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.

Autoimmune Hepatitis and Autoimmune Hepatitis Overlap With Sclerosing Cholangitis: Immunophenotype Markers in Children and Adolescents.

OBJECTIVE: The pathophysiology of autoimmune hepatitis (AIH) may involve the activation of immune cells and changes in the expression of cellular markers. The aim of the present study was to characterize the immunophenotype markers of lymphocytes and monocytes in the peripheral blood of children and adolescents with type 1 AIH and AIH overlap with sclerosing cholangitis (overlap syndrome [OS]). METHODS: This is a cross-sectional study of 20 children and adolescents diagnosed with type 1 AIH and 19 with OS. Fifteen healthy subjects were included as controls. Flow cytometric analysis was used to identify markers of inflammation and autoimmunity. RESULTS: The total number of CD4 T cells was higher in the AIH patients compared with the controls. The number of CD4 T cells expressing CCR3 and CD28 was higher in the AIH group than in the control group. CD45RO was more highly expressed in the AIH group, whereas CD45RA was more highly expressed in the OS group. In regard to CD8 T lymphocytes, the CCR3 expression was higher in both groups of patients. Patients with OS had the highest expression of CD45RA and CD25. In monocytes, human leukocyte antigen DR (HLA-DR) was less expressed in both groups of patients. CONCLUSIONS: Complex phenotype features may be involved in the pathophysiology of AIH, accounting for changes in immune system regulation mechanisms. In conclusion, even after good response to treatment, patients still have immune activity signals at the cellular level.

Factors Associated With Bleeding Secondary to Rupture of Esophageal Varices in Children and Adolescents With Cirrhosis.

OBJECTIVE: Bleeding of esophageal varices is the main cause of morbidity and mortality in children with portal hypertension. It is important to understand the factors related with a bleeding episode to evaluate more effective primary prophylaxis. The present study aims to describe the endoscopic and laboratory findings associated with upper gastrointestinal bleeding (UGIB) secondary to esophageal varices. METHOD: A cross-sectional study with 103 children and adolescents with cirrhosis, divided into a group that had experienced an episode of upper UGIB (35 patients) and a group without a history of UGIB (68 patients), was carried out. The esophageal and gastric varices were classified, and the portal hypertensive gastropathy, laboratory findings, and Child-Pugh classification were measured. RESULTS: Factors observed in univariate analysis to be associated with UGIB were the presence of esophageal varices of medium caliber or larger, portal hypertensive gastropathy, presence of red spots on esophageal varices, Child-Pugh class B or C, and hypoalbuminemia (P < 0.05). After multivariate logistic regression analysis, the significant factors were the presence of red spots on esophageal varices and the presence of gastric varices. When separated the autoimmune hepatitis, nonbiliary atresia patients (all patients except the patients with biliary atresia), and biliary atresia groups the findings in the univariate analysis were the presence of esophageal varices of medium or larger caliber, presence of red spots on varices, and presence of gastric varices in the autoimmune hepatitis patients and nonbiliary atresia patients and presence of red spots on esophageal varices, presence of gastric varices, and Child-Pugh classification B or C in biliary atresia group (P < 0.05). After multivariate logistic regression analysis, no statistical significance was found for any factor analyzed in any groups. CONCLUSIONS: The presence of gastric varices and red spots on esophageal varices were related to episodes of UGIB secondary to rupture of esophageal varices. When these findings are observed, indications for endoscopic primary prophylaxis should be evaluated. More studies are, however, necessary to better understand this problem.

Clinical Characteristics and Prognosis in Children and Adolescents With Autoimmune Hepatitis and Overlap Syndrome.

