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1.
Hepatology ; 69(2): 729-741, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30141205

RESUMO

Acute kidney injury in decompensated cirrhosis has limited therapeutic options, and novel mechanistic targets are urgently needed. Angiopoietin-2 is a context-specific antagonist of Tie2, a receptor that signals vascular quiescence. Considering the prominence of vascular destabilization in decompensated cirrhosis, we evaluated Angiopoietin-2 to predict clinical outcomes. Serum Angiopoietin-2 was measured serially in a prospective cohort of hospitalized patients with decompensated cirrhosis and acute kidney injury. Clinical characteristics and outcomes were examined over a 90-day period and analyzed according to Angiopoietin-2 levels. Primary outcome was 90-day mortality. Our study included 191 inpatients (median Angiopoietin-2 level 18.2 [interquartile range 11.8, 26.5] ng/mL). Median Model for End-Stage Liver Disease (MELD) score was 23 [17, 30] and 90-day mortality was 41%. Increased Angiopoietin-2 levels were associated with increased mortality (died 21.9 [13.9, 30.3] ng/mL vs. alive 15.2 [9.8, 23.0] ng/mL; P < 0.001), higher Acute Kidney Injury Network stage (stage I 13.4 [9.8, 20.1] ng/mL vs. stage II 20.0 [14.1, 26.2] ng/mL vs. stage III 21.9 [13.0, 29.5] ng/mL; P = 0.002), and need for renal replacement therapy (16.5 [11.3, 23.6] ng/mL vs. 25.1 [13.3, 30.3] ng/mL; P = 0.005). The association between Angiopoietin-2 and mortality was significant in unadjusted and adjusted Cox regression models (P ≤ 0.001 for all models), and improved discrimination for mortality when added to MELD score (integrated discrimination increment 0.067; P = 0.001). Conclusion: Angiopoietin-2 was associated with mortality and other clinically relevant outcomes in a cohort of patients with decompensated cirrhosis with acute kidney injury. Further experimental study of Angiopoietin/Tie2 signaling is warranted to explore its potential mechanistic and therapeutic role in this population.


Assuntos
Injúria Renal Aguda/sangue , Angiopoietina-2/sangue , Cirrose Hepática/sangue , Cirrose Hepática/mortalidade , Injúria Renal Aguda/etiologia , Idoso , Feminino , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/cirurgia , Transplante de Fígado , Masculino , Massachusetts/epidemiologia , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Curr Hepatol Rep ; 18(1): 36-48, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35722634

RESUMO

Purpose of review: To provide an overview of recent pharmacological treatments for portal hypertension evaluated in early clinical trials, with particular emphasis on the pathophysiological basis of their use. Recent findings: In patients with compensated cirrhosis, even small decreases in portal pressure (as small as 1 mmHg) are associated with a lower probability of decompensation. In patients with decompensated cirrhosis, portal pressure "response" to non-selective beta-blocker (NSBB) therapy is associated with a lower mortality. When present, significant portal hypertension persists even after elimination of the etiology of cirrhosis and this justifies the continued development of new drugs that target portal hypertension. Summary: Over several decades we have gained great depth in the understanding of portal hypertension, its mechanisms and complications. NSBBs, which act by reducing portal venous inflow (an extrahepatic target), are effective in reducing portal pressure and have been the mainstay of therapy for portal hypertension in the last 35 years -being effective in preventing decompensation and variceal hemorrhage. However, because not all patients will have a sufficient response to NSBB and some may be intolerant to NSBB, alternative drugs or drugs that will augment the effect of NSBB on portal pressure are being tested in pre-clinical and early-clinical trials. Many of these drugs target more than one of the intrahepatic or extrahepatic mechanisms implicated in the pathogenesis of portal hypertension in cirrhosis. Out of these proposed therapies, statins have emerged as the most promising new pharmacological therapy for the treatment of portal hypertension.

4.
Hemodial Int ; 22 Suppl 1: S22-S35, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29694720

RESUMO

Hepatitis C infection in patients with chronic kidney disease or kidney transplant carries higher morbidity and mortality compared to noninfected patients. Historically, patients with advanced kidney disease and kidney transplant recipients were undertreated given the multiple adverse effects and limited efficacy of interferon-based therapies for chronic hepatitis C. The development of direct-acting antivirals in the past few years has opened an unprecedented opportunity for treating these populations. However, the impaired renal clearance of some of these medications in patients with kidney disease, and the potential interactions of antiviral therapies with immunosuppressants after kidney transplantation, present some challenges in choosing the proper regimen. This review provides an overview of the essential pharmacokinetics and drug interactions of relevant antiviral therapies in the treatment of chronic hepatitis C in patients with advanced kidney disease and after kidney transplantation.


