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1.
Khirurgiia (Mosk) ; (9): 69-74, 2020.
Artigo em Russo | MEDLINE | ID: mdl-33030004

RESUMO

Critical limb ischemia, especially in the absence of autologous vein, prosthetic and native vascular infections are isolated diseases for which there currently doesn't have best surgical treatment. Vascular allografts may be the treatment of choice for these patients. In this analysis, we tried to reflect the directions of development of vascular allotransplantation, global trends related to indications for their use, methods of conservation, degradation and endothelial dysfunction. At the present time there doesn't have meta-analyzes on the efficiency of using arterial allografts or other options for implantation (synthetic graft, xenografts) for critical limb ischemia and graft and native infections. Now it is wrong to recommend using them always. Further studies of their performance are necessary. In addition, development of graft control techniques is also needed when rejection develops. Currently, there are no special diagnostic markers, the assessment of which could save patients with immune-mediated dilatation and dysfunction of allografts.


Assuntos
Artérias , Procedimentos Cirúrgicos Reconstrutivos , Aloenxertos , Humanos , Extremidade Inferior , Transplante Homólogo
4.
Arthroscopy ; 36(9): 2464-2465, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32891247

RESUMO

Despite its overall good results, meniscal allograft transplantation is considered a salvage procedure, and abstention from sport practice is considered a valid solution to preserve the transplanted meniscus as long as possible. However, many patients want to return to sport, and this is often beneficial for them. Therefore, we should know how meniscal allograft transplantation performs in terms of return to sport to better counsel our patients. It is thus of primary importance to discuss general and sport-related expectations with each patient, whom should be informed of the potential short- and long-term risks of strenuous or light sport activities. In particular, the high risk of reoperation, the long recovery time, and the potentially deleterious effect of sporting activity on graft survival should be quite clear to both surgeons and patients because, when it comes to return-to-sport decisions, "It takes two to tango"!


Assuntos
Menisco , Volta ao Esporte , Aloenxertos , Humanos , Meniscos Tibiais , Satisfação do Paciente
5.
Int J Periodontics Restorative Dent ; 40(5): 749-756R, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32926005

RESUMO

This investigation was designed to evaluate the long-term effectiveness of human placental allograft in root coverage procedures in terms of clinical and esthetic outcomes. Thirteen patients with 28 maxillary or mandibular recession defects > 4 mm deep were reexamined at 6 months and 5 years postoperatively. Overall, mean percentage of root coverage decreased from 65.58% ± 16.45% to 49.75% ± 19.40% with a greater stability of the gingival margin in the mandible. At 5 years, 18 sites maintained at least 2 mm of keratinized tissue. Gingival color and texture blended well with adjacent soft tissue area in 78.6% of treated sites.


Assuntos
Retração Gengival , Aloenxertos , Tecido Conjuntivo/transplante , Estética , Feminino , Gengiva , Humanos , Gravidez , Retalhos Cirúrgicos , Raiz Dentária , Resultado do Tratamento
6.
Ann Hematol ; 99(11): 2639-2648, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32889611