OBJECTIVES: This is a cohort study of 134 children and adolescents with a known diagnosis of autoimmune hepatitis (AIH). During follow-up, some of them developed autoimmune sclerosing cholangitis (ASC). This study describes the characteristics of the patients upon diagnosis, and their response to treatment and any complications, and compares the patients who developed ASC during follow-up (ASC group) with those who did not (AIH group). METHODS: A total of 73.1% of the patients were girls with a median age upon diagnosis of 10.41 (7.41-12.53) years. RESULTS: Of 134 patients, 28 (20.9%) developed cholestatic manifestations, with features of ASC. A few differences were observed between the AIH and ASC groups when they were analyzed by χ test, such as the smaller predominance of girls in ASC group (P = 0.04), and more common asymptomatic presentation in the ASC group (P = 0.01). Cirrhosis was observed in 68% of biopsies, with no significant difference between groups (P = 0.43). Of 16 deaths, 15 were in the AIH group and 1 in the ASC group (P = 0.22). Of 11 transplants, 10 were in the AIH group and one in the ASC group (P = 0.53). The presence of cirrhosis at baseline was associated with a smaller survival probability (P = 0.015). The survival rate by Kaplan-Meier method was 94% at 5 years and 80% at 10 years, and was similar in both the groups (P = 0.08). CONCLUSIONS: No statistically significant difference was observed between the groups in relation to prognosis and response to treatment.

Identifying Consistent Metrics from the Force-Time Curve of the Countermovement Jump in Combat Fighters and Physically Active Men.

We investigated the consistency of metrics obtained from the unweighting, braking, propulsive, and landing phases of the countermovement (CMJ) force-time curve in combat fighters and physically active men. Combat fighters (n=21) and physically actives (n=21) were tested for three days (2-7 days apart). Participants performed four maximal CMJ separated by 1-min for between-day comparisons. From force-time recording, the consistency of 16 CMJ metrics (peak and mean ground reaction forces (GRF), net impulse, and duration from each phase) was investigated using the intraclass correlation coefficient (ICC) and typical error (CVTE). We considered as "consistent" those metrics showing no systematic differences, ICC ≥ 0.75, and CVTE ≤ 10%. We further compared the CVTE between groups and pairs of trials (days). Participants demonstrated more consistency in the braking and propulsive phases, while the unweighting phase did not show any consistent metric. There was no evidence of a learning effect (systematic changes), but analysis appointed more consistency on days 2-3 than on days 1-2 (18 metrics presented lower CVTE while 11 presented higher). We identified braking and propulsive GRF (peak and mean) and propulsive impulse as consistent metrics for combat fighters, while only propulsive impulse for physically actives. The between-group analyses showed that 24 comparisons favored the combat fighters against only five favoring the physically actives. In conclusion, force-time metrics related to jumping strategy, like phase duration, are less consistent than those related to driven forces and jump output, probably because participants changed their jump strategy during testing days.

Can Creatine Supplementation Interfere with Muscle Strength and Fatigue in Brazilian National Level Paralympic Powerlifting?

The aim of the present study was to analyze the effect of creatine (Cr) supplementation on peak torque (PT) and fatigue rate in Paralympic weightlifting athletes. Eight Paralympic powerlifting athletes participated in the study, with 25.40 ± 3.30 years and 70.30 ± 12.15 kg. The measurements of muscle strength, fatigue index (FI), peak torque (PT), force (kgf), force (N), rate of force development (RFD), and time to maximum isometric force (time) were determined by a Musclelab load cell. The study was performed in a single-blind manner, with subjects conducting the experiments first with placebo supplementation and then, following a 7-day washout period, beginning the same protocol with creatine supplementation for 7 days. This sequence was chosen because of the lengthy washout of creatine. Regarding the comparison between conditions, Cr supplementation did not show effects on the variables of muscle force, peak torque, RFD, and time to maximum isometric force (p > 0.05). However, when comparing the results of the moments with the use of Cr and placebo, a difference was observed for the FI after seven days (U3: 1.12; 95% CI: (0.03, 2.27); p = 0.02); therefore, the FI was higher for placebo. Creatine supplementation has a positive effect on the performance of Paralympic powerlifting athletes, reducing fatigue index, and keeping the force levels as well as PT.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes.

OBJECTIVE: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. METHODS: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. RESULTS: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). CONCLUSIONS: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

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.

Relationships between Different Field Test Performance Measures in Elite Goalball Players.

