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1.
Ann Surg ; 278(5): e1026-e1034, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36692112

RESUMO

OBJECTIVE: To describe the rate of occult carcinoma deposits in total hepatectomy specimens from patients treated with liver transplant (LT) for colorectal liver metastases (CRLM). BACKGROUND: Previous studies have shown that patients with CRLM treated with systemic therapy demonstrate a high rate of complete radiographic response or may have disappearing liver metastases. However, this does not necessarily translate into a complete pathologic response, and residual invasive cancer may be found in up to 80% of the disappearing tumors after resection. METHODS: Retrospective review of 14 patients who underwent LT for CRLM, at 2 centers. Radiographic and pathologic correlation of the number of tumors and their viability before and after LT was performed. RESULTS: The median (interquartile range) number of tumors at diagnosis was 11 (4-23). The median number of chemotherapy cycles was 24 (16-37). Hepatic artery infusion was used in 5 patients (35.7%); 6 (42.9%) underwent surgical resection, and 5 (35.7%) received locoregional therapy. The indication for LT was unresectability in 8 patients (57.1%) and liver failure secondary to oncologic treatment in the remaining 6 (42.9%). Before LT, 7 patients (50%) demonstrated fluorodeoxyglucose-avid tumors and 7 (50%) had a complete radiographic response. Histopathologically, 11 patients (78.6%) had a viable tumor. Nine (64.2%) of the 14 patients were found to have undiagnosed metastases on explant pathology, with at least 22 unaccounted viable tumors before LT. Furthermore, 4 (57.1%) of the 7 patients who demonstrated complete radiographic response harbored viable carcinoma on explant pathology. CONCLUSIONS: A complete radiographic response does not reliably predict a complete pathologic response. In patients with unresectable CRLM, total hepatectomy and LT represent a promising treatment options to prevent indolent disease progression from disappearing CRLM.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Neoplasias Colorretais/patologia , Hepatectomia , Incidência , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Hepáticas/secundário
2.
Proc Natl Acad Sci U S A ; 117(50): 31729-31737, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33257568

RESUMO

Social influences on decision-making are particularly pronounced during adolescence and have both protective and detrimental effects. To evaluate how responsiveness to social signals may be linked to substance use in adolescents, we used functional neuroimaging and a gambling task in which adolescents who have and have not used substances (substance-exposed and substance-naïve, respectively) made choices alone and after observing peers' decisions. Using quantitative model-based analyses, we identify behavioral and neural evidence that observing others' safe choices increases the subjective value and selection of safe options for substance-naïve relative to substance-exposed adolescents. Moreover, the effects of observing others' risky choices do not vary by substance exposure. These results provide neurobehavioral evidence for a role of positive peers (here, those who make safer choices) in guiding adolescent real-world risky decision-making.


Assuntos
Comportamento do Adolescente/psicologia , Comportamento de Escolha , Influência dos Pares , Percepção Social/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adolescente , Feminino , Estilo de Vida Saudável , Humanos , Masculino , Assunção de Riscos , Transtornos Relacionados ao Uso de Substâncias/prevenção & controle
3.
HPB (Oxford) ; 24(9): 1425-1432, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35135723

RESUMO

BACKGROUND: Enhanced recovery after surgery (ERAS) components for liver resection lack standardization and compliance. We evaluated our ERAS protocol and describe the association of postoperative ERAS compliance with length of stay (LOS) and complications. METHODS: We retrospectively reviewed patients undergoing liver resection at our institution from 2016 to 2020. Pre- and post-ERAS outcomes and compliance at 72 h were compared with LOS and complications. LOS beyond 72 h was defined as LOS72. RESULTS: 210 patients were included. Post-ERAS patients had significantly shorter LOS (5.1 vs. 7.3 days, p = 0.0014) with no difference in 30-day mortality, morbidity, or readmissions. ERAS components associated with shorter LOS72 were regular diet (HR 1.73), fluid discontinuation (HR 1.63), drain removal (HR 1.94), multimodal and oral analgesia (HR 1.51), and ambulation >100 ft (HR 2.23). LOS72 was 1-day for ≥9 ERAS component compliance, 4-days for 6-8 components, and 6-days for <6 components. 30-day complication rates for patients with ≥9 components by postoperative day 3 (POD3) were significantly lower than those with 6-8 (12 vs 32%). CONCLUSION: ERAS decreases LOS after liver resection. Nutritional advancement, drain discontinuation, multimodal and oral analgesia, and ambulation >100 ft by POD3 are associated with decreased LOS72. Achieving ≥6 components by POD3 predicts decreased LOS72 and complications.


