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1.
Am J Transplant ; 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38642711

RESUMO

Biopsy-proven acute rejection (BPAR) occurs in approximately 10% of kidney transplant recipients in the first year, making superiority trials unfeasible. iBOX, a quantitative composite of estimated glomerular filtration rate, proteinuria, antihuman leukocyte antigen donor-specific antibody, and + full/- abbreviated kidney histopathology, is a new proposed surrogate endpoint. BPAR's prognostic ability was compared with iBOX in a pooled cohort of 1534 kidney transplant recipients from 4 data sets, including 2 prospective randomized controlled trials. Discrimination analyses showed mean c-statistic differences between both iBOX compared with BPAR of 0.25 (95% confidence interval: 0.17-0.32) for full iBOX and 0.24 (95% confidence interval: 0.16-0.32) for abbreviated iBOX, indicating statistically significantly higher c-statistic values for the iBOX prognosis of death-censored graft survival. Mean (± standard error) c-statistics were 0.81 ± 0.03 for full iBOX, 0.80 ± 0.03 for abbreviated iBOX, and 0.57 ± 0.03 for BPAR. In calibration analyses, predicted graft loss events from both iBOX models were not significantly different from those observed. However, for BPAR, the predicted events were significantly (P < .01) different (observed: 64; predicted: 70; full iBOX: 76; abbreviated iBOX: 173 BPAR). IBOX at 1-year posttransplant is superior to BPAR in the first year posttransplant in graft loss prognostic performance, providing valuable additional information and facilitating the demonstration of superiority of novel immunosuppressive regimens.

2.
J Hepatol ; 80(1): 99-108, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37722533

RESUMO

BACKGROUND & AIMS: There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US. METHODS: From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates. RESULTS: The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p = 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant. CONCLUSIONS: Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC. IMPACT AND IMPLICATIONS: The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation.


Assuntos
Colangite Esclerosante , Transplante de Fígado , Adulto , Humanos , Tacrolimo/uso terapêutico , Ciclosporina/uso terapêutico , Inibidores de Calcineurina , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/cirurgia , Colangite Esclerosante/etiologia , Análise de Intenção de Tratamento , Pontuação de Propensão , Imunossupressores/uso terapêutico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto
3.
Scand J Gastroenterol ; 59(4): 461-468, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38069811

RESUMO

BACKGROUND: Kidney disease is common after liver transplantation (LT), but postoperative kidney failure is difficult to predict. Current guidelines recommend simultaneous liver-kidney transplantation (SLKT) in patients with pre-LT estimated glomerular filtration rate (eGFR) below 30-40 mL/min, which might be too liberal. The aim of this study was to evaluate the risk of kidney failure after LT. We also assessed the predictive ability of pretransplantation eGFR using various equations. METHODS: This single-center study included patients undergoing primary LT 2006-2020. Patients undergoing simultaneous liver-kidney transplantations or on dialysis before LT were analysed separately. We calculated 5 different eGFR equations measured just before LT and assessed their predictive ability using Kaplan-Meier cumulative incidence estimates. RESULTS: Among 556 LT patients with a median follow-up of 5.0 years (IQR 2.0-8.5), 20 developed kidney failure during follow-up, 7 of them within 1-year post LT. Six of these 7 suffered from major perioperative complications. Depending on the eGFR equation used, the incidence of kidney failure within 1-year was 3.9-6.7% at pre-LT eGFR-values <30 mL/min, 1.2-3.1% at eGFR 30-60 mL/min, and 0.6-0.9% at eGFR >60 mL/min. CONCLUSIONS: Kidney failure within 1-year post-LT could not be reliably predicted by pre-LT eGFR. However, kidney failure was uncommon even in patients with severely reduced pre-LT glomerular filtration rate (eGFR <30 mL/min), and extremely rare in patients unaffected by major perioperative complications. Our data prompts further consideration regarding the guidelines for SLKT in patients with a reduced preoperative eGFR.