RESUMO

Extramedullary relapse (EMR) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) continues to remain a clinical challenge. The data on EMR in acute lymphoblastic leukemia (ALL) are currently limited. Herein, a retrospective analysis of 268 adult ALL patients who underwent allo-HSCT in our center between March 2008 and December 2017 was performed to analyze post-HSCT EMR. Ninety patients (33.58%) experienced relapse; 51(19.03%) experienced bone marrow relapse (BMR), whereas 39 (14.55%) experienced EMR. The 5-year cumulative EMR incidence (CEMRI) revealed that matched sibling donor (MSD)-HSCTs were more likely to develop EMR than unrelated donor (URD)- and haploidentical-related donor (HRD)-HSCTs (CEMRI: 24.02%, 7.69%, and 14.69% for MSD, URD, and HRD, respectively). Notably, MSD-HSCTs (URD vs MSD hazard ratio (HR) = 0.26, p = 0.015; HRD vs MSD HR = 0.46, p = 0.032), history of extramedullary disease (EMD) (HR = 2.45, p = 0.041), and T cell ALL (HR = 2.80, p = 0.012) were independent risk factors for EMR in the multivariate analysis. The median overall survival (OS) for all patients was 15.23 months. However, the OS of EMR patients was significantly longer (19.50 months) than that of BMR patients (12.90 months) (p = 0.003). Multivariate analyses revealed that the leading risk factors for post-relapse deaths were shorter intervals between HSCT and relapse (> 12 months vs ≤ 12 months, HR = 0.30, p < 0.001) and BMR (HR = 0.41, p = 0.002). In conclusion, EMR patients have better survival than BMR patients. ALL patients with allo-HSCT from MSDs, a history of EMD, and the T cell type were significantly associated with EMR.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
7.
Ann Hematol ; 99(11): 2529-2538, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32948913

RESUMO

INTRODUCTION: Since the 1970s outcome of aplastic anemia (AA) patients has improved significantly due to the introduction of immunosuppressive therapy (IST) and allogeneic hematopoietic transplantation (HCT). However, patients may suffer from persistent disease, relapse, clonal evolution, graft-versus-host disease and other late effects. Here, we analyse very long-term outcome of all AA patients at our institution comparing not only survival, but also response status and complications. METHODS: Patient charts of all 302 AA patients treated between 1973 and 2017 at the University Hospital Basel, Switzerland, were retrospectively analysed. RESULTS: First line treatment was IST in 226 (75%) and HCT in 76 (25%) patients. Overall survival at 30 years was similar in patients treated initially by HCT and IST (44% (±14%), and 40% (± 9%) respectively, with better results in more recent years. Partial and no response occurred more frequently after IST, relapse incidence after IST was 24 %, whereas non-engraftment and graft failure was documented in 15 patients (19 %) after HCT. Clonal evolution to myelodysplastic syndrome / acute myeloid leukemia was 16 % at 25 years in IST patients, 1.3 % in HCT patients, iron overload (18 versus 4 %, p = 0.002) and cardiovascular events (11 versus 1 %, p=0.011) occured significantly more often in IST than HCT treated patients. The majority of long-term survivors, 96% of those alive at 25 years, were in complete remission at last follow up, irrespective of the initial treatment modality. CONCLUSION: Very long term survivors after AA are those with stable hematopoietic recovery.


Assuntos
Anemia Aplástica , Hematopoese , Transplante de Células-Tronco Hematopoéticas , Imunossupressão , Recuperação de Função Fisiológica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aloenxertos , Anemia Aplástica/mortalidade , Anemia Aplástica/terapia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Ann Hematol ; 99(11): 2619-2628, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32960314

RESUMO

In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) achieving complete remission (CR). However, the role of autologous hematopoietic stem cell transplantation (auto-HSCT) in adult patients achieving complete molecular remission (CMR) is an alternative, less toxic treatment options, especially for the patients who lack suitable donors and are unfit for allo-HSCT. Thus, we conducted a systematic review and meta-analysis to compare the efficacy of allo-HSCT and auto-HSCT for the treatment of adult patients with Ph+ ALL. We searched the PubMed, Embase, Scopus, and Cochrane Library for studies published before June 2019 without language restriction. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS) and odds ratios (ORs) and 95% CIs for relapse rate (RR) and treatment-related mortality (TRM). Four prospective studies and one retrospective study were included with a total of 810 patients. We found auto-HSCT was superior to allo-HSCT in OS (HR = 1.42, 95% CI: 1.06-1.91, P = 0.02), and there was no difference between allo-HSCT and auto-HSCT for RFS (HR = 1.10, 95% CI: 0.86-1.40, P = 0.44) and RR (OR = 0.53, 95% CI: 0.22-1.26, P = 0.15). The risk of TRM for patients undergoing allo-HSCT was significantly higher than that of the patients who received auto-HSCT (OR = 5.06, 95% CI: 1.03-24.75, P = 0.05). Our meta-analysis shows that auto-HSCT may be an attractive and alternative treatment option for adult Ph+ ALL patients achieving CMR, with similar or better outcomes than allo-HSCT in the era of TKIs.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Taxa de Sobrevida
9.
S Afr Med J ; 110(7): 691-694, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32880349