Goalball is a Paralympic sport involving people with visual impairment. Little is known about the physical fitness of elite players of this sport, as previous studies only evaluated body composition and aerobic capacity. Thus, the aim of this study was to describe the performance of elite goalball players in different physical tests and to look for relationships between them. Eleven elite Brazilian goalball players, seven males and four females, were evaluated for body composition, maximal handgrip isometric force (MHGF), countermovement jump (CMJ), throwing velocity (TV) and the Yo-Yo intermittent recovery test level 1 (Yo-Yo IR1). Players produced 41.54 ± 8.41 kgf in MHGF, 34.81 ± 7.2 cm in CMJ, 14.21 ± 1.89 m∙s-1 in TV, and 505 ± 313 m in Yo-Yo IR1, with an estimated maximum oxygen consumption (VO2max) of 40.64 ± 2.63 mL∙kg-1∙min-1. Most performance tests exhibited moderate to high correlations among them, while the percentage of body fat correlated with both the CMJ and Yo-Yo IR1 results. The current study reveals that CMJ could be a valuable monitoring tool as it was correlated with all other performance tests. The highest correlation observed was with TV (r = 0.754; p < 0.05), which is a key capacity in goalball. Moreover, high levels of body fat could be detrimental to anaerobic performance.

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.

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.

[Type 1 autoimmune hepatitis in children and adolescents: assessment of immunosuppressive treatment withdrawal]. / 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. METHODS: 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 Hospital of Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil, between January 1986 and December 2001. RESULTS: We assessed 54 patients and selected 21, of whom 19 were female subjects (90.5%), aged between 5.7 and 17.6 years (median = 13.8 years), with a mean follow-up of 5.1+/-2.4 years (median = 4.4 years) and an average clinical and laboratory remission of 4.1+/-1.5 years (median = 4.1 years). Out of the 21 patients studied, 10 (47.6%) manifested some inflammatory activity that prevented the discontinuation of treatment, which was withdrawn in 11 patients (52.4%). Out of these, six patients (54.5%) presented reactivation of the disease and five maintained clinical and laboratory remission with a mean follow-up of 4+/-1 years (median = 3.9 years). The time interval between discontinuation of treatment and reactivation of the disease ranged from 29 days to 40.3 months (median = 2.2 months). CONCLUSIONS: We observed a high relapse rate (54.5%) in this group of patients with autoimmune hepatitis, which was more frequent within the first 12 months after treatment withdrawal, in addition to a high number of patients that presented some degree of inflammatory activity despite the long period of clinical and laboratory remission.

[Autoimmune hepatitis in children and adolescents: clinical study, diagnosis and therapeutic response]. / Hepatite auto-imune em crianças e adolescentes: estudo clínico, diagnóstico e resposta terapêutica.

OBJECTIVE: The aim of this study was to evaluate the clinical, laboratory and histopathological characteristics and the response to immunosuppression in children and adolescents with autoimmune hepatitis (AIH). METHODS: The present research is a descriptive study consisting of 39 children and adolescents with AIH who receive care at the Department of Pediatric Gastroenterology of Hospital das Clínicas (UFMG) from 1986 to 1998. RESULTS: Children's age ranged from 1.6 to 17 years (mean 8.7 +/- 3.49), most of them were females (87.2%). There were three types of clinical presentations: chronic (53.9%), acute (41%), and serious hepatic failure (5.1%). The most relevant laboratory parameters were the aminotransferases and gamma-globulin increase. Antinuclear antibodies were positive in 66.7% of the patients, while smooth muscle antibodies were positive in 52.8% and anti-LKM1 in 3% of the patients. In the histopathology the most important findings were the piecemeal necrosis (93.7%), moderate to severe portal inflammation (78.1%), definitive or incomplete cirrhosis (76.9%), absence of lesion of biliary ducts (93.7%) and presence of rosettes (90.6%). During the treatment, 77.8% obtained complete resolution, associated to side effects in 27.8% of them. Seven patients died (17.9%). During the treatment there was significant z score reduction (p<0.05) for height/age. CONCLUSIONS: After carrying out this study, we observed that the typical characteristics of AIH were: female sex, several clinical presentations, increased aminotransferase, and hypergammaglobulinemia. Histopathology showed a predominance of incipient and/or definitive cirrhosis associated with moderate to severe portal inflammation and piecemeal necrosis. Treatment using corticosteroids and azathioprine, turned out to be effective. However, the reduction in the height/age z score probably represents an adverse effect of corticoid treatment.