Assuntos
Recuperação Pós-Cirúrgica Melhorada , Hepatectomia/efeitos adversos , Humanos , Tempo de Internação , Fígado , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
4.
Liver Transpl ; 25(5): 724-733, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30589993

RESUMO

Outcomes for adult-to-adult living liver donors (LDs) are largely based on short-term data drawn from single-center studies. The aim of this study was to determine how living liver donation (LLD) impacts self-reported quality-of-life (QOL) up to 6 years after donation in a sample of residents from New York State. New York transplant programs are state-mandated to track LDs as part of a quality assurance and patient safety effort. Donor-reported QOL within 1 year of donation and longitudinal data over a 10-year period were analyzed. Self-reported surveys include the following domains: employment, finances, health/life insurance, activities of daily living, physical/emotional health, donor experience, relationships, and LD opinions. There were 220 LDs in New York (2004-2013) who completed a survey over the 10-year period with many donors completing surveys at several points in time. Overall, longterm LDs remain as comfortable about LLD as they were during the first year after donation (95%). The majority of LDs reported feeling as well as before LLD (72%). At 1 year after donation, 60% of subjects self-reported medical problems, and 30% reported emotional issues. However, the majority reported that they would willingly donate again. In conclusion, LDs remain satisfied with their decision to donate over time. A minority of LDs report longterm medical and emotional issues. The conclusions provide information for educational interventions to improve informed choice to those considering donation.


Assuntos
Comportamento de Escolha , Hepatectomia/efeitos adversos , Transplante de Fígado/efeitos adversos , Doadores Vivos/psicologia , Complicações Pós-Operatórias/psicologia , Adulto , Feminino , Hepatectomia/psicologia , Humanos , Transplante de Fígado/métodos , Transplante de Fígado/psicologia , Doadores Vivos/estatística & dados numéricos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Autorrelato/estatística & dados numéricos , Fatores de Tempo , Adulto Jovem
5.
Eur J Epidemiol ; 34(3): 225-233, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30673924

RESUMO

Causal inference for treatments with many versions requires a careful specification of the versions of treatment. Specifically, the existence of multiple relevant versions of treatment has implications for the selection of confounders. To illustrate this, we estimate the effect of organ transplantation using grafts from donors who died due to anoxic drug overdose, on recipient graft survival in the US. We describe how explicitly outlining the target trial (i.e. the hypothetical randomized trial which would answer the causal question of interest) to be emulated by an observational study analysis helps conceptualize treatment versions, guides selection of appropriate adjustment variables, and helps clarify the settings in which causal effects of compound treatments will be of value to decision-makers.


Assuntos
Fatores de Confusão Epidemiológicos , Transplante de Órgãos/métodos , Adulto , Idoso , Overdose de Drogas/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Doadores de Tecidos/estatística & dados numéricos , Resultado do Tratamento , Estados Unidos/epidemiologia
6.
Prog Transplant ; 27(3): 232-239, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-29187096

RESUMO

INTRODUCTION: Understanding living organ donors' experience with donation and challenges faced during the process is necessary to guide the development of effective strategies to maximize donor benefit and increase the number of living donors. METHODS: An anonymous self-administered survey, specifically designed for this population based on key informant interviews, was mailed to 426 individuals who donated a kidney or liver at our institution. Quantitative and qualitative methods including open and axial coding were used to analyze donor responses. FINDINGS: Of the 141 survey respondents, 94% would encourage others to become donors; however, nearly half (44%) thought the donation process could be improved and offered numerous suggestions. Five major themes arose: (1) desire for greater convenience in testing and scheduling; (2) involvement of previous donors throughout the process; (3) education and promotion of donation through social media; (4) unanticipated difficulties, specifically pain; and (5) financial concerns. DISCUSSION: Donor feedback has been translated into performance improvements at our hospital, many of which are applicable to other institutions. Population-specific survey development helps to identify vital patient concerns and provides valuable feedback to enhance the delivery of care.


