experience health-related anxiety in daily life. CONCLUSIONS: Our results demonstrate psychological stability and high self-esteem of young patients, as well as good integration into society and a high degree of normality during daily life after LT. Adherence rates are lower than anticipated and do not correlate with patients' understanding of their medical condition.
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Nível de Saúde , Transplante de Fígado/psicologia , Resiliência Psicológica , Atividades Cotidianas , Adolescente , Adulto , Fatores Etários , Ansiedade/epidemiologia , Criança , Feminino , Seguimentos , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Hospedeiro Imunocomprometido , Transplante de Fígado/estatística & dados numéricos , Masculino , Estudos Retrospectivos , Autoimagem , Transição para Assistência do Adulto/estatística & dados numéricos , Adulto JovemAssuntos
Síndrome Hepatopulmonar/cirurgia , Transplante de Fígado , Doença Hepática Terminal/cirurgia , Europa (Continente) , Humanos , Transplante de Fígado/mortalidade , Oxigênio/metabolismo , Modelos de Riscos Proporcionais , Sistema de Registros , Estudos Retrospectivos , Risco , Resultado do TratamentoRESUMO
Post-transplant hypertension (PTH) is a common complication in cyclosporine immunosuppressed patients; however choosing the right antihypertensive medication is challenging. In a long-term observational study (≤13y) we examined different antihypertensive medications on graft/patient survival of kidney recipients with pre-existing and PTH. Altogether thirty-three co-variables were analyzed including dose and type of immunosuppressive and antihypertensive medication, co-medications, serum biochemistries and the glomerular filtration rate (GFR). A Cox proportional-hazard multivariable survival model was developed to detect a Hazard Ratio (HR) of 3.0 at the Bonferroni corrected level αâ¯=â¯0.0015. Importantly, a significant relationship between immunosuppressive cyclosporine dose/serum concentration, systolic blood pressure (SBP) and GFR (pâ¯<â¯0.001) was observed with post-transplant hypertension being a major risk factor (HR6.1) for graft/patient survival. Although all medications lowered effectively elevated SBP the risk of graft failure/death was significantly increased when hypertension was treated with ACE inhibitors or ß-blockers (HR3.3 and 3.1) but not with angiotensin receptor- and/or Ca-channel blockers. Antihypertensive medication was associated with a decline in GFR but ß-blockers alone or in combination with ARB and/or CCB improved GFR. Neither BMI nor any of the drug combinations used in immunosuppression, i.e. prednisolone, mycophenolic acid, azathioprine and/or sirolimus influenced patient and/or graft survival while decision tree analyses informed on complex dependencies between immunosuppressive medications, dose of anti-hypertensive drug and diuretics in the management of hypertension. In conclusion, our study is suggestive for graft/patient survival to be influenced by the class of antihypertensive medication. A prospective randomized clinical trial is needed to confirm the results.
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Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Ciclosporina/efeitos adversos , Hipertensão/tratamento farmacológico , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Adolescente , Adulto , Idoso , Anti-Hipertensivos/efeitos adversos , Tomada de Decisão Clínica , Técnicas de Apoio para a Decisão , Árvores de Decisões , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Hipertensão/induzido quimicamente , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: One-third of 5-year survivors after liver resection for colorectal liver metastases (CLM) develop recurrence or tumor-related death. Therefore 10-year survival appears more adequate in defining permanent cure. The aim of this study was to develop prognostic models for the prediction of 10-year survival after liver resection for colorectal liver metastases. METHODS: N=965 cases of liver resection for CLM were retrospectively analyzed using univariable and multivariable regression analyses. Receiver operating curve analyses were used to assess the sensitivity and specificity of developed prognostic models and their potential clinical usefulness. RESULTS: The 10-year survival rate was 15.2%. Age at liver resection, application of chemotherapies of the primary tumor, preoperative Quick's value, hemoglobin level, and grading of the primary colorectal tumor were independent significant predictors for 10-year patient survival. The generated formula to predict 10-year survival based on these preoperative factors displayed an area under the receiver operating curve (AUROC) of 0.716. In regard to perioperative variables, the distance of resection margins and performance of right segmental liver resection were additional independent predictors for 10-year survival. The logit link formula generated with pre- and perioperative variables showed an AUROC of 0.761. CONCLUSION: Both prognostic models are potentially clinically useful (AUROCs >0.700) for the prediction of 10-year survival. External validation is required prior to the introduction of these models in clinical patient counselling.