[Application of the Pediatric Index of Mortality 2 in pediatric patients with complex chronic conditions]. / Aplicação do Pediatric Index of Mortality 2 em pacientes pediátricos com condição crônica complexa.

OBJECTIVE: To evaluate the performance of the Pediatric Index of Mortality 2 (PIM2) in a pediatric intensive care unit (PICU) with a high prevalence of patients with complex chronic conditions (CCCs), and compare the performance between patients with and without CCCs. METHODS: A prospective cohort study was conducted in a PICU in Brazil, with patients admitted between 2009 and 2011. The performance was evaluated through discrimination and calibration. Discrimination was assessed by calculating the area under the ROC curve, and calibration was determined using the Hosmer-Lemeshow goodness-of-fit test. RESULTS: A total of 677 patients were included in the study, of which 83.9% had a CCC. Overall mortality was 9.7%, with a trend of higher mortality among patients with CCCs when compared to patients without CCCs (10.3% vs. 6.4%, p = 0.27), but with no difference in the mean probability of death estimated by PIM2 (5.9% vs. 5.6%, p = 0.5). Discrimination was considered adequate in the general population (0.840) and in patients with and without CCCs (0.826 and 0.944). Calibration was considered inadequate in the general population and in patients with CCCs (p < 0.0001 and p < 0.0001), but it was considered adequate in patients without CCCs (p = 0.527). CONCLUSIONS: PIM2 showed poor performance in patients with CCCs and in the general population. This result may be secondary to differences in the characteristics between the study samples (high prevalence of patients with CCCs); the performance of the PIM2 should not be ruled out.

Histological evolution of fibrosis in patients with biliary atresia / Evolução histológica da fibrose em pacientes com atresia biliar

ABSTRACT Objective: To evaluate the evolution of histological findings of patients with biliary atresia (BA), emphasizing the progression of fibrosis by comparing the diagnostic liver biopsy to the surgical liver biopsy, performed during Kasai portoenterostomy. Methods: Retrospective study with 51 patients with BA submitted to portoenterostomy, and both diagnostic (DLB) and surgical liver biopsies (SLB). The samples were blindly reviewed by two pathologists. Results: Median age at DLB and at SLB was 69 and 77 days, respectively. The median time between biopsies was eight days. Cirrhosis was more frequent in SLB than in DLB, both according to the Metavir score (p = 0.006) and the Ishak score (p = 0.016). The Metavir score increased one or more points in 29/51 (56.9%), with evidence of progression to liver cirrhosis in 11/29 (37.9%) of those who had progression of fibrosis. Median age at surgery of those who had a progression of fibrosis was 77 days, while in those 11 who progressed to cirrhosis, this median was 92 days. Cirrhosis was seen in 12/51 (23.5%) SLB patients. The clinical variable age at surgery had a statistically significant difference regarding the presence or absence of cirrhosis in SLB (p = 0.024). Cirrhosis was not related to survival with native liver or biliary drainage. Conclusion: Most infants with BA have liver fibrosis at diagnosis and it progresses rapidly. The presence of cirrhosis is correlated with the age at surgery, which suggests the importance of this clinical variable in the evolution of fibrosis.

RESUMEN Objetivo: Analizar la evolución de los hallazgos histológicos de pacientes con atresia de vías biliares (AVB), resaltando la progresión de la fibrosis y comparando la biopsia hepática diagnóstica (BHD) con la biopsia hepática quirúrgica (BHQ) mediante la hepatoportoenterostomía de Kasai. Método: Estudio retrospectivo con 51 pacientes con AB sometidos a hepatoportoenterostomía, BHD y BHQ. Resultados: La edad mediana para BHD y BHQ fue 69 días y 77 días, respectivamente. El tiempo mediano entre las biopsias fue ocho días. La cirrosis fue más frecuente en la BHQ de lo que en la BHD, tanto de acuerdo con el escore de Metavir (p = 0,006) como con el escore de Ishak (p = 0,016). El escore de Metavir aumentó un punto o más en 29/51 (59,9%) pacientes, con evidencias de progresión hacia cirrosis hepática en 11/29 (37,9%), en los pacientes con progresión de la fibrosis. La edad mediana para cirugía de los que tuvieron progresión de la fibrosis fue 77 días; en los 11 que evolucionaron hacia cirrosis, esa mediana fue 92 días. La variable clínica de edad en el momento de la cirugía presentó diferencia estadísticamente significante con respecto a la presencia o ausencia de cirrosis (p = 0,024). La cirrosis no fue asociada a la sobrevida con hígado nativo o drenaje biliar. Conclusión: La mayor parte de los niños con AVB tiene fibrosis hepática en el momento del diagnóstico, y la enfermedad avanza rápidamente. La presencia de cirrosis está relacionada con la edad al momento de la cirugía, lo que sugiere la importancia de esa variable clínica en la evolución de la fibrosis.

