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1.
Clin Nucl Med ; 45(11): 923-924, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32910047

RESUMO

Renal melanoma is rare. We present a case with FDG-avid melanoma arising from renal allograft. This case indicates that melanoma can occur in the allograft, and it should be considered as a differential diagnosis of focal abnormal FDG uptake in the renal allograft.


Assuntos
Aloenxertos/patologia , Fluordesoxiglucose F18 , Transplante de Rim , Melanoma/diagnóstico por imagem , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Sci Rep ; 10(1): 14242, 2020 08 28.
Artigo em Inglês | MEDLINE | ID: mdl-32859929

RESUMO

The majority of liver grafts exhibit abnormal histological findings late after transplantation, even when liver enzymes are normal. Such subclinical graft injuries were associated with rejection and fibrosis progression in recent studies. The identification of non-invasive biomarkers for subclinical graft injury might help to individualize immunosuppression. Therefore, graft injury was assessed in 133 liver biopsies with normal/near normal liver enzymes from a prospective liver biopsy program. Cytokeratin-18 cell death marker (M65) and donor specific anti-HLA antibodies (DSA) were measured as non-invasive markers in paired plasma samples in addition to routine parameters. M65 was associated with subclinical graft injury but this association was too weak for reasonable clinical application. DSA positivity was associated with more graft inflammation (OR = 5.4) and more fibrosis (OR = 4.2). Absence of DSA excluded fibrosis in 87-89%, while presence of DSA excluded histological criteria for immunosuppression minimization attempts in 92-97%. While CK18 cell death marker had no diagnostic value for the detection of subclinical liver graft injury, DSA testing can help to preselect patients for immunosuppression reduction in case of DSA negativity, while DSA positivity should prompt elastography or liver biopsy for the assessment of subclinical graft injury.


Assuntos
Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Queratina-18/imunologia , Fragmentos de Peptídeos/imunologia , Adulto , Idoso , Aloenxertos/patologia , Biomarcadores/sangue , Biópsia , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressão , Isoanticorpos/imunologia , Queratina-18/análise , Queratina-18/sangue , Fígado/patologia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Doadores de Tecidos , Adulto Jovem
3.
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
4.
J Interv Cardiol ; 2020: 9835151, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733172

RESUMO

Background: Cardiac allograft vasculopathy (CAV) remains the Achilles' heel of long-term survival after heart transplantation (HTx). The severity and extent of CAV is graded with conventional coronary angiography (COR) which has several limitations. Recently, vessel fractional flow reserve (vFFR) derived from COR has emerged as a diagnostic computational tool to quantify the functional severity of coronary artery disease. Purpose: The present study assessed the usefulness of vFFR to detect CAV in HTx recipients. Methods: In HTx patients referred for annual check-up, undergoing surveillance COR, the extent of CAV was graded according to the criteria proposed by the international society of heart and lung transplantation (ISHLT). In addition, three-dimensional coronary geometries were constructed from COR to calculate pressure losses using vFFR. Results: In 65 HTx patients with a mean age of 53.7 ± 10.1 years, 8.5 years (IQR 1.90, 15.2) years after HTx, a total number of 173 vessels (59 LAD, 61 LCX, and 53 RCA) were analyzed. The mean vFFR was 0.84 ± 0.15 and median was 0.88 (IQR 0.79, 0.94). A vFFR ≤ 0.80 was present in 24 patients (48 vessels). HTx patients with a history of ischemic cardiomyopathy (ICMP) had numerically lower vFFR as compared to those with non-ICMP (0.70 ± 0.22 vs. 0.79 ± 0.13, p = 0.06). The use of vFFR reclassified 31.9% of patients compared to the anatomical ISHLT criteria. Despite a CAV score of 0, a pathological vFFR ≤ 0.80 was detected in 8 patients (34.8%). Conclusion: The impairment in epicardial conductance assessed by vFFR in a subgroup of patients without CAV according to standard ISHLT criteria suggests the presence of a diffuse vasculopathy undetectable by conventional angiography. Therefore, we speculate that vFFR may be useful in risk stratification after HTx.


