Severity of Ascites Is Associated with Increased Mortality in Patients with Cirrhosis Secondary to Biliary Atresia

Very few prior studies have investigated the presence of ascites as a prognostic factor in children with cirrhosis. To the best of our knowledge, there are no prior studies evaluating the relationship between severity of ascites and patient survival in children with biliary atresia and cirrhosis.Clinically detectable ascites is associated with decreased 1-year survival of children with biliary atresia. These patients should be treated with caution and prioritized for liver transplantation.Background Very few prior studies have investigated the presence of ascites as a prognostic factor in children with cirrhosis. To the best of our knowledge, there are no prior studies evaluating the relationship between severity of ascites and patient survival in children with biliary atresia and cirrhosis. Aims To evaluate the association between severity of ascites and survival of children with cirrhosis and biliary atresia. Methods All children with cirrhosis secondary to biliary atresia evaluated at our institution from 2000 to 2014 were included in this study. Patients were classified into four groups: NA = no ascites; A1 = grade 1 ascites; A2 = grade 2 ascites; and A3 = grade 3 ascites. The primary endpoint of the study was mortality within the first year after patient inclusion. Ninetyday mortality was also evaluated. Prognostic factors related to both endpoints also were studied. [...]info:eu-repo/semantics/publishedVersio

Osteodistrofia hepática: : revisão da literatura e relato de experiência pessoal em um grupo de crianças e adolescentes com colestase crônica

Hepatic osteodystrophy is the term used to define the metabolic bone diseaseassociated with chronic liver disease. It has been studied mainly in adults with chroniccholestasis, but it is equally prevalent in children and adolescents. The pathogenesisof hepatic osteodystrophy is unknown, however, it is likely to be multifactorial. Themajority of patients experience a progressive loss of bone mineral density, which causesskeletal fragility. Thus, patients are predisposed to loss of height, to bone pain, and tofracturing bones with minimal or no trauma. Bone mineral density may be measuredby dual photon absorptiometry. No specific therapy is available to treat or prevent theosteopenia of chronic liver disease. However, 1 year after liver transplant, most patientsdo regain bone mass. This review discusses the pathophysiology, diagnosis, andtreatment of hepatic osteodystrophy. In this review we also report our personal experience with 20 children and adolescents with chronic cholestasis receiving care atthe Pediatric Gastroenterology Unit at Hospital de Clínicas de Porto Alegre.Osteodistrofia hepática é o termo usado para definir a doença óssea metabólicaassociada à hepatopatia crônica. Estudada principalmente em indivíduos adultos comcolestase crônica, é igualmente prevalente em crianças e adolescentes hepatopatascrônicos. A patogênese é desconhecida mas parece ser multifatorial. Na maioria dospacientes, ocorre uma perda progressiva de densidade óssea, a qual causa importantefragilidade esquelética. Esta predispõe à perda de estatura, dor óssea e surgimentode fraturas associadas ou não a trauma. A densidade óssea mineral pode ser medidapor densitometria óssea de dupla emissão. Nenhuma medida, farmacológica ouprofilática, tem se mostrado efetiva em reduzir a osteopenia da hepatopatia crônica.Todavia, aproximadamente 1 ano após transplante hepático, observa-se aquisiçãode massa óssea em grande parte dos pacientes.Nesta revisão discutimos a fisiopatologia, o diagnóstico e o tratamento da osteodistrofiahepática e relatamos a nossa experiência com 20 pacientes com colestase crônicaacompanhados na unidade de Gastroenterologia Pediátrica do Hospital de Clínicasde Porto Alegre

Interaction between IRF6 and TGFA Genes Contribute to the Risk of Nonsyndromic Cleft Lip/Palate

Previous evidence from tooth agenesis studies suggested IRF6 and TGFA interact. Since tooth agenesis is commonly found in individuals with cleft lip/palate (CL/P), we used four large cohorts to evaluate if IRF6 and TGFA interaction contributes to CL/P. Markers within and flanking IRF6 and TGFA genes were tested using Taqman or SYBR green chemistries for case-control analyses in 1,000 Brazilian individuals. We looked for evidence of gene-gene interaction between IRF6 and TGFA by testing if markers associated with CL/P were overtransmitted together in the case-control Brazilian dataset and in the additional family datasets. Genotypes for an additional 142 case-parent trios from South America drawn from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), 154 cases from Latvia, and 8,717 individuals from several cohorts were available for replication of tests for interaction. Tgfa and Irf6 expression at critical stages during palatogenesis was analyzed in wild type and Irf6 knockout mice. Markers in and near IRF6 and TGFA were associated with CL/P in the Brazilian cohort (p<10-6). IRF6 was also associated with cleft palate (CP) with impaction of permanent teeth (p<10-6). Statistical evidence of interaction between IRF6 and TGFA was found in all data sets (p = 0.013 for Brazilians; p = 0.046 for ECLAMC; p = 10-6 for Latvians, and p = 0.003 for the 8,717 individuals). Tgfa was not expressed in the palatal tissues of Irf6 knockout mice. IRF6 and TGFA contribute to subsets of CL/P with specific dental anomalies. Moreover, this potential IRF6-TGFA interaction may account for as much as 1% to 10% of CL/P cases. The Irf6-knockout model further supports the evidence of IRF6-TGFA interaction found in humans. © 2012 Letra et al