RESUMO

BACKGROUND: The most common clinical indication for renal biopsy in the early post-transplant period is early graft dysfunction (EGD), which may present either as delayed graft function (DGF) or acute graft dysfunction. Even though it is a valuable diagnostic tool, renal allograft biopsy is not without risk of major complications. Recent studies have suggested that, with modern immunosuppressive induction regimens and more accurate ways to determine high immunological risk transplants, early acute rejection (AR) is uncommon and routine biopsy for EGD does not result in a change in management. OBJECTIVES: To describe the histological findings and complications of renal allograft biopsies for EGD in our setting, and to determine whether our current threshold for biopsy is appropriate. METHODS: This study was a retrospective audit that included all patients who underwent renal allograft biopsy within the first 30 days of transplantation at Groote Schuur Hospital, Cape Town, South Africa, from 1 June 2010 to 30 June 2018. The indication for biopsy was any patient who showed significant EGD, characterised by acute graft dysfunction or DGF with dialysis dependence. RESULTS: During the study period, 330 patients underwent renal transplantation, of whom 105 (32%) had an early biopsy and were included in the study. The median age of recipients was 39 (range 17 - 62) years, with 65% males and 35% females. The majority of donors were deceased donations after brain death (70%), with an overall median cold ischaemic time of 9 hours (interquartile range (IQR) 4 - 16). The average number of human leukocyte antigen mismatches was 5 (IQR 4 - 7). A donor-specific antibody was recorded for 18% of recipients and a panel-reactive antibody score of >30% was recorded for 21%. The median duration after transplant for biopsy was 8 (IQR 6 - 10) days. During the first month of EGD, AR was diagnosed in 42% of patients who underwent biopsies. In 21% of these patients, there was acute cellular rejection, in 16% antibody-mediated rejection, and in 5% both of these. Acute tubular necrosis was the primary finding in 32%, with acute interstitial nephritis in 8%, and acute calcineurin toxicity in 4% of cases. A significant biopsy-related complication was recorded in 3 patients: 1 small-bowel perforation repaired via laparotomy, and 2 vascular injuries successfully embolised by interventional radiology. CONCLUSIONS: Considering the relative safety and high rate of detection of AR, a liberal approach to renal biopsy for EGD remains justifiable in our setting.


Assuntos
Aloenxertos , Biópsia , Transplante de Rim , Rim/patologia , Adolescente , Adulto , Calcineurina/efeitos adversos , Auditoria Clínica , Feminino , Rejeição de Enxerto/diagnóstico , Humanos , Necrose Tubular Aguda/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/patologia , Disfunção Primária do Enxerto/diagnóstico , Estudos Retrospectivos , África do Sul , Adulto Jovem
10.
Adv Clin Exp Med ; 29(9): 1029-1037, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32871060

