RESUMO
Exposure to low temperatures has been associated with increased gastroesophageal variceal bleeding in patients with cirrhosis and portal hypertension; however, the mechanism remains unclear. Therefore, the aim of the present study was to evaluate the impact of environmental temperature reduction on portal hypertension and the role of adrenergic signaling pathways in this phenomenon. Male Sprague-Dawley rats underwent common bile duct ligation or partial portal vein ligation to induce liver cirrhosis and/or portal hypertension. The impacts of acute or chronic changes in environmental temperature were surveyed. The results showed that acute cooling from 25 to 15°C and 5°C increased the portal pressure by 10.6% and 15.5% in cirrhotic rats, and by 22.2% and 36.1% in portal hypertensive rats, respectively. The transient portal pressure surge started shortly after cooling, reached a peak within 5 min and returned to baseline after 10 min. Systemic vascular resistance, mean arterial pressure and splanchnic blood flow increased significantly at the same time. Plasma epinephrine and norepinephrine concentrations, phospholipase C, protein kinase C activity and myosin phosphorylation of peripheral arteries increased significantly in response to cooling. Phentolamine (an α-blocker) but not propranolol (a non-selective ß-blocker) dose-dependently inhibited the transient portal pressure surge and aforementioned molecular changes. In conclusion, environmental temperature reduction induced peripheral vasoconstriction via α-adrenergic pathways, and redistribution of blood flow to the splanchnic system led to a surge in transient portal pressure. Treatment with α-adrenergic receptor antagonists may exert additional benefits in controlling portal hypertension, especially on exposure to low temperatures.
Assuntos
Varizes Esofágicas e Gástricas , Hipertensão Portal , Ratos , Masculino , Animais , Pressão na Veia Porta , Temperatura , Fentolamina/farmacologia , Circulação Esplâncnica , Ratos Sprague-Dawley , Hemorragia Gastrointestinal , Antagonistas Adrenérgicos beta/farmacologia , Cirrose Hepática , Hemodinâmica , Norepinefrina/farmacologia , Epinefrina/farmacologia , Fosfolipases Tipo C , Proteína Quinase CRESUMO
Liver cirrhosis and portal hypertension is the end of chronic liver injury with hepatic, splanchnic and portosystemic collateral systems dysregulation. Liver injury is accompanied by gut dysbiosis whereas dysbiosis induces liver fibrosis, splanchnic angiogenesis and dysregulated vascular tones vice versa, making portal hypertension aggravated. It has been proved that intestinal microbiota transplantation alleviates dysbiosis. Nevertheless, the influences of microbiota transplantation on cirrhosis-related portal hypertension are not so clear. Liver cirrhosis with portal hypertension was induced by bile duct ligation (BDL) in rats. Sham rats were surgical controls. Rats randomly received vehicle, fecal or gut (terminal ileum) material transplantation. The results showed that microbiota transplantation from feces or gut material significantly reduced portal pressure in cirrhotic rats (P=0.010, 0.044). Hepatic resistance, vascular contractility, fibrosis and relevant protein expressions were not significantly different among cirrhotic rats. However, microbiota transplantation ameliorated splanchnic hyperdynamic flow and vasodilatation. Mesenteric angiogenesis, defined by whole mesenteric window vascular density, decreased in both transplantation groups and phosphorylated endothelial nitric-oxide synthase (eNOS) was down-regulated. Portosystemic shunts determined by splenorenal shunt (SRS) flow decreased in both transplantation groups (P=0.037, 0.032). Shunting severity assessed by microsphere distribution method showed consistent results. Compared with sham rats, cirrhotic rats lacked Lachnospiraceae. Both microbiota transplants increased Bifidobacterium. In conclusion, microbiota transplantation in cirrhotic rats reduced portal pressure, alleviated splanchnic hyperdynamic circulation and portosystemic shunts. The main beneficial effects may be focused on portosystemic collaterals-related events, such as hepatic encephalopathy and gastroesophageal variceal hemorrhage. Further clinical investigations are mandatory.