Assuntos
Transplante de Rim/psicologia , Transplante de Fígado/psicologia , Doadores Vivos/psicologia , Atitude Frente a Saúde , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários
7.
J Vasc Surg Cases Innov Tech ; 10(3): 101469, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38577692

RESUMO

Coronavirus disease 2019-related transplant hepatic pseudoaneurysms have not been reported but can be life-threatening. They can be either solitary or multiple and can grow rapidly within weeks. They should be classified as mycotic and treated on an emergent basis. Both stenting of the vessel and coil embolization can potentially be viable treatment options of coronavirus disease 2019-related pseudoaneurysms.

8.
Int Immunol ; 24(2): 97-106, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22190574

RESUMO

Hepatitis C virus (HCV) chronic infection is characterized by low-level or undetectable cellular immune response against HCV antigens. HCV proteins affect various intracellular events and modulate immune responses, although the mechanisms that mediate these effects are not fully understood. In this study, we examined the effect of HCV proteins on the differentiation of human peripheral blood monocytes to dendritic cells (DCs). The HCV core (HCVc) and non-structural 3 (NS3) proteins inhibited the expression of CD1a, CD1b and DC-SIGN during monocyte differentiation to DCs, while increasing some markers characteristic of macrophages (CD14 and HLA-DR) and also PD-L1 expression. Meanwhile, HCVc and NS3 could induce differentiating monocytes to secrete IL-10. However, anti-IL-10 mAb could not reverse HCVc and NS3 inhibition of monocyte differentiation into DCs. The HCVc and NS3 proteins increased IL-6 secretion both in immature and in fully differentiated DCs and also promoted CD4+ T-cell IL-17 production. Since T(h) 17 cells are active in many examples of immunopathology, these effects may contribute to HCV autoimmune responses in chronically infected patients.


Assuntos
Células Dendríticas/imunologia , Hepacivirus/imunologia , Antígenos da Hepatite C/imunologia , Hepatite C Crônica/imunologia , Células Th17/imunologia , Proteínas do Core Viral/imunologia , Proteínas não Estruturais Virais/imunologia , Antígenos CD/imunologia , Diferenciação Celular/imunologia , Células Cultivadas , Regulação da Expressão Gênica/imunologia , Humanos , Imunomodulação , Interleucina-10/imunologia , Interleucina-10/metabolismo , Interleucina-6/metabolismo
9.
BMC Gastroenterol ; 13: 9, 2013 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-23317091

RESUMO

BACKGROUND: Diabetes mellitus (DM) is identified as a negative prognostic indicator in hepatocellular carcinoma (HCC), though the basis for this is unknown. METHODS: This is a retrospective analysis of a prospectively collected database of 191 HCC patients treated at the University of Rochester Medical Center (URMC) with orthotopic liver transplantation between 1998-2008. Clinical characteristics were compared between patients with and without DM prior to liver transplantation and logistic regression analyses were conducted to assess the effect of DM on clinical outcomes including vascular invasion. RESULTS: Eighty-four of 191 (44%) transplanted patients had DM at time of transplantation. An association of DM with invasive disease was found among transplanted HCC patients where histologically confirmed macrovascular invasion was found in 20.2% (17/84) of diabetics compared to 9.3% of non-diabetics (10/107) (p=0.032). This difference also remained significant when adjusting for tumor size, number of nodules, age, obesity and etiologic risk factors in multivariate logistic regression analysis (OR=3.2, p=0.025). CONCLUSIONS: DM is associated with macrovascular invasion among a cohort of transplanted HCC patients.