RESUMO

BACKGROUND: The reconstruction of the anterior cruciate ligament (ACL) of the knee joint is the gold standard in complete ACL rupture treatment. One of the central discussion topics is choice of graft. OBJECTIVES: To assess the outcome of treatment after primary ACL reconstruction using allograft. MATERIAL AND METHODS: The study was a retrospective cohort study. Out of 372 male patients who had undergone primary unilateral intra-articular ACL reconstruction using strict inclusion and exclusion criteria, 61 patients who qualified for the study took part. Group I was made up of 31 patients with allograft, while Group II consisted of 30 patients involved with autograft. The Lachman test, Pivot-Shift test, Lysholm Knee Scoring scale, and 2000 International Knee Documentation Committee (IKDC) were used to evaluate the results. Follow-up time was 18 months. RESULTS: The knee joint regained anterior stability in subjective and objective assessments in all the patients in both groups. The subjective results were the following: in Group I, 96.6 ±3.08 points on the Lysholm scale and 94.79 ±6.53 points on the IKDC 2000 scale, while in Group II, 98.00 ±1.9 points on the Lysholm scale and 94.81 ±5.6 points on the IKDC 2000 scale. The group comparison of the results of the IKDC 2000 and Lysholm Scale obtained postoperatively showed no statistically significant differences between the 2 groups. CONCLUSIONS: Primary ACL reconstruction using an allograft is an effective procedure to counteract instability of the anterior knee joint. Comparative analysis of the results of primary ACL reconstruction in the treatment of anterior knee instability using autograft or allograft gives grounds for the possibility of individual selection of graft depending on what the patient's expectations are.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Aloenxertos , Ligamento Cruzado Anterior , Lesões do Ligamento Cruzado Anterior/cirurgia , Humanos , Articulação do Joelho , Masculino , Estudos Retrospectivos , Resultado do Tratamento
11.
Arthroscopy ; 36(8): 2275-2278, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32747067

RESUMO

The altered knee joint function and symptomatic state in younger patients after meniscectomy and progressive tibiofemoral arthritis remain an important unsolved treatment dilemma. Meniscal allograft transplantation has evolved as an acceptable treatment because there are few (if any) other options. The procedure is effective in most patients, who experience a decrease in tibiofemoral pain and improved knee function, even allowing a return to light recreational activities. However, biological remodeling of the implant occurs over time, with replacement of the complex circumferential and radial fibers with disorganized collagen tissues and altered cellular and proteoglycan components that affects load bearing and negates chondroprotective function. Positive patient outcomes may still be reported even with the loss of meniscal transplant function on magnetic resonance imaging giving a false-positive survivorship analysis. Repeated surgical procedures are frequent by 10 years. Patients are advised that meniscal allograft transplant surgery, although beneficial in the short term to buy time, is not curative.


Assuntos
Meniscos Tibiais , Sobrevivência , Aloenxertos , Humanos , Articulação do Joelho , Imagem por Ressonância Magnética , Medidas de Resultados Relatados pelo Paciente
12.
Medicine (Baltimore) ; 99(31): e21336, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756120

RESUMO

RATIONALE: Hepatic alveolar echinococcosis (HAE) presents a high pathogenicity and case fatality rate. The main treatment for HAE is surgical resection. Giant lesions in the liver and invasion of the pathogen into the retrohepatic inferior vena cava are usually associated with a poor prognosis when radical resection cannot be performed. PATIENT CONCERNS: A 56-year-old man who underwent hydatidectomy 7 years prior noted a recurrence of HAE. He was subsidized and admitted to our hospital for the purpose of surgical treatment. DIAGNOSIS: By computed tomography, angiography and three-dimensional (3D) computed tomography reconstruction images, multiple, giant HAE with 75% stenosis was confirmed. INTERVENTIONS: With the 3D visualization technique, we designed the surgical plan and performed radical resection of the lesions, including the invaded inferior vena cava, and maximized retention of normal liver tissue. The abdominal aorta of an organ donor was used for vascular allograft reconstruction. OUTCOMES: The patient recovered gradually after the operation. He was followed up for 3 months, and the reconstructed vein patency was good. LESSONS: The 3D visualization technique combined with a blood vessel allograft allowed us to expand indications for radical resection of extensive HAE.