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BACKGROUND: Conversion from calcineurin inhibitor (CNI) therapy to a mammalian target of rapamycin (mTOR) inhibitor following kidney transplantation may help to preserve graft function. Data are sparse, however, concerning the impact of conversion on posttransplant diabetes mellitus (PTDM) or the progression of pre-existing diabetes. METHODS: PTDM and other diabetes-related parameters were assessed post hoc in two large open-label multicenter trials. Kidney transplant recipients were randomized (i) at month 4.5 to switch to everolimus or remain on a standard cyclosporine (CsA)-based regimen (ZEUS, n = 300), or (ii) at month 3 to switch to everolimus, remain on standard CNI therapy or convert to everolimus with reduced-exposure CsA (HERAKLES, n = 497). RESULTS: There were no significant differences in the incidence of PTDM between treatment groups (log rank p = 0.97 [ZEUS], p = 0.90 [HERAKLES]). The mean change in random blood glucose from randomization to month 12 was also similar between treatment groups in both trials for patients with or without PTDM, and with or without pre-existing diabetes. The change in eGFR from randomization to month 12 showed a benefit for everolimus versus comparator groups in all subpopulations, but only reached significance in larger subgroups (no PTDM or no pre-existing diabetes). CONCLUSIONS: Within the restrictions of this post hoc analysis, including non-standardized diagnostic criteria and limited glycemia laboratory parameters, these data do not indicate any difference in the incidence or severity of PTDM with early conversion from a CsA-based regimen to everolimus, or in the progression of pre-existing diabetes. TRIAL REGISTRATION: clinicaltrials.gov , NCT00154310 (registered September 2005) and NCT00514514 (registered August 2007); EudraCT ( 2006-007021-32 and 2004-004346-40 ).
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Ciclosporina/administração & dosagem , Diabetes Mellitus/epidemiologia , Everolimo/administração & dosagem , Transplante de Rim/tendências , Estudos Multicêntricos como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Idoso , Ciclosporina/efeitos adversos , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/diagnóstico , Progressão da Doença , Everolimo/efeitos adversos , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , MasculinoRESUMO
Treatment of donation after brain death (DBD) donors with low-dose dopamine improves the outcomes after kidney and heart transplantation. This study investigates the course of liver allografts from multiorgan donors enrolled in the randomized dopamine trial between 2004 and 2007 (clinicaltrials.gov identifier: NCT00115115). There were 264 hemodynamically stable DBDs who were randomly assigned to receive low-dose dopamine. Dopamine was infused at 4 µg/kg/minute for a median duration of 6.0 hours (interquartile range, 4.4-7.5 hours). We assessed the outcomes of 212 liver transplantations (LTs) performed at 32 European centers. Donors and recipients of both groups were very similar in baseline characteristics. Pretransplant laboratory Model for End-Stage Liver Disease score was not different in recipients of a dopamine-treated versus untreated graft (18 ± 8 versus 20 ± 8; P = 0.12). Mean cold ischemia time was 10.6 ± 2.9 versus 10.1 ± 2.8 hours (P = 0.24). No differences occurred in biopsy-proven rejection episodes (14.4% versus 15.7%; P = 0.85), requirement of hemofiltration (27.9% versus 31.5%; P = 0.65), the need for early retransplantation (5.8% versus 6.5%; P > 0.99), the incidence of primary nonfunction (7.7% versus 8.3%; P > 0.99), and in-hospital mortality (15.4% versus 14.8%; P > 0.99). Graft survival was 71.2% versus 73.2% and 59.6% versus 62.0% at 2 and 3 years (log-rank P = 0.71). Patient survival was 76.0% versus 78.7% and 65.4% versus 69.4% at 1 and 3 years (log-rank P = 0.50). In conclusion, donor pretreatment with dopamine has no short-term or longterm effects on outcome after LT. Therefore, low-dose dopamine pretreatment can safely be implemented as the standard of care in hemodynamically stable DBDs.
