Midodrine and albumin for prevention of complications in patients with cirrhosis awaiting liver transplantation. A randomized placebo-controlled trial.

BACKGROUND & AIMS: Patients with decompensated cirrhosis on the waiting list for liver transplantation (LT) commonly develop complications that may preclude them from reaching LT. Circulatory dysfunction leading to effective arterial hypovolemia and activation of vasoconstrictor systems is a key factor in the pathophysiology of complications of cirrhosis. The aim of this study was to investigate whether treatment with midodrine, an alpha-adrenergic vasoconstrictor, together with intravenous albumin improves circulatory dysfunction and prevents complications of cirrhosis in patients awaiting LT. METHODS: A multicenter, randomized, double-blind, placebo-controlled trial (NCT00839358) was conducted, including 196 consecutive patients with cirrhosis and ascites awaiting LT. Patients were randomly assigned to receive midodrine (15-30 mg/day) and albumin (40 g/15 days) or matching placebos for one year, until LT or drop-off from inclusion on the waiting list. The primary endpoint was incidence of any complication (renal failure, hyponatremia, infections, hepatic encephalopathy or gastrointestinal bleeding). Secondary endpoints were mortality, activity of endogenous vasoconstrictor systems and plasma cytokine levels. RESULTS: There were no significant differences between both groups in the probability of developing complications of cirrhosis during follow-up (p = 0.402) or one-year mortality (p = 0.527). Treatment with midodrine and albumin was associated with a slight but significant decrease in plasma renin activity and aldosterone compared to placebo (renin -4.3 vs. 0.1 ng/ml.h, p < 0.001; aldosterone -38 vs. 6 ng/dl, p = 0.02, at week 48 vs. baseline). Plasma norepinephrine only decreased slightly at week 4. Neither arterial pressure nor plasma cytokine levels changed significantly. CONCLUSIONS: In patients with cirrhosis awaiting LT, treatment with midodrine and albumin, at the doses used in this study, slightly suppressed the activity of vasoconstrictor systems, but did not prevent complications of cirrhosis or improve survival. LAY SUMMARY: Patients with cirrhosis who are on the liver transplant waiting list often develop complications which prevent them from receiving a transplant. Circulatory dysfunction is a key factor behind a number of complications. This study was aimed at investigating whether treating patients with midodrine (a vasoconstrictor) and albumin would improve circulatory dysfunction and prevent complications. This combined treatment, at least at the doses administered in this study, did not prevent the complications of cirrhosis or improve the survival of these patients.

LEFT ventricular function assessed by echocardiography in cirrhosis: relationship to systemic hemodynamics and renal dysfunction.

BACKGROUND & AIMS: The current study aimed at assessing the potential role of cardiac abnormalities in the pathogenesis of circulatory and renal dysfunction in cirrhosis. METHODS: One hundred and fifty-two patients (34 without ascites, 95 with ascites without renal failure and 21 with hepatorenal syndrome) were evaluated using Doppler echocardiography. In 102 patients, diastolic function was assessed by measuring parameters related to ventricular filling velocity, mitral annulus velocity and left atrial dimensions. Cardiopulmonary pressures were also measured by cardiac catheterization in 54 patients. In 50 additional patients, left ventricular myocardial strain was performed to estimate myocardial contractility and systolic function. RESULTS: Grade 1 and 2 diastolic dysfunction was present in 41% and 16% of the patients, respectively. There was no patient with severe grade 3 diastolic dysfunction. Grade 2 diastolic dysfunction was associated with higher cardiopulmonary pressures but values were within the normal limits in all cases. Diastolic dysfunction directly correlated with liver failure but not with the degree of impairment in circulatory and renal function. The proportion of patients without or with grade 1 or 2 diastolic dysfunction was similar in patients with compensated cirrhosis, with ascites without renal failure or with hepatorenal syndrome despite marked differences in the degree of circulatory dysfunction, as indicated by plasma renin activity and noradrenaline concentration. The heart rate and systolic function were normal in all cases. There were no differences between patients without ascites, with ascites without renal failure or with HRS, despite marked differences in the activity of the renin-angiotensin system and sympathetic nervous system. These features indicate an impaired response of cardiac chronotropic and inotropic function to changes in systemic hemodynamics. CONCLUSIONS: These data indicates that: (1) diastolic dysfunction is frequent in cirrhosis but in most cases it is of mild degree and does not increase the cardiopulmonary pressure to abnormal levels. This feature, which may be due to the central hypovolemia of cirrhosis, probably accounts for the lack of symptoms associated with this condition. (2) Diastolic dysfunction in cirrhosis is unrelated to circulatory dysfunction, ascites and HRS. (3) In cirrhosis, there is a lack of response of the left ventricular systolic and chronotropic function to peripheral arterial vasodilation and activation of the sympathetic nervous system and this feature is an important contributory factor to the progression of circulatory dysfunction and the pathogenesis of ascites and HRS.