Assuntos
Equinococose Hepática/cirurgia , Hepatectomia/métodos , Enxerto Vascular/métodos , Aloenxertos/transplante , Aorta Abdominal/cirurgia , Equinococose Hepática/diagnóstico por imagem , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Veia Cava Inferior/cirurgia
14.
Transplantation ; 104(8): 1542-1552, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732830

RESUMO

Uncontrolled donation after circulatory death (uDCD) refers to donation from persons who die following an unexpected and unsuccessfully resuscitated cardiac arrest. Despite the large potential for uDCD, programs of this kind only exist in a reduced number of countries with a limited activity. Barriers to uDCD are of a logistical and ethical-legal nature, as well as arising from the lack of confidence in the results of transplants from uDCD donors. The procedure needs to be designed to reduce and limit the impact of the prolonged warm ischemia inherent to the uDCD process, and to deal with the ethical issues that this practice poses: termination of advanced cardiopulmonary resuscitation, extension of advanced cardiopulmonary resuscitation beyond futility for organ preservation, moment to approach families to discuss donation opportunities, criteria for the determination of death, or the use of normothermic regional perfusion for the in situ preservation of organs. Although the incidence of primary nonfunction and delayed graft function is higher with organs obtained from uDCD donors, overall patient and graft survival is acceptable in kidney, liver, and lung transplantation, with a proper selection and management of both donors and recipients. Normothermic regional perfusion has shown to be critical to achieve optimal outcomes in uDCD kidney and liver transplantation. However, the role of ex situ preservation with machine perfusion is still to be elucidated. uDCD is a unique opportunity to improve patient access to transplantation therapies and to offer more patients the chance to donate organs after death, if this is consistent with their wishes and values.


Assuntos
Seleção do Doador/métodos , Rejeição de Enxerto/prevenção & controle , Parada Cardíaca/mortalidade , Preservação de Órgãos/métodos , Transplante de Órgãos/métodos , Aloenxertos/provisão & distribução , Seleção do Doador/ética , Seleção do Doador/legislação & jurisprudência , Rejeição de Enxerto/etiologia , Acesso aos Serviços de Saúde , Parada Cardíaca/terapia , Humanos , Transplante de Órgãos/efeitos adversos , Transplante de Órgãos/ética , Transplante de Órgãos/legislação & jurisprudência , Perfusão/instrumentação , Perfusão/métodos , Ressuscitação/ética , Resultado do Tratamento , Isquemia Quente/efeitos adversos
15.
Transplantation ; 104(8): 1553-1559, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732831

RESUMO

Although over 90 000 people are on the kidney transplant waitlist in the United States, some kidneys that are viable for transplantation are discarded. Transplant surgeons are more likely to discard deceased donors with acute kidney injury (AKI) versus without AKI (30% versus 18%). AKI is defined using changes in creatinine from baseline. Transplant surgeons can use DonorNet data, including admission, peak, and terminal serum creatinine, and biopsy data when available to differentiate kidneys with AKI from those with chronic injury. Although chronic kidney disease is associated with reduced graft survival, an abundance of literature has demonstrated similar graft survival for deceased donors with AKI versus donors without AKI. Donors with AKI are more likely to undergo delayed graft function but have similar long-term outcomes as donors without AKI. The mechanism for similar graft survival is unclear. Some hypothesized mechanisms include (1) ischemic preconditioning; (2) posttransplant and host factors playing a greater role in long-term survival than donor factors; and (3) selection bias of transplanting only relatively healthy donor kidneys with AKI. Existing literature suggests transplanting more donor kidneys with stage 1 and 2 AKI, and cautious utilization of stage 3 AKI donors, may increase the pool of viable kidneys. Doing so can reduce the number of people who die on the waitlist by over 500 every year.


Assuntos
Lesão Renal Aguda/diagnóstico , Função Retardada do Enxerto/epidemiologia , Seleção do Doador/métodos , Rejeição de Enxerto/epidemiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/patologia , Aloenxertos/patologia , Aloenxertos/fisiopatologia , Aloenxertos/provisão & distribução , Biomarcadores/análise , Biópsia , Creatinina/sangue , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/fisiopatologia , Seleção do Doador/normas , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/fisiopatologia , Sobrevivência de Enxerto/fisiologia , Humanos , Rim/patologia , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Transplante de Rim/normas , Índice de Gravidade de Doença , Resultado do Tratamento , Estados Unidos/epidemiologia
16.
Transplantation ; 104(8): 1566-1573, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732833