RESUMO Objetivo: Avaliar a evolução dos achados histológicos de pacientes com atresia biliar (AB), enfatizando a progressão da fibrose e comparando a biópsia hepática diagnóstica (BHD) com a biópsia hepática cirúrgica (BHC), realizada durante a portoenterostomia de Kasai. Método: Estudo retrospectivo com 51 pacientes portadores de AB submetidos a portoenterostomia, BHD e BHC. Resultados: A idade mediana para BHD e BHC foi de 69 e 77 dias de idade, respectivamente. O tempo mediano entre as biópsias foi de oito dias. A cirrose foi mais frequente na BHC do que na BHD, tanto de acordo com o escore de Metavir (p = 0,006) quanto com o escore de Ishak (p = 0,016). O escore de Metavir aumentou um ou mais pontos em 29/51 (56,9%) pacientes, com evidências de progressão para cirrose hepática em 11/29 (37,9%), naqueles com progressão da fibrose. A idade mediana para cirurgia dos que tiveram progressão da fibrose foi de 77 dias; nos 11 que evoluíram para cirrose, essa mediana foi de 92 dias. A variável clínica da idade no momento da cirurgia apresentou diferença estatisticamente significativa em relação à presença ou à ausência de cirrose (p = 0,024). A cirrose não foi associada à sobrevida com fígado nativo ou drenagem biliar. Conclusão: A maioria das crianças com AB tem fibrose hepática no momento do diagnóstico, e a doença progride rapidamente. A presença de cirrose está correlacionada com a idade à cirurgia, o que sugere a importância dessa variável clínica na evolução da fibrose.

Autoimmune hepatitis in 828 Brazilian children and adolescents: clinical and laboratory findings, histological profile, treatments, and outcomes / Hepatite autoimune em 828 crianças e adolescentes brasileiros: achados clínicos e laboratoriais, perfil histológico, tratamentos e resultados

Abstract Objective: This large study with a long-term follow-up aimed to evaluate the clinical presentation, laboratory findings, histological profile, treatments, and outcomes of children and adolescents with autoimmune hepatitis. Methods: The medical records of 828 children and adolescents with autoimmune hepatitis were reviewed. A questionnaire was used to collect anonymous data on clinical presentation, biochemical and histological findings, and treatments. Results: Of all patients, 89.6% had autoimmune hepatitis-1 and 10.4% had autoimmune hepatitis-2. The female sex was predominant in both groups. The median age at symptom onset was 111.5 (6; 210) and 53.5 (8; 165) months in the patients with autoimmune hepatitis 1 and autoimmune hepatitis-2, respectively. Acute clinical onset was observed in 56.1% and 58.8% and insidious symptoms in 43.9% and 41.2% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively. The risk of hepatic failure was 1.6-fold higher for autoimmune hepatitis-2. Fulminant hepatic failure occurred in 3.6% and 10.6% of the patients with autoimmune hepatitis-1 and autoimmune hepatitis-2, respectively; the risk was 3.1-fold higher for autoimmune hepatitis-2. The gamma globulin and immunoglobulin G levels were significantly higher in autoimmune hepatitis-1, while the immunoglobulin A and C3 levels were lower in autoimmune hepatitis-2. Cirrhosis was observed in 22.4% of the patients; biochemical remission was achieved in 76.2%. The actuarial survival rate was 93.0%. A total of 4.6% underwent liver transplantation, and 6.9% died (autoimmune hepatitis-1: 7.5%; autoimmune hepatitis-2: 2.4%). Conclusions: In this large clinical series of Brazilian children and adolescents, autoimmune hepatitis-1 was more frequent, and patients with autoimmune hepatitis-2 exhibited higher disease remission rates with earlier response to treatment. Patients with autoimmune hepatitis-1 had a higher risk of death.