Assuntos
Transplante de Microbiota Fecal , Hipertensão Portal/microbiologia , Cirrose Hepática/fisiopatologia , Circulação Esplâncnica , Animais , Ductos Biliares/cirurgia , Modelos Animais de Doenças , Fezes/microbiologia , Microbioma Gastrointestinal , Hipertensão Portal/patologia , Ligadura , Masculino , Pressão na Veia Porta , Derivação Portossistêmica Cirúrgica , Ratos Sprague-DawleyRESUMO
We have shown that glycosylation of influenza A virus (IAV) hemagglutinin (HA), especially at position N-27, is crucial for HA folding and virus survival. However, it is not known whether the glycosylation of HA and the other two major IAV surface glycoproteins, neuraminidase (NA) and M2 ion channel, is essential for the replication of IAV. Here, we show that glycosylation of HA at N-142 modulates virus infectivity and host immune response. Glycosylation of NA in the stalk region affects its structure, activity, and specificity, thereby modulating virus release and virulence, and glycosylation at the catalytic domain affects its thermostability; however, glycosylation of M2 had no effect on its function. In addition, using IAV without the stalk and catalytic domains of NA as a live attenuated vaccine was shown to confer a strong IAV-specific CD8+ T-cell response and a strong cross-strain as well as cross-subtype protection against various virus strains.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Vírus da Influenza A/imunologia , Vacinas contra Influenza/imunologia , Células A549 , Animais , Anticorpos Antivirais/imunologia , Linfócitos T CD8-Positivos/imunologia , Linhagem Celular , Linhagem Celular Tumoral , Proteção Cruzada/imunologia , Cães , Feminino , Células HEK293 , Humanos , Influenza Humana/imunologia , Influenza Humana/prevenção & controle , Células Madin Darby de Rim Canino , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Virulência/imunologiaRESUMO
INTRODUCTION AND OBJECTIVES: Liver cirrhosis is characterized by increased intrahepatic resistance, splanchnic vasodilation/angiogenesis, and formation of portosystemic collateral vessels. Collaterals can cause lethal complications such as gastroesophageal variceal hemorrhage. Homocysteine is linked to vascular dysfunction and angiogenesis and higher levels have been reported in cirrhotic patients. It is also known that folic acid supplementation reverses the effects of homocysteine. However, the treatment effect in cirrhosis has yet to be investigated. MATERIAL AND METHODS: Liver cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (CBDL). The CBDL rats randomly received (1) vehicle; (2) dl-homocysteine thiolactone (1g/kg/day); (3) dl-homocysteine thiolactone plus folic acid (100mg/kg/day); or (4) folic acid. On the 29th day, hemodynamic parameters, liver and renal biochemistry, protein expressions of proangiogenic factors, mesenteric vascular density and portosystemic shunting were evaluated. RESULTS: In the cirrhotic rats, homocysteine increased mesenteric vascular density and the severity of shunting. It also up-regulated the protein expressions of mesenteric vascular endothelial growth factor (VEGF) and phosphorylated-endothelial nitric oxide synthase (p-eNOS). These effects were reversed by folic acid treatment (P<0.05). CONCLUSION: Folic acid ameliorated the adverse effects of homocysteine in the cirrhotic rats, which may be related to down-regulation of the VEGF-NO signaling pathway.
Assuntos
Circulação Colateral/efeitos dos fármacos , Ácido Fólico/farmacologia , Homocisteína/análogos & derivados , Cirrose Hepática/fisiopatologia , Neovascularização Patológica/induzido quimicamente , Sistema Porta/efeitos dos fármacos , Circulação Esplâncnica/efeitos dos fármacos , Complexo Vitamínico B/farmacologia , Animais , Ducto Colédoco , Hemodinâmica/efeitos dos fármacos , Homocisteína/farmacologia , Ligadura , Cirrose Hepática/complicações , Neovascularização Patológica/etiologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Óxido Nítrico Sintase Tipo III/efeitos dos fármacos , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação , Sistema Porta/patologia , Ratos , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Patients suffering from liver cirrhosis are often complicated with the formation of portosystemic collateral vessels, which is associated with the progression of a splanchnic hyperdynamic circulatory state. Alleviating pathological angiogenesis has thus been proposed to be a feasible treatment strategy. Indole-3-carbinol (C9H9NO, I3C) and 3,3'-diindolymethane (DIM), formed by the breakdown of glucosinolate glucobrassicin, are prevalent in cruciferous vegetables and have anti-angiogenesis properties. We aimed to evaluate their influences on portal hypertension, the severity of mesenteric angiogenesis, and portosystemic collaterals in cirrhosis. Sprague-Dawley rats with common bile duct ligation (CBDL)-induced liver cirrhosis or sham operation (surgical control) were randomly allocated to receive I3C (20 mg/kg/3 day), DIM (5 mg/kg/day) or vehicle for 28 days. The systemic and portal hemodynamics, severity of portosystemic shunting, mesenteric angiogenesis, and mesenteric proangiogenic factors protein expressions were evaluated. Compared to vehicle, both DIM and I3C significantly reduced portal pressure, ameliorated liver fibrosis, and down-regulated mesenteric protein expressions of vascular endothelial growth factor and phosphorylated Akt. DIM significantly down-regulated pErk, and I3C down-regulated NFκB, pIκBα protein expressions, and reduced portosystemic shunting degree. The cruciferous vegetable byproducts I3C and DIM not only exerted a portal hypotensive effect but also ameliorated abnormal angiogenesis and portosystemic collaterals in cirrhotic rats.