Assuntos
Aloenxertos , Doença da Artéria Coronariana , Reserva Fracionada de Fluxo Miocárdico , Transplante de Coração/efeitos adversos , Complicações Pós-Operatórias , Aloenxertos/irrigação sanguínea , Aloenxertos/patologia , Desenho Assistido por Computador , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/fisiopatologia , Vasos Coronários/diagnóstico por imagem , Feminino , Transplante de Coração/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Reprodutibilidade dos Testes , Medição de Risco/métodos
5.
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
6.
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
7.
Transplantation ; 104(8): 1633-1643, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732841

RESUMO

BACKGROUND: The cellular infiltrate in protocol liver biopsies (PB) following pediatric liver transplantation remains mostly uncharacterized, yet there is increasing concern about the role of inflammation and fibrosis in long-term liver allografts. We aimed to define cell types in PB and to analyze their relationship with donor-specific antibodies (DSA) and histological phenotype. METHODS: PB were performed at least 1 year after transplantation. We identified 4 phenotypes: normal, fibrosis, inflammation, inflammation with fibrosis. Cell types were counted after immunostaining for CD3, CD4, CD8, CD68, CD20, MUM1, and FoxP3. RESULTS: Forty-four patients underwent 1 PB between 2000 and 2015. Eleven percent (5/44) of PB displayed normal histology, 13.6% (6/44) fibrosis, 34.1% (15/44) inflammation, and 40.9% (18/44) inflammation and fibrosis. The main cell types in the portal tracts and lobules were CD3+ and CD68+ cells. Frequency of de novo DSA was 63% (27/44). The presence of CD8+ cells in the lobules was associated with fibrosis. Inflammation and fibrosis in PB were associated with the presence of circulating de novo DSA, number of de novo DSA, and C1q binding activity when compared to other phenotypes. CONCLUSIONS: T cells (CD3+) and macrophages (CD68+) were the most prevalent cell-types in PB. In the presence of inflammation, portal tracts were enriched in CD3+, CD20+ but displayed fewer CD68+. This coincided with the presence and number of de novo DSA. How these cellular and humoral actors interact is unclear, but peripheral DSA may be a marker of immune cellular activity in the seemingly quiescent allograft.


Assuntos
Doença Hepática Terminal/cirurgia , Rejeição de Enxerto/imunologia , Isoanticorpos/imunologia , Transplante de Fígado/efeitos adversos , Sistema Porta/imunologia , Adolescente , Adulto , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Biópsia , Criança , Pré-Escolar , Doença Hepática Terminal/diagnóstico , Doença Hepática Terminal/etiologia , Feminino , Fibrose , Seguimentos , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Antígenos HLA/imunologia , Teste de Histocompatibilidade/estatística & dados numéricos , Humanos , Imunidade Celular , Lactente , Isoanticorpos/análise , Fígado/irrigação sanguínea , Fígado/imunologia , Fígado/patologia , Doadores Vivos/estatística & dados numéricos , Macrófagos/imunologia , Masculino , Sistema Porta/citologia , Índice de Gravidade de Doença , Linfócitos T/imunologia , Transplantados/estatística & dados numéricos , Transplante Homólogo/efeitos adversos , Adulto Jovem
8.
Transplantation ; 104(8): 1695-1702, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732849

RESUMO

BACKGROUND: Reports about prognosis of adults receiving small pediatric-donor kidneys (PDK) as compared to those receiving elder pediatric or adult donor kidneys (ADKs) are controversial. This study aimed to examine the outcomes of adults receiving small PDK and possible prognostic factors. METHODS: The records of adults who received kidneys from donors < 10 years old at our center from July 1, 2011 to June 30, 2018 were reviewed. RESULTS: A total of 121 adults were small PDK recipients. Twenty-three patients received 29 biopsies or nephrectomy between 6 and 896 days posttransplantation days. Seven patients (30.4%) had pediatric donor glomerulopathy (PDG), which developed from 113 to 615 days posttransplantation. The incidence of proteinuria and hematuria was significantly higher in the PDG group. The characteristic pathological finding in PDG was irregular lamination and splintering of the glomerular basement membrane (GBM). Donor age, donor weight, and donor kidney volume were significantly less in PDG cases compared with the non-PDG cases. For the risk factors of PDG, increasing urinary RBC count during follow-up was an independent predictor, while increasing donor age and body weight were protective factors. PDG was not a significant risk factor for Scr increasing of PDKs. CONCLUSIONS: PDG is a potential cause of abnormal urinalysis in adults receiving small PDKs. The pathological characteristic change of PDG is splitting and lamination of GBM. Persistent hematuria after transplantation in recipients of PDK is a predictor of PDG development.