RESUMO

BACKGROUND: Xenogeneic organ transplantation has been proposed as a potential approach to fundamentally solve organ shortage problem. Xenogeneic immune responses across species is one of the major obstacles for clinic application of xeno-organ transplantation. The generation of glycoprotein galactosyltransferase α 1, 3 (GGTA1) knockout pigs has greatly contributed to the reduction of hyperacute xenograft rejection. However, severe xenograft rejection can still be induced by xenoimmune responses to the porcine major histocompatibility complex antigens swine leukocyte antigen class I and class II. METHODS: We simultaneously depleted GGTA1, ß2-microglobulin (ß2M), and major histocompatibility complex class II transactivator (CIITA) genes using clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins technology in Bamma pig fibroblast cells, which were further used to generate GGTA1ß2MCIITA triple knockout (GBC-3KO) pigs by nuclear transfer. RESULTS: The genotype of GBC-3KO pigs was confirmed by polymerase chain reaction and Sanger sequencing, and the loss of expression of α-1,3-galactose, SLA-I, and SLA-II was demonstrated by flow cytometric analysis using fluorescent-conjugated lectin from bandeiraea simplicifolia, anti-ß2-microglobulin, and swine leukocyte antigen class II DR antibodies. Furthermore, mixed lymphocyte reaction assay revealed that peripheral blood mononuclear cells from GBC-3KO pigs were significantly less effective than (WT) pig peripheral blood mononuclear cells in inducing human CD3CD4 and CD3CD8 T-cell activation and proliferation. In addition, GBC-3KO pig skin grafts showed a significantly prolonged survival in immunocompetent C57BL/6 mice, when compared with wild-type pig skin grafts. CONCLUSIONS: Taken together, these results demonstrate that elimination of GGTA1, ß2M, and CIITA genes in pigs can effectively alleviate xenogeneic immune responses and prolong pig organ survival in xenogenesis. We believe that this work will facilitate future research in xenotransplantation.


Assuntos
Rejeição de Enxerto/prevenção & controle , Xenoenxertos/imunologia , Transplante de Órgãos/métodos , Transplante Heterólogo/métodos , Aloenxertos/provisão & distribução , Animais , Animais Geneticamente Modificados/imunologia , Sistemas CRISPR-Cas/genética , Modelos Animais de Doenças , Feminino , Galactosiltransferases/genética , Galactosiltransferases/imunologia , Técnicas de Inativação de Genes/métodos , Genes MHC da Classe II/genética , Genes MHC da Classe II/imunologia , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Xenoenxertos/transplante , Humanos , Masculino , Camundongos , Transplante de Órgãos/efeitos adversos , Suínos/genética , Suínos/imunologia , Transplante Heterólogo/efeitos adversos , Microglobulina beta-2/genética , Microglobulina beta-2/imunologia
17.
Transplantation ; 104(8): 1580-1590, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732835