Assuntos
Transplante de Rim , Transplante de Fígado , Insuficiência Renal , Humanos , Transplante de Fígado/efeitos adversos , Rim , Insuficiência Renal/etiologia , Transplante de Rim/efeitos adversos , Taxa de Filtração Glomerular , Fatores de Risco , Estudos Retrospectivos
4.
Transpl Int ; 37: 12309, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495816

RESUMO

Delayed graft function (DGF) after kidney transplantation is common and associated with worse graft outcomes. However, little is known about factors affecting graft survival post-DGF. We studied the association of cold ischemia time (CIT) and Kidney Donor Profile Index (KDPI) with the long-term outcomes of deceased brain-dead donor kidneys with and without DGF. Data from Finland (n = 2,637) and from the US Scientific Registry of Transplant Recipients (SRTR) registry (n = 61,405) was used. The association of KDPI and CIT with the graft survival of kidneys with or without DGF was studied using multivariable models. 849 (32%) kidneys had DGF in the Finnish cohort. DGF and KDPI were independent risk factors for graft loss, [HR 1.32 (95% CI 1.14-1.53), p < 0.001, and HR 1.01 per one point (95% CI 1.01-1.01), p < 0.001, respectively], but CIT was not, [HR 1.00 per CIT hour (95% CI 0.99-1.02), p = 0.84]. The association of DGF remained similar regardless of CIT and KDPI. The US cohort had similar results, but the association of DGF was stronger with higher KDPI. In conclusion, DGF and KDPI, but not CIT, are independently associated with graft survival. The association of DGF with worse graft survival is consistent across different CITs but stronger among marginal donors.


Assuntos
Transplante de Rim , Humanos , Encéfalo , Função Retardada do Enxerto/etiologia , Sobrevivência de Enxerto , Transplante de Rim/métodos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Estudos Multicêntricos como Assunto
5.
Transpl Int ; 37: 12235, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38444997

RESUMO

The total burden of infections after transplantation has not been compared in detail between recipients of simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). We compared infection-related hospitalizations and bacteremias after transplantation during 1- and 5-year follow-up among 162 patients undergoing SPK. The control group consisted of 153 type 1 diabetics undergoing KTA with the inclusion criteria of donor and recipient age < 60, and BMI < 30. During the first year, SPK patients had more infection-related hospitalizations (0.54 vs. 0.31 PPY, IRR 1.76, p = <0.001) and bacteremias (0.11 vs. 0.01 PPY, IRR 17.12, p = <0.001) compared to KTA patients. The first infection-related hospitalizations and bacteremias occurred later during follow-up in KTA patients. SPK was an independent risk factor for infection-related hospitalization and bacteremia during the first year after transplantation, but not during the 5-year follow-up. Patient survival did not differ between groups, however, KTA patients had inferior kidney graft survival. SPK patients are at greater risk for infection-related hospitalizations and bacteremias during the first year after transplantation compared to KTA patients, however, at the end of the follow-up the risk of infection was similar between groups.


Assuntos
Bacteriemia , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Rim , Hospitalização , Pâncreas
6.
Am J Transplant ; 23(10): 1496-1506, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37735044

RESUMO

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies.


Assuntos
Transplante de Rim , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Terapia de Imunossupressão , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Ensaios Clínicos como Assunto
7.
Clin Transplant ; 37(8): e14992, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37076928

RESUMO

INTRODUCTION: Simultaneous pancreas-kidney transplantation (SPK) is an option for patients with type 1 diabetes (T1D) and kidney failure but can be associated with a high complication rate. Here we describe our 10-year experience since the launch of the SPK program. METHODS: This retrospective study included consecutive patients with T1D receiving SPK from March 14, 2010 to March 14, 2020 at Helsinki University Hospital. Portocaval anastomosis (i.e., systemic venous drainage) and enteric exocrine drainage were used. A specific team was trained for both pancreas retrieval and transplantation, postoperative care was standardized to include somatostatin analogues, antimicrobial treatment, and preoperatively initiated chemothrombopropylaxis. During program maturation donor criteria were expanded and logistical processes improved to minimize cold ischemia time. Clinical data were collected from a nationwide transplantation registry and patient records. RESULTS: A total of 166 SPKs were performed (median 2 per year in the first 3 years, 17.5 per year for the following 4 years, and 23 per year for the past 3 years). Seven patients (4.1%) died with a functioning graft with a median 43 months follow-up. One-year pancreas graft survival was 97.0%, 3-year pancreas graft survival was 96.1% and 5-year was 96.1%. Mean HbA1c was 36 mmol/mol (SD 5.57) and creatinine was 107 µmol/L (SD 34.69) at 1-year after transplantation. All kidney grafts were functioning at the end of follow-up. Complications required re-laparotomy in 39 (23%) patients, mostly due to a pancreas graft related problem (N = 28). No pancreas or kidney graft failure from thrombosis occurred. CONCLUSION: A planned, step-wise development of an SPK program offers a safe and effective treatment for patients with T1D and kidney failure.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante de Rim , Transplante de Pâncreas , Humanos , Transplante de Rim/efeitos adversos , Diabetes Mellitus Tipo 1/complicações , Finlândia , Estudos Retrospectivos , Resultado do Tratamento , Transplante de Pâncreas/efeitos adversos , Sobrevivência de Enxerto
8.
Transpl Int ; 36: 11332, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37470064