Albumin for bacterial infections other than spontaneous bacterial peritonitis in cirrhosis. A randomized, controlled study.

BACKGROUND & AIMS: Treatment with albumin in patients with cirrhosis and spontaneous bacterial peritonitis (SBP) prevents renal failure and improves survival. Whether albumin has similar beneficial effects in patients with infections other than SBP is unknown. METHODS: One hundred and ten patients with cirrhosis hospitalized for infections other than SBP were randomly assigned to receive antibiotics plus albumin (1.5 g/kgbw at diagnosis and 1 g/kgbw at day 3) (albumin group; n=56) or antibiotics alone (control group; n=54). The primary end point was survival at 3 months. Secondary end points were effects on renal and circulatory function. RESULTS: The renal function, as evaluated by differences in changes in serum creatinine and estimated glomerular filtration rate between the two groups, improved in patients treated with albumin. The circulatory function improved significantly in patients treated with albumin, but not in those from the control group. There was a trend for a lower frequency of type 1 hepatorenal syndrome in the albumin group compared to the control group (1 vs. 4 patients, respectively; p=n.s.). Probability of survival at 3 months was not significantly different among the two groups. However, when adjusted for factors with independent prognostic value, treatment with albumin was an independent predictive factor of survival. CONCLUSIONS: As compared with standard antibiotic therapy alone, treatment with albumin together with antibiotics has beneficial effects on the renal and circulatory function and shows a potential survival benefit. Further studies with large sample sizes should be performed to confirm these findings.

Predictors of response to therapy with terlipressin and albumin in patients with cirrhosis and type 1 hepatorenal syndrome.

UNLABELLED: Terlipressin plus albumin is an effective treatment for type 1 hepatorenal syndrome (HRS), but approximately only half of the patients respond to this therapy. The aim of this study was to assess predictive factors of response to treatment with terlipressin and albumin in patients with type 1 HRS. Thirty-nine patients with cirrhosis and type 1 HRS were treated prospectively with terlipressin and albumin. Demographic, clinical, and laboratory variables obtained before the initiation of treatment as well as changes in arterial pressure during treatment were analyzed for their predictive value. Response to therapy (reduction in serum creatinine <1.5 mg/dL at the end of treatment) was observed in 18 patients (46%) and was associated with an improvement in circulatory function. Independent predictive factors of response to therapy were baseline serum bilirubin and an increase in mean arterial pressure of >or=5 mm Hg at day 3 of treatment. The cutoff level of serum bilirubin that best predicted response to treatment was 10 mg/dL (area under the receiver operating characteristic curve, 0.77; P < 0.0001; sensitivity, 89%; specificity, 61%). Response rates in patients with serum bilirubin <10 mg/dL or >or=10 mg/dL were 67% and 13%, respectively (P = 0.001). Corresponding values in patients with an increase in mean arterial pressure >or=5 mm Hg or <5 mm Hg at day 3 were 73% and 36%, respectively (P = 0.037). CONCLUSION: Serum bilirubin and an early increase in arterial pressure predict response to treatment with terlipressin and albumin in type 1 HRS. Alternative treatment strategies to terlipressin and albumin should be investigated for patients with type 1 HRS and low likelihood of response to vasoconstrictor therapy.

