CLINICAL, LABORATORIAL AND EVOLUTIONARY ASPECTS OF PEDIATRIC PATIENTS WITH LIVER DISEASE DUE TO ALPHA 1-ANTITRYPSIN DEFICIENCY.

BACKGROUND: Alpha 1-antitrypsin deficiency (AATD) is a hereditary codominant autosomal disease. This liver disease ranges from asymptomatic cases to terminal illness, which makes early recognition and diagnosis challenging. It is the main cause of pediatric liver transplantation after biliary atresia. OBJECTIVE: To describe the clinical characteristics, as well as those of histologic and laboratory tests, phenotypic and/or genetic evaluation and evolution of a cohort of pediatric patients with AATD. METHODS: This is a retrospective observational study of 39 patients with confirmed or probable AATD (without phenotyping or genotyping, but with suggestive clinical features, low serum alpha 1-antitrypsin (AAT) level and liver biopsy with PAS granules, resistant diastasis). Clinical, laboratory and histological varia-bles, presence of portal hypertension (PH) and survival with native liver have been analyzed. RESULTS: A total of 66.7% of 39 patients were male (26/39). The initial manifestation was cholestatic jaundice in 79.5% (31/39). Liver transplantation was performed in 28.2% (11/39) of patients. Diagnosis occurred at an average of 3.1 years old and liver transplantation at 4.1 years of age. 89.2% (25/28) of the patients with confirmed AATD were PI*ZZ or ZZ. The average AAT value on admission for PI*ZZ or ZZ patients was 41.6 mg/dL. All transplanted patients with phenotyping or genotyping were PI*ZZ (or ZZ). Those who were jaundiced on admission were earlier referred to the specialized service and had higher levels of GGT and platelets on admission. There was no significant difference in the survival curve when comparing cholestatic jaundiced to non-cholestatic jaundiced patients on admission. Comparing patients who did or did not progress to PH, higher levels of AST and APRI score at diagnosis (P=0.011 and P=0.026, respectively) were observed and in the survival curves patients with PH showed impairment, with 20.2% survival with native liver in 15 years. CONCLUSION: Jaundice is an important clinical sign that motivates referral to a specialist, but it does not seem to compromise survival with native liver. Patients progressing to PH had higher AST, APRi score on admission and significantly impaired survival with native liver. It is important to pay attention to these signs in the follow-up of patients with AATD.

Aspectos clínicos, laboratoriais e evolutivos de pacientes pediátricos com doença hepática por deficiência de alfa 1-antitripsina / Clinical, laboratorial and evolutionary aspects of pediatric patients with liver disease due to alpha 1-antitrypsin deficiency

ABSTRACT Background: Alpha 1-antitrypsin deficiency (AATD) is a hereditary codominant autosomal disease. This liver disease ranges from asymptomatic cases to terminal illness, which makes early recognition and diagnosis challenging. It is the main cause of pediatric liver transplantation after biliary atresia. Objective: To describe the clinical characteristics, as well as those of histologic and laboratory tests, phenotypic and/or genetic evaluation and evolution of a cohort of pediatric patients with AATD. Methods: This is a retrospective observational study of 39 patients with confirmed or probable AATD (without phenotyping or genotyping, but with suggestive clinical features, low serum alpha 1-antitrypsin (AAT) level and liver biopsy with PAS granules, resistant diastasis). Clinical, laboratory and histological varia­bles, presence of portal hypertension (PH) and survival with native liver have been analyzed. Results: A total of 66.7% of 39 patients were male (26/39). The initial manifestation was cholestatic jaundice in 79.5% (31/39). Liver transplantation was performed in 28.2% (11/39) of patients. Diagnosis occurred at an average of 3.1 years old and liver transplantation at 4.1 years of age. 89.2% (25/28) of the patients with confirmed AATD were PI*ZZ or ZZ. The average AAT value on admission for PI*ZZ or ZZ patients was 41.6 mg/dL. All transplanted patients with phenotyping or genotyping were PI*ZZ (or ZZ). Those who were jaundiced on admission were earlier referred to the specialized service and had higher levels of GGT and platelets on admission. There was no significant difference in the survival curve when comparing cholestatic jaundiced to non-cholestatic jaundiced patients on admission. Comparing patients who did or did not progress to PH, higher levels of AST and APRI score at diagnosis (P=0.011 and P=0.026, respectively) were observed and in the survival curves patients with PH showed impairment, with 20.2% survival with native liver in 15 years. Conclusion: Jaundice is an important clinical sign that motivates referral to a specialist, but it does not seem to compromise survival with native liver. Patients progressing to PH had higher AST, APRi score on admission and significantly impaired survival with native liver. It is important to pay attention to these signs in the follow-up of patients with AATD.

