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1.
Rev. Pesqui. (Univ. Fed. Estado Rio J., Online) ; 11(5): 1202-1207, out.-dez. 2019. tab
Artigo em Inglês, Português | LILACS, BDENF - Enfermagem | ID: biblio-1022269

RESUMO

Objetivo: Avaliar as características clínicas e imunológica dos receptores de transplante renal. Métodos: estudo documental e retrospectivo, realizado em um Ambulatório do Hospital Geral de Fortaleza, Fortaleza, Ceará, Brasil, com pacientes internados no período de junho de 2012 a junho de 2014. A amostra foi composta por 300 pacientes submetidos ao transplante renal. As variáveis preditoras de interesse, foram subdivididas em: características prétransplante, características pós-transplante e características imunológicas. Utilizou-se testes de Pearson e Spearman para avaliar correlação entre variáveis. Resultados: Houve predomínio de pacientes do sexo masculino (65%), com faixa etária entre 44 e 56 anos (31,4%). Demonstrou-se relação estatisticamente significante entre o DSA e a disfunção do enxerto (p<0,04), Rejeição celular o Painel Reativo classe I (p< 0,05), o tempo de internação e a disfunção do enxerto (p<0,001) e entre o entre o HLA e o MISMATCH. Conclusão: Aponta-se a necessidade de um acompanhamento crítico e individualizado do paciente transplantado por parte dos profissionais para garantir o sucesso do transplante a longo prazo


Objective: The study's purpose has been to assess both clinical and immunological characteristics of renal transplant recipients. Methods: It is a documentary and retrospective study that was performed at the renal transplantation ambulatory from the Hospital Geral de Fortaleza (HGF), Fortaleza city, Ceará State, with patients hospitalized from June 2012 to June 2014. The sample consisted of 300 patients submitted to renal transplantation. The predictive variables of interest were subdivided in the following categories: pre-transplant characteristics, post-transplant characteristics and immunological characteristics. Pearson and Spearman tests were used to evaluate the correlation between variables. Results: There was a predominance of male patients (65%), with ages ranging from 44 to 56 years (31.4%). A statistically significant relationship was found between the Donor-Specific Antibody and Delayed Graft Function (p<0.04), Cellular Rejection and PanelReactive Antibody class I (p<0.05), duration of hospitalization and Delayed Graft Function (p<0.001) and also between the Human Leukocyte Antigen and MISMATCH. Conclusion: It is pointed out the need for a critical and individualized follow-up of the transplanted patient by the professionals to guarantee the long-term transplantation success


Objetivo: Evaluar las características clínicas e inmunológicas de lós receptores de trasplante renal. Métodos: estudio documental y retrospectivo realizado en una clínica del Hospital General de Fortaleza, Fortaleza, Ceará, Brasil, con pacientes ingresados desde junio de 2012 a junio de 2014. La muestra fue de 300 pacientes sometidos a trasplante de riñón. Las variables predictoras de interés, fueron subdivididas en: características pretrasplante, características post-transplante y características inmunológicas. Se utilizaron pruebas de Pearson y Spearman para evaluar la correlación entre variables. Resultados: Hubo un predominio de pacientes del sexo masculino (65%), con edades comprendidas entre 44 y 56 años (31,4%). Se demostró una relación estadísticamente significativa entre el DSA y la disfunción del injerto (p <0,04), el rechazo celular del panel reactivo clase I (p <0,05), el tiempo de internación y la disfunción del injerto (p <0,001) y entre el HLA y el MISMATCH. Conclusión: Se apunta la necesidad de un acompañamiento crítico e individualizado del paciente trasplantado por parte de los profesionales para garantizar el éxito del trasplante a largo plazo


Assuntos
Humanos , Masculino , Feminino , Imunologia de Transplantes , Transplante de Rim/estatística & dados numéricos , Continuidade da Assistência ao Paciente/estatística & dados numéricos , Brasil , Rejeição de Enxerto/epidemiologia
2.
Med Oncol ; 36(11): 94, 2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31605245