RESUMO

A brain-death-induced cytokine storm damages organs in an organ donor. However, a longer time period between declaration of brain death and organ procurement (procurement interval) is associated with improved outcomes in kidney, liver, heart, and lung transplantation. The aim of this study was to find the optimal procurement interval for pancreas transplantation. Association of procurement interval with pancreas graft outcomes was analyzed using multivariable models adjusted for variables possibly affecting procurement interval and outcomes. Altogether 10,119 pancreas transplantations were included from the Scientific Registry of Transplant Recipients. The median follow-up was 3.2 (IQR 1.01-6.50) years. During the first year, 832 (9.0%) grafts were lost, including 555 (6.0%) within the first 30 days. Longer procurement interval was associated with increased death-censored graft survival in a multivariable model (HR 0.944 95% CI 0.917-0.972, per 10-h increase, p < 0.001). A decreasing hazard of graft loss was observed also with 1-year, but not with 30-day graft survival. During 1-year follow-up, 953 (12.1%) patients had an acute rejection, and longer procurement interval was also associated with less acute rejections (OR 0.937 95% CI 0.900-0.976, per 10-h increase, p = 0.002) in the multivariable model. In conclusion, longer procurement interval is associated with improved long-term outcomes in pancreas transplantation.


Assuntos
Transplante de Rim , Transplante de Pâncreas , Obtenção de Tecidos e Órgãos , Humanos , Morte Encefálica , Doadores de Tecidos , Sobrevivência de Enxerto , Pâncreas , Encéfalo , Rejeição de Enxerto
9.
Transpl Int ; 36: 11785, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37901297

RESUMO

Despite advances in monitoring and treatment, cytomegalovirus (CMV) infections remain one of the most common complications after solid organ transplantation (SOT). CMV infection may fail to respond to standard first- and second-line antiviral therapies with or without the presence of antiviral resistance to these therapies. This failure to respond after 14 days of appropriate treatment is referred to as "resistant/refractory CMV." Limited data on refractory CMV without antiviral resistance are available. Reported rates of resistant CMV are up to 18% in SOT recipients treated for CMV. Therapeutic options for treating these infections are limited due to the toxicity of the agent used or transplant-related complications. This is often the challenge with conventional agents such as ganciclovir, foscarnet and cidofovir. Recent introduction of new CMV agents including maribavir and letermovir as well as the use of adoptive T cell therapy may improve the outcome of these difficult-to-treat infections in SOT recipients. In this expert review, we focus on new treatment options for resistant/refractory CMV infection and disease in SOT recipients, with an emphasis on maribavir, letermovir, and adoptive T cell therapy.


Assuntos
Antivirais , Infecções por Citomegalovirus , Humanos , Antivirais/uso terapêutico , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Acetatos/uso terapêutico , Ganciclovir/uso terapêutico
10.
Transpl Int ; 36: 11255, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37388858