Assuntos
Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/cirurgia , Complicações do Diabetes/complicações , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/cirurgia , Transplante de Fígado , Neovascularização Patológica/epidemiologia , Idoso , Carcinoma Hepatocelular/diagnóstico , Estudos de Coortes , Feminino , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Prospectivos , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento
10.
Curr Biol ; 33(18): R963-R965, 2023 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-37751711

RESUMO

Humans construct cognitive maps of the physical, imagined, and abstract world around us based on visually sampled information. A new study shows how the human brain can also use olfactory cues to form and use cognitive maps.


Assuntos
Encéfalo , Sinais (Psicologia) , Humanos , Olfato , Cognição
11.
JSLS ; 27(1)2023.
Artigo em Inglês | MEDLINE | ID: mdl-36818765

RESUMO

Introduction: Open transplant nephrectomy for failed renal allograft is an invasive procedure associated with significant perioperative morbidity and mortality. Minimally invasive surgical approaches have improved a variety of patient outcomes for many surgeries. Thus, robotic assisted transplant nephrectomy (RATN) potentially offers significant patient benefit. Although previously reported, there remains a paucity of data on RATN outcomes and techniques. Methods: Four perfused, high-fidelity hydrogel models were created using previously described techniques and used for simulated RATN. Subsequently performed institutional cases were included for analysis. Intra- and postoperative variables along with patient demographics were retrospectively obtained through parsing of patient records. Results: Simulated nephrectomy time was 67.33 minutes (35.75 - 98.91). Five patients underwent RATN. There were four male and one female patients. The average age was 47 years. The most common indication was abdominal pain secondary to rejection (3/5). Mean blood loss was 188 mL; mean operative time was 243 minutes, and mean length of stay was 4.5 days. Intraoperatively there were two incidences of small cystotomies. One patient was readmitted within 30 days for intraabdominal abscess. Conclusion: This study adds to the growing literature around RATN, demonstrating the feasibility of the technique and reporting good outcomes for this cohort.


Assuntos
Neoplasias Renais , Transplante de Rim , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/métodos , Nefrectomia/métodos
12.
Liver Transpl ; 18(9): 1100-9, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22577087

RESUMO

Invasive fungal infections (IFIs) are associated with a high mortality rate for liver transplantation (LT) recipients. To study the incidence of and risk factors for IFIs in LT recipients and the associated mortality rates, we retrospectively reviewed the records of first-time deceased donor LT recipients (January 2003 to December 2007). The incidence of IFIs was 12%. Non-albicans Candida species accounted for 55% of IFIs; 50% of these IFIs were Candida parapsilosis. Only 43% of Candida isolates were fluconazole-susceptible (minimum inhibitory concentration ≤ 8 µ/mL). All C. parapsilosis isolates were fluconazole-resistant, and this coincided with a surge of these isolates during a peak period of LT. Factors associated with IFIs included a creatinine level > 2 mg/mL [hazard ratio (OR) = 2.4, 95% confidence interval (CI) = 1.2-5.0, P = 0.01], a Model for End-Stage Liver Disease score > 25 (OR = 2.4, 95% CI = 1.2-4.9, P = 0.02), pretransplant fungal colonization (OR = 7.0, 95% CI = 3.2-15.3, P < 0.001), and a daily prophylactic fluconazole dosage < 200 mg (OR = 2.8, 95% CI = 1.1-7.4, P = 0.03). According to a multivariate analysis, only pretransplant fungal colonization was associated with IFIs (OR = 7.8, 95% CI = 3.9-16.2, P < 0.001). The 1-year patient survival rates with and without IFIs were 41% and 80%, respectively, and the survival rates with C. parapsilosis, other non-albicans Candida, and Candida albicans IFIs were 28%, 50%, and 75%, respectively. In conclusion, IFIs after LT (especially non-albicans Candida species and fluconazole-resistant C. parapsilosis) were associated with reduced survival. The risk factors highlight the importance of pretransplant risk assessments. The identification of pretransplant fungal colonization may allow for risk modifications before or at the time of LT. Additionally, the number of LT procedures and prophylactic strategies may affect institutional outbreaks of resistant Candida strains.