Assuntos
Glucosinolatos/farmacologia , Hipertensão Portal/tratamento farmacológico , Indóis/farmacologia , Cirrose Hepática/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Angiografia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Biomarcadores , Peso Corporal , Modelos Animais de Doenças , Hemodinâmica/efeitos dos fármacos , Hipertensão Portal/diagnóstico , Hipertensão Portal/etiologia , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Modelos Biológicos , Tamanho do Órgão , RatosRESUMO
Hepatopulmonary syndrome (HPS) is a lethal complication of cirrhosis characterized by hypoxia and overt intrapulmonary shunting. In this study, we investigated the effect of caffeine in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS. CBDL rats were randomly allocated to receive caffeine or vehicle for 14 days. On the 28th day after CBDL, mortality rate, hemodynamics, liver, and renal biochemistry parameters and arterial blood gas analysis were evaluated. Lung and liver were dissected for the evaluation of inflammation, angiogenesis and protein expressions. In another series with parallel groups, the intrapulmonary shunting was determined. Caffeine significantly reduced portal pressure (caffeine vs. control: 10.0 ± 3.7 vs. 17.0 ± 8.1 mmHg, p < 0.05) in CBDL rats. The mortality rate, mean arterial pressure, biochemistry data and hypoxia were similar between caffeine-treated and control groups. Caffeine alleviated liver fibrosis and intrahepatic angiogenesis but intrapulmonary inflammation and angiogenesis were not ameliorated. The hepatic VEGF/Rho-A protein expressions were down-regulated but the pulmonary inflammation- and angiogenesis-related protein expressions were not significantly altered by caffeine. Caffeine did not reduce the intrapulmonary shunting, either. Caffeine has been shown to significantly improve liver fibrosis, intrahepatic angiogenesis and portal hypertension in cirrhotic rats, however, it does not ameliorate HPS.
Assuntos
Inibidores da Angiogênese/uso terapêutico , Cafeína/uso terapêutico , Síndrome Hepatopulmonar/tratamento farmacológico , Cirrose Hepática/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cafeína/farmacologia , Modelos Animais de Doenças , Síndrome Hepatopulmonar/complicações , Síndrome Hepatopulmonar/patologia , Hipertensão Portal/complicações , Hipertensão Portal/tratamento farmacológico , Hipertensão Portal/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
Liver cirrhosis is characterized by portal hypertension. However, the alteration of portal hypertension-related derangements during cirrhosis resolution is not well known. The present study aimed to establish animal models with cirrhosis resolution and to investigate the relevant changes during this process. Male Sprague-Dawley rats were applied. In reverse thioacetamide (rTAA) model, rats were randomly allocated into four groups with control, thioacetamide (TAA) cirrhosis and rTAA groups that discontinued TAA for 4 or 8 weeks after cirrhosis induction. In reverse bile duct ligation (rBDL) model, rats received choledochoduodenal shunt surgery upon the establishment of cirrhosis and 4, 8, or 16 weeks were allowed after the surgery. At the end, portal hypertension-related parameters were evaluated. Cirrhosis resolution was observed in rTAA groups. Portal pressure (PP) decreased after cirrhosis resolution but remained higher than control group (control, TAA, rTAA4, rTAA8 (mmHg): 5.4 ± 0.3, 12.9 ± 0.3, 8.6 ± 0.4, 7.6 ± 0.6). Further survey found the increased splanchnic blood flow did not reduce during cirrhosis resolution. The extrahepatic pathological angiogenesis was not ameliorated (% of mesenteric window area: 1.2 ± 0.3, 7.3 ± 1.1, 8.3 ± 1.0, 11.3 ± 2.7). In collateral system, the shunting degree reduced while the vessels structure remained. The vascular contractility of all systems and nitric oxide (NO) production were normalized. In rBDL series, PP decreased in rBDL16 groups but the extrahepatic angiogenesis persisted. In conclusion, cirrhosis resolution attenuates but not completely normalizes portal hypertension because of persistently high splanchnic inflow and angiogenesis. In clinical setting, vascular complications such as varices could persist after cirrhosis resolution and further investigation to define the follow-up and treatment strategies is anticipated.