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Dopamina/administração & dosagem , Doença Hepática Terminal/cirurgia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Coleta de Tecidos e Órgãos/métodos , Adulto , Isquemia Fria/efeitos adversos , Doença Hepática Terminal/diagnóstico , Feminino , Rejeição de Enxerto/prevenção & controle , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Doadores de Tecidos , Resultado do TratamentoRESUMO
PURPOSE: This study aims to identify modifiable risk factors for de novo renal cell carcinoma (RCC) after kidney transplantation in a matched-pair approach matching for unmodifiable factors. PATIENTS AND METHODS: One thousand six hundred fifty-five adults who underwent kidney transplantation in the period 1 January 2000 to 31 December 2012 were analyzed. Patients with RCC after kidney transplantation were matched in a 1:2 ratio with those without RCC using the indication for transplantation, age at transplantation (± 10 years), recipient sex (male/female), number of received transplants, living organ donor transplantation (yes/no), and time of follow-up in days as matching criteria. The paired t test was used to compare continuous variables and the Cochran-Mantel-Haenszel test for categorical variables. Multivariable conditional logistic regression modeling was used to identify independent risk factors for RCC. RESULTS: In matched-pair analysis, a total number of 26 incident cases with RCC after kidney transplantation could be matched. Post-transplant RCC was significantly associated with longer durations of pre-transplant hemodialysis (p = 0.007) and post-transplant immunosuppression with cyclosporine (p = 0.029) and/or mycophenolate mofetil (p = 0.020) and with larger proportions of post-transplant time on mycophenolate mofetil (p = 0.046) and/or prednisolone medication (p = 0.042). Multivariable conditional logistic regression modeling revealed a significant risk increasing multiplicative factor interaction between the duration of pre-transplant dialysis (years) and the time of prednisolone usage (percent/100). Cyclosporine A usage and mycophenolate mofetil usage were also revealed as independent, significant risk factors for RCC development. CONCLUSIONS: Longer pre-transplant dialysis, cyclosporine-based protocols and/or intensified immunosuppression with additional mycophenolate mofetil, and larger proportions of time of prednisolone treatment during follow-up increase de novo RCC risk.
Assuntos
Carcinoma de Células Renais/etiologia , Imunossupressores/efeitos adversos , Falência Renal Crônica/terapia , Neoplasias Renais/etiologia , Transplante de Rim/efeitos adversos , Diálise Renal/efeitos adversos , Adulto , Idoso , Carcinoma de Células Renais/induzido quimicamente , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Imunossupressores/administração & dosagem , Falência Renal Crônica/cirurgia , Neoplasias Renais/induzido quimicamente , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêutico , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Prednisolona/uso terapêutico , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVES: Combined lung and liver transplantation (Lu-LTx) is an established therapy for patients with cystic fibrosis. The initial sequence has primarily been lung first. We changed the sequence to 'liver first' in 2006. The aim of this study is to present outcomes of this procedure. METHODS: The records of combined lung and liver transplant patients treated at our institution between April 1999 and November 2016 were reviewed retrospectively. RESULTS: A total of 27 patients received a combined Lu-LTx at our institute. Seventeen patients underwent Lu-LTx beginning with the lung transplantation. In this group, 5 patients had cystic fibrosis (lung first). The other 10 patients received the liver transplant first (liver first). All patients in this group had cystic fibrosis as underlying disease. The lung-first group showed a trend towards longer stays in the intensive care unit (ICU) and in the hospital [median 17 days in the ICU, interquartile range (IQR) 3-47 and 55 in-hospital days, IQR 29-108] than the liver-first group (median 6 days in the ICU, IQR 4-19 and 33 in-hospital days, IQR 26-63). The 90-day, 1- and 5-year survival rates were 80%, 60% and 20% in the lung-first group vs 90%, 79% and 79% in the liver-first group. CONCLUSIONS: We present the largest series of patients following combined Lu-LTx according to the liver-first approach. The liver-first sequence results in favourable outcomes in our cohort of combined lung and liver transplants.