Assuntos
Glomerulonefrite/patologia , Hematúria/epidemiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Proteinúria/epidemiologia , Adolescente , Adulto , Fatores Etários , Aloenxertos/anatomia & histologia , Aloenxertos/patologia , Biópsia , Peso Corporal , Criança , Pré-Escolar , Feminino , Seguimentos , Membrana Basal Glomerular/patologia , Sobrevivência de Enxerto , Hematúria/etiologia , Hematúria/patologia , Hematúria/urina , Humanos , Lactente , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Complicações Pós-Operatórias/urina , Prognóstico , Fatores de Proteção , Proteinúria/etiologia , Proteinúria/patologia , Proteinúria/urina , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Resultado do Tratamento , Adulto Jovem
9.
Transplantation ; 104(8): 1703-1711, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732850

RESUMO

BACKGROUND: There are limited data on the outcome of transplant recipients with familial Mediterranean fever (FMF)-associated AA amyloidosis. The aim of the present study is to evaluate demographic, clinical, laboratory, and prognostic characteristics and outcome measures of these patients. METHODS: Eighty-one renal transplant recipients with FMF-associated AA amyloidosis (group 1) and propensity score-matched transplant recipients (group 2, n = 81) with nonamyloidosis etiologies were evaluated in this retrospective, multicenter study. Recurrence of AA amyloidosis was diagnosed in 21 patients (group 1a), and their features were compared with 21 propensity score-matched recipients with FMF amyloidosis with no laboratory signs of recurrence (group 1b). RESULTS: The risk of overall allograft loss was higher in group 1 compared with group 2 (25 [30.9%] versus 12 [14.8%]; P = 0.015 [hazard ratio, 2.083; 95% confidence interval, 1.126-3.856]). Patients in group 1 were characterized by an increased risk of mortality compared with group 2 (11 [13.6%] versus 0%; P = 0.001 [hazard ratio, 1.136; 95% confidence interval, 1.058-1.207]). Kaplan-Meier analysis revealed that 5- and 10-year patient survival rates in group 1 (92.5% and 70.4%) were significantly lower than in group 2 (100% and 100%; P = 0.026 and P = 0.023, respectively). Although not reaching significance, overall, 5- and 10-year graft survival rates (57.1%, 94.7%, and 53.8%, respectively) in group 1a were worse than in group 1b (76.2%, 95%, and 77.8%, respectively; P = 0.19, P = 0.95, and P = 0.27, respectively). CONCLUSIONS: AA amyloidosis is associated with higher risk of mortality after kidney transplantation. Inflammatory indicators should be monitored closely, and persistent high levels of acute-phase reactants should raise concerns about amyloid recurrence in allograft.


Assuntos
Amiloidose/cirurgia , Febre Familiar do Mediterrâneo/complicações , Rejeição de Enxerto/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Adulto , Aloenxertos/imunologia , Aloenxertos/patologia , Amiloidose/imunologia , Amiloidose/mortalidade , Amiloidose/patologia , Biópsia , Febre Familiar do Mediterrâneo/imunologia , Febre Familiar do Mediterrâneo/mortalidade , Febre Familiar do Mediterrâneo/cirurgia , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/imunologia , Humanos , Estimativa de Kaplan-Meier , Rim/imunologia , Rim/patologia , Falência Renal Crônica/imunologia , Falência Renal Crônica/mortalidade , Falência Renal Crônica/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Proteína Amiloide A Sérica/imunologia , Proteína Amiloide A Sérica/metabolismo , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
10.
Transpl Infect Dis ; 22(5): e13382, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32583620