Assuntos
Circulação Colateral , Hemodinâmica , Hipertensão Portal/fisiopatologia , Cirrose Hepática Biliar/fisiopatologia , Cirrose Hepática Experimental/fisiopatologia , Fígado/irrigação sanguínea , Artéria Mesentérica Superior/fisiopatologia , Neovascularização Patológica , Circulação Esplâncnica , Animais , Ducto Colédoco/cirurgia , Hipertensão Portal/etiologia , Hipertensão Portal/patologia , Ligadura , Fígado/patologia , Circulação Hepática , Cirrose Hepática Biliar/etiologia , Cirrose Hepática Biliar/patologia , Cirrose Hepática Experimental/induzido quimicamente , Cirrose Hepática Experimental/patologia , Masculino , Pressão na Veia Porta , Veia Porta/fisiopatologia , Veia Porta/cirurgia , Ratos Sprague-Dawley , Tioacetamida , Fatores de TempoRESUMO
Patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) have a high risk of mortality. Few studies have reported prognostic factors for patients receiving plasma exchange (PE) for liver support. We conducted a retrospective analysis using data of 55 patients with severe ACLF (nâ¯=â¯45) and ALF (nâ¯=â¯10) who received standard-volume PE (1-1.5 plasma volume) in the ICU. Hepatitis B virus infection accounts for the majority of ACLF (87%) and ALF (50%) patients. PE significantly improved the levels of total bilirubin, prothrombin time and liver enzymes (P<0.05). Thirteen ACLF patients (29%) and one ALF patient (10%) underwent liver transplantation. Two ALF patients (20%) recovered spontaneously without transplantation. The overall in-hospital survival rates for ACLF and ALF patients were 24% and 30%, and the transplant-free survival rates were 0% and 20%, respectively. For the 14 transplanted patients, the one-year survival rate was 86%. Multivariate analysis showed that pre-PE hemoglobin (Pâ¯=â¯0.008), post-PE hemoglobin (Pâ¯=â¯0.039), and post-PE CLIF-C ACLF scores (Pâ¯=â¯0.061) were independent predictors of survival in ACLF. The post-PE CLIF-C ACLF scores ≥59 were a discriminator predicting the in-hospital mortality (area under the curveâ¯=â¯0.719, Pâ¯=â¯0.030). Cumulative survival rates differed significantly between patients with CLIF-C ACLF scores ≤ 58 and those with CLIF-C ACLF scores ≥ 59 after PE (P< 0.05). The findings suggest that PE is mainly a bridge for liver transplantation and spontaneous recovery is exceptional even in patients treated with PE. A higher improvement in the post-PE CLIF-C ACLF score is associated with a superior in-hospital survival rate.
Assuntos
Insuficiência Hepática Crônica Agudizada/terapia , Falência Hepática Aguda/terapia , Troca Plasmática/métodos , Insuficiência Hepática Crônica Agudizada/mortalidade , Insuficiência Hepática Crônica Agudizada/patologia , Estudos de Coortes , Feminino , Humanos , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Antibodies have been developed as therapeutic agents for the treatment of cancer, infection, and inflammation. In addition to binding activity toward the target, antibodies also exhibit effector-mediated activities through the interaction of the Fc glycan and the Fc receptors on immune cells. To identify the optimal glycan structures for individual antibodies with desired activity, we have developed an effective method to modify the Fc-glycan structures to a homogeneous glycoform. In this study, it was found that the biantennary N-glycan structure with two terminal alpha-2,6-linked sialic acids is a common and optimized structure for the enhancement of antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, and antiinflammatory activities.
Assuntos
Fragmentos Fc das Imunoglobulinas/química , Imunoglobulina G/química , Polissacarídeos/química , Rituximab/química , Acetilglucosamina/química , Acetilglucosamina/imunologia , Animais , Anticorpos Antivirais/química , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Citotoxicidade Celular Dependente de Anticorpos , Proteínas de Bactérias/metabolismo , Bacteroides fragilis/enzimologia , Linhagem Celular Tumoral , Feminino , Células HEK293 , Humanos , Fragmentos Fc das Imunoglobulinas/imunologia , Imunoglobulina G/imunologia , Linfoma de Células B/patologia , Camundongos , Camundongos Endogâmicos BALB C , Neuraminidase/metabolismo , Infecções por Orthomyxoviridae/prevenção & controle , Engenharia de Proteínas , Receptores de IgG/imunologia , Rituximab/imunologia , Ácidos Siálicos/química , Ácidos Siálicos/imunologia , Streptococcus pyogenes/enzimologia , Relação Estrutura-Atividade , Trastuzumab/química , Trastuzumab/imunologia , alfa-L-Fucosidase/metabolismoRESUMO
In liver cirrhosis, the altered levels of vasoactive substances, especially endothelin-1 (ET-1) and nitric oxide (NO) lead to elevated intrahepatic resistance, increased portal-systemic collaterals and abnormal intra- and extra-hepatic vascular responsiveness. These derangements aggravate portal hypertension-related complications such as gastro-oesophageal variceal bleeding. Homocysteine, a substance implicated in cardiovascular diseases, has been found with influences on vasoresponsiveness and angiogenesis. However, their relevant effects in liver cirrhosis have not been investigated. In the present study, liver cirrhosis was induced by common bile duct ligation (BDL) in Sprague-Dawley rats. In acute study, the results showed that homocysteine enhanced hepatic vasoconstriction to ET-1 but decreased portal-systemic collateral vasocontractility to arginine vasopressin (AVP). Homocysteine down-regulated hepatic phosphorylated endothelial NO synthase (p-eNOS) and p-Akt protein expressions. Inducible NOS (iNOS) and cyclooxygenase (COX)-2 expressions were up-regulated by homocysteine in splenorenal shunt (SRS), the most prominent intra-abdominal collateral vessel. In chronic study, BDL or thioacetamide (TAA) rats received homocysteine or vehicle for 14 days. The results revealed that homocysteine increased hepatic collagen fibre deposition and fibrotic factors expressions in both BDL- and TAA-induced liver fibrotic rats. Portal-systemic shunting and expressions of mesenteric angiogenetic factors [vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), PDGF receptor ß (PDGFRß) and p-eNOS] were also increased in BDL rats. In conclusion, homocysteine is harmful to vascular derangements and liver fibrosis in cirrhosis.