Infecções em pacientes pediátricos submetidos a transplante hepático

OBJECTIVE: To identify bacterial, viral, and fungal infections in the first 20 pediatric patients submitted to liver transplant at Hospital de Clínicas de Porto Alegre.PATIENTS AND METHODS: Twenty-one liver transplants were performed in 20&nbsp; infant and adolescent patients from March 1995 to September 1997, at Hospital deClínicas de Porto Alegre. All transplanted organs were taken from deceased donors with the same ABO blood type as the organ transplant recipient. Nine patientsreceived a whole liver transplant, and 11 patients received a reduced liver transplant. Bacterial infection was diagnosed by the existence of clinical and laboratory evidence;and/or by hemoculture; and/or by positive&nbsp; cultures. For the diagnosis of viral infections, patients were examined for Epstein Barr virus and for cytomegalovirus. For the diagnosis of fungal infection, hemocultures and secretion cultures were taken, and patients were also submitted to draining and sample collections, such as urine samples using a catheter.RESULTS: Of the 20 organ transplant recipient patients, two died within the first 24- 48 hours, and only four of the patients did not present any infections and/or positive cultures that were clinically significant. Fourteen patients had bacterial infection, and nine patients had more than one case of infection. The most frequently found organisms were Staphylococus aureus and epidermidis, and Xanthomonas maltophilia. Five transplant recipients were positive for cytomegalovirus antigenemia, and only one of these recipients was seronegative before the transplant. Fungal infection was diagnosed in two patients, and a third patient presented a positive culture of the biliary drain.CONCLUSIONS: Of the 20 liver transplant recipients, four died due to infection complications. By exerting a careful control, and establishing appropriate prophylacticand therapeutic measures, infection and its consequences may be reduced.OBJETIVO: Identificar infecções bacterianas, virais e fúngicas nos primeiros 20pacientes pediátricos submetidos a transplante de fígado no HCPA.PACIENTES E MÉTODOS: 21 transplantes foram realizados em 20 crianças eadolescentes, no período de março de 1995 a setembro de 1997, no HCPA. Todosos transplantes foram de doador cadavérico, do mesmo grupo sangüíneo ABO.Nove transplantes foram de fígado inteiro e 11, de fígado reduzido. O diagnósticode infecção bacteriana foi feito quando havia evidências clínico-laboratoriais e/ouhemocultura e/ou outros culturais positivos. Os vírus pesquisados foram citomegaloe Epstein Barr. Fungos eram pesquisados através de hemoculturas e culturas desecreções, drenos e coleções, cateteres e urina.RESULTADOS: Dos 20 pacientes transplantados, dois morreram nas primeiras24-48 horas e apenas quatro não apresentaram infecção e/ou culturais positivos,clinicamente significativos. Quatorze pacientes apresentaram infecção bacteriana,sendo que nove pacientes apresentaram mais do que um episódio infeccioso. Osorganismos mais freqüentes foram Staphylococus aureus e epidermidis eXantomonas maltophilia. Cinco receptores positivaram antigenemia para CMV, sendoque apenas um apresentava sorologia negativa no pré-transplante. Infecção fúngicafoi diagnosticada em dois pacientes e um terceiro paciente apresentou cultura dodreno biliar positiva.CONCLUSÕES: Dos 20 pacientes transplantados, quatro foram ao óbito porcomplicações infecciosas. Um controle cuidadoso e medidas profiláticas eterapêuticas adequadas podem diminuir infecções e suas conseqüências apóstransplante hepático

Parallel adaptation of rabbit populations to myxoma virus.

In the 1950s the myxoma virus was released into European rabbit populations in Australia and Europe, decimating populations and resulting in the rapid evolution of resistance. We investigated the genetic basis of resistance by comparing the exomes of rabbits collected before and after the pandemic. We found a strong pattern of parallel evolution, with selection on standing genetic variation favoring the same alleles in Australia, France, and the United Kingdom. Many of these changes occurred in immunity-related genes, supporting a polygenic basis of resistance. We experimentally validated the role of several genes in viral replication and showed that selection acting on an interferon protein has increased the protein's antiviral effect.This work was supported by grants from the Programa Operacional Potencial Humano–Quadro de Referência Estratégica Nacional funds from the European Social Fund and Portuguese Ministério da Ciência, Tecnologia e Ensino Superior to M.C. (IF/00283/2014/CP1256/CT0012), to P.J.E. (IF/00376/2015) and to J.M.A. (SFRH/BD/72381/2010). AM was supported by the European Research Council (grant 647787-LocalAdaptation). FJ was supported by the European Research Council (grant 281668). LL was supported by the European Research Council grant (339941-ADAPT). McFadden Lab is supported by National Institute of Health (NIH) grant R01 AI080607. S.C.G. holds a Sir Henry Dale Fellowship, co-funded by the Wellcome Trust and the Royal Society (098406/Z/12/Z)