Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Aliment Pharmacol Ther ; 49(6): 807-813, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30714184

RESUMO

BACKGROUND: Sarcopenia is associated with both increased wait-list mortality and mortality following liver transplantation. AIMS: To determine the course of sarcopenia from transplant evaluation until 1 year post-transplant, and its implications on hospitalisation and mortality following liver transplantation. METHODS: Two hundred and ninety-three transplant recipients from 2002 to 2006 had pre-transplant CT scans analysed at the third lumbar region for sarcopenia, myosteatosis and abdominal visceral fat content. Half the recipients had post-transplant CT scan for interpretation (161/293). RESULTS: Sarcopenia was present in 146/293 (50%) of the patients pre-transplant. There was a significant decrease in muscle mass (loss 2.0 ± 4.9 cm2 /m2 ; P < 0.001), and an increase in myosteatosis while awaiting liver transplantation. There was no significant change in abdominal visceral fat. For every 1 cm2 /m2 decrease in muscle mass there was an increase in post-transplant length of stay by 0.36 days (P = 0.005). Post-transplant, 98/161 (61%) of patients with CT imaging had sarcopenia (25 de novo and 73 persistent), with continued increase in myosteatosis, lower Hounsfield units (-5.0 [IQR -8.6 to 0.1]; P < 0.001) and an increase in abdominal visceral fat (4.9 [IQR -4.4 to 15.6] cm2 /m2 ; P < 0.001). There was no statistically significant difference in 1-year mortality in patients with de novo sarcopenia compared to patients with sarcopenia both pre- and post-transplant (HR 1.88; P = 0.088). CONCLUSIONS: Sarcopenia progresses up to 1 year following liver transplantation and is associated with an increase in post-transplant length of stay.

2.
Psychosomatics ; 60(1): 56-65, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30122643

RESUMO

BACKGROUND: Liver transplant candidates undergo psychosocial assessment as a component of their pretransplant evaluation. Global psychosocial assessment scales, including the Psychosocial Assessment of Candidates for Transplantation (PACT), capture and quantify these psychiatric and social variables. OBJECTIVE: Our primary aim was to assess for an association between global PACT score and survival in liver transplant recipients. METHODS: This retrospective cohort study examined records of all liver recipients at one U.S. Transplant Center from 2000 to 2012 with outcomes monitoring until 07/01/2016. We investigated for associations between the following variables and mortality: PACT score, age, gender, marital status, race, alcoholic liver disease (ALD), and body mass index (BMI). Statistical methods included Student's t-test, Wilcoxon rank sum test, chi-square, Fisher's exact test, Kaplan-Meier curve, and Cox proportional hazard models. RESULTS: Of 1040 liver recipients, 538 had a documented PACT score. Among these, PACT score was not associated with mortality. In women, a lower PACT score was associated with mortality (p = 0.003) even after adjustments for age, marital status, and BMI. Women with ALD had a 2-fold increased hazard of death (p = 0.012). Increasing age was associated with increased risk of death for the cohort as a whole (p = 0.019) and for men (p = 0.014). In men, being married and BMI were marginally protective (p = 0.10 and p = 0.13, respectively). CONCLUSIONS: Transplant psychosocial screening scales, specifically the PACT, identify psychosocial burden and may predict post-transplant outcomes in certain populations. In female liver recipients, lower PACT scores and ALD were associated with a greater risk of post-transplant mortality.


Assuntos
Cirrose Hepática Alcoólica/cirurgia , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Saúde Mental , Mortalidade , Apoio Social , Adolescente , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Estilo de Vida , Cirrose Hepática/cirurgia , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Psicologia , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
3.
Liver Transpl ; 25(1): 14-24, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30257063

