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1.
Am J Transplant ; 24(3): 362-379, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37871799

RESUMO

The Banff pancreas working schema for diagnosis and grading of rejection is widely used for treatment guidance and risk stratification in centers that perform pancreas allograft biopsies. Since the last update, various studies have provided additional insight regarding the application of the schema and enhanced our understanding of additional clinicopathologic entities. This update aims to clarify terminology and lesion description for T cell-mediated and antibody-mediated allograft rejections, in both active and chronic forms. In addition, morphologic and immunohistochemical tools are described to help distinguish rejection from nonrejection pathologies. For the first time, a clinicopathologic approach to islet pathology in the early and late posttransplant periods is discussed. This update also includes a discussion and recommendations on the utilization of endoscopic duodenal donor cuff biopsies as surrogates for pancreas biopsies in various clinical settings. Finally, an analysis and recommendations on the use of donor-derived cell-free DNA for monitoring pancreas graft recipients are provided. This multidisciplinary effort assesses the current role of pancreas allograft biopsies and offers practical guidelines that can be helpful to pancreas transplant practitioners as well as experienced pathologists and pathologists in training.


Assuntos
Transplante de Pâncreas , Transplante Homólogo , Biópsia , Isoanticorpos , Linfócitos T
2.
Xenotransplantation ; 31(1): e12845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38407937

RESUMO

The 2023 IXA conference, hosted in San Diego, CA, brimmed with excitement against the backdrop of recent innovations in both the pre-clinical and clinical realms with several first-in-human applications of xenotransplantation. The theme, "Pigs are flying," alluded to the adage that xenotransplantation would only become a clinical reality "when pigs fly," suggesting a day that might never come. The event witnessed significant attendance, with 600 participants-the highest in the history of an IXA-IPITA joint congress. Among the attendees were members of the Food and Drug Administration (FDA), the National Institutes of Health (NIH), and corporate sponsors deeply engaged in the field. We summarize the latest topics from the congress, ranging from the pros/cons of decedent models of xenotransplantation and genetic engineering of porcine heart valves, solid organs, and cells for clinical translation and their regulatory and ethical landscape.


Assuntos
Bioprótese , Próteses Valvulares Cardíacas , Estados Unidos , Suínos , Animais , Humanos , Transplante Heterólogo , Engenharia Genética , United States Food and Drug Administration
3.
Am J Transplant ; 23(1): 108-110, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36148600

RESUMO

Severe iliac artery calcification in patients with end-stage renal disease is a common barrier to listing for kidney transplant. While few surgical solutions to iliac calcification have been reported, improving treatment may thus improve access to transplant care. Here we present two cases of a novel application of remote endarterectomy of the external iliac artery to facilitate listing for renal transplant. Both patients were listed following remote endarterectomy, followed by successful renal transplants using the treated vessels.


Assuntos
Arteriosclerose , Falência Renal Crônica , Transplante de Rim , Humanos , Falência Renal Crônica/complicações , Falência Renal Crônica/cirurgia , Endarterectomia , Artéria Ilíaca/cirurgia
4.
Xenotransplantation ; 30(3): e12805, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37248796

RESUMO

After a significant hiatus imposed by the COVID-19 pandemic, we hereby restart Xenotransplantation literature updates. With the recently performed clinical xenotransplantation cases and the much-heightened interest in the field, we have determined that this is an optimal time to reinstate this section. There has been an invigorated focus on unique challenges posed by pig-to-human xenotransplantation, and specific attention will be given to this aspect. In this issue, we aimed to cover the gap and compiled the most relevant publications from March 2021 to March 2023.