RESUMO

BACKGROUND: Although short-term outcomes for liver transplantation have improved, patient and graft survival are limited by infection, cancer, and other complications of immunosuppression. Rapid induction of tolerance after liver transplantation would decrease these complications, improving survival and quality of life. Tolerance to kidneys, but not thoracic organs or islets, has been achieved in nonhuman primates and humans through the induction of transient donor chimerism. Since the liver is considered to be tolerogenic, we tested the hypothesis that the renal transplant transient chimerism protocol would induce liver tolerance. METHODS: Seven cynomolgus macaques received immune conditioning followed by simultaneous donor bone marrow and liver transplantation. The more extensive liver surgery required minor adaptations of the kidney protocol to decrease complications. All immunosuppression was discontinued on postoperative day (POD) 28. Peripheral blood chimerism, recipient immune reconstitution, liver function tests, and graft survival were determined. RESULTS: The level and duration of chimerism in liver recipients were comparable to those previously reported in renal transplant recipients. However, unlike in the kidney model, the liver was rejected soon after immunosuppression withdrawal. Rejection was associated with proliferation of recipient CD8 T effector cells in the periphery and liver, increased serum interleukin (IL)-6 and IL-2, but peripheral regulatory T cell (Treg) numbers did not increase. Antidonor antibody was also detected. CONCLUSIONS: These data show the transient chimerism protocol does not induce tolerance to livers, likely due to greater CD8 T cell responses than in the kidney model. Successful tolerance induction may depend on greater control or deletion of CD8 T cells in this model.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Rejeição de Enxerto/prevenção & controle , Transplante de Fígado/efeitos adversos , Quimeras de Transplante/imunologia , Condicionamento Pré-Transplante/métodos , Aloenxertos/imunologia , Animais , Medula Óssea/imunologia , Transplante de Medula Óssea/métodos , Modelos Animais de Doenças , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Fígado/imunologia , Transplante de Fígado/métodos , Macaca fascicularis , Linfócitos T Citotóxicos/imunologia , Tolerância ao Transplante , Transplante Homólogo/efeitos adversos
18.
Transplantation ; 104(8): 1591-1603, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732836

RESUMO

BACKGROUND: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high-acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. METHODS: A retrospective analysis (University of California Los Angeles [n = 145], Houston Methodist Hospital [n = 79]) was performed in all adults receiving CLKT at 2 high-volume transplant centers from February 2004 to January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. RESULTS: A total of 63 patients (28.1%) underwent delayed implantation of pumped kidneys during CLKT (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys during CLKT (eCLKT). Most recipients were high-acuity with median biologic model of end-stage liver disease (MELD) score of, 35 for dCLKT and 34 for eCLKT (P = ns). Pretransplant, dCLKT had longer intensive care unit stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-year patient and kidney survival (P = 0.02) and decreased length of stay (P = 0.001), kidney allograft failure (P = 0.012), and dialysis duration (P = 0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 mo posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (P = 0.013). CONCLUSIONS: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/epidemiologia , Transplante de Rim/efeitos adversos , Transplante de Fígado/efeitos adversos , Preservação de Órgãos/métodos , Idoso , Aloenxertos/imunologia , Aloenxertos/provisão & distribução , Isquemia Fria/instrumentação , Isquemia Fria/métodos , Isquemia Fria/estatística & dados numéricos , Doença Hepática Terminal/complicações , Estudos de Viabilidade , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Humanos , Rim/imunologia , Transplante de Rim/ética , Transplante de Rim/métodos , Transplante de Rim/estatística & dados numéricos , Transplante de Fígado/ética , Transplante de Fígado/métodos , Transplante de Fígado/estatística & dados numéricos , Masculino , Futilidade Médica/ética , Pessoa de Meia-Idade , Preservação de Órgãos/instrumentação , Preservação de Órgãos/estatística & dados numéricos , Perfusão/instrumentação , Perfusão/métodos , Perfusão/estatística & dados numéricos , Insuficiência Renal/etiologia , Insuficiência Renal/cirurgia , Estudos Retrospectivos , Fatores de Tempo , Tempo para o Tratamento/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/ética , Transplante Homólogo/métodos , Resultado do Tratamento
19.
Transplantation ; 104(8): 1604-1611, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732837