Resumo Objetivo: Este estudo com acompanhamento de longo prazo visou a avaliar o quadro clínico, os achados laboratoriais, o perfil histológico, os tratamentos e os resultados de crianças e adolescentes com hepatite autoimune. Métodos: Foram analisados os prontuários médicos de 828 crianças e adolescentes com HAI. Foi usado um questionário para coletar os dados anônimos sobre o quadro clínico, os achados bioquímicos e histológicos e os tratamentos. Resultados: De todos os pacientes, 89,6% tinham hepatite autoimune-1 e 10,4% hepatite autoimune-2. O sexo feminino foi predominante nos dois grupos. A idade média no início dos sintomas foi 111,5 (6; 210) e 53,5 (8; 165) meses nos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. Foi observado início clínico agudo em 56,1% e 58,8% e sintomas insidiosos em 43,9% e 41,2% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente. A probabilidade de insuficiência hepática foi 1,6 vezes maior para hepatite autoimune-2; 3,6% e 10,6% dos pacientes com hepatite autoimune-1 e hepatite autoimune-2, respectivamente, apresentaram insuficiência hepática fulminante; o risco foi 3,1 vezes maior para hepatite autoimune-2. Os níveis de gamaglobulina e imunoglobulina G foram significativamente maiores nos pacientes com hepatite autoimune-1, ao passo que os níveis de imunoglobulina A e C3 foram menores em pacientes com hepatite autoimune-2; 22,4% dos pacientes apresentaram cirrose e a remissão bioquímica foi atingida em 76,2%. A taxa de sobrevida atuarial foi de 93,0%. Um total de 4,6% pacientes foram submetidos a transplante de fígado e 6,9% morreram (hepatite autoimune-1: 7,5%; hepatite autoimune-2: 2,4%). Conclusões: Nesta grande série clínica de crianças e adolescentes brasileiros, a hepatite autoimune-1 foi mais frequente e os pacientes com hepatite autoimune-2 mostraram maiores taxas de remissão da doença com respostas mais rápidas aos tratamentos. Os pacientes com hepatite autoimune-1 apresentaram maior risco de óbito.

Application of the Pediatric Index of Mortality 2 in pediatric patients with complex chronic conditions, / Aplicação do Pediatric Index of Mortality 2 em pacientes pediátricos com condição crônica complexa

Objective: To evaluate the performance of the Pediatric Index of Mortality 2 (PIM2) in a pediatric intensive care unit (PICU) with a high prevalence of patients with complex chronic conditions (CCCs), and compare the performance between patients with and without CCCs. Methods: A prospective cohort study was conducted in a PICU in Brazil, with patients admitted between 2009 and 2011. The performance was evaluated through discrimination and calibration. Discrimination was assessed by calculating the area under the ROC curve, and calibration was determined using the Hosmer-Lemeshow goodness-of-fit test. Results: A total of 677 patients were included in the study, of which 83.9% had a CCC. Overall mortality was 9.7%, with a trend of higher mortality among patients with CCCs when compared to patients without CCCs (10.3% vs. 6.4%, p = 0.27), but with no difference in the mean probability of death estimated by PIM2 (5.9% vs. 5.6%, p = 0.5). Discrimination was considered adequate in the general population (0.840) and in patients with and without CCCs (0.826 and 0.944). Calibration was considered inadequate in the general population and in patients with CCCs (p < 0.0001 and p < 0.0001), but it was considered adequate in patients without CCCs (p = 0.527). Conclusions: PIM2 showed poor performance in patients with CCCs and in the general population. This result may be secondary to differences in the characteristics between the study samples (high prevalence of patients with CCCs); the performance of the PIM2 should not be ruled out. .