RESUMO Contexto: Deficiência de alfa 1-antitripsina (DAAT) é uma doença hereditária, de caráter autossômico codominante. A apresentação da doença hepática varia desde casos assintomáticos até doença terminal, o que dificulta reconhecimento e diagnóstico precoces. É a principal causa de transplante hepático pediátrico após atresia de vias biliares. Objetivo: Descrever as características clínicas, de exames laboratoriais, histológicos, avaliação fenotípica e/ou genética e sobrevida de uma coorte de pacientes pediátricos com DAAT. Métodos: Estudo observacional retrospectivo de 39 pacientes com diagnóstico de DAAT confirmada ou provável (sem fenotipagem ou genotipagem, mas com clínica sugestiva, baixo nível sérico de alfa 1-antitripsina (A1AT) e biópsia hepática com grânulos PAS, diástase resistentes). Variáveis clínicas, laboratoriais, histológicas, presença de hipertensão portal (HP) e sobrevida com fígado nativo foram analisadas. Resultados: Dos 39 pacientes, 66,7% eram do sexo masculino (26/39). A manifestação inicial foi icterícia colestática em 79,5% (31/39). Em 28,2% (11/39) houve necessidade de transplante hepático. O diagnóstico ocorreu com uma idade média de 3,1 anos e, o transplante hepático, 4,1 anos. Dos pacientes com DAAT confirmada, 89,2% (25/28) eram PI*ZZ ou ZZ. O valor médio de A1AT na admissão de pacientes PI*ZZ ou ZZ foi 41,6 mg/dL. Todos os transplantados com fenotipagem ou genotipagem eram PI*ZZ (ou ZZ). Os ictéricos à admissão foram referenciados mais cedo ao serviço especializado e apresentaram níveis mais elevados de GGT e plaquetas à admissão. Não houve diferença significativa na curva de sobrevida ao compararmos icterícia colestática ou não à admissão. Ao comparar os pacientes que progrediram ou não para HP, observou-se níveis mais elevados de AST e APRI escore ao diagnóstico (P=0,011 e P=0,026, respectivamente) e, nas curvas de sobrevida, pacientes com HP apresentaram comprometimento, com 20,2% de sobrevida com fígado nativo em 15 anos. Conclusão: Icterícia é um sinal clínico importante que motiva o encaminhamento ao especialista, mas parece não comprometer a sobrevida com fígado nativo. Pacientes com evolução para HP tiveram AST e escore APRi mais elevados à admissão e comprometimento significativo da sobrevida com fígado nativo. Importante atentar a esses sinais no seguimento de pacientes com DAAT.

PREDICTIVE FACTORS OF MORBIDITY ASSOCIATED WITH ESOPHAGEAL VARICEAL BLEEDING IN CHILDREN WITH PORTAL HYPERTENSION.

•Most data on the natural history of portal hypertension come from studies in adults. •The morbidity rate of upper gastrointestinal bleeding in children with portal hypertension tend to be underestimated. •This study showed the relevance of morbidity rates after variceal hemorrhage in pediatric patients, especially those with cirrhosis. •Patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications secondary to upper gastrointestinal bleeding and should be closely monitored. Background - Most data on the natural history of portal hypertension come from studies in adults. The morbidity rate of upper gastrointestinal bleeding (UGIB) in children with portal hypertension has not been systematically characterized. Objective - To describe the morbidity and mortality of UGIB in pediatric patients with portal hypertension and identify predictive factors for the occurrence of its main complications. Methods - This retrospective study included pediatric patients with cirrhotic portal hypertension or with extrahepatic portal vein obstruction (EHPVO). Mortality and UGIB complications within a period of up to 6 weeks of the bleeding were investigated. To determine the predictive factors of morbidity, a multivariate analysis was performed using logistic regression; all results were considered significant at P<0.05. Results - A total of 86 patients (51.2% with EHPVO and 48.8% with cirrhosis) had 174 bleeding events. Ascites was the most common complication (43.1% of all cases), being more prevalent in patients with cirrhosis (P<0.001). Cirrhosis was a predictor of the occurrence of any morbidity (OR 20.3). The need for blood transfusion was predictor of at least one complication (OR 5.8), ascites (OR 7.2) and infections (OR 3.8) in the general group and at least one complication (OR 11.3) and ascites (OR 5.8) in cirrhotic patients. The need for expansion was a predictor of any morbidity (OR 4.6) and infections (OR 3.9) in the general group, in addition to being predictor of infection in cirrhotic patients (OR 5.4). There were no deaths from UGIB in the six weeks post-bleeding. Conclusion - The study showed the relevance of morbidity after UGIB in pediatric patients with portal hypertension, especially in those with cirrhosis. The patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications related to upper gastrointestinal bleeding and should be closely monitored.

Fatores preditivos de morbidade associada à sangramento de varizes esofágicas em crianças com hipertensão porta / Predictive factors of morbidity associated with esophageal variceal bleeding in children with portal hypertension

ABSTRACT Background: Most data on the natural history of portal hypertension come from studies in adults. The morbidity rate of upper gastrointestinal bleeding (UGIB) in children with portal hypertension has not been systematically characterized. Objective: To describe the morbidity and mortality of UGIB in pediatric patients with portal hypertension and identify predictive factors for the occurrence of its main complications. Methods: This retrospective study included pediatric patients with cirrhotic portal hypertension or with extrahepatic portal vein obstruction (EHPVO). Mortality and UGIB complications within a period of up to 6 weeks of the bleeding were investigated. To determine the predictive factors of morbidity, a multivariate analysis was performed using logistic regression; all results were considered significant at P<0.05. Results: A total of 86 patients (51.2% with EHPVO and 48.8% with cirrhosis) had 174 bleeding events. Ascites was the most common complication (43.1% of all cases), being more prevalent in patients with cirrhosis (P<0.001). Cirrhosis was a predictor of the occurrence of any morbidity (OR 20.3). The need for blood transfusion was predictor of at least one complication (OR 5.8), ascites (OR 7.2) and infections (OR 3.8) in the general group and at least one complication (OR 11.3) and ascites (OR 5.8) in cirrhotic patients. The need for expansion was a predictor of any morbidity (OR 4.6) and infections (OR 3.9) in the general group, in addition to being predictor of infection in cirrhotic patients (OR 5.4). There were no deaths from UGIB in the six weeks post-bleeding. Conclusion: The study showed the relevance of morbidity after UGIB in pediatric patients with portal hypertension, especially in those with cirrhosis. The patients with hemodynamic instability requiring blood transfusion or expansion on admission are at increased risk of complications related to upper gastrointestinal bleeding and should be closely monitored.