Assuntos
COVID-19 , Pandemias , Humanos , Animais , Suínos , Transplante Heterólogo/métodos
5.
Transpl Int ; 35: 10855, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36568142

RESUMO

Donation-after-circulatory-death (DCD), donation-after-brain-death (DBD), and living-donation (LD) are the three possible options for liver transplantation (LT), each with unique benefits and complication rates. We aimed to compare DCD-, DBD-, and LD-LT-specific graft survival and biliary complications (BC). We collected data on 138 DCD-, 3,027 DBD- and 318 LD-LTs adult recipients from a single center and analyzed patient/graft survival. BC (leak and anastomotic/non-anastomotic stricture (AS/NAS)) were analyzed in a subset of 414 patients. One-/five-year graft survival were 88.6%/70.0% for DCD-LT, 92.6%/79.9% for DBD-LT, and, 91.7%/82.9% for LD-LT. DCD-LTs had a 1.7-/1.3-fold adjusted risk of losing their graft compared to DBD-LT and LD-LT, respectively (p < 0.010/0.403). Bile leaks were present in 10.1% (DCD-LTs), 7.2% (DBD-LTs), and 36.2% (LD-LTs) (ORs, DBD/LD vs. DCD: 0.7/4.2, p = 0.402/<0.001). AS developed in 28.3% DCD-LTs, 18.1% DBD-LTs, and 43.5% LD-LTs (ORs, DBD/LD vs. DCD: 0.5/1.8, p = 0.018/0.006). NAS was present in 15.2% DCD-LTs, 1.4% DBDs-LT, and 4.3% LD-LTs (ORs, DBD/LD vs. DCD: 0.1/0.3, p = 0.001/0.005). LTs w/o BC had better liver graft survival compared to any other groups with BC. DCD-LT and LD-LT had excellent graft survival despite significantly higher BC rates compared to DBD-LT. DCD-LT represents a valid alternative whose importance should increase further with machine/perfusion systems.


Assuntos
Transplante de Fígado , Obtenção de Tecidos e Órgãos , Adulto , Humanos , Transplante de Fígado/efeitos adversos , Estudos de Coortes , Morte Encefálica , Doadores Vivos , Estudos Retrospectivos , Sobrevivência de Enxerto , Doadores de Tecidos , Morte
6.
Xenotransplantation ; 28(3): e12681, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33759229

RESUMO

BACKGROUND: Xenotransplantation has made tremendous progress over the last decade. METHODS: We discuss kidney and heart xenotransplantation, which are nearing initial clinical trials. RESULTS: Life sustaining genetically modified kidney xenografts can now last for approximately 500 days and orthotopic heart xenografts for 200 days in non-human primates. Anti-swine specific antibody screening, preemptive desensitization protocols, complement inhibition and targeted immunosuppression are currently being adapted to xenotransplantation with the hope to achieve better control of antibody-mediated rejection (AMR) and improve xenograft longevity. These newest advances could probably facilitate future clinical trials, a significant step for the medical community, given that dialysis remains difficult for many patients and can have prohibitive costs. Performing a successful pig-to-human clinical kidney xenograft, that could last for more than a year after transplant, seems feasible but it still has significant potential hurdles to overcome. The risk/benefit balance is progressively reaching an acceptable equilibrium for future human recipients, e.g. those with a life expectancy inferior to two years. The ultimate question at this stage would be to determine if a "proof of concept" in humans is desirable, or whether further experimental/pre-clinical advances are still needed to demonstrate longer xenograft survival in non-human primates. CONCLUSION: In this review, we discuss the most recent advances in kidney and heart xenotransplantation, with a focus on the prevention and treatment of AMR and on the recipient's selection, two aspects that will likely be the major points of discussion in the first pig organ xenotransplantation clinical trials.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Animais , Animais Geneticamente Modificados , Rejeição de Enxerto/prevenção & controle , Xenoenxertos , Humanos , Terapia de Imunossupressão , Suínos , Transplante Heterólogo
7.
Transpl Int ; 33(11): 1516-1528, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32852857