Assuntos
Homocisteína/metabolismo , Cirrose Hepática/metabolismo , Animais , Arginina Vasopressina/metabolismo , Colágeno/metabolismo , Endotelina-1/genética , Endotelina-1/metabolismo , Humanos , Fígado/irrigação sanguínea , Fígado/metabolismo , Cirrose Hepática/genética , Masculino , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Fator de Crescimento Derivado de Plaquetas/metabolismo , Veia Porta/metabolismo , Ratos , Ratos Sprague-Dawley , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
BACKGROUND: Cirrhotic patients are susceptible to sepsis and critical illness-related corticosteroid insufficiency (CIRCI). Dehydroepiandrosterone sulfate (DHEAS) is a corticotropin-dependent adrenal androgen, which has immunostimulating and antiglucocorticoid effects. Considering the synchronized synthesis of cortisol and DHEAS and their opposing effects to each other, investigators have proposed measuring these two hormones as a ratio. Severe sepsis has been associated with low DHEAS, especially relative to high cortisol. Despite growing interest in the role of adrenal androgen replacement in critical illness, there have been no data about DHEAS and the DHEAS/cortisol ratio in patients with liver cirrhosis. We studied whether low concentrations of DHEAS and decreased DHEAS/cortisol ratio are associated with poor outcome in patients with liver cirrhosis and septic shock. METHODS: We recruited 46 cirrhotic patients with septic shock, and 46 noncirrhotic counterparts matched by age and sex. We evaluated adrenal function using the short corticotropin stimulation test and analyzed the relation between DHEAS and cortisol. RESULTS: While the nonsurvivors in the cirrhotic group had significantly lower baseline DHEAS, lower baseline DHEAS/cortisol ratio, and reduced increments of both DHEAS and cortisol upon corticotropin stimulation, the survivors had lower baseline cortisol. Cirrhotic patients with lower DHEAS/cortisol ratio (<1.50) had higher levels of interleukin-6 and tumor necrosis factor alpha, higher Sequential Organ Failure Assessment scores, and higher rates of CIRCI and hospital mortality. Using the area under the receiver operating characteristic (AUROC) curve, both DHEAS and the DHEAS/cortisol ratio demonstrated a good discriminative power for predicting hospital survival (AUROC 0.807 and 0.925 respectively). The cirrhotic group had lower DHEAS and DHEAS/cortisol ratio but higher rates of CIRCI and hospital mortality, compared to the noncirrhotic group. CONCLUSIONS: There is dissociation between cortisol (increased) and DHEAS (decreased) in those cirrhotic patients who succumb to septic shock. Low DHEAS/cortisol ratios are associated with more severe diseases, inflammation, and CIRCI and can serve as a prognostic marker. More investigations are needed to evaluate the role of adrenal androgen in this clinical setting.