Assuntos
Transplante de Fígado , Transplante de Pulmão , Adulto , Fibrose Cística/cirurgia , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Transplante de Fígado/mortalidade , Transplante de Fígado/estatística & dados numéricos , Transplante de Pulmão/efeitos adversos , Transplante de Pulmão/métodos , Transplante de Pulmão/mortalidade , Transplante de Pulmão/estatística & dados numéricos , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Conversion from calcineurin inhibitor (CNI) therapy to everolimus within 6 months after kidney transplantation improves long-term graft function but can increase the risk of mild biopsy-proven acute cellular rejection (BPAR). We performed a post-hoc analysis of histological data from a randomized trial in order to further analyze histologic information obtained from indication and protocol biopsies up to 5 years after transplantation. METHODS: Biopsy samples obtained up to 5 years post-transplant were analyzed from the randomized ZEUS study, in which kidney transplant patients were randomized at month 4.5 to switch to everolimus (n = 154) or remain on cyclosporine (CsA)-based immunosuppression (n = 146). All patients received mycophenolate and steroids. RESULTS: At least one investigator-initiated biopsy was undertaken in 53 patients in each group between randomization and year 5, with a mean (SD) of 2.6 (1.7) and 2.2 (1.4) biopsies per patient in the everolimus and CsA groups, respectively. In the everolimus and CsA groups, investigator-initiated biopsies showed (i) BPAR in 12.3 and 7.5% (p = 0.182) of patients, respectively, with episodes graded mild in 22/24 and 18/20 cases (ii) CsA toxicity lesions in 4.5 and 10.3% of patients (p = 0.076) (iii) antibody-mediated rejection in 0.6 and 2.7% of patients (p = 0.204), respectively. CONCLUSIONS: This analysis of histological findings in the ZEUS study to 5 years after kidney transplantation shows no increase in antibody-mediated rejection under everolimus-based therapy with a lower rate of CNI-related toxicity compared to a conventional CsA-based regimen, and confirms the preponderance of mild BPAR seen in the main study after the early switch to CsA-free everolimus therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00154310 . Date of registration: September 12, 2005.
Assuntos
Ciclosporina/administração & dosagem , Substituição de Medicamentos/tendências , Everolimo/administração & dosagem , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Transplante de Rim/tendências , Adolescente , Adulto , Idoso , Substituição de Medicamentos/métodos , Feminino , Sobrevivência de Enxerto/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto JovemRESUMO
Changes in recipient and donor characteristics are redefining the role of induction in liver transplant recipients. Older recipients are more common, with greater concomitant comorbidity. Moderate or severe renal dysfunction is now estimated to affect 40% of liver transplant recipients. Donors are also becoming older, and other factors such as more frequent non-alcoholic fatty liver disease (NAFLD) compromise the quality of some grafts. Rejection rates are now relatively low (~10%) but some patients have a markedly increased risk such as younger recipients and those undergoing re-transplantation. Induction immunosuppression is associated with a significant reduction in rejection risk but due to various factors universal induction is not justified. Steroid-free therapy without induction increases the risk of biopsy-proven acute rejection (BPAR) but randomized trials have shown that induction with an interleukin-2 antagonist receptor (IL-2RA) agent or with rabbit antithymocyte globulin (rATG) maintains immunosuppressive efficacy in steroid-free regimens. Delayed calcineurin inhibitor (CNI) initiation (e.g. to days 4-5 post-transplant) can prevent deterioration of renal function during the first year post-transplant, but requires induction with an IL-2RA agent or rATG to maintain early immunosuppressive efficacy. IL-2RA induction may be inadequate to ensure a low risk of rejection in a steroid-free regimen combined with delayed tacrolimus. Randomized trials of CNI withdrawal at month 1 post-transplant have only achieved an acceptable rate of BPAR when induction is administered. In terms of safety, an increased rate of infection does not seem to be a concern. The most recent large-scale analyses have not indicated any evidence for an increased risk of malignancy, or specifically post-transplant lymphoproliferative disease. In summary, the place of induction in the management of liver transplant patients is becoming established. Selective use in high-risk individuals to avoid graft rejection is still relevant, but the key rationale for induction is to facilitate steroid-sparing and CNI-sparing regimens to reduce long-term complications.