RESUMO

The success of pancreas islet isolation largely depends on donor characteristics, including extracellular matrix composition of which collagen is the main element. We hypothesized that isolation yields are proportional to collagen digestion percentage, and aimed to determine a threshold that predicts isolation success. The amount of pancreas collagen (I-V) was determined using colorimetry prior to and after the digestion process in 52 human islet isolations. Collagen I-V and VI were also assessed histologically. We identified a collagen digestion threshold of ≥ 60% as an independent factor beyond which an islet preparation has a ninefold increased odds of yielding ≥ 250 000 islet equivalents (IEQ) (P = 0.009) and a sixfold increased odds of being transplanted (P = 0.015). Preparations with ≥ 60% collagen digestion (n = 35) yielded 283 017 ± 164 214 IEQ versus 180 142 ± 85 397 in the < 60% collagen digestion group (n = 17) (P = 0.016); respectively 62.9% versus 29.4% of those were transplanted (P = 0.024). Common donor characteristics, initial collagen content, enzyme blend, and digestion times were not associated with collagen digestion percentage variations. Donor age positively correlated with the amount of collagen VI (P = 0.013). There was no difference in islet graft survival between high and low digestion groups. We determined that a 60% pancreas collagen digestion is the threshold beyond which an islet isolation is likely to be successful and transplanted.


Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Separação Celular , Colágeno , Digestão , Humanos , Pâncreas , Estudos Prospectivos
8.
NMR Biomed ; 32(8): e4109, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31131943

RESUMO

Clinical use of MRSI is limited by the level of experience required to properly translate MRSI examinations into relevant clinical information. To solve this, several methods have been proposed to automatically recognize a predefined set of reference metabolic patterns. Given the variety of metabolic patterns seen in glioma patients, the decision on the optimal number of patterns that need to be used to describe the data is not trivial. In this paper, we propose a novel framework to (1) separate healthy from abnormal metabolic patterns and (2) retrieve an optimal number of reference patterns describing the most important types of abnormality. Using 41 MRSI examinations (1.5 T, PRESS, TE 135 ms) from 22 glioma patients, four different patterns describing different types of abnormality were detected: edema, healthy without Glx, active tumor and necrosis. The identified patterns were then evaluated on 17 MRSI examinations from nine different glioma patients. The results were compared against BraTumIA, an automatic segmentation method trained to identify different tumor compartments on structural MRI data. Finally, the ability to predict future contrast enhancement using the proposed approach was also evaluated.


Assuntos
Algoritmos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Glioma/diagnóstico por imagem , Glioma/patologia , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Reprodutibilidade dos Testes
9.
Dis Colon Rectum ; 62(9): 1105-1116, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31318772