RESUMO

BACKGROUND: The impact of COVID-19 on heart transplant (HTx) recipients remains unclear, particularly in the early post-transplant period. METHODS: We share novel insights from our experience in five HTx patients with COVID-19 (three within 2 months post-transplant) from our institution at the epicenter of the pandemic. RESULTS: All five exhibited moderate (requiring hospitalization, n = 3) or severe (requiring ICU and/or mechanical ventilation, n = 2) illness. Both cases with severe illness were transplanted approximately 6 weeks before presentation and acquired COVID-19 through community spread. All five patients were on immunosuppressive therapy with mycophenolate mofetil (MMF) and tacrolimus, and three that were transplanted within the prior 2 months were additionally on prednisone. The two cases with severe illness had profound lymphopenia with markedly elevated C-reactive protein, procalcitonin, and ferritin. All had bilateral ground-glass opacities on chest imaging. MMF was discontinued in all five, and both severe cases received convalescent plasma. All three recent transplants underwent routine endomyocardial biopsies, revealing mild (n = 1) or no acute cellular rejection (n = 2), and no visible viral particles on electron microscopy. Within 30 days of admission, the two cases with severe illness remain hospitalized but have clinically improved, while the other three have been discharged. CONCLUSIONS: COVID-19 appears to negatively impact outcomes early after heart transplantation.


Assuntos
Aloenxertos/patologia , Endocárdio/patologia , Rejeição de Enxerto/patologia , Transplante de Coração/efeitos adversos , Miocárdio/patologia , Idoso , Aloenxertos/imunologia , Aloenxertos/ultraestrutura , Biópsia , /epidemiologia , Endocárdio/imunologia , Endocárdio/ultraestrutura , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Miocárdio/imunologia , Miocárdio/ultraestrutura , Cidade de Nova Iorque/epidemiologia , Pandemias , Estudos Retrospectivos , /isolamento & purificação , Índice de Gravidade de Doença , Fatores de Tempo
11.
Am J Respir Cell Mol Biol ; 63(4): 490-501, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32551854

RESUMO

Telomere dysfunction is associated with multiple fibrotic lung processes, including chronic lung allograft dysfunction (CLAD)-the major limitation to long-term survival following lung transplantation. Although shorter donor telomere lengths are associated with an increased risk of CLAD, it is unknown whether short telomeres are a cause or consequence of CLAD pathology. Our objective was to test whether telomere dysfunction contributes to the pathologic changes observed in CLAD. Histopathologic and molecular analysis of human CLAD lungs demonstrated shortened telomeres in lung epithelial cells quantified by teloFISH, increased numbers of surfactant protein C immunoreactive type II alveolar epithelial cells, and increased expression of senescence markers (ß-galactosidase, p16, p53, and p21) in lung epithelial cells. TRF1F/F (telomere repeat binding factor 1 flox/flox) mice were crossed with tamoxifen-inducible SCGB1a1-cre mice to generate SCGB1a1-creTRF1F/F mice. Following 9 months of tamoxifen-induced deletion of TRF1 in club cells, mice developed mixed obstructive and restrictive lung physiology, small airway obliteration on microcomputed tomography, a fourfold decrease in telomere length in airway epithelial cells, collagen deposition around bronchioles and adjacent lung parenchyma, increased type II aveolar epithelial cell numbers, expression of senescence-associated ß-galactosidase in epithelial cells, and decreased SCGB1a1 expression in airway epithelial cells. These findings demonstrate that telomere dysfunction isolated to airway epithelial cells leads to airway-centric lung remodeling and fibrosis similar to that observed in patients with CLAD and suggest that lung epithelial cell telomere dysfunction may be a molecular driver of CLAD.


Assuntos
Aloenxertos/patologia , Células Epiteliais Alveolares/patologia , Pulmão/fisiologia , Telômero/genética , Aloenxertos/metabolismo , Células Epiteliais Alveolares/metabolismo , Animais , Biomarcadores/metabolismo , Senescência Celular/genética , Humanos , Pulmão/metabolismo , Transplante de Pulmão/métodos , Camundongos , Fibrose Pulmonar/genética , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Uteroglobina/genética , Uteroglobina/metabolismo
13.
Expert Opin Pharmacother ; 21(11): 1367-1376, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32401066

RESUMO

INTRODUCTION: Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Its peculiar pathophysiology involves multifactorial pathways including immune-mediated and metabolic risk factors, which are associated with the development of specific pathological lesions. The often diffuse and chronic nature of the disease reduces the effectiveness of revascularization procedures, and pharmacological prevention of the disease is the sole therapeutic approach with some proven efficacy. AREAS COVERED: In this article, after briefly outlining the risk factors for CAV, the authors revise the potential pharmacological approaches that may reduce the burden of CAV. While several therapies have shown convincing efficacy in terms of CAV prevention diagnosed by coronary imaging, very few have been reported to improve prognosis with any meaningful level of evidence. EXPERT OPINION: The authors believe that a customizable approach is necessary for clinical practice given the currently available evidence. Furthermore, it is important, in the future, to address the glaring therapeutic gap of an effective treatment against donor-specific antibodies, whose effect on endothelial injury is currently one of the major mechanisms of CAV development and for which no pharmacological treatment is currently available.