RESUMO

In elective pancreatic surgery, somatostatin-analogues pasireotide and octreotide are variably used to reduce postoperative complications, but knowledge on their role in pancreas transplantation is limited. This study compared pasireotide and octreotide for their association with complications after simultaneous pancreas-kidney transplantation (SPK). This retrospective study included consecutive patients undergoing SPK's from July 2013 to July 2022. Between July 2013 and April 2020, octreotide was administered 0.1 mg s.c. once daily and between May 2020 and July 2022 pasireotide was administered 0.9 mg twice daily, both until third postoperative day. Complications within 90 days postoperatively were collected, and reoperation rate and Comprehensive Complication index (CCI) ≥ 33.7 (morbidity equal to one reoperation) were used as primary outcomes. Of the 213 patients undergoing SPK, 150 patients received octreotide and 63 pasireotide. Baseline characteristics were comparable. Reoperation rate was 25.3% (n = 38) and 17.5% (n = 11) (p = 0.213) and rate of CCI ≥ 33.7 was 40.7% (n = 61) and 30.2% (n = 19) (p = 0.148) in octreotide and pasireotide groups, respectively. When adjusted with donor BMI, pancreas donor risk index, and donor sex, receiving pasireotide translated into OR 0.49 (95% CI: 0.25-0.96 p = 0.037) for CCI ≥ 33.7. Pasireotide was independently associated with lower postoperative morbidity within 90 days of SPK compared to octreotide.


Assuntos
Transplante de Rim , Octreotida , Humanos , Octreotida/uso terapêutico , Transplante de Rim/efeitos adversos , Estudos Retrospectivos , Somatostatina/uso terapêutico , Pâncreas
11.
Transpl Int ; 36: 11951, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37822449

RESUMO

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6 months to 24 months posttransplant in pivotal or exploratory drug therapeutic studies.


Assuntos
Transplante de Rim , Humanos , Imunossupressores/uso terapêutico , Terapia de Imunossupressão , Rejeição de Enxerto/prevenção & controle
12.
Int J Cancer ; 150(11): 1779-1791, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35041762

RESUMO

Cancer is a significant cause of morbidity and mortality after solid organ transplantation (SOT) and related to lifelong immunosuppression. This retrospective registry study assessed for the first time in Finland population-based cancer risk and cancer mortality after all SOTs (lung and childhood transplantations included) as standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs). Data from transplant registries were linked with the data of Finnish Cancer Registry and Statistics Finland. We followed 6548 consecutive first SOT recipients from 1 January 1987 to 31 December 2016 translating to 66 741 person-years (median follow-up time 8.9 years [interquartile range 4.0-15.1]). In total, 2096 cancers were found in 1483 patients (23% of all patients). Majority of cancers (53%) were nonmelanoma skin cancers (NMSCs). The overall SIR was 3.6 (95% confidence interval [CI]: 3.5-3.8) and the SIR excluding NMSCs was 2.2 (95% CI: 2.0-2.3). SIR for all cancers was highest for heart (5.0) and lowest for liver (2.7) recipients. Most common cancer types after NMSCs were non-Hodgkin lymphoma (NHL), SIR 9.9 (95% CI: 8.5-11.4) and kidney cancer, SIR 7.3 (95% CI: 6.0-8.8). Cancer-related deaths were 17% (n = 408) of all deaths after first month post transplantation. SMR for all cancers was 2.5 (95% CI: 2.2-2.7) and for NHL 13.6 (95% CI: 10.7-16.8). Notably, overall SIR for cancer was lower in later period (2000-2016), 3.0 (95% CI: 2.8-3.2), than in earlier period (1987-1999), 4.3 (95% CI: 4.0-4.5), P < .001. Decrease in cancer incidence was temporally associated with major changes in immunosuppression in the 2000s.


Assuntos
Neoplasias , Transplante de Órgãos , Neoplasias Cutâneas , Criança , Estudos de Coortes , Finlândia/epidemiologia , Humanos , Incidência , Neoplasias/epidemiologia , Neoplasias/etiologia , Transplante de Órgãos/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Neoplasias Cutâneas/complicações
13.
Am J Transplant ; 22(12): 2869-2879, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36030513