RESUMO Contexto: A maioria dos dados sobre a história natural da hipertensão porta provém de estudos em adultos. A morbidade associada à hemorragia digestiva alta (HDA) em crianças com hipertensão porta ainda não foi sistematicamente estudada. Objetivo: Descrever a morbimortalidade da HDA em pacientes pediátricos com hipertensão porta e identificar fatores preditivos para a ocorrência de suas principais complicações. Métodos: Este estudo retrospectivo incluiu pacientes pediátricos com hipertensão porta cirrótica ou com obstrução extra-hepática da veia porta (OEHVP). A mortalidade e as complicações da HDA foram estudadas até seis semanas após o sangramento. Para determinar os fatores preditivos de morbidade, foi realizada análise multivariada por meio de regressão logística; todos os resultados foram considerados significativos com P<0,05. Resultados: Oitenta e seis pacientes (51,2% com OEHVP e 48,8% com cirrose) tiveram 174 eventos hemorrágicos. A ascite foi a complicação mais comum (43,1% de todos os casos), sendo mais prevalente em pacientes com cirrose (P<0,001). A cirrose foi preditor da ocorrência de pelo menos uma complicação (OR 20,3). A necessidade de transfusão sanguínea foi preditora de pelo menos uma complicação (OR 5,8), ascite (OR 7,2) e infecções (OR 3,8) no grupo geral e pelo menos uma complicação (OR 11,3) e ascite (OR 5,8) nos cirróticos. A necessidade de expansão foi preditor de qualquer morbidade (OR 4,6) e infecções (OR 3,9) no grupo geral, além de ser preditor de infecção em cirróticos (OR 5,4). Não houve óbitos por HDA nas 6 semanas pós-sangramento. Conclusão: O estudo mostrou a relevância da morbidade após HDA em pacientes pediátricos com hipertensão porta, principalmente naqueles com cirrose. Os pacientes com instabilidade hemodinâmica que necessitam de transfusão de sangue ou expansão na admissão têm risco aumentado de complicações relacionadas à hemorragia digestiva alta e devem ser monitorados de perto.

Abnormalities of Cardiac Situs and Heart Disease Diagnosed by Echocardiography in Patients with Biliary Atresia

Abstract Background: Left isomerism (LI) is a common finding in patients with biliary atresia (BA), and it can be identified by echocardiography. Several comorbidities may be present in patients with LI, including heart disease. Objective: To investigate the prevalence of LI and heart disease in children (< 18 years of age) with BA followed-up at Hospital das Clínicas, UFMG. Methods: This is a cross-sectional study involving patients diagnosed with BA between February 2016 and April 2020 who underwent transthoracic echocardiography and, in case of situs abnormalities, also electrocardiography. Results: Our study recruited 58 patients (mean age: 3.08 years; female/male ratio: 1.5:1). The general prevalence of situs abnormalities was 8.6% (5/58) and the most common one was LI (4/5 or 80%). One patient had situs inversus. Among patients with situs abnormalities, the general prevalence of heart disease was 80% (4/5), apart from anomalies of the inferior vena cava), with pulmonary valve stenosis (PVS) as the only change seen (75% of mild forms and 25% of moderate forms). Among patients with situs abnormalities, the prevalence of rhythm changes was 80% (4/5), and low atrial rhythm was the most common finding (3/4 or 75%). Conclusion: The prevalence of situs abnormalities in our sample was similar to that described in the literature. We observed an exclusive prevalence of PVS and a high prevalence of rhythm changes among patients with LI. Although the diagnosis of isomerism does not initially add much cardiovascular risk to the sample, possible late deterioration should be considered.

Mild Phenotype of Arthrogryposis, Renal Dysfunction, and Cholestasis Syndrome 1 Caused by a Novel VPS33B Variant.

The arthrogryposis, renal dysfunction, and cholestasis syndrome (ARCS) is an autosomal recessive multisystem disease caused by variants in VPS33B or VIPAS39. The classical presentation includes congenital joint contractures, renal tubular dysfunction, cholestasis, and early death. Additional features include ichthyosis, central nervous system malformations, platelet dysfunction, and severe failure to thrive. We studied three patients with cholestasis, increased aminotransferases, normal gamma-glutamyl transferase, and developmental and language delay. Whole exome sequencing analysis identified VPS33B variants in all patients: patients 1 and 2 presented a novel homozygous variant at position c.1148T>A. p.(Ile383Asn), and patient 3 was compound heterozygous for the same c.1148T>A. variant, in addition to the c.940-2A>G. variant. ARCS is compatible with the symptomatology presented by the studied patients. However, most patients that have been described in the literature with ARCS had severe failure to thrive and died in the first 6 months of life. The three patients studied here have a mild ARCS phenotype with prolonged survival. Consequently, we believe that the molecular analysis of the VPS33B and VIPAS39 should be considered in patients with normal gamma-glutamyl transferase cholestasis.

PERCUTANEOUS ENDOSCOPIC GASTROSTOMY IN CHILDREN AND ADOLESCENTS: 15-YEARS' EXPERIENCE OF A TERTIARY CENTER.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is an important option for enteral nutrition for both children and adults. It is considered a safe, effective, and advantageous technique in comparison to other complementary feeding routes. It allows continuous feeding, the feeding of patients with swallowing disorders due to neurological causes or others, and the administration of non-palatable diets or medications, all with low rates of complications and mortality. OBJECTIVE: This study aimed to evaluate the main indications and complications of PEG in pediatric patients. In addition, the impact on the nutritional status of patients undergoing PEG was also compared with weight, body mass index (BMI), and height according to references from the World Health Organization. METHODS: This observational and retrospective study included 152 children and adolescents who underwent PEG between January/2003 and December/2018. Patients up to 18 years of age at the time of the procedure were included. Complications related to the procedure were classified as minor or major. Patients with PEG indication for nutritional supplementation were evaluated for weight gain, height, and BMI, using the Z score at the day of the procedure and six months, 1 year, and 2 years after the procedure. RESULTS: Indications for PEG were: swallowing disorder of neurological cause (67.1%), need for nutritional supplementation (25%), swallowing disorder of mechanical origin (6.6%), and indication of gastric decompression (1.3%). Minor complications occurred in 57.8% of patients and major complications in 9.8% of patients. The traction technique corresponded to 92.1% and puncture to 7.9%. The death rate was 1.3%. Thirty-eight patients had an indication for nutritional supplementation. In these patients, there was a gradual increase in both BMI and weight, reaching statistically significant differences (P=0.0340 and P= 0.0105, respectively). These differences were more evident in chronic renal disease patients. Height did not vary significantly (P=0.543). CONCLUSION: PEG proved to be an advantageous option as an auxiliary feeding method in pediatric patients. Dysphagia of neurological origin was the main indication followed by the need for nutritional supplementation. PEG has low frequency of major complications and mortality. This study also showed the importance of PEG in patients who need nutritional supplementation, as it enabled patients to move from undernutrition to normal weight ranges.