RESUMO

Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a variety of solid tumors; nonetheless, they have not been well investigated and are still recognized as a relative contraindication for patients with a liver transplantation (LT) history, since ICIs treatment might potentially lead to graft rejection. The program death-1 (PD-1) and the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) pathways are implicated in the tolerance of transplanted organ, as well as blockade of the pathways, which contribute to eliminating tumors and may inadvertently lead to peripheral transplant rejection. Currently, no guidelines are available regarding the treatment for ICIs patients with a prior LT history. Therefore, this study was carried out to review the recent studies, attempting to introduce the ICIs-related graft rejection after LT from various aspects. We believed that ICIs could be given for the well-informed patients receiving LT and developed recurrence in a controlled setting. Typically, these patients should be treated according to a clinical care path or a prospective clinical trial, so as obtain a persistent anti-tumor immune response in the meantime of avoiding graft rejection, adjust the immunosuppression, reduce the possibility of graft loss following rejection, and have the opportunity to develop biomarkers for tumor response and transplant rejection.


Assuntos
Antineoplásicos Imunológicos/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Transplante de Fígado , Antineoplásicos Imunológicos/imunologia , Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Antígeno B7-H1/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno CTLA-4/imunologia , Rejeição de Enxerto/imunologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia
4.
Lancet ; 394(10205): 1274-1285, 2019 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-31533905

RESUMO

The main goal of treatment for type 1 diabetes is to control glycaemia with insulin therapy to reduce disease complications. For some patients, technological approaches to insulin delivery are inadequate, and allogeneic islet transplantation is a safe alternative for those patients who have had severe hypoglycaemia complicated by impaired hypoglycaemia awareness or glycaemic lability, or who already receive immunosuppressive drugs for a kidney transplant. Since 2000, intrahepatic islet transplantation has proven efficacious in alleviating the burden of labile diabetes and preventing complications related to diabetes, whether or not a previous kidney transplant is present. Age, body-mass index, renal status, and cardiopulmonary status affect the choice between pancreas or islet transplantation. Access to transplantation is limited by the number of deceased donors and the necessity of immunosuppression. Future approaches might include alternative sources of islets (eg, xenogeneic tissue or human stem cells), extrahepatic sites of implantation (eg, omental, subcutaneous, or intramuscular), and induction of immune tolerance or encapsulation of islets.


Assuntos
Diabetes Mellitus Tipo 1/cirurgia , Células Secretoras de Insulina/transplante , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressão , Resultado do Tratamento
5.
BMJ ; 366: l4923, 2019 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-31530561

RESUMO

OBJECTIVE: To develop and validate an integrative system to predict long term kidney allograft failure. DESIGN: International cohort study. SETTING: Three cohorts including kidney transplant recipients from 10 academic medical centres from Europe and the United States. PARTICIPANTS: Derivation cohort: 4000 consecutive kidney recipients prospectively recruited in four French centres between 2005 and 2014. Validation cohorts: 2129 kidney recipients from three centres in Europe and 1428 from three centres in North America, recruited between 2002 and 2014. Additional validation in three randomised controlled trials (NCT01079143, EudraCT 2007-003213-13, and NCT01873157). MAIN OUTCOME MEASURE: Allograft failure (return to dialysis or pre-emptive retransplantation). 32 candidate prognostic factors for kidney allograft survival were assessed. RESULTS: Among the 7557 kidney transplant recipients included, 1067 (14.1%) allografts failed after a median post-transplant follow-up time of 7.12 (interquartile range 3.51-8.77) years. In the derivation cohort, eight functional, histological, and immunological prognostic factors were independently associated with allograft failure and were then combined into a risk prediction score (iBox). This score showed accurate calibration and discrimination (C index 0.81, 95% confidence interval 0.79 to 0.83). The performance of the iBox was also confirmed in the validation cohorts from Europe (C index 0.81, 0.78 to 0.84) and the US (0.80, 0.76 to 0.84). The iBox system showed accuracy when assessed at different times of evaluation post-transplant, was validated in different clinical scenarios including type of immunosuppressive regimen used and response to rejection therapy, and outperformed previous risk prediction scores as well as a risk score based solely on functional parameters including estimated glomerular filtration rate and proteinuria. Finally, the accuracy of the iBox risk score in predicting long term allograft loss was confirmed in the three randomised controlled trials. CONCLUSION: An integrative, accurate, and readily implementable risk prediction score for kidney allograft failure has been developed, which shows generalisability across centres worldwide and common clinical scenarios. The iBox risk prediction score may help to guide monitoring of patients and further improve the design and development of a valid and early surrogate endpoint for clinical trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT03474003.