RESUMO

BACKGROUND: Enhanced recovery program is a multimodal, multidisciplinary-team, evidence-based care approach to reduce perioperative surgical stress, decrease morbidity and hospital stay, and improve recovery after surgery. This program may be most beneficial for elderly (≥70 y), but sparse series have investigated this question. OBJECTIVE: Feasibility and efficiency of a dedicated enhanced recovery program in the elderly as compared with standard care were studied. DESIGN: This was a nonblinded, randomized controlled study. SETTINGS: This study was conducted in a single high-volume university hospital. PATIENTS: A total of 150 eligible elderly patients undergoing elective colorectal surgery were included. INTERVENTIONS: Enhanced recovery after colorectal elective surgery in elderly patients was studied. MAIN OUTCOME MEASURES: The primary outcome was 30-day postoperative morbidity. Additional outcomes included hospital stay, readmission, postoperative pain, opioid consumption, independence preservation, and protocol compliance. RESULTS: An enhanced recovery program reduces postoperative morbidity according to Clavien-Dindo classification by 47% as compared with standard care (35% vs 65%; p = 0.0003), total number of complications (54 vs 118; p = 0.0003), and infectious complications (13 vs 29; p = 0.001). No anastomotic leak was recorded in the enhanced recovery group versus 5 for the standard group (p = 0.01). The enhanced recovery program resulted in shorter hospital stay (7 vs 12 d; p = 0.003) and better independence preservation (home discharge, 87% vs 67%; p = 0.005). A high protocol compliance of 77.2% could be achieved in this population. According to multivariate analysis, enhanced recovery program was strongly associated with reduced morbidity (OR = 0.23 (95% CI, 0.09-0.57); p = 0.001), less severe complications (OR = 0.36 (95% CI, 0.15-0.84); p = 0.02), and shorter hospital stay (OR = 2.07 (95% CI, 1.33-3.22); p = 0.001). LIMITATIONS: Limitations were a single-center recruitment and the impossibility of subject or healthcare professional blinding attributed to the nature of this multimodal program. CONCLUSIONS: Enhanced recovery program is safe and improves postoperative recovery in elderly patients with decreased morbidity, shorter hospital stay, and better maintenance of independence. It should therefore be considered as a standard of care for elective colorectal surgery in elderly patients. See Video Abstract at http://links.lww.com/DCR/A981. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT01646190. ENSAYO CONTROLADO ALEATORIZADO DE UN PROGRAMA DE RECUPERACIÓN INTENSIFICADA DEDICADO A PACIENTES DE EDAD AVANZADA DESPUÉS DE CIRUGÍA COLORECTAL: El Programa de Recuperación Intensificada es un enfoque de atención multimodal, multidisciplinaria y basada en evidencia para reducir el estrés quirúrgico perioperatorio, disminuir la morbilidad y la estancia hospitalaria, y mejorar la recuperación después de la cirugía. Este programa puede ser más beneficioso para las personas mayores (≥70 años), pero pocas series han investigado esta pregunta. OBJETIVO: Viabilidad y eficiencia del Programa de Recuperación Intensificada dedicado en personas de edad avanzada en comparación con la atención estándar. DISEÑO:: Este fue un estudio controlado, aleatorizado, sin método ciego. ESCENARIO: Este estudio se realizó en un único hospital universitario de alto volumen. PACIENTES: Un total de 150 pacientes de edad avanzada elegibles sometidos a cirugía colorrectal electiva fueron incluidos. INTERVENCIONES: Recuperación Intensificada después de cirugía electiva colorrectal en pacientes de edad avanzada. PRINCIPALES MEDIDAS DE RESULTADO: El resultado primario fue la morbilidad postoperatoria a 30 días. Los resultados adicionales incluyeron estancia hospitalaria, reingreso, dolor postoperatorio, consumo de opioides, preservación de la independencia y cumplimiento del protocolo. RESULTADOS: El Programa de Recuperación Intensificada reduce la morbilidad postoperatoria según la clasificación de Clavien-Dindo en un 47% en comparación con la atención estándar (35% vs 65%; p = 0.0003), número total de complicaciones (54 vs 118; p = 0.0003) y complicaciones infecciosas (13 vs 29; p = 0.001). No se registró ninguna fuga anastomótica en el grupo de Recuperación Intensificada frente a 5 para el grupo estándar (p = 0.01). El Programa de Recuperación Intensificada dio como resultado una estancia hospitalaria más corta (7 contra 12 días; p = 0.003) y una mejor conservación de la independencia (alta hospitalaria: 87% vs 67%; p = 0.005). Se pudo lograr un alto cumplimiento del protocolo del 77.2% en esta población. De acuerdo con el análisis multivariable, el Programa de Recuperación Intensificada se asoció fuertemente con la reducción de morbilidad (OR = 0.23; IC 95%: 0.09-0.57; p = 0.001), menos complicaciones graves (OR = 0.36; IC 95%: 0.15-0.84; p = 0.02) y estancia hospitalaria más corta (OR = 2.07; IC 95%: 1.33-3.22; p = 0.001). LIMITACIONES: Las limitaciones fueron un centro único de reclutamiento y la imposibilidad de que los pacientes o el profesional de la salud tuvieran cegamiento debido a la naturaleza de este programa multimodal. CONCLUSIONES: El Programa de recuperación Intensificada es seguro y mejora la recuperación postoperatoria en pacientes de edad avanzada, con menor morbilidad, menor estancia hospitalaria y mejor mantenimiento de la independencia. Por lo tanto, debe considerarse como un estándar de atención para la cirugía colorrectal electiva en pacientes de edad avanzada. Vea el Resumen en video en http://links.lww.com/DCR/A981.