Assuntos
Aloenxertos/efeitos dos fármacos , Inibidores de Calcineurina/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Transplante de Coração/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Imunossupressores/uso terapêutico , Aloenxertos/irrigação sanguínea , Aloenxertos/imunologia , Aloenxertos/patologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Antioxidantes/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/imunologia , Doença da Artéria Coronariana/patologia , Humanos , Inibidores da Agregação de Plaquetas/uso terapêutico , Fatores de Risco , Resultado do Tratamento
14.
Int J Mol Sci ; 21(7)2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32235494

RESUMO

Renal transplantation is the preferred treatment of end stage renal disease, but allograft survival is limited by the development of interstitial fibrosis and tubular atrophy in response to various stimuli. Much effort has been put into identifying new protein markers of fibrosis to support the diagnosis. In the present work, we performed an in-depth quantitative proteomics analysis of allograft biopsies from 31 prevalent renal transplant patients and correlated the quantified proteins with the volume fraction of fibrosis as determined by a morphometric method. Linear regression analysis identified four proteins that were highly associated with the degree of interstitial fibrosis, namely Coagulation Factor XIII A chain (estimate 18.7, adjusted p < 0.03), Uridine Phosphorylase 1 (estimate 19.4, adjusted p < 0.001), Actin-related protein 2/3 subunit 2 (estimate 34.2, adjusted p < 0.05) and Cytochrome C Oxidase Assembly Factor 6 homolog (estimate -44.9, adjusted p < 0.002), even after multiple testing. Proteins that were negatively associated with fibrosis (p < 0.005) were primarily related to normal metabolic processes and respiration, whereas proteins that were positively associated with fibrosis (p < 0.005) were involved in catabolic processes, cytoskeleton organization and the immune response. The identified proteins may be candidates for further validation with regards to renal fibrosis. The results support the notion that cytoskeleton organization and immune responses are prevalent processes in renal allograft fibrosis.


Assuntos
Aloenxertos/patologia , Transplante de Rim , Rim/patologia , Complexo 2-3 de Proteínas Relacionadas à Actina/análise , Adulto , Idoso , Biomarcadores/análise , Fator XIII/análise , Feminino , Fibrose , Humanos , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Proteômica , Uridina Fosforilase/análise
15.
Lancet Gastroenterol Hepatol ; 5(5): 507-514, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32277903

RESUMO

The survival of patients with alcohol-related liver disease who receive a liver transplant has steadily improved to reach 80-85% at 1 year post-transplantation. The standard requirement for liver transplant-abstinence from alcohol for 6 months before transplantation-has been applied widely, but few data support the use of this rule as the sole criterion for selecting candidates for liver transplantation. When determining the suitability of a patient for transplantation, many liver transplant programmes now try to balance the period of abstinence against the risk of death associated with the severity of liver damage. Data accumulated since 2011 suggest that early liver transplantation (ie, transplantation without a specific period of abstinence) in patients with severe alcoholic hepatitis who do not respond to medical therapy is an effective therapeutic strategy. Further studies are needed to help refine the selection of patients with alcohol-related liver disease who have been abstinent for less than 6 months as suitable liver transplant candidates, and to improve the treatment of alcohol use disorder in those patients who have received a liver transplant.