Gastrostomia endoscópica percutânea em crianças e adolescentes: 15 anos de experiência em um hospital terciário / Percutaneous endoscopic gastrostomy in children and adolescents: 15-years' experience of a tertiary center

ABSTRACT BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) is an important option for enteral nutrition for both children and adults. It is considered a safe, effective, and advantageous technique in comparison to other complementary feeding routes. It allows continuous feeding, the feeding of patients with swallowing disorders due to neurological causes or others, and the administration of non-palatable diets or medications, all with low rates of complications and mortality. OBJECTIVE: This study aimed to evaluate the main indications and complications of PEG in pediatric patients. In addition, the impact on the nutritional status of patients undergoing PEG was also compared with weight, body mass index (BMI), and height according to references from the World Health Organization. METHODS: This observational and retrospective study included 152 children and adolescents who underwent PEG between January/2003 and December/2018. Patients up to 18 years of age at the time of the procedure were included. Complications related to the procedure were classified as minor or major. Patients with PEG indication for nutritional supplementation were evaluated for weight gain, height, and BMI, using the Z score at the day of the procedure and six months, 1 year, and 2 years after the procedure. RESULTS: Indications for PEG were: swallowing disorder of neurological cause (67.1%), need for nutritional supplementation (25%), swallowing disorder of mechanical origin (6.6%), and indication of gastric decompression (1.3%). Minor complications occurred in 57.8% of patients and major complications in 9.8% of patients. The traction technique corresponded to 92.1% and puncture to 7.9%. The death rate was 1.3%. Thirty-eight patients had an indication for nutritional supplementation. In these patients, there was a gradual increase in both BMI and weight, reaching statistically significant differences (P=0.0340 and P= 0.0105, respectively). These differences were more evident in chronic renal disease patients. Height did not vary significantly (P=0.543). CONCLUSION: PEG proved to be an advantageous option as an auxiliary feeding method in pediatric patients. Dysphagia of neurological origin was the main indication followed by the need for nutritional supplementation. PEG has low frequency of major complications and mortality. This study also showed the importance of PEG in patients who need nutritional supplementation, as it enabled patients to move from undernutrition to normal weight ranges.

RESUMO CONTEXTO: A gastrostomia endoscópica percutânea (GEP) é uma importante opção de nutrição enteral para crianças e adultos, sendo considerada uma técnica segura, eficaz e vantajosa em comparação às outras vias de alimentação complementar. Permite a alimentação contínua, a alimentação em pacientes com distúrbios de deglutição de causa neurológica ou outros, a administração de dietas ou medicamentos não palatáveis, todos com baixos índices de complicações e mortalidade. OBJETIVO: Avaliar as principais indicações e complicações de pacientes pediátricos submetidos à GEP e o impacto no estado nutricional de pacientes submetidos à GEP para suplementação nutricional, comparando peso, índice de massa corporal (IMC) e estatura com referências da Organização Mundial de Saúde. MÉTODOS: Estudo observacional e retrospectivo de 152 crianças e adolescentes submetidos à GEP, no período de janeiro/2003 a dezembro/2018. Foram incluídos pacientes até 18 anos de idade na época do procedimento. As complicações relacionadas ao procedimento foram divididas em menores e maiores. Pacientes com indicação de GEP para suplementação nutricional foram avaliados quanto ao ganho de peso, altura e IMC, por meio do escore Z no dia do procedimento e 6 meses; 1 ano; e 2 anos após o procedimento. RESULTADOS: As indicações para GEP foram distúrbio de deglutição de causa neurológica (67,1%), necessidade de suplementação nutricional (25%), distúrbio de deglutição de origem mecânica (6,6%), e indicação de descompressão gástrica (1,3%). Complicações menores ocorreram em 57,8% dos pacientes e complicações maiores em 9,8%. A técnica de tração correspondeu a 92,1% e a punção, 7,9%. A taxa de mortalidade foi de 1,3%. Trinta e oito pacientes tinham indicação de suplementação nutricional. Nestes, houve aumento gradativo tanto do IMC quanto do peso, com variação estatisticamente significativa da mediana P=0,0340 e P=0,0105, respectivamente, mais evidente nos pacientes renais crônicos. A altura não variou significativamente (P=0,543). CONCLUSÃO: A GEP mostrou-se uma opção vantajosa como forma auxiliar de alimentação em pacientes pediátricos, tendo como principais indicações a disfagia de causa neurológica e a necessidade de suplementação nutricional, com baixa prevalência de complicações maiores e mortalidade. Este estudo também mostrou a importância da GEP em pacientes com necessidade de suplementação nutricional, possibilitando a passagem dos pacientes desnutridos para escores nutricionais de peso adequados à idade.

Non-invasive Predictors of Esophageal Varices With a High Risk of Bleeding in Pediatric Cirrhotic Patients.

