Alexandre Rodrigues Ferreira

Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function

Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on T cells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4(+) T cell transfer, Rag2(-/-)Il10rb(-/-) mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb(-/-) anti-inflammatory macrophages ameliorated colitis induction by WT CD4(+) T cells in Rag2(-/-)Il10rb(-/-) mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans.

Clinical and Laboratory Predictors of Esophageal Varices in Children and Adolescents With Portal Hypertension Syndrome

Objectives: To determine the clinical and laboratory parameters that may predict the presence of esophageal varices in children and adolescents with portal hypertension. Patients and Methods: Overall, 111 patients with portal hypertension and no previous history of digestive bleeding underwent esophagogastroduodenoscopy for detection of esophageal varices. A univariate analysis initially was carried out, followed by a logistic regression analysis to identify the independent variables associated with the presence of esophageal varices. Sensitivity and specificity rates, positive predictive value, negative predictive value, and the accuracy of the predictive variables identified among cirrhotic patients were calculated with the esophagogastroduodenoscopy as the reference test. Results: Sixty percent of patients had esophageal varices on the first esophagogastroduodenoscopy. Patients with portal vein thrombosis and congenital hepatic fibrosis were 6.15-fold more likely to have esophageal varices than cirrhotic patients. When we analyzed 85 cirrhotic patients alone, splenomegaly and hypoalbuminemia remained significant indicators of esophageal varices. Only spleen enlargement showed appropriate sensitivity and negative predictive value (97.7% and 91.7%, respectively) to be used as a screening test for esophageal varices among cirrhotic patients. Conclusions: In reference services and research protocols, endoscopic screening should be performed in all patients with portal vein thrombosis and congenital hepatic fibrosis. Among cirrhotic patients, the indication should be conditioned to clinical evidence of splenomegaly or hypoalbuminemia. For clinicians, the recommendation is to emphasize the orientations given to guardians of patients with portal vein thrombosis and congenital hepatic fibrosis as to the risk of digestive bleeding. Cirrhotic patients with hypoalbuminemia and splenomegaly should receive the same orientations.

Effect of treatment of hepatic histopathology in children and adolescents with autoimmune hepatitis.

Objective: To evaluate the effects of treatment on liver histopathology of children and adolescents diagnosed with autoimmune hepatitis. Patients and Methods: Histopathological evaluation of liver biopsies performed at diagnosis or early during treatment, compared with biopsies after immunosuppressive treatment of 20 children and adolescents diagnosed with autoimmune hepatitis who presented clinical and biochemical remission for at least 24 months. Liver histopathology was assessed by 2 pathologists. Agreement between their interpretations was analyzed with κ statistics. Results: The age at diagnosis of the 20 patients varied from 1.7 years to 11.6 years (median = 6.6 years); 18 were females. The mean duration of clinical and biochemical remission, up to performance of liver biopsy, was 4.1 years. The mean interval between the initial and posttreatment biopsies was 4.6 years (range 2–9.7 years). Assessing the necroinflammatory activity, a mean reduction by 6.3 (observer 1) and 7.3 (observer 2) in the grading score was observed (P = 0.00000). When staging was assessed, a mean reduction by 1.8 (observers 1 and 2) in the score was observed after treatment (P = 0.00008), and there was no progression toward cirrhosis. No regression of cirrhosis was observed. Conclusions: On histopathological evaluation, the immunosuppressive treatment improved the fibrosis scores, with an arrest in its progression and no development into cirrhosis. Fibrosis control is mainly associated with regression of necroinflammatory activity, which is the main treatment component in autoimmune hepatitis.

Portal vein thrombosis in children and adolescents.

OBJECTIVE To review the literature on portal vein thrombosis in children and adolescents, focusing on its diagnosis, complications and treatment. SOURCES OF DATA The medical literature of the past 10 years was reviewed using the PubMed and MEDLINE search engines, with major focus on portal vein thrombosis and its clinical outcomes. The following keywords or expressions were used for the web search: portal vein thrombosis, extra-hepatic portal vein obstruction, prognosis, children, portal hypertension, esophagogastric varices. Additionally, we also reviewed the articles cited in the references of the initially selected papers, as well as relevant textbooks. SUMMARY OF THE FINDINGS Portal vein thrombosis is one of the most common causes of portal hypertension among children. The initial clinical manifestation is characterized either by episodes of upper gastrointestinal bleeding or by splenomegaly on routine clinical examination. The major complications include upper gastrointestinal bleeding, hypersplenism secondary to splenomegaly, growth retardation, and portal biliopathy. The diagnosis is made by abdominal Doppler ultrasonography. Treatment is targeted at the complications and includes primary and secondary prophylaxis against upper gastrointestinal bleeding (which results from the rupture of esophageal varices), and portosystemic shunting in selected cases. CONCLUSIONS Portal vein thrombosis is one of the major triggers of upper gastrointestinal bleeding in children. Bleeding episodes have a remarkable effect on the quality of life of affected patients. Thus, appropriate diagnosis and treatment are needed in order to reduce morbidity and mortality.