Assuntos
Colectomia/reabilitação , Doenças do Colo/reabilitação , Defecação/fisiologia , Procedimentos Cirúrgicos Eletivos/reabilitação , Laparoscopia/reabilitação , Cuidados Pós-Operatórios/métodos , Recuperação de Função Fisiológica , Idoso , Doenças do Colo/fisiopatologia , Doenças do Colo/cirurgia , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Tempo de Internação , Masculino
10.
Int J Mol Sci ; 20(6)2019 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-30875826

RESUMO

BACKGROUND: Interleukin-1 (IL-1)ß and IL-1 receptor antagonist (IL-1Ra) have been proposed as important mediators during chronic liver diseases. We aimed to determine whether the modulation of IL-1ß signaling with IL-1Ra impacts on liver fibrosis. METHODS: We assessed the effects of IL-1ß on human hepatic stellate cells (HSC) and in mouse models of liver fibrosis induced by bile duct ligation (BDL) or carbon tetrachloride treatment (CCl-4). RESULTS: Human HSCs treated with IL-1ß had increased IL-1ß, IL-1Ra, and MMP-9 expressions in vitro. HSCs treated with IL-1ß had reduced α-smooth muscle actin expression. These effects were all prevented by IL-1Ra treatment. In the BDL model, liver fibrosis and Kuppfer cell numbers were increased in IL-1Ra KO mice compared to wild type mice and wild type mice treated with IL-1Ra. In contrast, after CCl-4 treatment, fibrosis, HSC and Kupffer cell numbers were decreased in IL-1Ra KO mice compared to the other groups. IL-1Ra treatment provided a modest protective effect in the BDL model and was pro-fibrotic in the CCl-4 model. CONCLUSIONS: We demonstrated bivalent effects of IL-1Ra during liver fibrosis in mice. IL-1Ra was detrimental in the CCl-4 model, whereas it was protective in the BDL model. Altogether these data suggest that blocking IL-1-mediated inflammation may be beneficial only in selective liver fibrotic disease.


Assuntos
Actinas/genética , Proteína Antagonista do Receptor de Interleucina 1/genética , Interleucina-1beta/genética , Cirrose Hepática/genética , Metaloproteinase 9 da Matriz/genética , Animais , Tetracloreto de Carbono/efeitos adversos , Contagem de Células , Células Cultivadas , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Técnicas de Inativação de Genes , Humanos , Células de Kupffer/citologia , Células de Kupffer/efeitos dos fármacos , Células de Kupffer/imunologia , Cirrose Hepática/etiologia , Cirrose Hepática/imunologia , Masculino , Camundongos , Regulação para Cima
11.
Stroke ; 49(6): 1355-1362, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29769241

RESUMO

BACKGROUND AND PURPOSE: Patients with embolic large-vessel occlusion may present with additional coincidental acute occlusions within or distant from the involved territory, referred to as multivessel occlusion (MVO). Purpose of this study was to assess prevalence of MVO, associated factors, and clinical relevance in patients undergoing endovascular stroke treatment. METHODS: Image data of consecutive endovascular candidates (n=720) with direct access to angiography were extracted from a prospective registry. Prevalence of MVO was assessed with multimodal magnetic resonance imaging/computed tomography and confirmed by intra-arterial angiography. Explorative analysis of associated factors and clinical relevance was evaluated using multivariable logistic regression including variables with P<0.15 in univariate comparison. Good functional outcome was defined as modified Rankin Scale score ≤2 at day 90. RESULTS: MVO was present in 10.7% of patients (95% confidence interval [CI], 6.4%-13.0%). Two, 3, and 4 concomitant occlusions were found in 80.5%, 16.9%, and 2.6% of MVO cases, respectively. Detection rate on initial radiological report was 54.5%. Downstream MVO was present in around one third of MVO (n=27/77, 35.1%), whereas all other MVO (n=50/77, 64.9%) occurred in different territories. Independent factors related to MVO were statin treatment (adjusted odds ratio [aOR], 0.477; 95% CI, 0.276-0.827), higher systolic blood pressure (aOR per mm Hg increase, 1.014; 95% CI, 1.005-1.023), and primary occlusion site M2 (aOR, 1.870; 95% CI, 1.103-3.170). MVO was related to lower rates of successful reperfusion (aOR, 0.549; 95% CI, 0.316-0.953) and lower rates of good functional outcome (aOR, 0.437; 95% CI, 0.207-0.923). CONCLUSIONS: Every tenth patient subjected to angiography for endovascular stroke treatment experienced MVO in our series, and only half were prospectively identified on preinterventional diagnostic imaging. Patients with MVO had higher baseline systolic blood pressure and were less often medicated with statins, an observation that warrants external validation and evaluation regarding causality. Occurrence of MVO has implication for treatment decisions, negatively affects endovascular treatment success, and is predictive of worse clinical outcome.