OBJECTIVES: To evaluate non-invasive predictive factors of varices with a high risk of bleeding in pediatric cirrhotic patients. METHODS: This retrospective, cross-sectional study included data from 158 children with cirrhosis, median age of 5.38 years (interquartile [IQ] 2.08-11.52 years), and no history of upper gastrointestinal bleeding. Patients underwent an endoscopy to screen for esophageal varices. Varices with a high risk of bleeding were defined as those with a medium to large caliber, presence of red spots, or the presence of gastric varices and identified as high-risk varices (HRV). Laboratory and clinical factors were evaluated as possible predictors of HRV. RESULTS: HRV were detected in 30 children (19%) after the first endoscopy. In the multivariate analysis, only the risk score (RS), as described by Park et al, and the aspartate aminotransferase-to-platelet ratio index (APRi) were predictive of HRV. The best non-invasive predictor of HRV was the RS with an area under the receiver operating characteristic curve of 0.764. When used a cut-off point of -1.2, the sensitivity of the RS was 90% and specificity was 53%. The use of RS or APRi correctly identified 96% of children with HRV. CONCLUSIONS: The described predictors allow the correct identification of patients with HRV. The association of RS >-1.2 or APRi >1.4 has a good sensitivity to identify HRV and to prevent unnecessary endoscopy in about one-third of children with no HRV.

Evaluation of the prevalence and factors associated with acute kidney injury in a pediatric intensive care unit.

OBJECTIVE: To assess the prevalence of acute kidney injury in pediatric intensive care unit according to diagnostic criteria - pediatric risk, injury, failure, loss, end-stage renal disease, Acute Kidney Injury Network and Acute Kidney Injury Work Group, or Kidney Disease: Improving Global Outcomes -, and determining factors associated with acute kidney injury as well as its outcome. METHODOLOGY: This was a cross-sectional monocentric observational study, including patients aged between 29 days and 17 years who were admitted to the pediatric intensive care unit between January 1, 2012 and December 31, 2016. To evaluate the association between the study variables and acute kidney injury, the log-binomial generalized univariate and multivariate linear models were adjusted. RESULTS: The study included 1131 patients, with prevalence of acute kidney injury according to the Acute Kidney Injury Network and Kidney Disease: Improving Global Outcomes criteria of 12.6% and of 12.9% according to the pediatric risk, injury, failure, loss, end-stage renal disease. In the multivariate analysis of older children (PR 1.007, 95% CI: 1.005-1.009), sepsis (PR 1.641, 95% CI: 1.128-2.387), demand for ventilatory support (PR 1.547, 95% CI: 1.095-2.186), and use of vasoactive amines (PR 2.298, 95% CI: 1.681-3.142) constituted factors associated with statistical significance to the development of acute kidney injury. The mortality rate among those with acute kidney injury was 28.7%. CONCLUSION: Older children, diagnosis of sepsis, demand for ventilatory support, and use of vasoactive amines were correlated with a higher risk of developing acute kidney injury. The mortality associated with acute kidney injury was elevated; it is crucial that all measures that ensure adequate renal perfusion are taken for patients with risk factors, to avoid the installation of the disease.

ADVERSE EVENTS RELATED TO MECHANICAL VENTILATION IN A PEDIATRIC INTENSIVE CARE UNIT.

OBJECTIVE: To identify the prevalence and factors associated with adverse events (AE) related to invasive mechanical ventilation in patients admitted to the Pediatric Intensive Care Unit (PICU) of a tertiary public hospital. METHODS: This is a cross-sectional study from July 2016 to June 2018, with data collected throughout patients' routine care in the unit by the care team. Demographic, clinical and ventilatory characteristics and adverse events were analysed. The logistic regression model was used for multivariate analysis regarding the factors associated with AE. RESULTS: Three hundred and six patients were included, with a total ventilation time of 2,155 days. Adverse events occurred in 66 patients (21.6%), and in 11 of those (16.7%) two AE occurred, totalling 77 events (36 AE per 1000 days of ventilation). The most common AE was post-extubation stridor (25.9%), followed by unplanned extubation (16.9%). Episodes occurred predominantly in the afternoon shift (49.3%) and associated with mild damage (54.6%). Multivariate analysis showed a higher occurrence of AE associated with length of stay of 7 days or more (Odds Ratio [OR]=2.6; 95% confidence interval [95%CI] 1.49-4.66; p=0.001). CONCLUSIONS: The results of the present study show a significant number of preventable adverse events, especially stridor after extubation and accidental extubation. The higher frequency of these events is associated with longer hospitalization.

Adverse events related to mechanical ventilation in a pediatric intensive care unit / Eventos adversos relacionados à ventilação mecânica em uma unidade de terapia intensiva pediátrica

ABSTRACT Objective: To identify the prevalence and factors associated with adverse events (AE) related to invasive mechanical ventilation in patients admitted to the Pediatric Intensive Care Unit (PICU) of a tertiary public hospital. Methods: This is a cross-sectional study from July 2016 to June 2018, with data collected throughout patients' routine care in the unit by the care team. Demographic, clinical and ventilatory characteristics and adverse events were analysed. The logistic regression model was used for multivariate analysis regarding the factors associated with AE. Results: Three hundred and six patients were included, with a total ventilation time of 2,155 days. Adverse events occurred in 66 patients (21.6%), and in 11 of those (16.7%) two AE occurred, totalling 77 events (36 AE per 1000 days of ventilation). The most common AE was post-extubation stridor (25.9%), followed by unplanned extubation (16.9%). Episodes occurred predominantly in the afternoon shift (49.3%) and associated with mild damage (54.6%). Multivariate analysis showed a higher occurrence of AE associated with length of stay of 7 days or more (Odds Ratio [OR]=2.6; 95% confidence interval [95%CI] 1.49-4.66; p=0.001). Conclusions: The results of the present study show a significant number of preventable adverse events, especially stridor after extubation and accidental extubation. The higher frequency of these events is associated with longer hospitalization.