Mentoria científica na graduação em Medicina: repercussões na satisfação, engajamento e produção discente / Scientific mentoring in undergraduate medical school: impacts on student satisfaction, engagement and production

Resumo: Introdução: A mentoria é uma estratégia acadêmica que está cada vez mais presente no curso de Medicina por promover benefícios, como a criação de ambientes de acolhimento e afetividade, e discussão de conteúdos médicos e de temas relacionados à formação profissional. Entretanto, pouco se discute acerca dessa estratégia com finalidades científicas. Objetivo: Este estudo teve como objetivos descrever a implementação do programa de mentorias científicas, investigar a percepção dos estudantes sobre a sua implantação e execução, além de mensurar indicadores de êxito. Método: Trata-se de estudo seccional descritivo, realizado em um curso de graduação em Medicina, localizado em Salvador/Bahia. Foram incluídos estudantes do terceiro ao quarto ano da graduação. Aplicou-se um questionário virtual, estruturado, anônimo, com perguntas objetivas relacionadas ao perfil discente, às percepções sobre o programa de mentorias científicas e à publicação dos trabalhos de conclusão de curso (TCC). Resultado: Dos 143 estudantes participantes, houve predominância de solteiros (90,9%), pardos (46,2%), do sexo feminino (72,0%), com idade de 25,3 ± 5,54 anos, que não participaram de programas de iniciação científica (88,8%). Dentre aqueles que participaram das mentorias (n = 101), 97,1% afirmaram que elas contribuíram para o desenvolvimento do TCC, 98,0% se mostraram favoráveis à manutenção de sua oferta e 85,0% consideraram a estratégia inovadora. No recorte temporal de dois semestres letivos, apresentaram-se 131 TCC, dos quais 27,5% foram publicados contando com a participação de 19 professores, com média de 1,89 produção/professor. Conclusão: Os estudantes de Medicina são favoráveis à implementação do sistema de mentorias científicas, tendo essa estratégia se mostrado factível e eficaz.

Abstract: Introduction: Mentoring is an academic strategy that is increasingly present in the medical course, as it promotes benefits such as the creation of welcoming and affective environments, discussion of medical content and topics related to professional training. However, little is discussed about this strategy for scientific purposes. Objectives: To describe the implementation of the scientific mentoring program, investigate the students' perception of its implementation and performance, in addition to measuring success indicators. Methods: This was a cross-sectional, descriptive study carried out in an undergraduate medical course, located in Salvador/Bahia. Students from the 3rd to the 4th year of undergraduate school were included. A virtual, structured, anonymous questionnaire was applied, with objective questions related to the students' profile, their perceptions in relation to the scientific mentorship program and the publication of the Term Paper (TP). Results: Of the 143 participating students, there was a predominance of single (90.9%), brown (46.2%), female individuals (72.0%), aged 25.3±5.54 years, those who did not participate in Undergraduate Research programs (88.8%). Among those who participated in mentorships (n=101), 97.1% considered that they contributed to the development of the TP, 98.0% are in favor of maintaining its offer and 85.0% consider the strategy to be innovative. In the time frame of two academic semesters, 131 TPs were presented, of which 27.5% were published with the participation of 19 teachers, with an average of 1.89 productions/teacher. Conclusion: Medical students are in favor of implementing the scientific mentoring system, and this strategy has shown to be feasible and effective.

Análise da soropositividade do anti-HBs em profiss ionais de saúde / Analysis of the seropositivity of the anti-HBs in health professionals

O risco de se contrair a hepatite B entre os profissionais de saúde é maior do que o da população geral adulta. Os objetivos do estudo foram analisar a soropositividade do anti-HBs em profissionais de saúde, analisar o perfil dos que responderam à vacinação, definir o esquema vacinal recebido e identificar condições que reduziram a resposta vacinal. O estudo foi um inquérito soro-epidemiológico transversal. Entre 1/1/2004 e 31/07/2006,foram realizadas 111 5 sorologias para a titulação do anti-HBs em profissionais de saúde de um hospital privado do município do Rio de Janeiro, de risco baixo ou alto para a ocorrência de acidentes pérfuro-cortantes. Dos exames realizados, 729 foram reagentes e 386 não reagentes, caracterizando uma soropositividade de 65,4% (IC 95%: 62,6 ? 68,2). As idades foram mais elevadas no grupo não reagente (p<0,001). Em ambos os grupos predominaram as mulheres, porém a maior proporção do sexo feminino ocorreu no grupo reagente (p=0,009). Verificamos um maior número de profissionais de alto risco no grupo reagente (p<0,001) e um maior número de vacinados contra a hepatite B (p<0,001) e com o esquema completo (p<0,001) no grupo reagente. Com relação à história de transfusão ou doação de sangue, história de tabagismo, índice de massa corporal, prática de atividade física, uso de álcool e acidentes de trabalho, não se observou diferença entre os grupos. Os profissionais da área de saúde deveriam ser vacinados com o esquema proposto pela Organização Mundial de Saúde. Avaliação da soropositividade deveria ser realizada periodicamente.