Assuntos
Complicações Pós-Operatórias/epidemiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Trombectomia/efeitos adversos , Idoso , Angiografia Cerebral/métodos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores de Risco , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Resultado do Tratamento
12.
Magn Reson Med ; 80(6): 2339-2355, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29893995

RESUMO

PURPOSE: To improve the detection of peritumoral changes in GBM patients by exploring the relation between MRSI information and the distance to the solid tumor volume (STV) defined using structural MRI (sMRI). METHODS: Twenty-three MRSI studies (PRESS, TE 135 ms) acquired from different patients with untreated GBM were used in this study. For each MRSI examination, the STV was identified by segmenting the corresponding sMRI images using BraTumIA, an automatic segmentation method. The relation between different metabolite ratios and the distance to STV was analyzed. A regression forest was trained to predict the distance from each voxel to STV based on 14 metabolite ratios. Then, the trained model was used to determine the expected distance to tumor (EDT) for each voxel of the MRSI test data. EDT maps were compared against sMRI segmentation. RESULTS: The features showing abnormal values at the longest distances to the tumor were: %NAA, Glx/NAA, Cho/NAA, and Cho/Cr. These four features were also the most important for the prediction of the distances to STV. Each EDT value was associated with a specific metabolic pattern, ranging from normal brain tissue to actively proliferating tumor and necrosis. Low EDT values were highly associated with malignant features such as elevated Cho/NAA and Cho/Cr. CONCLUSION: The proposed method enables the automatic detection of metabolic patterns associated with different distances to the STV border and may assist tumor delineation of infiltrative brain tumors such as GBM.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Glioma/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Algoritmos , Ácido Aspártico/análogos & derivados , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Neoplasias Encefálicas/patologia , Colina/metabolismo , Creatina/metabolismo , Glioma/patologia , Voluntários Saudáveis , Humanos , Reconhecimento Automatizado de Padrão , Análise de Regressão
13.
Transpl Int ; 31(5): 465-477, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29210109

RESUMO

The field of xenotransplantation has fluctuated between great optimism and doubts over the last 50 years. The initial clinical attempts were extremely ambitious but faced technical and ethical issues that prompted the research community to go back to preclinical studies. Important players left the field due to perceived xenozoonotic risks and the lack of progress in pig-to-nonhuman-primate transplant models. Initial apparently unsurmountable issues appear now to be possible to overcome due to progress of genetic engineering, allowing the generation of multiple-xenoantigen knockout pigs that express human transgenes and the genomewide inactivation of porcine endogenous retroviruses. These important steps forward were made possible by new genome editing technologies, such as CRISPR/Cas9, allowing researchers to precisely remove or insert genes anywhere in the genome. An additional emerging perspective is the possibility of growing humanized organs in pigs using blastocyst complementation. This article summarizes the current advances in xenotransplantation research in nonhuman primates, and it describes the newly developed genome editing technology tools and interspecific organ generation.