RESUMO Objetivo: Identificar a prevalência e os fatores associados a eventos adversos (EA) relacionados à ventilação mecânica (VM) invasiva em pacientes internados na Unidade de Terapia Intensiva Pediátrica (UTIP) de hospital público terciário. Métodos: Trata-se de estudo transversal realizado entre julho de 2016 e junho de 2018, com dados coletados ao longo da rotina de atendimento dos pacientes na unidade pela equipe assistencial. Neste estudo, foram analisados características demográficas, clínicas, ventilatórias e os EA ocorridos. O modelo de regressão logística foi utilizado para análise multivariada quanto aos fatores associados aos EA. Resultados: Neste estudo, foram incluídos 306 pacientes, com tempo de ventilação total de 2.155 dias. Ocorreram EA em 66 pacientes (21,6%), dos quais 11 (16,7%) sofreram dois EA, totalizando 77 eventos (36 EA por mil dias de ventilação). O EA mais comum foi o estridor pós-extubação (25,9%), seguido da extubação não planejada (16,9%). Os episódios ocorreram predominantemente no turno da tarde (49,3%) e associados a grau de dano leve (54,6%). Na análise multivariada, observou-se maior ocorrência de EA associado a tempo de internação igual ou superior a sete dias (Odds Ratio [OR]=2,6, intervalo de confiança de 95% [IC95%)]1,49-4,66, p=0,001). Conclusões: Evidenciou-se número significativo de EA que podem ser prevenidos, destacando-se o estridor pós-extubação e a extubação acidental, com ocorrência mais frequentemente associada ao maior tempo de internação.

EVENTS ASSOCIATED WITH THE OCCURRENCE OF INTRACRANIAL HYPERTENSION IN PEDIATRIC PATIENTS WITH SEVERE CRANIOENCEPHALIC TRAUMA AND MONITORING OF INTRACRANIAL PRESSURE.

OBJECTIVE: To determine the events associated with the occurrence of intracranial hypertension (ICH) in pediatric patients with severe cranioencephalic trauma. METHODS: This was a prospective cohort study of patients 18 years old and younger with cranioencephalic trauma, scores below nine on the Glasgow Coma Scale, and intracranial pressure monitoring. They were admitted between September, 2005 and March, 2014 into a Pediatric Intensive Care Unit. ICH was defined as an episode of intracranial pressure above 20 mmHg for more than five minutes that needed treatment. RESULTS: A total of 198 children and adolescents were included in the study, of which 70.2% were males and there was a median age of nine years old. ICH occurred in 135 (68.2%) patients and maximum intracranial pressure was 36.3 mmHg, with a median of 34 mmHg. A total of 133 (97.8%) patients with ICH received sedation and analgesia for treatment of the condition, 108 (79.4%) received neuromuscular blockers, 7 (5.2%) had cerebrospinal fluid drainage, 105 (77.2%) received mannitol, 96 (70.6%) received hyperventilation, 64 (47.1%) received 3% saline solution, 20 (14.7%) received barbiturates, and 43 (31.9%) underwent a decompressive craniectomy. The events associated with the occurrence of ICH were tomographic findings at the time of admission of diffuse or hemispheric swelling (edema plus engorgement). The odds ratio for ICH in patients with Marshall III (diffuse swelling) tomography was 14 (95%CI 2.8-113; p<0.003), and for those with Marshall IV (hemispherical swelling) was 24.9 (95%CI 2.4-676, p<0.018). Mortality was 22.2%. CONCLUSIONS: Pediatric patients with severe cranioencephalic trauma and tomographic alterations of Marshall III and IV presented a high chance of developing ICH.

Endoscopic prophylaxis and factors associated with bleeding in children with extrahepatic portal vein obstruction.

OBJECTIVES: This study aimed to evaluate factors associated with upper digestive hemorrhage and primary and secondary endoscopic prophylaxis outcomes in children with extrahepatic portal vein obstruction. METHODS: This observational and prospective study included 72 children with extrahepatic portal vein obstruction who were followed from 2005 to 2017. Risk factors associated with upper digestive hemorrhage and the results of primary and secondary prophylaxis of these patients were evaluated. RESULTS: Fifty patients (69.4%) had one or more episodes of bleeding during follow-up, with a median age at first hemorrhage of 4.81 years. The multivariate analysis showed that medium- to large-caliber esophageal varices were associated with an 18-fold risk of upper digestive hemorrhage (95% CI: 4.33-74.76; p < 0.0001). Primary prophylaxis was administered to 14 patients, with eradication in 85.7%; however, 14.3% of these patients had hemorrhages during the follow-up period and 41.7% had a relapse of varices. Secondary prophylaxis was administered to 41 patients. Esophageal varices were eradicated in 90.2% of patients. There were relapse and re-bleeding of esophageal varices in 45.9% and 34.1% of the children, respectively. CONCLUSION: Primary and secondary endoscopic prophylaxes showed high rates of esophageal varix eradication, but with significant relapses. Eradication of esophageal varices cannot definitively prevent recurrent upper digestive hemorrhage, since bleeding from alternate sites can occur. Medium- and large-caliber esophageal varices were associated with upper digestive hemorrhage in patients with extrahepatic portal vein obstruction. To the best of the authors' knowledge, this study is the first to evaluate bleeding risk factors in children with extrahepatic portal vein obstruction.

Events associated with the occurrence of intracranial hypertension in pediatric patients with severe cranioencephalic trauma and monitoring of intracranial pressure / Eventos associados à ocorrência de hipertensão intracraniana em pacientes pediátricos com traumatismo cranioencefálico grave e monitoração da pressão intracraniana

ABSTRACT Objective: To determine the events associated with the occurrence of intracranial hypertension (ICH) in pediatric patients with severe cranioencephalic trauma. Methods: This was a prospective cohort study of patients 18 years old and younger with cranioencephalic trauma, scores below nine on the Glasgow Coma Scale, and intracranial pressure monitoring. They were admitted between September, 2005 and March, 2014 into a Pediatric Intensive Care Unit. ICH was defined as an episode of intracranial pressure above 20 mmHg for more than five minutes that needed treatment. Results: A total of 198 children and adolescents were included in the study, of which 70.2% were males and there was a median age of nine years old. ICH occurred in 135 (68.2%) patients and maximum intracranial pressure was 36.3 mmHg, with a median of 34 mmHg. A total of 133 (97.8%) patients with ICH received sedation and analgesia for treatment of the condition, 108 (79.4%) received neuromuscular blockers, 7 (5.2%) had cerebrospinal fluid drainage, 105 (77.2%) received mannitol, 96 (70.6%) received hyperventilation, 64 (47.1%) received 3% saline solution, 20 (14.7%) received barbiturates, and 43 (31.9%) underwent a decompressive craniectomy. The events associated with the occurrence of ICH were tomographic findings at the time of admission of diffuse or hemispheric swelling (edema plus engorgement). The odds ratio for ICH in patients with Marshall III (diffuse swelling) tomography was 14 (95%CI 2.8-113; p<0.003), and for those with Marshall IV (hemispherical swelling) was 24.9 (95%CI 2.4-676, p<0.018). Mortality was 22.2%. Conclusions: Pediatric patients with severe cranioencephalic trauma and tomographic alterations of Marshall III and IV presented a high chance of developing ICH.