RESUMO

In March 2009, the Scandiatransplant acceptable mismatch program (STAMP) was introduced as a strategy toward improving kidney allocation to highly sensitized patients. Patients with a transplantability score ≤ 2% are potential candidates for the program. Samples are analyzed and acceptable antigens (HLA-A, B, C, DRB1, DRB3/4/5, DQB1, DQA1, DPB1, DPA1) are defined by the local tissue typing laboratory and finally evaluated by a steering committee. In the matching algorithm, patients have the highest priority when the donor's antigens are all among the recipient's own or acceptable HLA antigens. In the period from 2009 to 2020, we have transplanted 278 highly sensitized kidney patients through the program. The graft survival of the STAMP patients was compared with 9002 deceased donor kidney-transplanted patients, transplanted in the same time period. The 10-year graft survival was 73.4% (95% CI: 60.3-90.0) for STAMP and 82.9% (95% CI: 81.6-84.3) for the reference group. (p = .2). In conclusion, the 10-year allograft survival demonstrates that the STAMP allocation algorithm is immunological safe. The program is continuously monitored and evaluated, and the introduction of matching for all HLA loci is a huge improvement to the program and demonstrate technical adaptability as well as clinical flexibility in a de-centralized organization.


Assuntos
Transplante de Rim , Humanos , Teste de Histocompatibilidade , Doadores de Tecidos , Antígenos HLA , Sobrevivência de Enxerto
14.
Br J Surg ; 109(11): 1131-1139, 2022 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-35983583

RESUMO

BACKGROUND: Highly utilized risk scores for clinically relevant postoperative pancreatic fistula (CR-POPF) have guided clinical decision-making in pancreatoduodenectomy. However, none has been successfully developed for distal pancreatectomy. This study aimed to develop and validate a new fistula risk score for distal pancreatectomy. METHODS: Patients undergoing distal pancreatectomy at Helsinki University Hospital, Finland from 2013 to 2021, and at Karolinska University Hospital, Sweden, from 2010 to 2020, were included retrospectively. The outcome was CR-POPF, according to the 2016 International Study Group of Pancreatic Surgery definition. Preoperative clinical demographics and radiological parameters such as pancreatic thickness and duct diameter were measured. A logistic regression model was developed, internally validated with bootstrapping, and the performance assessed in an external validation cohort. RESULTS: Of 668 patients from Helsinki (266) and Stockholm (402), 173 (25.9 per cent) developed CR-POPF. The final model consisted of three variables assessed before surgery: transection site (neck versus body/tail), pancreatic thickness at transection site, and diabetes. The model had an area under the receiver operating characteristic curve (AUROC) of 0.904 (95 per cent c.i. 0.855 to 0.949) after internal validation, and 0.798 (0.748 to 0.848) after external validation. The calibration slope and intercept on external validation were 0.719 and 0.192 respectively. Four risk groups were defined in the validation cohort for clinical applicability: low (below 5 per cent), moderate (at least 5 but below 30 per cent), high (at least 30 but below 75 per cent), and extreme (75 per cent or more). The incidences in these groups were 8.7 per cent (11 of 126), 22.0 per cent (36 of 164), 63 per cent (57 of 91), and 81 per cent (17 of 21) respectively. CONCLUSION: The DISPAIR score after distal pancreatectomy may guide decision-making and allow a risk-adjusted outcome comparison for CR-POPF.


Assuntos
Pancreatectomia , Fístula Pancreática , Humanos , Pancreatectomia/efeitos adversos , Fístula Pancreática/diagnóstico , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco
15.
Clin Transplant ; 36(2): e14537, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34797574

RESUMO

Cytomegalovirus (CMV) infection remains a major challenge in solid organ transplantation. Ganciclovir has changed the prognosis, but with the expense of possible viral resistance. New antiviral drugs, such as letermovir, have not been studied sufficiently in kidney and pancreas transplant recipients. We reviewed abdominal organ transplants recipients with CMV infection from the national transplant registry and identified patients treated with letermovir from electronic medical records. We report on letermovir treatment in one kidney and three simultaneous pancreas and kidney (SPK) transplant patients with refractory or ganciclovir-resistant CMV infection (UL54/ UL97 mutation). In SPK patients, persistent leukopenia undermined immunosuppressive and antiviral treatment, favoring life-threatening bacterial infections or ganciclovir resistance. All patients achieved viral clearance after letermovir monotherapy of 1.5-6 months. Letermovir was well tolerated and leukopenia resolved. Adjustments of calcineurin inhibitor doses were challenging. One acute rejection occurred because of under immunosuppression. After the end of treatment, recurrent low-grade CMV-DNAemia was common requiring reinitiating antiviral therapy to achieve viral clearance. To conclude, letermovir was a well-tolerated valuable option for the treatment of refractory or resistant CMV infection in kidney and pancreas transplantation.