Assuntos
Sulfato de Desidroepiandrosterona/administração & dosagem , Quimioterapia Combinada/métodos , Hidrocortisona/administração & dosagem , Choque Séptico/tratamento farmacológico , Adulto , Idoso , Distribuição de Qui-Quadrado , Sulfato de Desidroepiandrosterona/uso terapêutico , Feminino , Humanos , Hidrocortisona/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Choque Séptico/mortalidade , Estatísticas não ParamétricasRESUMO
BACKGROUND: Proteinuria is a manifestation of renal dysfunction and it has been demonstrated to be a significant prognostic factor in various clinical situations. The study was designed to analyze prognosis of patients receiving liver transplantation as well as to determine predictive performance of perioperative proteinuria. METHODS: We retrospectively reviewed data of patients who had received a liver transplant in a medical center between 2002 and 2010. Demographic information and clinical characteristic parameters were recorded on the day of intensive care unit admission before operation and on postoperative days 1, 7, and 14. RESULTS: Among a total of 323 patients, in-hospital mortality and 90-day mortality rates were 13.0 % (42/323) and 14.2 % (46/323), respectively. Patients with proteinuria on admission had higher rates of acute kidney injury (26.8 % vs. 8.8 %, p < 0.001), severe infection episodes (48.8 % vs. 30.7 %, p = 0.023), hospital death (31.1 % vs. 10.1 %, p < 0.001), and 90-day mortality (37.7 % vs. 10.9 %, p < 0.001). Multivariate analysis showed that proteinuria on admission and Sequential Organ Failure Assessment (SOFA) score were independent predictors of in-hospital mortality. The discriminatory ability of proteinuria plus SOFA was even better than that of SOFA alone, especially on postoperative day 1. CONCLUSIONS: The presence of proteinuria before liver transplantation is supposed to be recognized as a negative predictor for in-hospital survival. Moreover, the presence of proteinuria after liver transplantation can assist in the early prediction of poor short-term prognosis for patients receiving liver transplantation.
Assuntos
Doença Hepática Terminal/cirurgia , Transplante de Fígado/efeitos adversos , Proteinúria/etiologia , Idoso , Cuidados Críticos , Doença Hepática Terminal/complicações , Doença Hepática Terminal/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Escores de Disfunção Orgânica , Valor Preditivo dos Testes , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Predicting severity of pancreatitis is an important goal. Clinicians are still searching for novel and simple biomarkers that can better predict persistent organ failure (OF). Lipoproteins, especially high-density lipoprotein (HDL), and apolipoprotein A-I (APO A-I), have been shown to have anti-inflammation effects in various clinical settings. Severe acute pancreatitis (SAP) is associated with hypo-lipoproteinemia. We studied whether the concentrations of HDL and APO A-I can predict persistent OF in patients with predicted SAP admitted to the ICU. METHODS: In 66 patients with predicted SAP, we prospectively evaluated the relationship between lipid levels, inflammatory cytokines and clinical outcomes, including persistent OF and hospital mortality. Blood samples were obtained within 24 hours of admission to the ICU. RESULTS: HDL and APO A-I levels were inversely correlated with various disease severity scores. Patients with persistent OF had lower levels of HDL and APO A-I, while those with transient OF had lower levels of interleukin-6, tumor necrosis factor-α and lower rates of hospital mortality. Meanwhile, hospital non-survivors had lower concentrations of HDL, and APO A-I compared to the survivors. By using the area under the receiver operating characteristic (AUROC) curve, both HDL and APO A-I demonstrated an excellent discriminative power for predicting persistent OF among all patients (AUROC 0.912 and 0.898 respectively) and among those with OF (AUROC 0.904 and 0.895 respectively). Pair-wise comparison of AUROC showed that both HDL and APO A-I had better discriminative power than C-reactive protein to predict persistent OF. CONCLUSIONS: Serum levels of HDL and APO A-I at admission to the ICU are inversely correlated with disease severity in patients with predicted SAP and can predict persistent OF in this clinical setting.
Assuntos
Apolipoproteína A-I/sangue , Lipoproteínas HDL/sangue , Pancreatite/sangue , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Pancreatite/fisiopatologia , Prognóstico , Estudos Prospectivos , Curva ROC , Sepse/mortalidade , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/sangueRESUMO
OBJECTIVES: Critical illness-related corticosteroid insufficiency can adversely influence the prognosis of critically ill patients. However, its impact on the outcomes of patients with cirrhosis and acute gastroesophageal variceal bleeding remains unknown. We evaluated adrenal function using short corticotropin stimulation test in patients with cirrhosis and gastroesophageal variceal bleeding. The main outcomes analyzed were 5-day treatment failure and 6-week mortality. DESIGN: Prospective observational study. SETTING: Ten-bed gastroenterology-specific medical ICU at a 3,613-bed university teaching hospital in Taiwan. PATIENTS: Patients with liver cirrhosis and acute gastroesophageal variceal bleeding. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated adrenal function using short corticotropin stimulation test in 157 episodes of gastroesophageal variceal bleeding in 143 patients with cirrhosis. Critical illness-related corticosteroid insufficiency occurred in 29.9% of patients. The patients with critical illness-related corticosteroid insufficiency had higher rates of treatment failure and 6-week mortality (63.8% vs 10.9%, 42.6% vs 6.4%, respectively; p < 0.001). The cumulative rates of survival at 6 weeks were 57.4% and 93.6% for the critical illness-related corticosteroid insufficiency group and normal adrenal function group, respectively (p < 0.001). The cortisol response to corticotropin was inversely correlated with Model for End-Stage Liver Disease and Child-Pugh scores and positively correlated with the levels of high-density lipoprotein and total cholesterol. Hypovolemic shock, high-density lipoprotein, platelet count, and bacterial infection at inclusion are independent factors predicting critical illness-related corticosteroid insufficiency, whereas critical illness-related corticosteroid insufficiency, Model for End-Stage Liver Disease score, hypovolemic shock, hepatocellular carcinoma, and active bleeding at endoscopy are independent factors to predict treatment failure. Multivariate analysis also identified Model for End-Stage Liver Disease score, hypovolemic shock, and bacterial infection at inclusion as independent factors associated with 6-week mortality. CONCLUSIONS: Critical illness-related corticosteroid insufficiency is common in cirrhotic patients with acute gastroesophageal variceal bleeding and is an independent factor to predict 5-day treatment failure.