Trombose de veia porta em crianças e adolescentes

OBJETIVO: Apresentar uma revisao atualizada de trombose de veia porta na infância e adolescencia, enfatizando o diagnostico, suas complicacoes e tratamento. FONTE DOS DADOS: Foi realizada revisao da literatura, dos ultimos 10 anos, atraves de pesquisa bibliografica na Internet nos principais sites de busca medica, como o PubMed e MEDLINE, com enfoque na doenca trombose de veia porta e suas repercussoes clinicas. As principais palavras-chave e expressoes pesquisadas foram: portal vein thrombosis, extra-hepatic portal vein obstruction, prognosis, children, portal hypertension, esophagogastric varices. Alem disso, foram consultados os artigos citados nas referencias dos trabalhos selecionados na pesquisa inicial e dos livros textos. SINTESE DOS DADOS: A trombose de veia porta e uma das causas mais comuns de hipertensao porta na infância. A apresentacao clinica inicial pode ser atraves de episodios de hemorragia digestiva ou da presenca de esplenomegalia em exame clinico de rotina. As principais complicacoes sao a hemorragia digestiva, hiperesplenismo secundario a esplenomegalia, retardo de crescimento e biliopatia portal. O diagnostico e realizado atraves da ultra-sonografia abdominal com Doppler. O tratamento e direcionado para as complicacoes, incluindo profilaxia primaria e secundaria de hemorragia digestiva, consequente a ruptura de varizes esofagicas, e derivacoes porto-sistemicas, em casos selecionados. CONCLUSOES:A trombose de veia porta e uma das causas mais importantes de hemorragia digestiva em criancas. Esses episodios acarretam impacto importante na qualidade de vida dos pacientes acometidos. Dessa forma, uma abordagem diagnostica e terapeutica adequada e desejavel na tentativa de se reduzir a morbimortalidade.

Distúrbio de coagulação em crianças e adolescentes com traumatismo cranioencefálico moderado e grave

OBJECTIVES: To describe the epidemiological profile of children and adolescents with moderate to severe traumatic brain injury admitted to an intensive care unit; to describe the frequency of coagulation disorders in these patients; to determine the relationship between coagulopathy and trauma severity; to assess the factors associated with coagulopathy; and to assess the effect of coagulopathy on the mortality of these patients. METHODS: Cross-sectional study with 301 patients aged up to 16 years admitted to an intensive care unit due to moderate to severe traumatic brain injury, carried out over a 5-year period. The coagulation profile was associated with clinical, epidemiological and CT findings. Univariate and multivariate analyses were used to check the association between coagulopathy and mortality. RESULTS: Minimum age was 23 days, and maximum age was 16 years (mean of 7.9 years). About 77% of patients had coagulopathy, whose occurrence was directly associated with the severity of the trauma, but not with the rise in mortality. The factors associated with the presence of coagulopathy were the following: severity of the traumatic brain injury (OR = 2.83; 95%CI 1.58-5.07), diagnosis of brain swelling on cranial computed tomography (OR = 2.11; 95%CI 1.13-4.07) and occurrence of chest and/or abdominal injury (OR = 2.07; 95%CI 1.11-4.00). Approximately 35% of patients died. The multivariate analysis showed that the factors associated with an increased risk of death were presence of sodium disorders (OR = 5.56; 95%CI 2.90-10.65), hypotension in the intensive care unit (OR = 12.58; 95%CI 4.40-35.00) and acute respiratory distress syndrome (OR = 13.57; 95%CI 1.51-121.66). CONCLUSION:The development of coagulopathy is a frequent complication in patients with moderate to severe traumatic brain injury. Even though it is not closely associated with death in this study, it may be regarded as a marker of injury severity.