Assuntos
Infecções por Citomegalovirus , Transplante de Rim , Leucopenia , Transplante de Pâncreas , Acetatos , Antivirais/uso terapêutico , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Ganciclovir/uso terapêutico , Humanos , Rim , Transplante de Rim/efeitos adversos , Leucopenia/tratamento farmacológico , Transplante de Pâncreas/efeitos adversos , Quinazolinas
16.
Transpl Int ; 35: 10364, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118016

RESUMO

Brain death-induced cytokine storm is thought to harm transplantable organs. However, longer procurement times have been associated with non-inferior or better outcomes in kidney, heart, and lung transplants, while optimal procurement time for liver allografts is unknown. Our aim was to analyze the association of time interval from brain death to organ procurement with liver allograft outcomes in two nationwide cohorts. The association of procurement interval with graft survival and short-term complications was analysed in multivariable models. Altogether 643 and 58,017 orthotopic liver transplantations from brain-dead donors were included from Finland between June 2004 and December 2017 and the US between January 2008 and August 2018, respectively. Median time from brain death to organ procurement was 10.5 h in Finland and 34.6 h in the US. Longer interval associated with better graft survival (non-linearly, p = 0.016) and less acute rejections (OR 0.935 95% CI 0.894-0.978) in the US cohort, and better early allograft function (p = 0.005; Beta -0.048 95% CI -0.085 -(-0.011)) in the Finnish cohort, in multivariable models adjusted with Donor Risk Index, recipient age, Model for End-Stage Liver Disease and indication for transplantation. Progressive liver injury after brain death is unlikely. Rushing to recover seems unnecessary; rest and repair might prove beneficial.


Assuntos
Doença Hepática Terminal , Transplante de Fígado , Obtenção de Tecidos e Órgãos , Encéfalo , Morte Encefálica , Humanos , Índice de Gravidade de Doença
17.
Transpl Int ; 35: 10329, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592446

RESUMO

While great progress has been made in transplantation medicine, long-term graft failure and serious side effects still pose a challenge in kidney transplantation. Effective and safe long-term treatments are needed. Therefore, evidence of the lasting benefit-risk of novel therapies is required. Demonstrating superiority of novel therapies is unlikely via conventional randomized controlled trials, as long-term follow-up in large sample sizes pose statistical and operational challenges. Furthermore, endpoints generally accepted in short-term clinical trials need to be translated to real-world (RW) care settings, enabling robust assessments of novel treatments. Hence, there is an evidence gap that calls for innovative clinical trial designs, with RW evidence (RWE) providing an opportunity to facilitate longitudinal transplant research with timely translation to clinical practice. Nonetheless, the current RWE landscape shows considerable heterogeneity, with few registries capturing detailed data to support the establishment of new endpoints. The main recommendations by leading scientists in the field are increased collaboration between registries for data harmonization and leveraging the development of technology innovations for data sharing under high privacy standards. This will aid the development of clinically meaningful endpoints and data models, enabling future long-term research and ultimately establish optimal long-term outcomes for transplant patients.


Assuntos
Transplante de Rim , Ensaios Clínicos Pragmáticos como Assunto , Medição de Risco , Ensaios Clínicos como Assunto/normas , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Ensaios Clínicos Pragmáticos como Assunto/normas , Projetos de Pesquisa/normas
18.
Transpl Infect Dis ; 24(2): e13814, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35182406

RESUMO

AIM: The burden of sexually transmitted infections (STI) among solid-organ transplant recipients is currently unknown. We studied the risk of STIs among kidney transplant recipients compared with the general population in a nationwide cohort. METHODS: Between 2002 and 2019, all microbiological findings of Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum (syphilis), and human immunodeficiency virus among kidney transplant recipients <65 years and transplanted between 1995 and 2017 in our country were captured from statutory national registries. Data from the general population of Finland, population 5.5 million, were used for comparisons. Incidence of STIs and age and sex-adjusted standardized incidence ratios (SIR) were calculated. RESULTS: Altogether 3612 transplantations, with a total follow-up of 27 069 person-years were included. A total of 30 STIs microbiological findings of STI were confirmed in 25 patients: C. trachomatis (N = 27), N. gonorrhoeae (N = 2), and syphilis (N = 1). No hospitalizations associated with STIs were detected. The risk of STI after kidney transplantation was significantly lower compared to the general population (SIR, 0.57, 95% CI 0.39-0.80). The lower risk of STIs was more pronounced in female patients (SIR 0.40, 95% CI 0.20-0.74), whereas in male patients the difference was statistically not significant (SIR 0.69, 95% CI 0.44-1.04). Of the confirmed STI cases, 30% were detected in patients who received their transplants during adolescence. CONCLUSIONS: Within the Finnish kidney transplant population, the age and sex-adjusted incidence of sexually transmitted infections is not higher compared to the general population. Highest frequency of infections was seen among patients transplanted during adolescence.