Assuntos
Antifúngicos/uso terapêutico , Candida , Farmacorresistência Fúngica , Fluconazol/uso terapêutico , Transplante de Fígado/efeitos adversos , Micoses/epidemiologia , Micoses/microbiologia , Adolescente , Adulto , Idoso , Candida/classificação , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Distribuição de Qui-Quadrado , Feminino , Humanos , Incidência , Estimativa de Kaplan-Meier , Transplante de Fígado/mortalidade , Modelos Logísticos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Minnesota/epidemiologia , Análise Multivariada , Micoses/tratamento farmacológico , Micoses/mortalidade , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
13.
Prog Transplant ; 32(4): 292-299, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36039516

RESUMO

Introduction: Despite strong public support, organ donor registration rates (RR) continue to lag while need only grows. In the United States, the traditional registration site is the Department of Motor Vehicles (DMV), however Primary care provider (PCP) offices have been considered as alternate locations for increasing RR. Methods: Twelve PCP offices across 2 New York Counties were subjected to a control week where participants received only a registration opportunity and an intervention week with the addition of a motivational poster and informational brochure. Zip code level sociodemographic data were obtained for each site. RR from the DMV over the same period served as historical control. Results: There were 1292 participants in the control phase and 1099 in the experimental phase. New registration rate for the control was 33.8% (289/897); experimental phase 7.88% (61/769); DMV registration 21.02% (1902/9050). The intervention was associated with a significant decrease in registrations (OR 0.181 (95% CI 0.135-0.244, P < 0.001)). Offices were clustered based on sociodemographic factors and regressed in 2 clusters. Lower educational attainment was associated with lower registration in the first but not second cluster (OR = 0.948 (0.923-0.974, P < 0.001)). Conclusions: This study provided evidence that PCP offices were a feasible site for organ donor registration and calls into question the efficacy of written materials-only interventions for increasing organ donor RR. It reiterated the negative effect of lower educational attainment on registration and suggested future studies focus on more active methods of engagement.


Assuntos
Obtenção de Tecidos e Órgãos , Humanos , Estados Unidos , New York , Sistema de Registros , Doadores de Tecidos , Atenção Primária à Saúde
14.
JAMA Surg ; 157(6): 524-530, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35353121

RESUMO

Importance: Colorectal cancer is a leading cause of cancer-related death, and nearly 70% of patients with this cancer have unresectable colorectal cancer liver metastases (CRLMs). Compared with chemotherapy, liver transplant has been reported to improve survival in patients with CRLMs, but in North America, liver allograft shortages make the use of deceased-donor allografts for this indication problematic. Objective: To examine survival outcomes of living-donor liver transplant (LDLT) for unresectable, liver-confined CRLMs. Design, Setting, and Participants: This prospective cohort study included patients at 3 North American liver transplant centers with established LDLT programs, 2 in the US and 1 in Canada. Patients with liver-confined, unresectable CRLMs who had demonstrated sustained disease control on oncologic therapy met the inclusion criteria for LDLT. Patients included in this study underwent an LDLT between July 2017 and October 2020 and were followed up until May 1, 2021. Exposures: Living-donor liver transplant. Main Outcomes and Measures: Perioperative morbidity and mortality of treated patients and donors, assessed by univariate statistics, and 1.5-year Kaplan-Meier estimates of recurrence-free and overall survival for transplant recipients. Results: Of 91 evaluated patients, 10 (11%) underwent LDLT (6 [60%] male; median age, 45 years [range, 35-58 years]). Among the 10 living donors, 7 (70%) were male, and the median age was 40.5 years (range, 27-50 years). Kaplan-Meier estimates for recurrence-free and overall survival at 1.5 years after LDLT were 62% and 100%, respectively. Perioperative morbidity for both donors and recipients was consistent with established standards (Clavien-Dindo complications among recipients: 3 [10%] had none, 3 [30%] had grade II, and 4 [40%] had grade III; donors: 5 [50%] had none, 4 [40%] had grade I, and 1 had grade III). Conclusions and Relevance: This study's findings of recurrence-free and overall survival rates suggest that select patients with unresectable, liver-confined CRLMs may benefit from total hepatectomy and LDLT.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Transplante de Fígado , Adulto , Feminino , Humanos , Transplante de Fígado/efeitos adversos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
15.
Gastroenterology ; 138(1): 305-14, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19769973