RESUMO

Sarcopenia and frailty are commonly encountered in patients with end-stage liver disease and are associated with adverse clinical outcomes, including decompensation and wait-list mortality. The impact of these entities in patients with differing disease etiologies has not been elucidated. We aim to ascertain the change in their prevalence over time on the wait list and determine their impact on hospitalization, delisting, and wait-list survival, specifically for patients with nonalcoholic steatohepatitis (NASH) and alcoholic liver disease (ALD). Adult patients who were evaluated for their first liver transplant from 2014 to 2016 with a primary diagnosis of NASH (n = 136) or ALD (n = 129) were included. Computed tomography scans were used to determine the presence of sarcopenia and myosteatosis. Frailty was diagnosed using the Rockwood frailty index. Patients with NASH had a significantly lower prevalence of sarcopenia (22% versus 47%; P < 0.001) but a significantly higher prevalence of frailty (49% versus 34%; P = 0.03) when compared with patients with ALD at the time of listing. In patients with NASH, sarcopenia was not associated with adverse events, but a higher frailty score was associated with an increased length of hospitalization (P = 0.05) and an increased risk of delisting (P = 0.02). In patients with ALD, univariate analysis showed the presence of sarcopenia was associated with an increased risk of delisting (P = 0.01). In conclusion, sarcopenia and frailty occur with differing prevalence with variable impact on outcomes in wait-listed patients with NASH and ALD.


Assuntos
Doença Hepática Terminal/complicações , Fragilidade/epidemiologia , Hepatopatias Alcoólicas/complicações , Hepatopatia Gordurosa não Alcoólica/complicações , Sarcopenia/epidemiologia , Adulto , Idoso , Doença Hepática Terminal/patologia , Doença Hepática Terminal/cirurgia , Feminino , Fragilidade/diagnóstico , Fragilidade/etiologia , Humanos , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/cirurgia , Transplante de Fígado/normas , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/cirurgia , Seleção de Pacientes , Prevalência , Estudos Retrospectivos , Sarcopenia/diagnóstico , Sarcopenia/etiologia , Listas de Espera/mortalidade
4.
Transplantation ; 103(1): e14-e21, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29994981

RESUMO

BACKGROUND: Hepatic steatosis is strongly associated with cardiovascular disease in the general population. Whether recurrent or de novo, it can occur in the allograft, but the impact on survival and long-term clinical outcomes remains unclear. In this study, we aim to determine both the frequency and impact of allograft steatosis on long-term posttransplant outcomes. METHODS: A retrospective review of 588 adult liver transplant (LT) recipients (1999-2006) was performed. Cox regression analysis (time-dependent) was used to evaluate differences in time to steatosis post-LT, patient survival, and cardiovascular outcomes. RESULTS: Mean age 51.9 ± 10.6 years, 64.6% males, underlying nonalcoholic steatohepatitis (NASH) (9.4%), previous tobacco (52%), pre-LT diabetes mellitus (30.3%), pre-LT hypertension (23.2%), and known cardiovascular disease (9.7%). Overall, 254 recipients developed allograft steatosis (at 10 years: 77.6% NASH recipients, 44.7% Non-NASH recipients). Risk factors for allograft steatosis were female sex (hazard ratio [HR], 1.47; 95% confidence interval [CI], 1.09-2.00; P = 0.014), hepatitis C virus diagnosis (HR, 2.49; 95% CI, 1.77-3.94; P < 0.001), and time-dependent BMI (per unit: HR, 1.08; 95% CI, 1.05-1.10; P < 0.001). Allograft steatosis was not associated with post-LT survival (P = 0.25) nor cardiovascular events (HR, 1.08; 95% CI, 0.73-1.59; P = 0.70). Underlying NASH associated with cardiovascular events (HR, 2.04; 95% CI, 1.37-3.04; P < 0.001). CONCLUSIONS: Allograft steatosis is common but not associated with survival or cardiovascular events in this study. Larger prospective studies are needed to better define the natural history of allograft steatosis.