Coagulation disorder in children and adolescents with moderate to severe traumatic brain injury

OBJECTIVES To describe the epidemiological profile of children and adolescents with moderate to severe traumatic brain injury admitted to an intensive care unit; to describe the frequency of coagulation disorders in these patients; to determine the relationship between coagulopathy and trauma severity; to assess the factors associated with coagulopathy; and to assess the effect of coagulopathy on the mortality of these patients. METHODS Cross-sectional study with 301 patients aged up to 16 years admitted to an intensive care unit due to moderate to severe traumatic brain injury, carried out over a 5-year period. The coagulation profile was associated with clinical, epidemiological and CT findings. Univariate and multivariate analyses were used to check the association between coagulopathy and mortality. RESULTS Minimum age was 23 days, and maximum age was 16 years (mean of 7.9 years). About 77% of patients had coagulopathy, whose occurrence was directly associated with the severity of the trauma, but not with the rise in mortality. The factors associated with the presence of coagulopathy were the following: severity of the traumatic brain injury (OR=2.83; 95%CI 1.58-5.07), diagnosis of brain swelling on cranial computed tomography (OR=2.11; 95%CI 1.13-4.07) and occurrence of chest and/or abdominal injury (OR=2.07; 95%CI 1.11-4.00). Approximately 35% of patients died. The multivariate analysis showed that the factors associated with an increased risk of death were presence of sodium disorders (OR=5.56; 95%CI 2.90-10.65), hypotension in the intensive care unit (OR=12.58; 95%CI 4.40-35.00) and acute respiratory distress syndrome (OR=13.57; 95%CI 1.51-121.66). CONCLUSION The development of coagulopathy is a frequent complication in patients with moderate to severe traumatic brain injury. Even though it is not closely associated with death in this study, it may be regarded as a marker of injury severity.

Endoscopic dilatation of esophageal strictures in children and adolescents

OBJECTIVE To assess the causes of esophageal stricture in pediatric patients and their response to endoscopic dilatation. METHODS Retrospective analysis of clinical and endoscopic data obtained from children and adolescents with esophageal stricture submitted to endoscopic dilatation between July 1993 and January 2003. RESULTS A total of 125 patients aged between 1 month and 16 years were included in the study. Among the types of stenosis, postoperative (43.2%), corrosive (27.2%) and peptic (21.6%) strictures were the most prevalent. Those patients with corrosive esophageal stricture needed more dilatation sessions. Five cases of esophageal perforation and one case of hemorrhage occurred due to complications during the procedure. Good response to endoscopic treatment was described in 74.4% of cases, but better results were obtained from patients with peptic esophageal stricture. CONCLUSIONS Endoscopic treatment of esophageal strictures in children and adolescents yields good results and has a low rate of complications. Corrosive esophageal strictures have a higher morbidity and require more dilatation sessions.

Accuracy of echogenic periportal enlargement image in ultrasonographic exams and histopathology in differential diagnosis of biliary atresia

OBJECTIVES To define the sensitivity, specificity and accuracy of the ultrasound triangular cord sign and hepatic histopathology, in isolation or in combination, for diagnostic differentiation between biliary atresia and intrahepatic cholestasis. METHODS This was a retrospective study carried out between January 1990 and December 2004. Fifty-one cases of biliary atresia and 45 of intrahepatic cholestasis were analyzed. Histopathology was performed blind by a pathologist. The triangular cord sign was identified in ultrasound reports as the only diagnostic sign of biliary atresia. Sensitivity, specificity and accuracy were calculated for the triangular cord sign and histology both in isolation and in combination. The gold standard for diagnosis of biliary atresia was the appearance of the extrahepatic biliary tree via laparotomy. RESULTS The triangular cord sign alone had sensitivity of 49%, specificity of 100% and accuracy of 72.5%. Histopathology compatible with extrahepatic biliary obstruction alone had 90.2% sensitivity, 84.6% specificity and 87.8% accuracy. The triangular cord sign and histopathology in isolation or combination resulted in sensitivity of 93.2%, specificity of 85.7% and accuracy of 90.3%. CONCLUSIONS Finding the triangular cord sign on ultrasound is an indication for laparotomy. If the triangular cord sign is negative, liver biopsy is indicated; if histopathology reveals signs of biliary atresia, explorative laparotomy is indicated. In cases where the triangular cord sign is absent and histopathology indicates neonatal hepatitis or other intrahepatic cholestasis, clinical treatment or observation are recommended in accordance with the diagnosis.

Hepatite auto-imune tipo 1 em crianças e adolescentes: avaliação da suspensão do tratamento imunossupressor

Objective: To assess treatment withdrawal in children and adolescents with autoimmune hepatitis, with clinical and laboratory remission for a minimum period of 24 months, determining the relapse rate after treatment withdrawal. Method: This is a descriptive, retrospective and partially prospective study of 21 children and adolescents with type 1 autoimmune hepatitis treated at the Outpatient Division of Pediatric Hepatology, Teaching