The risk of acquiring hepatitis B is higher among health professionals than in the rest of the general adult population. The objectives of the present study were to analyze the seropositivity of the anti-HBs in health professionals, to analyze the profile of the health professionals that responded to the vaccination, to characterize the vaccination scheme received, and to identify the conditions that reduced the response to the vaccine. The study was a sero-epidemiologic transversal survey. From 1/1/2004 to 31/07/2006, 1115 serologic tests were utilized for detection of the anti-HBs in the serum of the health professionals from a private general hospital in the municipality of Rio de Janeiro, with low or high risk of occurrence of perforate-cutting accidents. From the tests carried out, 729 were reactive and 386 non-reactive, characterizing a seropositivity in 65.4% of the tested professionals (IC 95%: 62.6 ? 68.2). The subjects in the non-reactive group (p<0.001) were older, and in both groups the large majority was female, though among reactive group the proportion was higher (p= 0.009). In the reactive group (p<0.001) a greater number of high risk health professionals were found, as well as a greater number of health professionals who had been vaccinated against hepatitis B (p<0.001) with the complete scheme (p<0.001). No difference between reactive and non-reactive groups was observed regarding blood transfusion or donation, history of smoking, body mass index, physical activity, alcohol consumption, and occupational accidents. It is known that professionals of the health area must be vaccinated according to the scheme proposed by the World Health Organization, therefore. seropositivity should be evaluated periodically.

Valor preditivo do hematócrito na caracterização precoce da pancreatite aguda grave / Predictive value of hematocrit on early characterization of severe acute pancreatitis

Introdução: Ao longo da última década, muitos testes têm sido investigados como possíveis marcadores precoces de gravidade na pancreatite aguda (PA). Acredita-se que, identificando a doença mais cedo, seja possível modificar sua evolução e mortalidade. Entre os marcadores recentemente estudados com esse fim, destaca-se o hematócrito (ht). Objetivo: Determinar a prevalência da PA grave, descrever a sua apresentação clínica e identificar o papel do ht como um fator preditivo de gravidade, comparando-o com os critérios de Ranson, com a proteina C reativa titulada (PCRt) e com os achados de tomagrafia computadorizada. Pacientes e Métodos: Foram estudados os pacientes internados com o diagnóstico de PA nos hospitais da Rede D'Or-RJ, entre junho de 2000 e dezembro de 2002. Os exames realizados foram aqueles inerentes à assistência médica prestada. De acordo com os Critérios de Atlanta, os pacientes foram divididos em dois grupos: leve e grave. Resultadoss: Foram incluídos 49 pacientes no estudo, sendo cinco (10,2por cento) casos graves. A etiologia mais comum foi a PA biliar (65,3por cento). Os grupos foram semelhantes em idade, sexo, amilase, lipase e nos demais exames laboratoriais realizados. No grupo grave houve predomínio de complicações sistêmicas, como hipotensão, sepse e insuficiência respiratória, em comparação com as complicações locais. Não houve diferença significativa entre os dois grupos nos valores de ht e PCRt com 24 e 48 horas após o início dos sintomas. O custo e o tempo da internação foram maiores no grupo grave (p<0,001). Conclusão: A prevalência de PA grave foi baixa. Não houve manifestações clínicas ou laboratoriais específicas de gravidade na fase precose da doença. O hematócrito também não foi um fator preditivo de gravidade

Porfiria cutânea tarda, esclerodermia e vírus da hepatite C: revisão da literatura a propósito de um caso / Porphyria cutanea tarda, scleroderma and hepatitis C virus: literature review based on a case

Embora a associação de PCT, esclerodermia e HCV seja uma ocorrência rara, é importante conhecer as particularidades dessa condição. O presente artigo discute a patogênese, os resultados clínicos e o tratamento

Tumor epitelial sólido cístico papilar de pâncreas: relato de um caso / Solid epithelial papilary-cystic pancreatic tumos: report of a case

Mulher de 25 anos admitida com dor abdominal, dispepsia e massa abdominal palpável. Suspeiçäo diagnóstica de tumor pancreático pela apresentaçäo clínica e achados de exames complementares, como USG abdominal e RM do pâncreas. Confirmaçäo histopatológica de tumor epitelial sólido-cístico papilar de pâncreas, na pe;a cirúrgica