Objetivo Avaliar o desempenho do Pediatric Index of Mortality 2 (PIM2) em Unidade de Terapia Intensiva Pediátrica (UTIP) com alta prevalência de pacientes com condições crônicas complexas (CCC), e comparar o desempenho entre pacientes com e sem CCC. Métodos: Estudo de coorte prospectivo, realizado em UTIP no Brasil, com pacientes admitidos entre 2009 e 2011. O desempenho foi avaliado através da discriminação e calibração. A discriminação foi avaliada através do cálculo da área sob a curva ROC e a calibração através do teste de ajuste de Hosmer-Lemeshow. Resultados: Foram incluídos no estudo 677 pacientes, com 83,9% deles apresentando uma CCC. A mortalidade geral foi 9,7%, com tendência de maior mortalidade entre pacientes com CCC quando comparados com pacientes sem CCC (10,3% vs. 6,4%; p = 0,27), porém sem diferença na média de probabilidade de morte estimada pelo PIM2 (5,9% vs. 5,6%; p = 0,5). A discriminação foi considerada adequada na população geral (0,840) e nos pacientes com e sem CCC (0,826 e 0,944). A calibração foi considerada inadequada na população geral e nos pacientes com CCC (p < 0,0001 e p < 0,0001), porém foi considerada adequada nos pacientes sem CCC (p = 0,527). Conclusões: O PIM2 apresentou desempenho inadequado nos pacientes com CCC e na população geral. O desempenho inadequado pode ser secundário à diferença das características entre as amostras do estudo (alta prevalência de pacientes com CCC), e o desenvolvimento do escore não pode ser descartado. .

Acurácia diagnóstica do espessamento ecogênico periportal à ultra-sonografia e da histopatologia no diagnóstico diferencial da atresia biliar / Accuracy of echogenic periportal enlargement image in ultrasonographic exams and histopathology in differential diagnosis of biliary atresia

OBJETIVOS: Definir a sensibilidade, especificidade e a acurácia do espessamento ecogênico periportal à ultra-sonografia e da histopatologia hepática, isolados ou em conjunto, na distinção diagnóstica entre atresia biliar e as colestases intra-hepáticas. MÉTODOS: Trata-se de estudo retrospectivo realizado entre janeiro de 1990 e dezembro de 2004. Foram analisados 51 casos de atresia biliar e 45 com colestase intra-hepática. A histopatologia foi realizada por uma patologista de forma cega. O espessamento ecogênico periportal foi pesquisado na ultra-sonografia como único sinal diagnóstico de atresia biliar. Foram calculados os índices de sensibilidade, especificidade e acurácia do espessamento ecogênico periportal e da histologia isoladamente ou associados. O padrão-ouro utilizado para o diagnóstico de atresia biliar foi o aspecto da via biliar extra-hepática à laparotomia. RESULTADOS: O espessamento ecogênico periportal revelou sensibilidade de 49 por cento, especificidade de 100 por cento e acurácia de 72,5 por cento. A histopatologia compatível com obstrução biliar extra-hepática conferiu sensibilidade de 90,2 por cento, especificidade de 84,6 por cento e acurácia de 87,8 por cento. O espessamento ecogênico periportal e a histopatologia isolados ou associados proporcionaram sensibilidade de 93,2 por cento, especificidade de 85,7 por cento e acurácia de 90,3 por cento. CONCLUSÕES: A evidência do espessamento ecogênico periportal na ultra-sonografia é indicação de laparotomia. Se o espessamento ecogênico periportal é negativo, está indicada a biopsia hepática; se a histopatologia revelar sinais de atresia biliar, impõe-se a laparotomia exploradora. Nos casos de espessamento ecogênico periportal negativo com histopatologia de hepatite neonatal ou de outras colestases intra-hepáticas, recomenda-se o acompanhamento ou o tratamento clínico conforme o diagnóstico.

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 percent, specificity of 100 percent and accuracy of 72.5 percent. Histopathology compatible with extrahepatic biliary obstruction alone had 90.2 percent sensitivity, 84.6 percent specificity and 87.8 percent accuracy. The triangular cord sign and histopathology in isolation or combination resulted in sensitivity of 93.2 percent, specificity of 85.7 percent and accuracy of 90.3 percent. 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.