Assuntos
Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado , Seleção de Pacientes , Abstinência de Álcool , Consumo de Bebidas Alcoólicas/psicologia , Alcoolismo/complicações , Alcoolismo/terapia , Aloenxertos/patologia , Hepatite Alcoólica/cirurgia , Humanos , Hepatopatias Alcoólicas/etiologia , Hepatopatias Alcoólicas/psicologia , Período Pós-Operatório
16.
Int J Mol Sci ; 21(6)2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32213927

RESUMO

The clinical significance of renal transplant biopsies displaying borderline changes suspicious for T-cell mediated rejection (TCMR) or interstitial fibrosis and tubular atrophy (IFTA) with interstitial inflammation has not been well defined. Molecular profiling to evaluate renal transplant biopsies using microarrays has been shown to be an objective measurement that adds precision to conventional histology. We review the contribution of transcriptomic analysis in surveillance and indication biopsies with borderline changes and IFTA associated with variable degrees of inflammation. Transcriptome analysis applied to biopsies with borderline changes allows to distinguish patients with rejection from those in whom mild inflammation mainly represents a response to injury. Biopsies with IFTA and inflammation occurring in unscarred tissue display a molecular pattern similar to TCMR while biopsies with IFTA and inflammation in scarred tissue, apart from T-cell activation, also express B cell, immunoglobulin and mast cell-related genes. Additionally, patients at risk for IFTA progression can be identified by genes mainly reflecting fibroblast dysregulation and immune activation. At present, it is not well established whether the expression of rejection gene transcripts in patients with fibrosis and inflammation is the consequence of an alloimmune response, tissue damage or a combination of both.


Assuntos
Rejeição de Enxerto/genética , Transplante de Rim/efeitos adversos , Transcriptoma , Aloenxertos/imunologia , Aloenxertos/patologia , Aloenxertos/normas , Animais , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Humanos
17.
Biomed Res Int ; 2020: 9358989, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32190690

RESUMO

Introduction. In the field of orthopaedic surgery, the use of osteogenic material in larger defects is essential. Autograft and allograft are both known methods, and autograft is believed to be the best choice. But autograft is associated with additional invasive procedures which can prove difficult in fragile patients and can cause local side effect after bone harvest. For feasible purposes, the use of allograft is hereby rising and comparing efficacies, and the differences between autograft and allograft are essential for the clinical outcome for the patients. Method: 24 female Norwegian brown rats were included, 12 normal rats and 12 induced with osteoporosis (OP). OP inducement was verified in vivo by bone volume fraction (BV/TV) at 90 days after ovariectomy (OVX). The primary surgery in each rat consisted of a 2.5 × 3 mm hole in the proximal tibia, bilaterally. Autograft and allograft were randomly allocated in the right and left tibia. After an observation of 21 days, the rats were sacrificed. Tibia samples were harvested, micro-CT scanned for bone inducement and microarchitectural properties, and then embedded for histology. Results: The OP induction was verified three months after the OVX by a reduction of 68.5% in the trabecular bone BV/TV compared to normal bone. Microarchitectural analysis and histology showed no significant differences in the bone-forming capabilities between autograft and allograft in normal or osteoporotic bone after 3 weeks. Conclusion: This study did not demonstrate any difference between autograft and allograft in a normal or osteoporotic rat tibial defect model after 21 days, suggesting allograft is a good alternative to autograft.


Assuntos
Aloenxertos/patologia , Autoenxertos/patologia , Transplante Ósseo , Osso e Ossos/patologia , Animais , Densidade Óssea , Feminino , Osteoporose/patologia , Ovariectomia/métodos , Ratos , Tíbia/patologia , Transplante Autólogo/efeitos adversos , Transplante Autólogo/métodos , Transplante Homólogo/efeitos adversos , Transplante Homólogo/métodos , Microtomografia por Raio-X
18.
Transplantation ; 104(6): 1177-1186, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32091485