Assuntos
Antivirais/uso terapêutico , Interações Medicamentosas/imunologia , Quimioterapia Combinada/métodos , Hepatite C Crônica/tratamento farmacológico , Transplante de Rim/métodos , Insuficiência Renal Crônica/tratamento farmacológico , Antivirais/farmacocinética , Antivirais/farmacologia , Hepatite C Crônica/patologia , Humanos , Insuficiência Renal Crônica/patologia , Resultado do Tratamento
5.
Clin J Am Soc Nephrol ; 12(10): 1615-1623, 2017 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-28882857

RESUMO

BACKGROUND AND OBJECTIVES: Hepatitis C virus infection is common in patients with CKD and leads to accelerated progression to ESRD. Sofosbuvir is a potent direct-acting antiviral therapy against hepatitis C virus; however, there are concerns about its safety in patients with CKD. The objective of our study was to determine the safety and efficacy of sofosbuvir in patients with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We studied a retrospective observational cohort of patients with CKD defined by eGFR<60 ml/min per 1.73 m2, ≥30 mg albuminuria per 1 g creatinine, or ≥200 mg proteinuria per 1 g creatinine who received sofosbuvir-based therapy in a large health care system. Regression models were constructed to predict likelihood of sustained virologic response, detect adverse events, and examine changes in eGFR from baseline to follow-up. RESULTS: Ninety-eight patients with CKD (42% stage 1 or 2 CKD and 58% stage 3 CKD) were included. Mean age was 62 years old, 78% were men, and 65% were white. Additionally, 49% of patients had diabetes, 38% of patients had cirrhosis, and 33% of patients had prior solid organ transplant. Overall sustained virologic response was 81% and varied by regimen used and viral genotype. Average baseline eGFR was equivalent to average on-treatment eGFR, but seven patients experienced a rise in creatinine ≥1.5 times baseline while taking sofosbuvir; all but one recovered. In patients with eGFR<60 ml/min per 1.73 m2 at baseline (stage 3 CKD), regression models showed that hepatitis C cure was associated with a 9.3 (95% confidence interval, 0.44 to 18) ml/min per 1.73 m2 improvement in eGFR during the 6-month post-treatment follow-up period. Adverse events were common (81%), but serious adverse events (17%) and treatment discontinuations (8%) were uncommon. CONCLUSIONS: Sofosbuvir-based direct-acting antiviral therapy is safe and effective in a cohort of patients with CKD infected with hepatitis C.


Assuntos
Antivirais/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Rim/efeitos dos fármacos , Insuficiência Renal Crônica/complicações , Sofosbuvir/uso terapêutico , Idoso , Albuminúria/complicações , Albuminúria/fisiopatologia , Antivirais/efeitos adversos , Quimioterapia Combinada , Feminino , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Sofosbuvir/efeitos adversos , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento
7.
Rev. centroam. obstet. ginecol ; 17(1,supl): S5-S12, ene.-mar. 2012.
Artigo em Espanhol | LILACS | ID: lil-734044

RESUMO

Los avances en el manejo de enfermedades del embarazo y la reducción de la mortalidad materna han sido puntos clave de conferencias internacionales desde finales de los años ochenta y de la Cumbre del Milenio del año 2000. Las estadísticas nacionales de MM a lo largo del tiempo son cruciales para orientar la planificación de programas de salud sexual y reproductiva, y guiar las labores de promoción y la investigaciòn a nivel internacional...


Assuntos
Feminino , Hemorragia Pós-Parto/mortalidade , Hemorragia Pós-Parto/prevenção & controle , Mortalidade Materna/tendências , América Central
8.
Rev. centroam. obstet. ginecol ; 13(2,n.esp): 2-48, abr.-jun. 2008.
Artigo em Espanhol | LILACS | ID: lil-733722

RESUMO

El estudio de la mortalidad materna ha sido el objetivo principal para la evaluación y monitoreo de las unidades responsables de ofrecer atención materna. Los eventos de pacientes obstétricas casi-muertas se han definido como mujeres embarazadas con una condición que complicó la gestación y que pudo haber culminado en una muerte materna. El término casi-muerta (near-miss) fue utilizado por primera vez en 1991 por Stones.