RESUMO

BACKGROUND & AIMS: Kupffer cells (KC) are important innate immune cells of the liver, functioning as scavenging sinusoidal phagocytes and transducers of pattern recognition signals, including those of toll-like receptors (TLRs). The hepatitis C virus core protein (HCVc) engages TLR2 on peripheral blood monocytes and induces production of multiple inflammatory cytokines. We examined the effects of HCVc on human primary KC functions. METHODS: KC were isolated from living donor allografts and stimulated with HCVc and/or ligands for TLRs. KC were examined for production of cytokines, expression of programmed death-ligand 1 (PD-L1), secretion of type 1 interferons (IFNs), and expression of the apoptosis-inducing protein tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL). RESULTS: HCVc acts as a ligand for TLR2 on human KC, inducing them to secrete interleukin (IL)-1beta, TNF-alpha, and IL-10 and up-regulate cell surface PD-L1. HCVc blocked TLR3-mediated secretion of IFN-alpha, IFN-beta, and cell surface expression of the cytotoxic molecule TRAIL. Inhibition of phosphoinositide 3 kinase with LY294002 blocked the up-regulation of PD-L1 by TLR ligands and the TLR3-specific induction of TRAIL and type 1 IFNs. CONCLUSIONS: KC are intravascular macrophages that are continuously exposed to, and tolerant of, bacterial TLR ligands, which are delivered via the portal circulation. By mimicking a bacterial TLR2 ligand and effectively blocking the TLR3-mediated, double-stranded RNA-induced antiviral response, HCVc might appear to exploit this unique aspect of immunity in the liver.


Assuntos
Hepacivirus , Hepatite C/metabolismo , Hepatite C/virologia , Células de Kupffer/virologia , Proteínas do Core Viral/metabolismo , Antígenos CD/metabolismo , Antígeno B7-H1 , Células Cultivadas , Hepatite C/imunologia , Humanos , Interferon gama/metabolismo , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Células de Kupffer/imunologia , Células de Kupffer/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptor 2 Toll-Like/metabolismo , Receptor 3 Toll-Like/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação para Cima/fisiologia
16.
Cell Immunol ; 271(2): 286-91, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21802664

RESUMO

Natural killer (NK) cells are a component of innate immunity against viral infections through their rapid cytotoxic activity and cytokine production. However, intra-hepatic NK cells' ability to respond to virus is still mostly unknown. Our results show that the synthetic dsRNA polyinosinic-polycytidylic acid (poly I:C), a mimic of a common product of viral infections, activates NK cells directly in the context of cytokines found in the liver, i.e.: poly I:C plus inflammatory cytokines (IL-18, IL-12, and IL-2) induced NK cell IFN-γ production and TRAIL expression, and anti-inflammatory cytokines (TGF-ß and IL-10) inhibit NK cell IFN-γ production. Neutralization of IFN-γ blocks poly I:C plus inflammatory cytokines-induced NK cell TRAIL expression, suggesting that IFN-γ is an autocrine differentiation factor for these cells. A better understanding of the intra-hepatic NK cell activation against viral infection may help in the design of therapies and vaccines for the control of viral hepatitis.