Assuntos
Rejeição de Enxerto/etiologia , Transplante de Rim , Adulto , Idoso , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Reprodutibilidade dos Testes , Medição de Risco/métodos , Estados Unidos/epidemiologia
6.
Zhonghua Yan Ke Za Zhi ; 55(9): 713-716, 2019 Sep 11.
Artigo em Chinês | MEDLINE | ID: mdl-31495156

RESUMO

Graft rejection and endothelial cell loss were believed to be the main reasons for graft edema following keratoplasty. With the application of various molecular biological detection methods in ophthalmology, virus infection has emerged and become an important contributing factor for graft failure. This review focused on the etiology, clinical manifestation and diagnosis methods for virus infection following keratoplasty, and discussed possible prevention and treatment.(Chin J Ophthalmol, 2019, 55: 713-716).


Assuntos
Transplante de Córnea , Rejeição de Enxerto , Infecção da Ferida Cirúrgica , Contagem de Células , Transplante de Córnea/efeitos adversos , Humanos , Ceratoplastia Penetrante , Complicações Pós-Operatórias
8.
Emerg Med Clin North Am ; 37(4): 679-705, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31563202

RESUMO

Renal transplants are becoming more and more frequent in the United States and worldwide. Studies demonstrate that these patients inevitably end up visiting an emergency department. In addition to typical medical and surgical problems encountered in the general population, this group of patients has unique problems arising from their immunocompromised state and also due to side effects of the medications required. This article discusses these risks and management decisions that the emergency department physician should be aware of in order to prevent adverse outcomes for the patient and transplanted kidney.


Assuntos
Serviço Hospitalar de Emergência , Transplante de Rim/efeitos adversos , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/terapia , Humanos , Infecção da Ferida Cirúrgica/diagnóstico , Infecção da Ferida Cirúrgica/terapia
9.
Khirurgiia (Mosk) ; (9): 80-85, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31532171

RESUMO

This article discusses the need to implement effective methods for monitoring immune status and rehabilitation of patients after kidney transplantation. Induction of immunological tolerance which allows minimizing or even completely canceling supportive immunosuppressive therapy is one of the key tasks in the field of organ transplantation. Regulatory T-cells (TREGs) play an important role in maintaining immunological homeostasis, including limiting kidney transplant rejection, and potentially contribute to the development of immunological tolerance. At the same time, for the introduction of TREG therapy into clinical practice, it is necessary to overcome a number of unsolved problems, such as induction and cultivation of a sufficient number of TREG cells for therapeutic action as well as reducing the risks associated with TREG conversion to effector lymphocytes or an undesirable non-specific immunosuppressive effect. This review examines both the impact of common post-transplant pharmacological immunosuppression approaches on TREGs and the therapeutic potential of TREG cell cultures in prevention of kidney transplant rejection. The questions of ex vivo TREG manufacturing process and possible threats of applying cell technologies in this branch of transplantology were considered.


Assuntos
Terapia Baseada em Transplante de Células e Tecidos/métodos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Transplante de Rim/efeitos adversos , Linfócitos T Reguladores/imunologia , Rejeição de Enxerto/etiologia , Humanos , Tolerância Imunológica/imunologia , Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/reabilitação , Imunologia de Transplantes/imunologia
10.
Nat Biotechnol ; 37(10): 1137-1144, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31427818

RESUMO

The utility of autologous induced pluripotent stem cell (iPSC) therapies for tissue regeneration depends on reliable production of immunologically silent functional iPSC derivatives. However, rejection of autologous iPSC-derived cells has been reported, although the mechanism underlying rejection is largely unknown. We hypothesized that de novo mutations in mitochondrial DNA (mtDNA), which has far less reliable repair mechanisms than chromosomal DNA, might produce neoantigens capable of eliciting immune recognition and rejection. Here we present evidence in mice and humans that nonsynonymous mtDNA mutations can arise and become enriched during reprogramming to the iPSC stage, long-term culture and differentiation into target cells. These mtDNA mutations encode neoantigens that provoke an immune response that is highly specific and dependent on the host major histocompatibility complex genotype. Our results reveal that autologous iPSCs and their derivatives are not inherently immunologically inert for autologous transplantation and suggest that iPSC-derived products should be screened for mtDNA mutations.


Assuntos
DNA Mitocondrial/genética , Epitopos/genética , Epitopos/imunologia , Doença Enxerto-Hospedeiro/imunologia , Células-Tronco Pluripotentes Induzidas , Animais , Antígenos , Transplante de Células/métodos , Células-Tronco Embrionárias , Rejeição de Enxerto/imunologia , Humanos , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mutação , Transplante Autólogo
11.
Khirurgiia (Mosk) ; (8): 59-62, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31464276

RESUMO

The use of allogenic materials in reconstructive surgery is of great scientific interest due to high availability of donor tissues. The positive aspects of allogenous tissue transplantation are complicated by the histological incompatibility of donor tissue and recipient organism. This incompatibility results hypersensitivity reaction towards the allogenous transplant followed by rejection of allogenic tissue and even death in some cases. Cellular biological incompatibility may be managed by decellularization of allogenous organs and tissues prior to transplantation. The improvement of decellularization techniques will facilitate application of allogenous tissues in complex reconstructive procedures and significantly increase the capabilities of reconstructive surgery.


Assuntos
Aloenxertos/imunologia , Células/imunologia , Engenharia Tecidual/métodos , Imunologia de Transplantes , Transplante Homólogo/métodos , Aloenxertos/citologia , Rejeição de Enxerto/imunologia , Procedimentos Cirúrgicos Reconstrutivos , Tecidos Suporte , Imunologia de Transplantes/imunologia
12.
Biomater Sci ; 7(9): 3729-3740, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31403142

RESUMO

Targeted delivery of immunosuppressants to allografts can increase the concentrations of drugs in pathological tissues, improve therapeutic effects and reduce unfavorable side effects. Therefore, we synthesized FK506-loaded microbubbles (FK506-MBs) for site-specific release of FK506 into transplanted hearts by the ultrasound-targeted microbubble destruction (UTMD) technique. The average particle size of FK506-MBs was 1.65 ± 0.32 µm and they had high drug loading and encapsulation efficiency. The in vivo drug concentration in transplanted hearts that were treated with FK506-MBs plus UTMD was about 1.64-fold higher than that in grafts that received free FK506 at the same dosage. The degree of graft rejection in the FK506-MB plus UTMD group was lower than those of other groups. Both infiltration of T cells and secretion of inflammatory cytokines were significantly reduced in the FK506-MB plus UTMD group. More importantly, the mean survival time of the grafts was significantly longer (16.00 ± 0.89 day) than those of the PBS group (6.66 ± 1.36 day) and the FK506 group (12.83 ± 1.17 day). In addition, we also found that the concentration of FK506 in whole blood was lower in the FK506-MB plus UTMD group than that in the FK506 group, which would be beneficial for reducing the side effects. Hence, our results showed that combining FK506-MBs with UTMD was an effective strategy to deliver FK506 to transplanted hearts, which can increase the local drug concentration and enhance its efficacy on rejection. Ultrasound-targeted drug release is safe and radiation-free, with great potential for clinical transformation, and could also be extended to the treatment of other graft rejection cases, such as liver transplantation, kidney transplantation and so on.


Assuntos
Portadores de Fármacos/química , Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração , Imunossupressores/farmacocinética , Miocárdio/metabolismo , Tacrolimo/farmacocinética , Animais , Liberação Controlada de Fármacos , Estudos de Viabilidade , Imunossupressores/administração & dosagem , Masculino , Microbolhas , Fosfatidilcolinas/química , Fosfatidiletanolaminas/química , Polietilenoglicóis/química , Ratos , Tacrolimo/administração & dosagem , Ultrassonografia
13.
Int J Clin Pharmacol Ther ; 57(10): 506-519, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31397274

RESUMO

OBJECTIVE: Mycophenolate mofetil (MMF) is widely used as an immunosuppressant for the prophylaxis of acute organ rejection in recipients of solid organ transplants. MATERIALS AND METHODS: We have compared, in healthy subjects, the pharmacokinetics of mycophenolic acid when MMF was administered in the form of the innovator product CellCept (F. Hoffmann-La Roche Ltd.) or one of three commercially available generics, Renodapt (Biocon Ltd.), Mycept (Panacea Biotec), or Cellmune (Cipla Ltd.). The study was powered to detect a 20% difference in mean formulation performance measures, but not to formally evaluate bioequivalence. Geometric mean ratios of maximum concentrations (Cmax) and areas under plasma concentration-time curves were calculated. RESULTS: Comparing generics against each other, the differences in point estimates of the geometric mean ratios of Cmax of two of the comparisons were either borderline within (Renodapt/Cellmune) or clearly outside (Mycept/Cellmune) a region of 80 - 125% around the reference mean, indicating that bioequivalence between these generics may be difficult to show. CONCLUSION: Physicians in the field of transplantation should be aware of the potential risk of altering the therapeutic outcome when switching from one preparation of MMF to another. ClinicalTrials.gov identifier: NCT02981290.


Assuntos
Medicamentos Genéricos/farmacocinética , Imunossupressores/farmacocinética , Ácido Micofenólico/farmacocinética , Equivalência Terapêutica , Estudos Cross-Over , Rejeição de Enxerto , Humanos
14.
Stud Health Technol Inform ; 264: 10-14, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31437875

RESUMO

Kidney transplantation is recommended for patients with End-Stage Renal Disease (ESRD). However, complications, such as graft rejection are hard to predict due to donor and recipient variability. This study discusses the role of machine learning (ML) in predicting graft rejection following kidney transplantation, by reviewing the available related literature. PubMed, DBLP, and Scopus databases were searched to identify studies that utilized ML methods, in predicting outcome following kidney transplants. Fourteen studies were included. This study reviewed the deployment of ML in 109,317 kidney transplant patients from 14 studies. We extracted five different ML algorithms from reviewed studies. Decision Tree (DT) algorithms revealed slightly higher performance with overall mean Area Under the Curve (AUC) for DT (79.5% ± 0.06) was higher than Artificial Neural Network (ANN) (78.2% ± 0.08). For predicting graft rejection, ANN and DT were at the top among ML models that had higher accuracy and AUC.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Aprendizado de Máquina , Sobrevivência de Enxerto , Humanos , Doadores de Tecidos
15.
Cornea ; 38(9): 1077-1082, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31394551

RESUMO

PURPOSE: To compare the outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) with Descemet membrane endothelial keratoplasty (DMEK) for the treatment of failed penetrating keratoplasty (PKP). METHODS: This is a retrospective chart review of patients with failed PKP who underwent DMEK or DSAEK. The median follow-up time for both groups was 28 months (range 6-116 months). Data collection included demographic characteristics, number of previous corneal transplants, previous glaucoma surgeries, best-corrected visual acuity, endothelial cell density, graft detachment and rebubble rate, rejection episodes, and graft failure. RESULTS: Twenty-eight eyes in the DMEK group and 24 eyes in the DSAEK group were included in the analysis. Forty-three percent of eyes in the DMEK group and 50% of eyes in the DSAEK group had to be regrafted because of failure (P = 0.80). The most common reason for failure was persistent graft detachment (58%) in the DMEK group and secondary failure (58%) in the DSAEK group; hence, the time between endothelial keratoplasty and graft failure differed significantly between the groups (P = 0.02). Six eyes (21%) in the DMEK group and 7 eyes (29%) in the DSAEK group developed graft rejection (P = 0.39). Rejection was the cause of failure in 67% and 71% in the DMEK and DSAEK groups, respectively. The best-corrected visual acuity 6 months after surgery was better in the DMEK group compared with the DSAEK group (P = 0.051). CONCLUSIONS: Both DSAEK and DMEK have a role in treating PKP failure. Primary failure due to persistent graft detachment was significantly higher in the DMEK group, although the overall failure rate in the medium term was similar.