RESUMO

BACKGROUND: Donor livers with ≥30% macrosteatosis (steatotic livers) represent a possible expansion to the donor pool, but are frequently discarded as they are associated with an increased risk of mortality and graft loss. We hypothesized that there are certain recipient phenotypes that would tolerate donor steatosis well, and are therefore best suited to receive these grafts. METHODS: Using national registry data from the Scientific Registry of Transplant Recipients between 2006 and 2017, we compared 2048 liver transplant recipients of steatotic livers with 69 394 recipients of nonsteatotic (<30%) livers. We identified recipient factors that amplified the impact of donor steatosis on mortality and graft loss using interaction analysis, classifying recipients without these factors as preferred recipients. We compared mortality and graft loss with steatotic versus nonsteatotic livers in preferred and nonpreferred recipients using Cox regression. RESULTS: Preferred recipients of steatotic livers were determined to be first-time recipients with a model for end-stage liver disease 15-34, without primary biliary cirrhosis, and not on life support before transplant. Preferred recipients had no increased mortality risk (hazard ratio [HR]: 0.921.041.16; P = 0.5) or graft loss (HR: 0.931.031.15; P = 0.5) with steatotic versus nonsteatotic livers. Conversely, nonpreferred recipients had a 41% increased mortality risk (HR: 1.171.411.70; P < 0.001) and 39% increased risk of graft loss (HR: 1.161.391.66; P < 0.001) with steatotic versus nonsteatotic livers. CONCLUSIONS: The risks of liver transplantation with steatotic donor livers could be minimized by appropriate recipient matching.


Assuntos
Doença Hepática Terminal/cirurgia , Fígado Gorduroso/diagnóstico , Rejeição de Enxerto/epidemiologia , Transplante de Fígado/efeitos adversos , Seleção de Pacientes , Adulto , Idoso , Aloenxertos/patologia , Aloenxertos/provisão & distribução , Modificador do Efeito Epidemiológico , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/mortalidade , Fígado Gorduroso/patologia , Feminino , Rejeição de Enxerto/patologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/cirurgia , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Reoperação/estatística & dados numéricos , Medição de Risco , Índice de Gravidade de Doença , Transplantados/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia
20.
Transplantation ; 104(8): 1612-1618, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732838

RESUMO

BACKGROUND: Steatotic donor livers (SDLs, ≥30% macrosteatosis on biopsy) are often declined, as they are associated with a higher risk of graft loss, even though candidates may wait an indefinite time for a subsequent organ offer. We sought to quantify outcomes for transplant candidates who declined or accepted an SDL offer. METHODS: We used Scientific Registry of Transplant Recipients offer data from 2009 to 2015 to compare outcomes of 759 candidates who accepted an SDL to 13 362 matched controls who declined and followed candidates from the date of decision (decline or accept) until death or end of study period. We used a competing risk framework to understand the natural history of candidates who declined and Cox regression to compare postdecision survival after declining versus accepting (ie, what could have happened if candidates who declined had instead accepted). RESULTS: Among those who declined an SDL, only 53.1% of candidates were subsequently transplanted, 23.8% died, and 19.4% were removed from the waitlist. Candidates who accepted had a brief perioperative risk period within the first month posttransplant (adjusted hazard ratio [aHR]: 2.493.494.89, P < 0.001), but a 62% lower mortality risk (aHR: 0.310.380.46, P < 0.001) beyond this. Although the long-term survival benefit of acceptance did not vary by candidate model for end-stage liver disease (MELD), the short-term risk period did. MELD 6-21 candidates who accepted an SDL had a 7.88-fold higher mortality risk (aHR: 4.807.8812.93, P < 0.001) in the first month posttransplant, whereas MELD 35-40 candidates had a 68% lower mortality risk (aHR: 0.110.320.90, P = 0.03). CONCLUSIONS: Appropriately selected SDLs can decrease wait time and provide substantial long-term survival benefit for liver transplant candidates.


Assuntos
Seleção do Doador/estatística & dados numéricos , Doença Hepática Terminal/cirurgia , Fígado Gorduroso/patologia , Transplante de Fígado/métodos , Transplantados/estatística & dados numéricos , Idoso , Aloenxertos/patologia , Aloenxertos/provisão & distribução , Biópsia , Tomada de Decisões , Doença Hepática Terminal/mortalidade , Fígado Gorduroso/diagnóstico , Feminino , Seguimentos , Humanos , Fígado/patologia , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Período Perioperatório/mortalidade , Período Perioperatório/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Transplantados/psicologia , Resultado do Tratamento , Estados Unidos/epidemiologia , Listas de Espera/mortalidade
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