RESUMO Objetivo: Determinar eventos associados à ocorrência de hipertensão intracraniana (HIC) em pacientes pediátricos com traumatismo cranioencefálico grave. Métodos: Trata-se de coorte prospectiva de pacientes de até 18 anos, com traumatismo cranioencefálico, pontuação abaixo de nove na Escala de Coma de Glasgow e monitoração da pressão intracraniana, admitidos entre setembro de 2005 e março de 2014 em unidade de terapia intensiva pediátrica. A HIC foi definida como episódio de pressão intracraniana acima de 20 mmHg por mais de cinco minutos e com necessidade de tratamento. Resultados: Incluídas 198 crianças e adolescentes, 70,2% masculinos, mediana de idade de nove anos. A HIC ocorreu em 135 (68,2%) pacientes; valor máximo de pressão intracraniana de 36,3; mediana 34 mmHg. Receberam sedação e analgesia para tratamento da HIC 133 (97,8%) pacientes, 108 (79,4%) receberam bloqueadores neuromusculares, 7 (5,2%) drenagem de líquor, 105 (77,2%) manitol, 96 (70,6%) hiperventilação, 64 (47,1%) solução salina a 3%, 20 (14,7%) barbitúricos e 43 (31,9%) foram submetidos à craniectomia descompressiva. Os eventos associados à ocorrência de HIC foram os achados tomográficos à admissão de swelling (edema mais ingurgitamento) difuso ou hemisférico. A razão de chance para que pacientes com classificação tomográfica Marshall III (swelling difuso) apresentassem HIC foi 14 (IC95% 2,8-113; p<0,003) e para aqueles com Marshall IV (hemisférico) foi 24,9 (IC95% 2,4-676; p<0,018). A mortalidade foi de 22,2%. Conclusões: Pacientes pediátricos com traumatismo cranioencefálico grave e alterações tomográficas tipo Marshall III e IV apresentaram grande chance de desenvolver HIC.

Colelitíase na infância e adolescência: abordagem diagnóstica e tratamento / Cholelithiasis in childhood and adolescence: diagnostic approach and treatment

Com exceção dos casos decorrentes de doença hemolítica crônica, a colelitíase biliar é pouco comum na infância e adolescência quando comparada aos adultos. No entanto, nas últimas décadas observou-se importante aumento da incidência da doença na pediatria, principalmente em adolescentes do sexo feminino. Os fatores de risco associados à colelitíase têm se assemelhado àqueles encontrados nos adultos e o cálculo de colesterol é o principal responsável pelo aumento da prevalência. Acredita-se que a maioria dos pacientes pediátricos com colelitíase biliar apresente sintomas inespecíficos; a cólica biliar típica é encontrada mais frequentemente em crianças mais velhas. O tratamento padrão para a colelitíase sintomática é o tratamento cirúrgico com retirada da vesícula biliar, sendo a colecistectomia videolaparoscópica preferível à cirurgia aberta devido ao menor tempo de recuperação e de internação hospitalar. Contudo, na colelitíase assintomática o tratamento deve ser individualizado, sendo indicada a cirurgia em casos selecionados. O objetivo desta revisão é apresentar os principais aspectos da doença calculosa biliar na infância e contribuir para maior suspeição clínica da doença entre os pediatras, aprimorando a abordagem diagnóstica e a definição terapêutica adequada.

Excluding the cases resulting from chronic hemolytic disease, cholelithiasis is uncommon in childhood and adolescence when compared to adults. However, in recent decades there has been noted an increased incidence of the disease in pediatrics, especially in female adolescents. The risk factors associated with cholelithiasis have been similar to those found in adults and cholesterol stones are the main responsible for the increase of the prevalence. The majority of pediatric patients with cholelithiasis have no specific symptoms; typical biliary colic is found more often among older children. The standard treatment for symptomatic cholelithiasis is surgery to remove the gallbladder; the laparoscopic cholecystectomy is preferable to open surgery because of the shorter recovery time and hospital stay. However, in asymptomatic cholelithiasis treatment must be individualized and surgery is indicated in selected cases. The aim of this review is to present the main aspects of gallstone disease in childhood and contribute to greater clinical suspicion of the disease among pediatricians, improving the diagnostic approach and the appropriate therapeutic definition.