Assuntos
Interferon gama/metabolismo , Interleucina-18/metabolismo , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Fígado/citologia , Fígado/imunologia , Ligante Indutor de Apoptose Relacionado a TNF/metabolismo , Receptor 3 Toll-Like/metabolismo , Sinergismo Farmacológico , Humanos , Interferon gama/antagonistas & inibidores , Interleucina-10/administração & dosagem , Interleucina-10/metabolismo , Subunidade p35 da Interleucina-12/administração & dosagem , Subunidade p35 da Interleucina-12/metabolismo , Interleucina-18/administração & dosagem , Interleucina-2/administração & dosagem , Interleucina-2/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Fígado/metabolismo , Poli I-C/administração & dosagem , Poli I-C/farmacologia , Proteínas Recombinantes/administração & dosagem , Fator de Crescimento Transformador beta/administração & dosagem , Fator de Crescimento Transformador beta/metabolismo
17.
Clin Transplant ; 25(2): 213-21, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-20331690

RESUMO

Acute renal failure is a significant risk factor for death in patients with liver failure. The goal of this study was to analyze the impact of peri-transplant dialysis on the long-term mortality of liver transplant recipients. We performed a single-center, retrospective cohort study of 743 adult liver transplants; patients who received first liver transplants were divided into four groups: those who received more than one dialysis treatment (hemodialysis [HD], continuous veno-venous hemodialysis [CVVH]) pre-orthotopic liver transplantation (OLT), post OLT, pre- and post OLT, and those not dialyzed. There was no statistically significant difference in the mean survival time for patients who were not dialyzed or dialyzed only pre-OLT. Mean survival times were markedly reduced in patients dialyzed post OLT or both pre- and post OLT compared with those never dialyzed. Mortality risk in a Cox proportional hazards model correlated with hemodialysis post OLT, intra-operative vasopressin or neosynephrine, donor age >50 yr, Cr >1.5 mg/dL at transplant, and need for subsequent retransplant. Risk of post-OLT dialysis was correlated with pre-OLT dialysis, intra-operative levophed, pre-OLT diabetes, African American race, pre-OLT Cr >1.5, and male gender. We conclude that renal failure requiring hemodialysis post liver transplant, irrespective of pre-transplant dialysis status, is a profound risk factor for death in liver transplant recipients.


Assuntos
Rejeição de Enxerto/mortalidade , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Transplante de Fígado/efeitos adversos , Diálise Renal/mortalidade , Adulto , Estudos de Coortes , Feminino , Seguimentos , Humanos , Falência Renal Crônica/etiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
18.
Liver Transpl ; 16(1): 42-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20035520

RESUMO

The number of liver donors has not measurably increased since 2004 and has begun to decrease. Although many waitlisted patients may be suitable candidates to receive a living donor graft, they are often reticent to discuss living donation with close friends and family, partly because of a lack of knowledge about donor health and quality of life outcomes after donation. The objective of this study was to test the effectiveness of an educational intervention that uses testimonials and self-report data from living donors in New York State. The study had an independent sample pretest (n = 437) and posttest (n = 338) design with posttest, between-subjects comparison for intervention exposure. All waitlisted patients at 5 liver transplant centers in New York were provided a peer-based educational brochure and DVD either by mail or at the clinic. The outcome measures were liver candidates' knowledge and self-efficacy to discuss living donation with family and friends. The number and proportion of individuals who presented to centers for living liver donation evaluation were also measured. Liver transplant candidates' self-efficacy to discuss living donation and their knowledge increased from the pretest period to the posttest period. Those exposed to the peer-based intervention reported significantly greater knowledge, a greater likelihood of discussing donation, and increased self-efficacy in comparison with those not exposed to the intervention. The results did not differ by age, length of time on the waiting list, education, or ethnicity. In comparison with the preintervention period, living donation increased 42%, and the number of individuals who presented for donation evaluation increased by 74%.