Assuntos
Infecções por HIV , Transplante de Rim , Infecções Sexualmente Transmissíveis , Adolescente , Chlamydia trachomatis , Estudos de Coortes , Feminino , Infecções por HIV/epidemiologia , Humanos , Incidência , Transplante de Rim/efeitos adversos , Masculino , Prevalência , Infecções Sexualmente Transmissíveis/epidemiologia
19.
Am J Transplant ; 21(5): 1848-1856, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33252189

RESUMO

Seasonal influenza causes morbidity and mortality after organ transplantation. We quantified the detection of laboratory-confirmed influenza among kidney transplant recipients compared to the general population in a nationwide cohort. All laboratory-confirmed cases of influenza and hospitalizations due to influenza among all kidney transplant recipients in our country between 1995 and 2017 were captured with database linkage from statutory national registries. Data from the general population of Finland, population 5.5 million, were used for comparisons. Annual incidences of influenza and hospitalizations due to influenza, and standardized incidence ratios (SIR) were calculated. Altogether 3904 kidney transplant recipients with a total follow-up of 37 175 patient-years were included. Incidence of laboratory-confirmed influenza was 9.0 per 1000 patient years in 2003-2019, and 18.0 per 1000 patient years during 2015-2019. The risk of laboratory-confirmed influenza was significantly higher among kidney transplant recipients compared to the general population (SIR 5.1, 95% CI 4.5-5.7). SIR for hospitalization due to influenza was 4.4 (95% CI 3.4-4.7). Mortality of the hospitalized patients was 9%, and 5% of the patients with laboratory-confirmed influenza. Detection of laboratory-confirmed influenza is increased fivefold and risk of hospitalization due to influenza more than fourfold among kidney transplant recipients compared to the general population.


Assuntos
Influenza Humana , Transplante de Rim , Estudos de Coortes , Humanos , Incidência , Influenza Humana/diagnóstico , Influenza Humana/epidemiologia , Transplante de Rim/efeitos adversos , Laboratórios , Fatores de Risco , Transplantados
20.
Nephrol Dial Transplant ; 36(9): 1742-1753, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-33585931

RESUMO

BACKGROUND: Publications from the last decade have increased knowledge regarding long-term risks after kidney donation. We wanted to perform a survey to assess how transplant professionals in Europe inform potential kidney donors regarding long-term risks. The objectives of the survey were to determine how they inform donors and to what extent, and to evaluate the degree of variation. METHODS: All transplant professionals involved in the evaluation process were considered eligible, regardless of the type of profession. The survey was dispatched as a link to a web-based survey. The subjects included questions on demographics, the information policy of the respondent and the use of risk calculators, including the difference of relative and absolute risks and how the respondents themselves understood these risks. RESULTS: The main finding was a large variation in how often different long-term risks were discussed with the potential donors, i.e. from always to never. Eighty percent of respondents stated that they always discuss the risk of end-stage renal disease, while 56% of respondents stated that they always discuss the risk of preeclampsia. Twenty percent of respondents answered correctly regarding the relationship between absolute and relative risks for rare outcomes. CONCLUSIONS: The use of written information and checklists should be encouraged. This may improve standardization regarding the information provided to potential living kidney donors in Europe. There is a need for information and education among European transplant professionals regarding long-term risks after kidney donation and how to interpret and present these risks.


Assuntos
Transplante de Rim , Humanos , Rim , Transplante de Rim/efeitos adversos , Doadores Vivos , Inquéritos e Questionários , Coleta de Tecidos e Órgãos
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