Assuntos
Transplante de Fígado/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/cirurgia , Adulto , Aloenxertos , Doenças Cardiovasculares/epidemiologia , Comorbidade , Feminino , Humanos , Incidência , Transplante de Fígado/mortalidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Minnesota/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/mortalidade , Prevalência , Recidiva , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
5.
Hepatology ; 66(6): 2055-2065, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28777879

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. Up to one third of individuals with NAFLD will develop nonalcoholic steatohepatitis (NASH), which is associated with progression to cirrhosis and is rapidly becoming the leading indication for liver transplantation. Sarcopenia is defined as a progressive and generalized loss of skeletal muscle mass, strength, and function. It is observed in up to 60% of patients with end-stage liver disease and portends a poor prognosis. Recent studies have shown that sarcopenia is a novel risk factor for developing NAFLD. Pathophysiological mechanisms relating sarcopenia and NASH may include insulin resistance (IR) and increased inflammation. IR leads to accumulation of triglycerides in both muscle tissue and the liver. It also exacerbates proteolysis and leads to muscle depletion. Chronic inflammation leads to liver injury and progression of fibrosis. The inflammatory milieu also stimulates protein catabolism. Viewing skeletal muscle as an endocrine organ that secretes various salutary myokines may help us understand its role in the development of steatosis. A better understanding of the pathophysiology will aid in developing physical and pharmacological therapeutic interventions. In this review, we will explore the complex inter-relationships between sarcopenia and NASH. We will discuss the impact of sarcopenia in patients with NASH and therapeutic options for the management of sarcopenia. (Hepatology 2017;66:2055-2065).


Assuntos
Hepatopatia Gordurosa não Alcoólica/complicações , Sarcopenia/complicações , Animais , Gerenciamento Clínico , Humanos , Hepatopatia Gordurosa não Alcoólica/terapia , Sarcopenia/diagnóstico , Sarcopenia/terapia
6.
Biol Blood Marrow Transplant ; 22(9): 1710-1716, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27343721

RESUMO

Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment for patients with blood disorders and genetic diseases. Approximately 70% of the HSCTs currently performed in the United States use stems cells from an unrelated donor who donated voluntarily. Medical students (MS) are a young, diverse, influential population whose willingness to engage in altruistic acts, such as donating stem cells, may be correlated with knowledge on the topic. A literature gap exists in MS perspectives towards HSCT and the bone marrow registry (BMR) and prior studies suggest that misconceptions about donation deter MS from participation on the BMR, which may decrease opportunities to educate other potential donors. We performed a cross-sectional survey among the 4-year cohort of MS at Mayo Medical School in Rochester, Minnesota. The questionnaire evaluated multiple areas including whether MS were current members of the BMR and/or prior blood donors, MS current knowledge on donor eligibility (DE) and the donation process (DP), MS familiarity with HSCT and the DP, and MS attitudes towards joining the BMR and towards donating stem cells. The responses were analyzed and assessed alongside a self-reported, standardized scale measuring students' altruistic behaviors. There were 99 out of 247 potential respondents (40%), with 45% (n = 44) of MS in preclinical years 1 or 2, 37% (n = 37) in clinical years 3 or 4, and 18% (n = 18) in research or alternative portions of their training, of which 43% (n = 41) in total were current BMR members. BMR status correlated positively with prior blood donation (P = .015) and female sex (P = .014). Respondents had a 57.7% and 63.7% average correct response rate regarding knowledge of DE and DP, respectively, with knowledge of DE not surprisingly higher in BMR members (P < .0001). The majority of MS surveyed, 68% (n = 65), had learned about HSCT during medical school. BMR status correlated with the following attitudes towards donating stem cells: lower concern with all evaluated aspects of HSCT-time, cost, pain, and side effects (for all subsections, P < .05) but not with the altruism score (P = .32). The mean altruism score for respondents was 59.9 ± 11.3 (of a possible 100 points) with no significant difference in age, race, sex, level of training, or participation in the BMR. Altruism scores did not directly correlate with lower concern with aspects of time, cost, and pain of HSCT but did with long-term side effects (P = .021). This latter correlation was regardless of BMR status. Among MS, positive predictors for participation in the BMR included prior blood donation and female sex. BMR status did not ensure knowledge of all aspects of donating stem cells, but it correlated with less concern regarding the DP and was unrelated to altruism score. Improving knowledge gaps regarding the BMR and HSCT for the next generation of physicians and health care providers through expanded medical education curriculum may be beneficial to for the recruitment and retention of donor populations to the BMR.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Células-Tronco Hematopoéticas/citologia , Doadores Vivos/provisão & distribução , Motivação , Estudantes de Medicina/psicologia , Adulto , Altruísmo , Custos e Análise de Custo , Estudos Transversais , Feminino , Humanos , Doadores Vivos/psicologia , Masculino , Dor , Sistema de Registros , Inquéritos e Questionários , Adulto Jovem
7.
Nat Commun ; 6: 6855, 2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25897778