Assuntos
Transplante Heterólogo , Animais , Animais Geneticamente Modificados , Edição de Genes , Rejeição de Enxerto/etiologia , Humanos , Primatas , Suínos , Quimeras de Transplante , Transplante Heterólogo/efeitos adversos
14.
Transpl Int ; 31(8): 917-929, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29603452

RESUMO

The microbiological safety of islet preparations is paramount. Preservation medium contamination is frequent, and its impact on islet yield and function remains unclear. Microbiological samples collected during islet isolations from 2006 to 2016 were analyzed and correlated to isolation and allo- and autotransplantation outcomes. Microbial contamination of preservation medium was found in 64.4% of processed donor pancreases (291/452). We identified 464 microorganisms including Staphylococcus (253/464, 54.5%), Streptococcus (31/464, 6.7%), and Candida species (25/464, 5.4%). Microbial contamination was associated with longer warm and cold ischemia times and lower numbers of postpurification islet equivalents, purity, transplant rate, and stimulation index (all P < 0.05). Six percent of the preparations accepted for transplantation showed microbial contamination after isolation (12/200); 9 of 12 were Candida species. Six patients were transplanted with a sample with late microbial growth discovered after the infusion. Insulin independence rate was not affected. This risk of transplanting a contaminated islets preparation was reduced by half following the implementation of an additional sampling after 24 h of islet culture. Pancreas preservation fluid microbial contamination is associated with lower transplant rate and poorer in vitro function, but not with changes in graft survival. Culture medium testing 1 day after isolation reduces the risk of incidental transplantation with contaminated islets.


Assuntos
Contaminação de Medicamentos/estatística & dados numéricos , Transplante das Ilhotas Pancreáticas/estatística & dados numéricos , Soluções para Preservação de Órgãos , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Ilhotas Pancreáticas/microbiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
15.
FASEB J ; 30(2): 748-60, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26534832

RESUMO

The major feature of the human pancreatic islet architecture is the organization of endocrine cells into clusters comprising central ß cells and peripheral α cells surrounded by vasculature. To have an insight into the mechanisms that govern this unique islet architecture, islet cells were isolated, and reaggregation of α and ß cells into islet-like structures (pseudoislets) after culture or transplantation into mice was studied by immunohistology. The pseudoislets formed in culture displayed an unusual cell arrangement, contrasting with the transplanted pseudoislets, which exhibited a cell arrangement similar to that observed in native pancreatic islet subunits. The pattern of revascularization and the distribution of extracellular matrix around transplanted pseudoislets were alike to those observed in native pancreatic islets. This organization of transplanted pseudoislets occurred also when revascularization was abolished by treating mice with an anti-VEGF antibody, but not when contact with extracellular matrix was prevented by encapsulation of pseudoislets within alginate hydrogel. These results indicate that the maintenance of islet cell arrangement is dependent on in vivo features such as extracellular matrix but independent of vascularization.


Assuntos
Matriz Extracelular/patologia , Células Secretoras de Glucagon/patologia , Células Secretoras de Insulina/patologia , Transplante das Ilhotas Pancreáticas , Animais , Matriz Extracelular/metabolismo , Células Secretoras de Glucagon/metabolismo , Xenoenxertos , Humanos , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos SCID
16.
Xenotransplantation ; 29(1): e12736, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35166408
17.
Xenotransplantation ; 24(4)2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28736957

RESUMO

Blastocyst complementation refers to the injection of cells into a blastocyst. The technology allows for the creation of chimeric animals, which have the potential to be used as an unlimited source of organ donors. Pluripotent stem cells could be generated from a patient in need of a transplantation and injected into a large animal blastocyst (potentially of a pig), leading to the creation of organ(s) allowing immunosuppression-free transplantation. Various chimera combinations have already been generated, but one of the most recent steps leads to the creation of human-pig chimeras, which could be studied at an embryo stage. Although still far from clinical reality, the potential application is almost unlimited. The present review illustrates the historical steps of intra- and interspecific blastocyst complementation in rodents and large animals, specifically looking at its potential for generation of organ grafts. We also speculate on how it could change transplant indications, on its economic impact, and on the linked ethical concerns.


Assuntos
Blastocisto/metabolismo , Quimera/metabolismo , Células-Tronco Pluripotentes/citologia , Transplante Heterólogo , Animais , Diferenciação Celular/fisiologia , Proteínas do Sistema Complemento/metabolismo , Humanos , Suínos
18.
Ann Vasc Surg ; 44: 414.e5-414.e9, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28479435

RESUMO

A 61-year-old man received a living-donor kidney graft for an end-stage renal disease. In the postoperative course, the patient was oliguric and needed dialysis. The postoperative Doppler showed a normal peak systolic velocity and maintained parenchymal perfusion associated with a parvus tardus signal. The patient was operated, and a kinked renal artery was found. To reposition the artery, the distal iliac artery was clamped, sectioned, shortened, and reanastomosed after a 90° axial rotation. This innovative technic allowed restoration of a normal flow in the parenchyma and avoided an additional clamping, cooling, ischemia, and reanastomosis/reperfusion of the graft. Postoperative diuresis immediately raised >100 mL/hr and creatinine durably returned to normal values.


Assuntos
Função Retardada do Enxerto/cirurgia , Transplante de Rim/efeitos adversos , Doadores Vivos , Artéria Renal/cirurgia , Doenças Vasculares/cirurgia , Anastomose Cirúrgica , Angiografia por Tomografia Computadorizada , Função Retardada do Enxerto/diagnóstico por imagem , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/fisiopatologia , Humanos , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Artéria Renal/diagnóstico por imagem , Artéria Renal/fisiopatologia , Circulação Renal , Reoperação , Resultado do Tratamento , Doenças Vasculares/diagnóstico por imagem , Doenças Vasculares/etiologia , Doenças Vasculares/fisiopatologia
19.
Rev Med Suisse ; 12(523): 1174-9, 2016 Jun 15.
Artigo em Francês | MEDLINE | ID: mdl-27487622

RESUMO

The detection rate of cystic lesions of the pancreas has increased following the widespread use of high-resolution imaging technologies. CT-scan, MRI and echo-endoscopy are diagnostic modalities. Pseudocyst is the most common lesion. It is benign and can be managed with endoscopic treatment. Mucinous cystic neoplasia and Intraductal Papillary Mucinous Neoplasia (IPMN) carry a risk for malignant transformation. The surgical treatment of these lesions has to be discussed by a multidisciplinary board. Serous cystic neoplasia and pseudopapillar and solid neoplasia are two rare types of lesion. The aim of this article is to present the diagnostic pathway and the management of these lesions from the general practitioner point of view.


Assuntos
Cisto Pancreático/diagnóstico , Comportamento Cooperativo , Diagnóstico Diferencial , Diagnóstico por Imagem , Humanos , Cisto Pancreático/cirurgia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/cirurgia , Equipe de Assistência ao Paciente , Atenção Primária à Saúde , Encaminhamento e Consulta
20.
Rev Med Suisse ; 12(523): 1190-4, 2016 Jun 15.
Artigo em Francês | MEDLINE | ID: mdl-27487625

RESUMO

In 2016, peritoneal carcinomatosis can be considered as a chronic disease that can be treated and sometimes cured. Hyperthermic Intra PEritoneal Chemotherapy (HIPEC) is a procedure developed in the eighties. Combined with CytoReductive (CR) surgery, this protocol underwent a considerable expansion in Washington Cancer Institute. CR combined with HIPEC was demonstrated to be the only curative treatment for PseudoMyxoma Peritonei syndrome (PMP). It is actually approved in the management of peritoneal carcinomatosis of ovarian, colorectal, or peritoneal primitive (mesothelioma) origin but is still studied for gastric cancer. CR/HIPEC is associated with an important mortality and morbidity. This article takes stock of indications to CR/HIPEC.


Assuntos
Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Peritoneais/terapia , Quimioterapia do Câncer por Perfusão Regional , Humanos
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