Assuntos
Córtex Suprarrenal/metabolismo , Estado Terminal/mortalidade , Varizes Esofágicas e Gástricas/mortalidade , Hemorragia Gastrointestinal/mortalidade , Cirrose Hepática/mortalidade , Testes de Função do Córtex Suprarrenal , Adulto , Idoso , Comorbidade , Varizes Esofágicas e Gástricas/epidemiologia , Feminino , Hemorragia Gastrointestinal/epidemiologia , Humanos , Unidades de Terapia Intensiva , Cirrose Hepática/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , TaiwanRESUMO
BACKGROUND AND AIM: Increasing evidence supports that proteinuria is a useful tool in several clinical situations. Cirrhotic patients with proteinuria admitted to intensive care units (ICUs) have high mortality rates. This study analyzed the outcomes of critically ill cirrhotic patients and determined the prognostic value of proteinuria. METHODS: A total of 230 cirrhotic patients were admitted to the ICU of a hospital in Taiwan between March 2008 and February 2011. We prospectively collected data, including demographic parameters and clinical characteristics, of patients on day 1 of admission to the ICU and analyzed these variables as predictors of mortality. RESULTS: The overall ICU, hospital, and 90-day mortality rates were 54%, 60%, and 63%, respectively. The patients with proteinuria had higher rates of acute kidney injury (84% vs. 53%, P<0.001), ICU death (60% vs. 25%, P<0.001), and 90-day mortality (79% vs. 40%, P<0.001). Patients with proteinuria had a hazard ratio for 90-day mortality of 2.800 (P<0.001; 95% CI, 1.927-4.069). Multivariate analysis showed that proteinuria and the Sequential Organ Failure Assessment score were predictors of short-term prognosis. CONCLUSIONS: Proteinuria in critically ill cirrhotic patients is associated with increased complications of liver cirrhosis, ICU mortality, and poor short-term prognosis.
Assuntos
Injúria Renal Aguda/fisiopatologia , Mortalidade Hospitalar , Cirrose Hepática/fisiopatologia , Proteinúria/etiologia , Injúria Renal Aguda/complicações , Injúria Renal Aguda/mortalidade , Adulto , Idoso , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Cirrose Hepática/complicações , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Estudos Prospectivos , TaiwanRESUMO
PURPOSE: The responses of polyps to light essentially determine the diagnostic capability of an endoscopy system in differentiating adenomas from hyperplastic polyps. Compared with white light colonoscopy (WLC), narrow-band imaging (NBI) is expected to improve the diagnostic capability. The diagnostic capabilities of WLC and NBI are evaluated and compared based on the polyp responses. METHODS: The following WLC and NBI images were retrospectively reviewed and categorized: 195 images and polyps (89 WLC, 106 NBI) with the best visual quality were categorized in the best image group (BG), and 484 images of 242 polyps (both WLC and NBI) were categorized in the paired image group (PG). For each reflection of light used for WLC or NBI, the polyp responses were objectively expressed as reflection features. The reflection features were then used to establish a classification model for identifying adenomas. The diagnostic capability of reflection feature or classification model was measured by the area under the receiver operating characteristic curve (AUC). RESULTS: In both image groups, the diverse and heterogeneous features of the polyp responses enabled accurate identification of adenomas, regardless of the light source used for WLC and NBI. For differential diagnosis of adenomas and hyperplastic polyps, the WLC and NBI did not significantly differ in BG (AUC, 0.905 and 0.922, respectively; P = 0.690) or in PG (AUC, 0.782 and 0. 769, respectively; P = 0.755). CONCLUSIONS: Using WLC and NBI as classification models is effective in differential diagnosis of colorectal polyps and exhibited similar capabilities.