Assuntos
Feminino , Inquéritos de Morbidade , Mortalidade Materna/tendências , Gestantes , América Central
10.
Acta gastroenterol. latinoam ; 12(2): 149-53, 1982.
Artigo em Inglês | LILACS | ID: lil-8542

RESUMO

La presion intrahepatica fue medida en 172 sujetos (148 de los cuales tenian enfermedad hepatica por alcoholismo cronico; los restantes, sujetos con normal funcion y estructura hepatica, actuaron como controles). Los criterios patologicos usados para clasificar la enfermedad hepatica causada por alcoholismo fueron: lesiones minima, esteatosis, hepatitis sin fibrosis, hepatitis con fibrosis y cirrosis. Los incrementos en los valores de la presion intrahepatica estan directamente relacionados con el grado de dano estructural del higado. Cuando se efectuan conjuntamente la manometria intrahepatica y la biopsia hepatica, constituyen utiles parametros en el diagnostico del estado histologico y hemodinamico del higado en la hepatopatia por alcoholismo cronico


Assuntos
Humanos , Pressão Arterial , Hepatopatias Alcoólicas , Manometria
11.
Acta gastroenterol. latinoam ; 15(2): 67-80, abr.-jun. 1985. tab, ilus
Artigo em Espanhol | LILACS | ID: lil-27647

RESUMO

Presentamos las pautas diagnósticas, revisando los datos clínicos, radiológicos, endoscópicos e histológicos de 35 pacientes con Esófago de Barrett (EB) (metaplasia columnar en esófago distal). Las características clínicas son las de una esofagitis severa de larga evolución, aunque la metaplasia por sí misma, es asintomática y su clínica depende del grado de inflamación. La radiología nos revela algunos datos como reflujo GE, hernia hiatal, úlceras o estenosis, y tal vez el doble contraste haga sospechar el endobraquiesófago (EBE). La endoscopía nos proporciona datos precisos sobre la altura del EBE, úlceras, estenosis e inflamacion. La histología nos aclara el tipo de metaplasia columnar (cardial o transicional, gástrica fúndica, intestinal o especializada, ó mixta). La etiología congénita o adquirida, sujeta a controversia, puede ser aclarada con un método inmuno histoquímico, le de la Peroxidasa anti-Peroxidasa (PAP) revelándonos la presencia de células secretoras de Gastrina (G) en los casos congénitos


Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Esôfago de Barrett/diagnóstico , Gastrinas/metabolismo , Esôfago de Barrett/etiologia , Esôfago/patologia , Esôfago , Esofagoscopia
12.
Acta gastroenterol. latinoam ; 17(2): 85-96, abr.-jun. 1987. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-48516

RESUMO

Esta claro que el CP está presente en mayor o menor grado en diversa patología gastroduodenal, fundamentalmente en gastritis crónica superficial activa, úlcera gástrica y úlcera duodenal con metaplasia gástrica. Tambien se lo encuentra en gastritis crónica atrófica y en menor porcentaje si ésta tiene metaplasia intestinal, así como en algunos estómagos normales. No se lo halla en duodeno histológicamente normal ni en esófago. Como nos llamó la atención que no se hubiera realizado ninguna publicación en EB, nos dispusimos a realizar retrospectivamente, la búsqueda del CP en la metaplasia columnar del esófago distal. Su incidencia resultó elevada, 88.88% aún en aquellos casos con metaplasia intestinal, y con úlcera de Barret. Utilizamos coloración de Gram y Warthin-Starry con Alcian-Blue, y clasificándolos dentro de los Grados establecidos por Marshall y Warren. Elaboramos asimismo la discusión sobre algunos hechos fisiopatológicos, como la presencia de infiltrado PMN en todos los casos, y su importancia en el mantenimiento de la metaplasia, de las úlceras de Barrett y su posible papel en el desarrolo del adenocarcinoma


Assuntos
Adulto , Pessoa de Meia-Idade , Humanos , Masculino , Feminino , Esôfago de Barrett/microbiologia , Campylobacter/isolamento & purificação , Idoso de 80 Anos ou mais , Esôfago de Barrett , Doenças do Esôfago/microbiologia , Neoplasias Esofágicas/microbiologia , Esofagoscopia , Esôfago/patologia
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