Doença Hepática Gordurosa Não Alcoólica em crianças e adolescentes / Non-alcoholic fatty liver disease in childhood and adolescence

A obesidade infantil é uma epidemia mundial. São várias as comorbidades associadas à obesidade, destacando-se a doença hepática gordurosa não alcoólica (DHGNA), um termo abrangente que envolve desde a esteatose hepatocelular simples até quadros mais avançados de esteato-hepatite, fibrose e cirrose hepática. Atualmente, é a segunda maior causa de transplante hepático em adultos nos Estados Unidos, com potencial de se tornar a primeira nas próximas décadas. Associado a este panorama, ainda existe o desafio do diagnóstico, uma vez que os critérios clínicos e laboratoriais ainda são controversos, especialmente em crianças. A biópsia é o padrão ouro, entretanto é um procedimento invasivo e sujeito a riscos. Por isso, a dosagem de enzimas hepáticas e a ultrassonografia abdominal são utilizadas para triagem e avaliação, apesar de suas limitações. O tratamento de DHGNA deve obrigatoriamente incluir a abordagem da obesidade. Por isso, os pilares do tratamento envolvem a mudança do estilo de vida e dos hábitos alimentares. Embora a eficácia de várias medicações venha sendo estudada, a alimentação saudável e a atividade física permanecem como a mais importante estratégia de prevenção e tratamento da DHGNA na infância e adolescência. A equipe multidisciplinar deve, junto ao paciente e a família, construir uma rotina de hábitos alimentares e atividades físicas adequadas para cada caso. (AU)

Childhood obesity is a worldwide epidemic. There are several comorbidities associated with obesity, including non-alcoholic fatty liver disease (NAFLD), a wide term that ranges from a hepatocellular steatosis to more advanced steatohepatitis, fibrosis and liver cirrhosis. This is the second major cause of liver transplant in adults in the United States, with the potential to become the first one in the next few decades. Associated with this scenario, the challenge of diagnosis still exists, since screening is still controversial, especially in children. Biopsy is the gold standard, but it is an invasive and risky procedure. Therefore liver enzymes and abdominal ultrasound are used for screening and assessment although their limitations. Treatment of NAFLD should involve an approach to obesity with focus in lifestyle intervention and healthy diet. While the efficacy of several medications has been investigated in children, healthy diet and physical activity remain the only prevention and treatment strategies for paediatric NAFLD. A multidisciplinary team should, together with the patient and a family, build a routine of healthy eating and physical activities (AU)

HLA-DRB1 GENE POLYMORPHISMS IN PEDIATRIC PATIENTS WITH TYPE 1 AUTOIMMUNE HEPATITIS AND TYPE 1 AUTOIMMUNE HEPATITIS OVERLAP SYNDROME WITH AUTOIMMUNE CHOLANGITIS.

BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1. OBJECTIVE: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group). METHODS: This is a cross-sectional study of 25 pediatric patients diagnosed with type 1 AIH and 18 with OS. Fifty-seven healthy individuals were included as controls. The polymorphisms of the HLA-DRB1 gene were evaluated by PCR and included HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*13. RESULTS: Our results showed that the presence of the allele HLA-DRB1*13 increased the chance of autoimmune cholangitis (OR=3.96, CI 1.07 to 14.61, P=0.04). The HLA-DRB1*04 and HLA- DRB1*07 have no association with the AIH and autoimmune cholangitis in a young sample. CONCLUSION: This work demonstrates an association of the main polymorphisms in the HLA-DRB1 gene to AIH with or without cholangitis in a Brazilian sample.

Polimorfismos do gene HLA-DRB1 em pacientes pediátricos com hepatite autoimune tipo 1 e hepatite autoimune associada à colangite autoimune / Hla-drb1 gene polymorphisms in pediatric patients with type 1 autoimmune hepatitis and type 1 autoimmune hepatitis overlap syndrome with autoimmune cholangitis

ABSTRACT BACKGROUND: Autoimmune hepatitis (AIH) is a rare chronic inflammatory liver disease associated with a loss of immunological tolerance to self-antigens. Susceptibility to AIH is partially determined by the presence of genes related to human leukocyte antigen (HLA), mainly allelic variants of DRB1. OBJECTIVE: The purpose of this study was to investigate the frequencies of the polymorphisms in HLA-DRB1 gene in children and adolescents with type 1 AIH and type 1 AIH overlap syndrome with autoimmune cholangitis (overlap syndrome, OS) in comparison to healthy sex and age-matched individuals (control group). METHODS: This is a cross-sectional study of 25 pediatric patients diagnosed with type 1 AIH and 18 with OS. Fifty-seven healthy individuals were included as controls. The polymorphisms of the HLA-DRB1 gene were evaluated by PCR and included HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07, and HLA-DRB1*13. RESULTS: Our results showed that the presence of the allele HLA-DRB1*13 increased the chance of autoimmune cholangitis (OR=3.96, CI 1.07 to 14.61, P=0.04). The HLA-DRB1*04 and HLA- DRB1*07 have no association with the AIH and autoimmune cholangitis in a young sample. CONCLUSION: This work demonstrates an association of the main polymorphisms in the HLA-DRB1 gene to AIH with or without cholangitis in a Brazilian sample.

RESUMO CONTEXTO: Hepatite autoimune (HAI) é uma doença hepática inflamatória crônica, rara, associada à perda da tolerância imunológica aos auto-antígenos. A susceptibilidade à HAI é parcialmente determinada pela presença de genes relacionados ao antígeno leucocitário humano (HLA), principalmente variantes alélicas do DRB1. OBJETIVO: O objetivo deste estudo foi investigar a frequência de polimorfismos no gene HLA-DRB1 em crianças e adolescentes com HAI tipo 1 e HAI tipo 1 associada à colangite autoimune, em comparação com indivíduos saudáveis pareados por sexo e idade (grupo controle). MÉTODOS: Este é um estudo transversal de 25 pacientes pediátricos com diagnóstico de HAI tipo 1 e 18 com HAI associada à colangite autoimune. Cinquenta e sete indivíduos saudáveis foram incluídos como controles. Os polimorfismos do gene HLA-DRB1 foram avaliados por PCR e incluíram HLA-DRB1*03, HLA-DRB1*04, HLA-DRB1*07 e HLA-DRB1*13. RESULTADOS: Nossos resultados mostraram que a presença do alelo HLA-DRB1*13 aumentou a chance de colangite autoimune (OR=3,96; IC 1,07 a 14,61; P=0,04). O HLA-DRB1*04 e o HLA-DRB1*07 não apresentam associação com a HAI e colangite autoimune no grupo de pacientes mais jovens. CONCLUSÃO: Este trabalho demonstra uma associação dos principais polimorfismos no gene HLA-DRB1 à HAI com ou sem colangite na população brasileira.