Assuntos
Pólipos do Colo/diagnóstico , Colonoscopia/métodos , Luz , Imagem de Banda Estreita/métodos , Doenças Retais/patologia , Adenoma/diagnóstico , Pólipos do Colo/patologia , Diagnóstico Diferencial , HumanosRESUMO
BACKGROUND: Cirrhotic patients admitted to an intensive care unit (ICU) have high mortality rates. The present study compared the characteristics and outcomes of critically ill patients admitted to the ICU with and without cirrhosis using the matched Acute Physiology and Chronic Health Evaluation III (APACHE III) and Sequential Organ Failure Assessment (SOFA) scores. METHODS: A retrospective case-control study was performed at the medical ICU of a tertiary-care hospital between January 2006 and December 2009. Patients were admitted with life-threatening complications and were matched for APACHE III and SOFA scores. Of 336 patients enrolled in the study, 87 in the cirrhosis or noncirrhosis group were matched according to the APACHE III scores. Another 55 patients with cirrhosis were matched to the 55 patients without cirrhosis according to the SOFA scores. Demographic data, aetiology of ICU admission, and laboratory variables were also evaluated. RESULTS: The overall hospital mortality rate in the patients with cirrhosis in the APACHE III-matched group was more than that in their counterparts (73.6% vs 57.5%, P = .026) but the rate did not differ significantly in the SOFA-matched group (61.8% vs 67.3%). In the APACHE III-matched group, the SOFA scores of patients with cirrhosis were significantly higher than those of patients without cirrhosis (P < .001), whereas the difference in APACHE III scores was nonsignificant between the SOFA-matched patients with and without cirrhosis. CONCLUSIONS: Score-matched analytical data showed that the SOFA scores significantly differentiated the patients admitted to the ICU with cirrhosis from those without cirrhosis in APACHE III-matched groups, whereas difference in the APACHE III scores between the patients with and without cirrhosis were nonsignificant in the SOFA-matched group.
Assuntos
Estado Terminal/mortalidade , Mortalidade Hospitalar , Cirrose Hepática/fisiopatologia , APACHE , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Unidades de Terapia Intensiva , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Estudos RetrospectivosRESUMO
Cutaneous metastases are rare and seldom present at the time of first diagnosis of cancer. Data from various studies show that 1-12% of lung cancer patients experience tumor spread to the skin. The scalp, chest, and abdomen are favored sites of skin metastases from lung cancers, but metastases to multiple skin sites in a single patient are rarely reported. We describe a 56-year-old lung adenocarcinoma patient, initially diagnosed with steatocystoma multiplex who responded well to gefitinib treatment. The efficacy of conventional chemotherapy for cutaneous metastases has been limited because of the relatively poor blood supply to the skin. It has been demonstrated that tyrosine kinase inhibitor (TKI), gefitinib, has significant clinical benefit in lung cancer patients with epidermal growth factor receptor (EGFR) mutation even in metastases to the brain. However, the therapeutic response to gefitinib in patients with skin metastases is seldom mentioned in the literature. We report one case of lung adenocarcinoma with multiple skin metastases that were successfully treated with gefitinib.
RESUMO
Backgrounds and Aims: Patients with cirrhosis are susceptible to sepsis and septic shock. Cirrhotic patients also have increased capillary permeability and are prone to developing volume overload. Patients with septic shock may have an enhanced pulmonary vascular permeability index (PVPI) and extravascular lung water index (EVLWI), both of which are associated with an unfavorable prognosis. It is plausible that pre-existing hyperpermeability may deteriorate when cirrhotic patients develop septic shock. However, it remains unknown whether PVPI and EVLWI can predict the prognosis of cirrhotic patients with septic shock. Pulse Indicator Continuous Cardiac Output (PiCCO) is an established tool to measure PVPI and EVLWI. Therefore, we conducted this retrospective study to investigate the prognostic significance of PVPI and EVLWI in cirrhotic patients with septic shock using PiCCO monitoring. Methods: We included 83 patients with liver cirrhosis and septic shock. EVLW indexed to actual body weight (aEVLWI), EVLW indexed to predicted body weight (pEVLWI), PVPI, disease severity scores, and other biomarkers were analyzed. We collected the PiCCO data on the first 2 days. Results: The overall 28-day mortality was 43.4%. The values of PVPI, aEVLWI, and pEVLWI on day 2 (PVPID2, aEVLWID2, EVLWID2) were significantly higher in non-survivors. The discriminating power of PVPID2 and EVLWID2 to predict 28-day mortality was tested using the area under a ROC curve. The areas under ROC curves (mean ± SEM) were 0.713 ± 0.061 and 0.650 ± 0.063 for PVPID2 and pEVLWID2. In the multivariate analysis, PVPID2, bilirubin, and lactate were independent factors which predicted 28-day mortality. Conclusions: Higher levels of PVPID2 and pEVLWID2 are associated with higher 28-day mortality rates in cirrhotic patients with septic shock. PVPI and pEVLWI may be useful to guide fluid management in this clinical setting.