RESUMO

Auditory sensory hair cells depend on stereocilia with precisely regulated lengths to detect sound. Since stereocilia are primarily composed of crosslinked, parallel actin filaments, regulated actin dynamics are essential for controlling stereocilia length. Here we assessed stereocilia actin turnover by monitoring incorporation of inducibly expressed ß-actin-GFP in adult mouse hair cells in vivo and by directly measuring ß-actin-GFP turnover in explants. Stereocilia actin incorporation is remarkably slow and restricted to filament barbed ends in a small tip compartment, with minimal accumulation in the rest of the actin core. Shorter rows of stereocilia, which have mechanically gated ion channels, show more variable actin turnover than the tallest stereocilia, which lack channels. Finally, the proteins ADF and AIP1, which both mediate actin filament severing, contribute to stereocilia length maintenance. Altogether, the data support a model whereby stereocilia actin cores are largely static, with dynamic regulation at the tips to maintain a critical length.


Assuntos
Citoesqueleto de Actina/fisiologia , Actinas/fisiologia , Mecanotransdução Celular/fisiologia , Órgão Espiral/fisiologia , Animais , Clonagem Molecular , Regulação da Expressão Gênica/fisiologia , Camundongos , Órgão Espiral/ultraestrutura
8.
J Neurosci ; 33(19): 8114-21, 2013 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-23658152

RESUMO

Stereocilia are actin-based protrusions on auditory sensory hair cells that are deflected by sound waves to initiate the conversion of mechanical energy to neuronal signals. Stereocilia maintenance is essential because auditory hair cells are not renewed in mammals. This process requires both ß-actin and γ-actin as knock-out mice lacking either isoform develop distinct stereocilia pathology during aging. In addition, stereocilia integrity may hinge on immobilizing actin, which outside of a small region at stereocilia tips turns over with a very slow, months-long half-life. Here, we establish that ß-actin and the actin crosslinking protein fascin-2 cooperate to maintain stereocilia length and auditory function. We observed that mice expressing mutant fascin-2 (p.R109H) or mice lacking ß-actin share a common phenotype including progressive, high-frequency hearing loss together with shortening of a defined subset of stereocilia in the hair cell bundle. Fascin-2 binds ß-actin and γ-actin filaments with similar affinity in vitro and fascin-2 does not depend on ß-actin for localization in vivo. Nevertheless, double-mutant mice lacking ß-actin and expressing fascin-2 p.R109H have a more severe phenotype suggesting that each protein has a different function in a common stereocilia maintenance pathway. Because the fascin-2 p.R109H mutant binds but fails to efficiently crosslink actin filaments, we propose that fascin-2 crosslinks function to slow actin depolymerization at stereocilia tips to maintain stereocilia length.


Assuntos
Actinas/metabolismo , Proteínas de Transporte/metabolismo , Células Ciliadas Auditivas/citologia , Proteínas dos Microfilamentos/metabolismo , Estereocílios/fisiologia , Estimulação Acústica , Actinas/deficiência , Actinas/genética , Envelhecimento/genética , Animais , Benzofuranos , Caderinas/genética , Proteínas de Transporte/genética , Eletroencefalografia , Receptor alfa de Estrogênio/genética , Potenciais Evocados Auditivos do Tronco Encefálico/genética , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Feminino , Células Ciliadas Auditivas/metabolismo , Células Ciliadas Auditivas/ultraestrutura , Perda Auditiva de Alta Frequência/genética , Perda Auditiva de Alta Frequência/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Proteínas dos Microfilamentos/genética , Microscopia de Força Atômica , Mutação/genética , Fenótipo , Ligação Proteica/genética , Quinolinas , Estereocílios/ultraestrutura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA