Recanalization of portal vein thrombosis after pediatric liver transplantation: Efficacy and safety of the transsplenic access.

BACKGROUND: Endovascular management of portal vein thrombosis (PVT) is challenging. Transsplenic access (TSA) is growing as an access option to the portal system but with higher rates of bleeding complications. The aim of this article is to evaluate the efficacy and safety of transsplenic portal vein recanalization (PVR) using a metallic stent after pediatric liver transplantation. MATERIALS AND METHODS: This is a retrospective review of 15 patients with chronic PVT who underwent PVR via TSA between February 2016 and December 2020. Two children who had undergone catheterization of a mesenteric vein tributary by minilaparotomy were excluded from the patency analysis but included in the splenic access analysis. The technical and clinical success of PVR and complications related to the procedure via TSA were evaluated. RESULTS: Thirteen children with PVT were treated primarily using the TSA. The mean age was 4.1 years (range, 1.5-13.7 years), and the most common clinical presentation was hypersplenism (60%). Technically successful PVR was performed in 11/13 (84.6%) children, and clinical success was achieved in 9/11 (81.8%) children. No major complications were observed, and one child presented moderate pain in the TSA (from a total of 17 TSA). The median follow-up was 48.2 months. The median primary patency was 9.9 months. Primary patency in the first 4 years was 75%, and primary assisted patency was 100% in the follow-up period. CONCLUSIONS: Transsplenic PVR is a safe and effective method for the treatment of PVT after pediatric liver transplantation.

Hepatic venous reconstruction of the left lateral segment with emphasis on anomalous hepatic vein in pediatric liver transplantation.

Left lateral segment grafts have become a suitable option in pediatric liver transplantation (PLT). The correlation between hepatic vein (HV) reconstruction and outcome is relevant when assessing the safe use of these grafts. We retrospectively reviewed the medical records prospectively collected from a pediatric living donor liver transplantation database and conducted a comparative analysis of the different left lateral segment graft types according to HV reconstruction. Donor, recipient, and intraoperative variables were analyzed. Post-transplant outcomes included vascular complications such as hepatic vein outflow obstruction, early (≤30 d) and late (>30 d) PVT, hepatic artery thrombosis, and graft survival. From February 2017 to August 2021, 303 PLTs were performed. According to venous anatomy, the distribution of the left lateral segment was as follows: single HV (type I) in 174 (57.4%), close HVs, simple venoplasty for reconstruction (type II) in 97 (32.01%), anomalous hepatic vein (AHV) with a distance between the HVs orifices that allowed simple venoplasty (type IIIA) in 25 (8.26%) and AHV with a distance between the HVs orifices requiring homologous venous graft interposition (type IIIB) in 07 (2.31%) grafts. Type IIIB grafts came from male donors ( p =0.04) and had a higher mean donor height ( p =0.008), a higher mean graft weight, and a higher graft-to-recipient weight ratio, both p =0.002. The median follow-up time was 41.4 months. The overall cumulative graft survival was 96.3%, and comparative graft survival showed no difference (log-rank p =0.61). No hepatic vein outflow obstructions were observed in this cohort study. There was no statistically significant difference in the post-transplant outcomes between the graft types. The venous reconstruction of the AHV with homologous venous graft interposition had similar outcomes in the short and long term.

Mudanças Organizacionais decorrentes de uma ação educacional ofertada a distância para professores / Organizational changes resulting from an educational action offered at distance to teachers / Cambios organizativos resultantes de acción educativa oferecida a distancia a los maestros

Alterações nas organizações decorrentes, exclusivamente, da participação dos funcionários em ações educacionais configuram Mudança Organizacional. Esta pesquisa objetivou identificar mudanças organizacionais ocorridas devido a um curso de formação de professores ofertado a distância. Os dados foram coletados por meio de entrevistas semiestruturadas realizadas com dez egressos do curso e de um questionário qualitativo online, ao qual responderam noventa e sete egressos. A Análise de Conteúdo temática deu origem a quatro categorias referentes à ocorrência de Mudanças Organizacionais. As categorias "Uso de metodologias ativas de ensino" e "Estratégias de recuperação de aprendizagem" foram as mais frequentes nas respostas dos participantes. O estudo buscou contribuir para a avaliação e planejamento de ações educacionais ofertadas a distância, visando identificar mudanças organizacionais e os desafios para sua concretização.

Changes in organizations resulting exclusively from the participation of employees in educational actions constitute Organizational Change. This research aimed to identify organizational changes that occurred due to a distance teacher training course. Data were collected through semi-structured interviews carried out with ten graduates of the course and an online qualitative questionnaire, to which ninety-seven graduates responded. The data were analyzed through thematic Content Analysis and originated four categories related to the occurrence of Organizational Changes. The categories "Use of active teaching methodologies" and "Learning recovery strategies" were the most frequent in the participants' responses. The study aimed to contribute to the evaluation and planning of educational actions offered at a distance, aiming to identify organizational changes and the challenges for their implementation.

Los cambios en las organizaciones que resultan exclusivamente de la participación de los empleados en acciones educativas constituyen un cambio organizacional. Esta investigación tuvo como objetivo identificar los cambios organizacionales que ocurrieron debido a un curso de capacitación docente ofrecido a distancia. Los datos fueron recolectados a través de entrevistas semiestructuradas realizadas con diez egresados del curso y un cuestionario cualitativo en línea, al que respondieron noventa y siete egresados. El análisis de contenido temático dio lugar a cuatro categorías. Las categorías "Uso de metodologías de enseñanza activa" y "Estrategias de recuperación del aprendizaje" fueron las más frecuentes en las respuestas de los participantes. El estudio buscó contribuir a la evaluación y planificación de acciones educativas ofrecidas a distancia, con el objetivo de identificar cambios organizacionales y los desafíos para su implementación.

Impact of COVID-19 Infection on Children and Adolescents after Liver Transplantation in a Latin American Reference Center.

Background: The COVID-19 infection has received the attention of the scientific community due to its respiratory manifestations and association with evolution to severe acute respiratory syndrome (SARS-CoV-2). There are few studies characterizing SARS-CoV-2 in pediatric immunocompromised patients, such as liver transplanted patients. The aim of this study was to analyze the outcomes of the largest cohort of pediatric liver transplant recipients (PLTR) from a single center in Brazil who were infected with COVID-19 during the pandemic. Methods: Cross-sectional study. Primary outcomes: COVID-19 severity. The Cox regression method was used to determine independent predictors associated with the outcomes. Patients were divided into two groups according to the severity of COVID-19 disease: moderate−severe COVID and asymptomatic−mild COVID. Results: Patients categorized as having moderate−severe COVID-19 were younger (12.6 months vs. 82.1 months, p = 0.03), had a higher prevalence of transplantation from a deceased donor (50% vs. 4.3%, p = 0.02), and had a higher prevalence of COVID infection within 6 months after liver transplantation (LT) (75% vs. 5.7%, p = 0.002). The independent predictor of COVID-19 severity identified in the multivariate analysis was COVID-19 infection <6 months after LT (HR = 0.001, 95% CI = 0.001−0.67, p = 0.03). Conclusion: The time interval of less than 6 months between COVID-19 infection and LT was the only predictor of disease severity in pediatric patients who underwent liver transplantation.

Pediatric liver transplantation activity in a high-volume program during the COVID-19 pandemic in Brazil.

BACKGROUND: The impact of the COVID pandemic on liver transplant (LT) programs varied among countries. Few data are available about that impact in pediatric liver transplant (PLT) programs. This study aimed at comparing the data of our program in Brazil (2019 vs. 2020). METHODS: Retrospective cohort study. RESULTS: One hundred and seventy-four PLT were performed in the period (93% living donors). Patients were divided into two groups according to the LT date: pre-COVID-19 period (march/2019-February/2020) and COVID-19 period (March/2020-February 2021). In the pre-COVID-19 period, 97 LTs were performed, and 77 LTs were performed in the COVID-19 period. Patients in the COVID-19 period were younger (10.9 months vs. 16 months, p 0.009), had higher PELD scores (15 vs. 14, p 0.04), more ascites (66.2 vs. 51.5%, p 0.03), and more frequently hospitalized before LT (27.3 vs. 17.5%). However, there was no difference in post-LT complications, retransplantation nor survival rates. Six (6.2%) patients from pre-COVID-19 period were COVID positive at a median of 15.5 months (14-17.5), and 6 (7.8%) patients from COVID-19 period were COVID positive at a median of 3 months (20 days-6 months) from LT. There was neither mortality nor complications in those patients. Four (33%) were hospitalized, and one had prolonged intubation. Four (33%) were asymptomatic, 4 (33%) had upper airways symptoms, and the remaining had gastrointestinal symptoms. CONCLUSION: Overall, PLT was not affected during COVID-19 period. Even though patients from COVID-19 period were sicker, there was no significant impact in LT outcomes. All the recipients who tested positive for COVID had a favorable outcome.

Adaptação e evidências de validade de um instrumento de mudança organizacional no contexto da educação a distância / Adaptation and evidence of validity of an organizational change instrument in the context of distance education / La adaptación y la evidencia de la validez de un instrumento de cambio organizacional en el contexto de la educación a distancia

A efetividade da educação a distância na formação e capacitação de professores é uma questão que, apesar de não recente, mostra-se um desafio teórico e prático. A Mudança Organizacional está relacionada aos efeitos produzidos com os programas de Treinamento, Desenvolvimento e Educação de Pessoas que causam alterações nos processos da instituição, sem configurar o atendimento dos objetivos organizacionais. Essa pesquisa objetivou adaptar e verificar evidências de validade do instrumento de Mudança Organizacional no contexto de educação a distância. O instrumento foi aplicado a 793 egressos de um curso de formação de professores da rede de ensino do estado de São Paulo e posteriormente passou por análises descritivas, exploratórias e confirmatórias. Os resultados demonstraram evidências de validade do construto e o bom ajuste do modelo, tendo o instrumento suas estruturas fatoriais provadas. O estudo mostra-se relevante devida à escassez de instrumentos que mensuram essa variável no contexto de educação a distância.

The effectiveness of e-learning in teacher education and training is an issue that, although not recent, proves to be a theoretical and practical challenge. Organizational change is related to the effects produced by the training, development and education of people programs that cause changes in the institution's processes, without configuring the fulfillment of organizational objectives. This research aimed to adapt and verify evidence of validity of the organizational change instrument in e-learning. The instrument was applied to 793 graduates of a teacher education course in the state of São Paulo and subsequently underwent descriptive, exploratory, and confirmatory analyses. The results showed evidence of construct validity and good fit of the model, with the instrument having its factor structures proven. The study is relevant due to the scarcity of instruments that measure this variable in the context of e-learning.

La efectividad de la educación a distancia en la formación y capacitación de profesores es un tema que, aunque no sea reciente, es un desafío teórico y práctico. El cambio organizacional está relacionado con los efectos producidos por los programas de capacitación, desarrollo y educación de las personas que promueven cambios en los procesos de la institución, sin configurar el cumplimiento de los objetivos organizacionales. Esta investigación tuvo como objetivo adaptar y verificar las evidencias de la validez del instrumento de cambio organizacional en la educación a distancia. Se aplicó el instrumento a una muestra de 793 egresados de un curso de formación docente en el estado de São Paulo y posteriormente se sometió a análisis descriptivos, exploratorios y confirmatorios. Los resultados mostraron evidencias de la validez del constructo y un buen ajuste del modelo, y las estructuras de factores del instrumento fueron probadas. El estudio es relevante debido a la escasez de instrumentos que evalúan esa variable en el contexto de la educación a distancia.

Progressive Familial Intrahepatic Cholestasis Associated With USP53 Gene Mutation in a Brazilian Child.

ABSTRACT: A case of low-γ-glutamyltranspetidase cholestasis associated with ubiquitin-specific peptidase 53 (USP53) gene mutation in a Brazilian child is described. Transient jaundice and hypocholia started at the age of 10 days. Liver enzymes, total bilirubin, and total bile acids were elevated at presentation. During follow-up, he developed cholelithiasis treated with cholecystectomy, and an intracranial hemorrhage resolved with full recovery. At last, evaluation at the age of 18 months, he was not jaundiced and had normal liver tests, but experienced from moderate pruritus despite treatment with rifampicin and ursodeoxycholic acid. A genetic study revealed novel homozygous mutations c.1687_1688delinsC p.Ser563Profs∗25 in the USP53 gene. His parents carried the same heterozygous mutation in the USP53 gene.

Impact of hypoxemia on pediatric liver transplantation for hepatopulmonary syndrome.

BACKGROUND: The treatment of choice for patients with cirrhosis and HPS is LT. The clinical manifestations associated with hypoxemia result in limitations and a poor health-related quality of life of affected patients. The present report aims to study the differences in outcomes between patients with PaO2  < 50 mm Hg and those with PaO2  ≥ 50 mm Hg. METHODS: This was a retrospective study of 21 patients under 18 years of age conducted from 2001 to 2018; the patients were divided into 2 groups: G1-PaO2  ≥ 50 mm Hg, 11 patients, and G2-PaO2  < 50 mm Hg, 10 patients. Demographic, clinical, laboratory, and perioperative data; outcome variables; and post-transplant survival were compared between the groups. RESULTS: In total, 2/11 (18.2%) patients in G1 and 8/10 (80%) patients in G2 required supplemental oxygen therapy at home (P = .005). Patients in G2 required prolonged MV (median 8.5 days in G2 vs 1 day in G1, P = .015) and prolonged ICU and hospital stays (P = .002 and P = .001, respectively). Oxygen weaning time was longer in G2 (median 127.5 days) than in G1 (median 3 days; P = .004). One (9.1%) patient in G1 and three (30%) patients in G2 died (P = .22). The survival at 90 months was 90.9% in G1 and 70% in G2 (P = .22). CONCLUSION: The survival between groups was similar. Patients with very severe HPS required a longer MV time, longer ICU and hospital stays, and a longer O2 weaning time than those with mild, moderate, or severe HPS.

Maple syrup urine disease in Brazilian patients: variants and clinical phenotype heterogeneity.

BACKGROUND: Maple syrup urine disease (MSUD) is an autosomal recessive inherited metabolic disease caused by deficient activity of the branched-chain α-keto acid dehydrogenase (BCKD) enzymatic complex. BCKD is a mitochondrial complex encoded by BCKDHA, BCKDHB, DBT, and DLD genes. MSUD is predominantly caused by Variants in BCKDHA, BCKDHB, and DBT genes encoding the E1α, E1ß, and E2 subunits of BCKD complex, respectively. The aim of this study was to characterize the genetic basis of MSUD by identifying the point variants in BCKDHA, BCKDHB, and DBT genes in a cohort of Brazilian MSUD patients and to describe their phenotypic heterogeneity. It is a descriptive cross-sectional study with 21 MSUD patients involving molecular genotyping by Sanger sequencing. RESULTS: Eight new variants predicted as pathogenic were found between 30 variants (damaging and non-damaging) identified in the 21 patients analyzed: one in the BCKDHA gene (p.Tyr120Ter); five in the BCKDHB gene (p.Gly131Val, p.Glu146Glnfs * 13, p.Phe149Cysfs * 9, p.Cys207Phe, and p.Lys211Asn); and two in the DBT gene (p.Glu148Ter and p.Glu417Val). Seventeen pathogenic variants were previously described and five variants showed no pathogenicity according to in silico analysis. CONCLUSION: Given that most of the patients received late diagnoses, the study results do not allow us to state that the molecular features of MSUD variant phenotypes are predictive of clinical severity.

Technical Choices in Pediatric Living Donor Liver Transplantation: The Path to Reduce Vascular Complications and Improve Survival.

Pediatric living donor liver transplantation (PLDLT) is a successful therapeutic option for children with chronic and acute liver disease. After early transplant results, many technical advancements were introduced in the field to reduce the rate of complications and improve survival. The aim of this study is to present the outcomes of 975 primary PLDLTs in 3 periods: initial practice (period 1, 29 patients, January 1995 to December 1999), second period (period 2, 331 patients, January 2000 to December 2009), and third period (period 3 [P3], 615 patients, January 2010 to September 2019). Among the technical refinements introduced in P3 are the use of hyperreduced left lateral segment grafts, abdominal wall prosthetic mesh closure, double hepatic artery anastomosis, and increased use of vascular grafts for portal vein reconstruction. The outcomes included significant reductions of hepatic artery thrombosis (HAT), early portal vein thrombosis (EPVT), and retransplantation, with better patient and graft survival in P3. Additional analyses showed that the factors independently associated with worse 90-day patient survival were HAT, EPVT, and increasing Pediatric End-Stage Liver Disease score. In conclusion, the introduction of technical refinements in P3, in addition to improvements in patient care, determined a reduction in EPVT, HAT, and retransplantation. Consequently, patient and graft survival rates increased in all time points studied.

The development of transversal competence of health service managers.

In their pedagogical projects, health management courses focus on multidisciplinarity, interdisciplinarity, comprehensiveness and transversality, whose main merit is to question health issues from different theoretical perspectives. Analyzing these issues under many perspectives does not necessarily mean the development of transversal competences. The development and application of these competences suppose going beyond integrating curricular contents and theory/practice. They depend on how the knowledge will be articulated to changes at organizational, sectorial and institutional levels and on the coevolution between these competences and changes. It is understood that health services manager role is effectively transversal when he/she: (i) acts at organizational boundaries, fostering interaction between organizations and other actors in the system; (ii) provides (and receives) feedback to (and from) these actors; and (iii) these feedbacks help decision makers to undertake organizational changes to respond to the environment and shape it.

Lysosomal acid lipase deficiency in Brazilian children: a case series / Deficiência de lipase ácida lisossomal em crianças brasileiras: casuística

Abstract Objective: To describe the demographic, clinical, laboratory and molecular characteristics of patients with lysosomal acid lipase deficiency. Methods: A retrospective review of the medical records of children with the disease. Results: Seven children with lysosomal acid lipase deficiency (5 male; 2 female); 6 were mixed race, and 1 was black. The mean ages at the first onset of symptoms and at diagnosis were 5.0 years (4 months to 9 years) and 6.9 years (3-10 years), respectively. Symptom manifestations at onset were: 3 patients had abdominal pain, one had bone/joint pain due to rickets, and 1 had chronic diarrhea and respiratory insufficiency due to interstitial pneumonitis. One was asymptomatic, and clinical suspicion arose due to hepatomegaly. Six patients had hepatomegaly, and none had splenomegaly. Two patients were siblings. Enzymatic assay and molecular analysis confirmed the diagnoses. Genetic analysis revealed a rare pathogenic variant (p.L89P) in three patients, described only once in medical literature and never described in Brazil. None of those patients were related to each other. Lysosomal acid lipase deficiency was previously described as an autosomal recessive disease, but three patients were heterozygous and undoubtedly had the disease (low enzyme activity, suggestive lab findings and clinical symptoms). Conclusion: This case series supports that lysosomal acid lipase deficiency can present with highly heterogeneous signs and symptoms among patients, but it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. We describe a rare variant in three non-related patients that may suggest a Brazilian genotype for lysosomal acid lipase deficiency.

Resumo: Objetivo: Descrever as características demográficas, clínicas, laboratoriais e moleculares de pacientes com deficiência de lipase ácida lisossomal. Métodos: Análise retrospectiva dos prontuários médicos de crianças com a deficiência de lipase ácida lisossomal. Resultados: Sete crianças com deficiência de lipase ácida lisossomal (5 M:2F); seis eram pardas e uma negra. As faixas etárias no início dos sintomas e no diagnóstico foram 5 anos (4 meses a 9 anos) e 6,9 anos (3 a 10 anos), respectivamente. As manifestações dos sintomas no início foram as que seguem: três pacientes apresentaram dor abdominal, um apresentou dor nos ossos/articulações devido a raquitismo e um apresentou diarreia crônica e insuficiência respiratória devido à pneumonite intersticial. Os outros não apresentaram sintomas e a suspeita clínica surgiu devido à hepatomegalia. Seis pacientes apresentaram hepatomegalia e um apresentou esplenomegalia. Dois pacientes eram irmãos. O ensaio enzimético e a análise molecular confirmaram os diagnósticos. A análise genética revelou uma variante patogênica rara (p.L89P) em três pacientes, descrita uma única vez na literatura médica e nunca descrita no Brasil. Nenhum desses pacientes tinha parentesco com os outros. A deficiência de lipase ácida lisossomal foi anteriormente descrita como uma doença recessiva autossômica, porém três pacientes eram heterozigotos e, sem dúvida, apresentaram a doença (atividade enzimática baixa, achados laboratoriais sugestivos e sintomas clínicos). Conclusão: Esta casuística afirma que a deficiência de lipase ácida lisossomal pode se manifestar com sinais e sintomas altamente heterogêneos entre os pacientes, porém deve ser considerada em crianças que apresentam sintomas gastrointestinais associados à dislipidemia. Descrevemos uma variante rara em três pacientes não relacionados que pode sugerir um genótipo brasileiro para deficiência de lipase ácida lisossomal.

UPDATE OF THE BRAZILIAN SOCIETY OF HEPATOLOGY RECOMMENDATIONS FOR DIAGNOSIS AND MANAGEMENT OF AUTOIMMUNE DISEASES OF THE LIVER.

New data concerning the management of autoimmune liver diseases have emerged since the last single-topic meeting sponsored by the Brazilian Society of Hepatology to draw recommendations about the diagnosis and treatment of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), overlap syndromes of AIH, PBC and PSC and specific complications and topics concerning AIH and cholestatic liver diseases. This manuscript updates those previous recommendations according to the best evidence available in the literature up to now. The same panel of experts that took part in the first consensus document reviewed all recommendations, which were subsequently scrutinized by all members of the Brazilian Society of Hepatology using a web-based approach. The new recommendations are presented herein.

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.

Lysosomal acid lipase deficiency in Brazilian children: a case series.

OBJECTIVE: To describe the demographic, clinical, laboratory and molecular characteristics of patients with lysosomal acid lipase deficiency. METHODS: A retrospective review of the medical records of children with the disease. RESULTS: Seven children with lysosomal acid lipase deficiency (5 male; 2 female); 6 were mixed race, and 1 was black. The mean ages at the first onset of symptoms and at diagnosis were 5.0 years (4 months to 9 years) and 6.9 years (3-10 years), respectively. Symptom manifestations at onset were: 3 patients had abdominal pain, one had bone/joint pain due to rickets, and 1 had chronic diarrhea and respiratory insufficiency due to interstitial pneumonitis. One was asymptomatic, and clinical suspicion arose due to hepatomegaly. Six patients had hepatomegaly, and none had splenomegaly. Two patients were siblings. Enzymatic assay and molecular analysis confirmed the diagnoses. Genetic analysis revealed a rare pathogenic variant (p.L89P) in three patients, described only once in medical literature and never described in Brazil. None of those patients were related to each other. Lysosomal acid lipase deficiency was previously described as an autosomal recessive disease, but three patients were heterozygous and undoubtedly had the disease (low enzyme activity, suggestive lab findings and clinical symptoms). CONCLUSION: This case series supports that lysosomal acid lipase deficiency can present with highly heterogeneous signs and symptoms among patients, but it should be considered in children presenting with gastrointestinal symptoms associated with dyslipidemia. We describe a rare variant in three non-related patients that may suggest a Brazilian genotype for lysosomal acid lipase deficiency.

Domino Liver Transplant in Maple Syrup Urine Disease: Technical Details of Cases in Which the First Surgery Involved a Living Donor.

BACKGROUND: Data describing the technical aspects of living donor (LD) domino liver transplantation (DLT) in maple syrup urine disease (MSUD) are limited. The largest published series includes only 3 cases. One great challenge of this procedure is to ensure adequate vascular stumps for the LD, the MSUD patient, and the recipient of the domino graft. Here, we describe our experience in 11 cases of LD-DLT in MSUD, highlighting the technical aspects of LD-DLT. METHODS: From September 2012 to September 2017, 11 patients with MSUD underwent LD liver transplantation at our institution, and MSUD livers were used as domino grafts in 11 children. RESULTS: (1) MSUD patients: 10 patients received a left lateral segment. The donor's left hepatic vein (HV) was anastomosed to the confluence of the recipient's 3 HVs. No vascular grafts (VG) were required for portal vein (PV) anastomosis. Single arterial anastomosis was performed with microsurgery in 10 of 11 patients. (2) MSUD graft recipients: In 8 cases, HV reconstruction was performed between the graft's HV confluence and the recipient's HV confluence, and in 3 cases, a vena cava triangulation was necessary; 6 MSUD grafts required HV venoplasty. No VG were needed for HV reconstruction. VG were used for PV reconstruction in 3 cases due to sclerotic PV. In 2 cases, double arterial anastomoses were performed in the MSUD liver. All patients remain alive and well. CONCLUSIONS: Living donor liver transplantation followed by DLT for MSUD is a complex procedure and demands technical refinement. Special attention must be paid to vascular reconstruction.

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.

The development of transversal competence of health service managers / O desenvolvimento da competência transversal dos gestores de serviços de saúde

ABSTRACT In their pedagogical projects, health management courses focus on multidisciplinarity, interdisciplinarity, comprehensiveness and transversality, whose main merit is to question health issues from different theoretical perspectives. Analyzing these issues under many perspectives does not necessarily mean the development of transversal competences. The development and application of these competences suppose going beyond integrating curricular contents and theory/practice. They depend on how the knowledge will be articulated to changes at organizational, sectorial and institutional levels and on the coevolution between these competences and changes. It is understood that health services manager role is effectively transversal when he/she: (i) acts at organizational boundaries, fostering interaction between organizations and other actors in the system; (ii) provides (and receives) feedback to (and from) these actors; and (iii) these feedbacks help decision makers to undertake organizational changes to respond to the environment and shape it.

RESUMO Em seus projetos pedagógicos, os cursos de gestão de saúde privilegiam a multidisciplinaridade, interdisciplinaridade, integralidade e transversalidade, cujo principal mérito é problematizar as questões da saúde sob diferentes perspectivas teóricas. Analisar as questões da área da saúde a partir de diversos prismas não implica necessariamente no desenvolvimento de competências transversais. O desenvolvimento e a aplicação dessas competências pressupõem ir além da integração entre conteúdos curriculares e entre teoria e prática. Dependem de como os conhecimentos serão articulados às mudanças nos níveis organizacional, setorial e institucional e da coevolução entre essas competências e essas mudanças. Entende-se que a atuação do gestor de serviços de saúde é efetivamente transversal quando: (i) atua nas fronteiras organizacionais, fomentando a interação entre as organizações e outros atores do sistema; (ii) provê (e recebe) feedbacks para esses (desses) atores; e (iii) esses feedbacks auxiliam os tomadores de decisão a empreender mudanças organizacionais, de modo a responder ao ambiente e a moldá-lo.

Outcomes of liver transplantation in pediatric recipients with cardiovascular disease.

LT exerts considerable stress on the heart perioperatively. Limited data exist on impact of cardiovascular diseases on LT children. This study evaluated the outcomes of children with CVD who underwent LT and compared with pretransplant findings. From 518 LT recipients, 82 (15.8%) had CVD. Sixty patients were classified as low-risk adjustment for congenital heart surgery 1 (RACHS 1 and 2). Five patients were classified as RACHS ≥3. The most common echocardiographic finding in the CVD patients (25/82) was ASD. CVD patients had more abnormal EKG (32.4% vs 14.5%, P < .001), abnormal chest X-ray (11.8% vs 1.4%, P < .001), and altered echocardiography (89.7% vs 15.4%, P < .001) findings compared with the No-CVD group pretransplant. Post-transplant, significant differences between groups were observed related to abnormal EKG (14.7% vs 7.0%, P = .03) and echocardiography (48.5% vs 3.2%, P < .01) findings. Pretransplant ASD spontaneously closed in 22 patients. At 1 and 5 years post-transplant, there was no difference in the survival rate between groups (P = .96). The prevalence of CVD in recipients of LT was high, and its presence was associated with significantly higher cardiac decompensation before and after LT. Minor and moderate cardiovascular disease did not impact the long-term survival.

Twenty Years of Experience in Pediatric Living Donor Liver Transplantation: Focus on Hepatic Artery Reconstruction, Complications, and Outcomes.

BACKGROUND: Hepatic artery thrombosis (HAT) increases morbidity and mortality after liver transplantation (LT). The identification of risk factors for HAT may aid transplant teams in the development of strategies aimed at reducing HAT. This article describes the risk factors for HAT and outcomes after LT. METHODS: This report describes a retrospective study (1995 to 2015) of primary pediatric living donor LT (LDLT). Pretransplant and technical variables were included in the study. Binary logistic regression was used for data analysis. RESULTS: This study included 656 primary LDLT. The median age, body weight, and pediatric end-stage liver disease score at the time of transplant were 13 months, 8.4 kg and 15, respectively. Twenty-one (3.2%) patients developed HAT. Intraoperative HAT (odds ratio, 62.63; 95% confidence interval, 12.64-310.19; P < 0.001) and the use of liver grafts with a graft-to-recipient weight ratio less than 1.1% (odds ratio, 24.46; 95% confidence interval, 4.55-131.56; P < 0.001) retained statistical significance in the multivariate model. Patient and graft survivals were significantly worse in cases with HAT. The overtime trend analysis revealed a decrease in the incidence of HAT (P = 0.008) and an increase in the use of 2-arterial anastomosis (P < 0.001). CONCLUSIONS: A graft-to-recipient weight ratio of 1.1% or less and intraoperative HAT were independently associated with HAT. Trend analysis further revealed a significant reduction in the incidence of HAT over time, as well as the increased use of 2 hepatic arteries for anastomosis during graft implantation. The double artery anastomosis may represent an extra protection to pediatric recipients undergoing LDLT.