Assuntos
Transplante de Fígado/educação , Doadores Vivos , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , New York , Grupo Associado , Qualidade de Vida , Autoeficácia
19.
Clin Transplant ; 24(1): 104-11, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-19239480

RESUMO

INTRODUCTION: Recurrence of hepatitis C virus (HCV) in hepatic allograft is a major concern after successful liver transplant (LTx). AIM: To examine the response rate to pegylated interferon (PEG-IFN) and ribavirin in post-LTx patients with HCV recurrence. PATIENTS AND METHODS: Between January 2003 and September 2006, 60 patients with biopsy proven HCV recurrence (46 males and 14 females) received PEG-IFN 2a (n = 40) or IFN 2b (n = 20) with ribavirin. All patients were followed until July 2007. RESULTS: Fourteen patients (23.3%) tolerated antiviral therapy for less than six months and 10 (16.7%) discontinued therapy between six and 11 months. PEG-IFN dose was reduced in 21 (35%) patients and ribavirin dose was reduced in 16 (26.7%) patients. Overall, 55% patients achieved end of treatment response (EOT) and 35% sustained virological response (SVR). Mean Hepatitis Activity Index and Fibrosis Score pre-therapy was 5.8 +/- 1.9 and 1.7 +/- 1.3 and post-therapy, it was 4.4 +/- 2.1 and 2.4 +/- 1.6, respectively. Overall, three yr patient and graft survival was 73.9% and 69.2%, respectively. The patients with SVR had significantly lower viral load compared with other groups (p = 0.028). CONCLUSION: PEG-IFN and ribavirin therapy achieved 55% EOT and 35% SVR; 60% patients tolerated therapy. Biochemical response was observed in all groups of patients irrespective of virological response.


Assuntos
Antivirais/uso terapêutico , Hepatite C/tratamento farmacológico , Interferon-alfa/uso terapêutico , Transplante de Fígado , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Estudos de Coortes , Feminino , Hepatite C/mortalidade , Hepatite C/cirurgia , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Recidiva , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Liver Transpl ; 15(10): 1204-8, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19790151

RESUMO

Traditionally, patients who die with a malignancy have been excluded from donation. However, it has become a common practice to accept organs from donors that have low-grade tumors or tumors with low metastatic potential. The aim of this study was to analyze our experience with the use of liver grafts from donors with central nervous system (CNS) tumors. A retrospective review of 1173 liver transplants performed between 1992 and 2006 identified 42 donors diagnosed with a CNS tumor. Thirty-two tumors were malignant, and 10 tumors were benign. Forty-two liver transplant recipients received livers from these donors. All patients were followed until May 2007 with a mean follow-up of 29 +/- 17 months. Among 42 donors, there were 28 males and 14 females. The mean donor risk index was 1.78 +/- 0.39. Twenty (47.6%) of the CNS tumors were glioblastoma multiforme (astrocytoma grade IV), 11 (26.2%) were other astrocytomas, and 1 (2.4%) was an anaplastic ependymoma. Twenty (62.5%) neoplasms were grade IV tumors, 8 (25%) were grade II tumors, and 4 (12.5%) were grade III tumors. Over 80% of the patients had at least 1 kind of invasive procedure violating the blood-brain barrier. The rate of recurrence for the entire group was 2.4% (all CNS tumors). There were 7 (7.2%) deaths in all. The most common cause of death was sepsis (n = 3, 7.2%). There was no difference in survival between recipients of grafts from donors with CNS tumors and recipients of grafts from donors without CNS tumors (1 year: 82% versus 83.3%, P = not significant; 3 years: 77.4% versus 72%, P = not significant). In conclusion, in our experience, despite violation of the blood-brain barrier and high-grade CNS tumors, recurrence was uncommon. Grafts from these donors are often an overlooked source of high-quality organs from younger donors and can be appropriately used, particularly in patients who, despite low Model for End-Stage Liver Disease scores, carry a high risk of mortality.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Hepatopatias/terapia , Transplante de Fígado/métodos , Obtenção de Tecidos e Órgãos/métodos , Adulto , Barreira Hematoencefálica , Neoplasias do Sistema Nervoso Central/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos , Fatores de Tempo , Doadores de Tecidos , Resultado do Tratamento
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