Assuntos
Doenças da Córnea/cirurgia , Lâmina Limitante Posterior/cirurgia , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior , Ceratoplastia Penetrante , Adulto , Idoso , Idoso de 80 Anos ou mais , Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Feminino , Rejeição de Enxerto/cirurgia , Sobrevivência de Enxerto , Humanos , Ceratoplastia Penetrante/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Acuidade Visual
16.
J Cancer Res Clin Oncol ; 145(11): 2779-2791, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31446489

RESUMO

PURPOSE: To evaluate serum procalcitonin (PCT) and C-reactive protein (CRP) as diagnostic biomarkers of transplant-related adverse events (TRAE) in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). METHODS: This study analyzed PCT and CRP levels of 214 pediatric patients with a median age of 8.5 years (0.4-17.8 years) undergoing allogeneic HSCT with respect to major TRAE. RESULTS: 26 patients (12.1%) did not experience TRAE (control group), and 188 (87.9%) experienced median 2 (range 1-4) TRAE. Median CRP and PCT were highly and significantly increased during sepsis/SIRS and bacteremia (17.24 mg/dl | 6.30 ng/ml; p < 0.0001 vs. prior values), graft rejection (14.73 mg/dl | 3.20 ng/ml; p < 0.0001), and liver GvHD (6.88 mg/dl | 2.29 ng/ml; p < 0.01). Strong CRP increases and slight/minimal/no PCT increases occurred during fungemia (8.85 mg/dl | 0.72 ng/ml; p < 0.001), intestinal GvHD (8.73 mg/dl | 1.06 ng/ml; p < 0.0001), VOD (10.84 mg/dl | 0.59 ng/ml; p < 0.01), mucositis (8.84 mg/dl | 0.81 ng/ml; p < 0.0001), and viremia (3.62 mg/dl; p < 0.0001 | 0.43 ng/ml; below normal limit). During skin GvHD, CRP and PCT were slightly increased (2.03 mg/dl | 0.93 ng/ml; p < 0.0001). CONCLUSIONS: CRP and PCT did not show congruent changes during TRAE. PCT was a clinically relevant marker for the early detection and differentiation of severe mucositis and sepsis/SIRS and bacteremia during the critical neutropenic period after HSCT. PCT helped to discriminate acute intestinal GvHD from adenovirus viremia and liver GvHD from hepatic VOD. Thus, PCT may be a valuable parameter to enable a prompt and appropriate treatment during these complications, improving patient outcomes.


Assuntos
Bacteriemia/diagnóstico , Proteína C-Reativa/análise , Rejeição de Enxerto/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Pró-Calcitonina/sangue , Sepse/diagnóstico , Adolescente , Bacteriemia/sangue , Bacteriemia/etiologia , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Diagnóstico Precoce , Feminino , Seguimentos , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Doença Enxerto-Hospedeiro/sangue , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Sepse/sangue , Sepse/etiologia , Transplante Homólogo
17.
BJOG ; 126(11): 1310-1319, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31410987

RESUMO

Uterine transplantation restores reproductive anatomy in women with absolute uterine factor infertility and allows the opportunity to conceive, experience gestation, and acquire motherhood. The number of cases being performed is increasing exponentially, with detailed outcomes from 45 cases, including nine live births, now available. In light of the data presented herein, including detailed surgical, immunosuppressive and obstetric outcomes, the feasibility of uterine transplantation is now difficult to refute. However, it is associated with significant risk with more than one-quarter of grafts removed because of complications, and one in ten donors suffering complications requiring surgical repair. TWEETABLE ABSTRACT: Uterine transplantation is feasible in women with uterine factor infertility, but is associated with significant risk of complication.


Assuntos
Sobrevivência de Enxerto/fisiologia , Imunossupressão/métodos , Infertilidade Feminina/cirurgia , Transplante de Órgãos , Doadores de Tecidos , Útero/transplante , Adulto , Feminino , Rejeição de Enxerto , Humanos , Nascimento Vivo , Pessoa de Meia-Idade , Transplante de Órgãos/métodos , Gravidez , Resultado do Tratamento , Adulto Jovem
18.
Transplant Proc ; 51(6): 1699-1705, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399160