RESUMO

BACKGROUND: The detrimental role of platelets in sinusoidal endothelial cell (SEC) injury during liver transplantation (LT) has been previously addressed after static cold storage (SCS), however, it is currently unknown after normothermic ex vivo liver perfusion (NEVLP). METHODS: Pig LT was performed with livers from heart-beating donors or donation after circulatory death (DCD) donors subjected to SCS or NEVLP (n = 5/group). RESULTS: All pigs except for 1 (DCD-SCS-group) survived 4 days. The heart-beating donor- and DCD-NEVLP-groups showed significantly lower aspartate transaminase-levels compared with the SCS-groups 3 hours post-LT (P = 0.006), on postoperative day (POD) 2 (P = 0.005), POD3 (P = 0.007), and on POD4 (P = 0.012). Post-LT total platelet count recovered faster in the NEVLP than in the SCS-groups at 12 hours (P = 0.023) and 24 hours (P = 0.0038). Intrahepatic sequestration of platelets was significantly higher in the SCS-groups 3 hours postreperfusion and correlated with severity of SEC injury. In both SCS-groups, levels of tumor growth factor-ß were higher 3 hours post-LT, on POD1 and on POD3. Moreover, platelet factor 4 levels and platelet-derived extracellular vesicles were increased in the SCS-groups. Hyaluronic acid levels were significantly higher in the SCS-groups, indicating a higher grade of endothelial cell dysfunction. Platelet inhibition achieved by pretreatment with clopidogrel (n = 3) partly reversed the detrimental effects on SEC injury and therefore provided further evidence of the important role of platelets in ischemia/reperfusion injury and SEC injury. CONCLUSIONS: Normothermic perfusion of liver grafts before transplantation effectively reduced platelet aggregation and SEC injury, which translated into an improved posttransplant organ function.


Assuntos
Endotélio Vascular/patologia , Transplante de Fígado/métodos , Preservação de Órgãos/métodos , Traumatismo por Reperfusão/prevenção & controle , Coleta de Tecidos e Órgãos/métodos , Aloenxertos/irrigação sanguínea , Aloenxertos/citologia , Aloenxertos/patologia , Animais , Capilares/citologia , Capilares/patologia , Isquemia Fria/efeitos adversos , Modelos Animais de Doenças , Células Endoteliais/patologia , Endotélio Vascular/citologia , Sobrevivência de Enxerto , Humanos , Fígado/irrigação sanguínea , Fígado/citologia , Fígado/patologia , Transplante de Fígado/efeitos adversos , Masculino , Soluções para Preservação de Órgãos , Agregação Plaquetária , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/patologia , Sus scrofa , Coleta de Tecidos e Órgãos/efeitos adversos
19.
Transplant Proc ; 52(2): 530-533, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32033833

RESUMO

The compression of the renal parenchyma due to a subcapsular hematoma, also known as the "Page kidney," is a potentially serious but treatable complication of renal biopsy. Hypertension is very common and, in some cases, renal failure may be present. In kidney transplantation, it is a not well-described entity. Rapid intervention is essential to avoid irreversible damage of the graft and preserve its function. We report 2 cases of acute renal failure due to Page kidney in patients with renal transplant after a percutaneous biopsy with successful recovery after surgical treatment. In addition, we conducted a literature review in order to describe the clinical characteristics of this infrequent complication in patients with a history of renal transplant.


Assuntos
Lesão Renal Aguda/etiologia , Biópsia/efeitos adversos , Hematoma/etiologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Aloenxertos/patologia , Humanos , Rim/patologia , Masculino
20.
Transplant Proc ; 52(2): 515-518, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32037064

RESUMO

IgA nephropathy (IgAN) recurrence in the renal graft is variable. Several factors can influence the risk of recurrence of IgAN and renal graft failure. We carried out a retrospective observational study between the years 1990 and 2018. The study group was patients diagnosed, by means of biopsy, as having post-renal transplant (RT) IgAN in our hospital in the study period. The control group was patients with pre-RT histologic diagnosis of IgAN who did not develop recurrence of the disease after the RT. A total of 1535 RTs were performed in our center in the study period. Of those, 24 patients developed IgAN in the renal graft. The time elapsed from the RT to the development of allograft IgAN was 7 (SD, 5.3) years. The patients with allograft IgAN tended to be younger (P = .069), and HLA-DR4 was more common in these patients (P = .078). We observed a very significant difference in the use of induction immunosuppressive therapy (study group vs control group: 13.6% vs 57.7%, P < .001). The 3 patients who presented crescents in the biopsy specimen lost the renal graft. As in the native kidney, the presence of crescents is an indicator of poor prognosis. In our experience, the patients with post-RT IgAN received induction therapy less frequently; this finding would support the conclusion that such treatments should be applied to patients with pre-RT diagnosis of IgAN.


Assuntos
Glomerulonefrite por IGA/imunologia , Imunossupressão/efeitos adversos , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/imunologia , Adulto , Aloenxertos/imunologia , Aloenxertos/patologia , Biópsia , Feminino , Sobrevivência de Enxerto , Humanos , Imunossupressão/métodos , Imunossupressores/efeitos adversos , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos
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