RESUMO

BACKGROUND: Rejection and infection are 2 major complications affecting the health and survival of patients receiving an allograft organ transplantation. We describe a diagnostic assay that simultaneously monitors for rejection and infection in recipients of kidney transplant by sequencing of cell-free DNA (cfDNA) in plasma. METHODS: By using cfDNA in plasma, we established a noninvasive method that simultaneously monitors rejection and infection in patients with a history of organ transplant. A total of 6200 single-nucleotide polymorphisms were captured by liquid hybridization and sequenced by next-generation sequencing. The donor-derived cfDNA (ddcfDNA) level was calculated based on maximum likelihood estimation, without relying on the donor's genotype. We also analyzed the nonhuman cfDNA to test for infections in the patients' plasma. RESULTS: Artificial ddcfDNA levels quantified by a donor-dependent and donor-independent algorithm were significantly correlated, with the multivariate coefficient of determination, or R2 value, of 0.999. This technique was applied on 30 patients (32 samples) after kidney transplantation, and a significant difference was observed on the ddcfdNA levels between nonrejection and rejection. Furthermore, 1 BK virus infection and 1 cytomegalovirus infection were revealed by this method, and the enrichment efficiency of the viral sequences was 114 and 489 times, respectively, which are consistent with clinical results. CONCLUSION: This method can be used to simultaneously monitor for acute rejection as well as a broad spectrum of infections for patients of allograft organ transplant because it provides comprehensive information for clinicians to optimize immunosuppression therapy.


Assuntos
Ácidos Nucleicos Livres/sangue , Rejeição de Enxerto/diagnóstico , Infecção/diagnóstico , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Adulto , Algoritmos , Feminino , Rejeição de Enxerto/sangue , Humanos , Hospedeiro Imunocomprometido , Infecção/sangue , Infecção/imunologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue
19.
Transplant Proc ; 51(6): 1744-1753, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399162

RESUMO

INTRODUCTION: Depletion therapy in high immunologic risk (HR) patients by antithymocyte globulin (rATG) induces lymphopenia and subsequent compartmental repopulation of T-cell subsets. rATG is also given to patients receiving kidneys from donations after cardiac death (DCDs) to mitigate innate immune activation associated with the DCD process. METHODS: We compared the T-cell response with rATG in both HR and DCD kidney recipients. We examined the reconstitution of T-cell subsets after rATG treatment in HR and DCD recipients (n = 19 per group) by multicolor flow cytometry. RESULTS: Following treatment, there was a rapid drop in the frequency of T cells in both groups, which persisted over 28 days. HR patients had an early surge in the frequency of CD4+ naïve, effector-memory, and regulatory T cells. Although we found a significant proliferation of the T cells in both groups, the DCD cohort had a blunted response as well as reduced CD4+ T-cell immune-reactivity compare with the HR group. CONCLUSIONS: Our data suggest that there is a lack of significant homeostatic proliferative response in DCD recipients following rATG, and CD4+ T cells may be less reactive in the DCD group than previously thought, indicating that rATG treatment may not have to be considered a first-line induction therapy in DCD recipients.


Assuntos
Soro Antilinfocitário/uso terapêutico , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Subpopulações de Linfócitos T/efeitos dos fármacos , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Doadores de Tecidos
20.
Transplant Proc ; 51(6): 1758-1762, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399163

RESUMO

BACKGROUND: Although tacrolimus is an effective immunosuppressive drug used for preventing biopsy proven acute rejection (BPAR) in kidney transplanted patients, its nephrotoxicity may compromise renal function and lead to delayed initiation because of its side effects. This study aimed to evaluate the safety of early initiation of tacrolimus in the occurrence of BPAR during the first 90 days post transplant. METHODS: We conducted a retrospective cohort study involving 315 patients who underwent kidney transplantation from 2015 to 2017. Comparisons were performed between 2 groups according to whether the start time of tacrolimus therapy was delayed or not delayed. Cox proportional hazards models were used to examine the association between variables and the occurrence of BPAR. RESULTS: The incidence of BPAR was 14.9% (n = 47) and it was significantly higher in the delayed group (19.4% vs 6.4%; P = .002). Delayed initiation tacrolimus group was significantly associated with the risk of BPAR (hazard ratio: 2.95; P < .036). The overall mortality rate was 2.5% (n = 8) and there was no association between delayed initiation therapy and death (P = .56). CONCLUSION: Our study confirmed that delayed initiation of tacrolimus in patients with delayed graft function is associated with a high risk of BPAR.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Tacrolimo/administração & dosagem , Tempo para o Tratamento , Adulto , Estudos de Coortes , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Incidência , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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