Proton Pump Inhibitor Use, Fatigue, and Health-Related Quality of Life in Kidney Transplant Recipients:Results From the TransplantLines Biobank and Cohort Study

Rationale &amp; Objective: Prior studies report that the use of proton pump inhibitors (PPIs) can adversely affect gut microbiota and gastrointestinal uptake of micronutrients, in particular iron and magnesium, and are used frequently by kidney transplant recipients. Altered gut microbiota, iron deficiency, and magnesium deficiency have been implicated in the pathogenesis of chronic fatigue. Therefore, we hypothesized that PPI use may be an important and underappreciated cause of fatigue and reduced health-related quality of life (HRQoL) in this population. Study Design: Cross-sectional study. Setting &amp; Participants: Kidney transplant recipients (≥1 year after transplantation) enrolled in the TransplantLines Biobank and Cohort Study. Exposure: PPI use, PPI type, PPI dosage, and duration of PPI use. Outcome: Fatigue and HRQoL, assessed using the validated Checklist Individual Strength 20 Revised questionnaire and Short Form-36 questionnaire. Analytical Approach: Logistic and linear regression. Results: We included 937 kidney transplant recipients (mean age 56 ± 13 years, 39% female) at a median of 3 (1-10) years after transplantation. PPI use was associated with fatigue severity (regression coefficient 4.02, 95% CI, 2.18 to 5.85, P &lt; 0.001), a higher risk of severe fatigue (OR 2.05, 95% CI, 1.48 to 2.84, P &lt; 0.001), lower physical HRQoL (regression coefficient −8.54, 95% CI, −11.54 to −5.54, P &lt; 0.001), and lower mental HRQoL (regression coefficient −4.66, 95% CI, −7.15 to −2.17, P &lt; 0.001). These associations were independent of potential confounders including age, time since transplantation, history of upper gastrointestinal disease, antiplatelet therapy, and the total number of medications. They were present among all individually assessed PPI types and were dose dependent. Duration of PPI exposure was only associated with fatigue severity. Limitations: Residual confounding and inability to assess causal relationships. Conclusions: PPI use is independently associated with fatigue and lower HRQoL among kidney transplant recipients. PPI use might be an easily accessible target for alleviating fatigue and improving HRQoL among kidney transplant recipients. Further studies examining the effect of PPI exposure in this population are warranted. Plain-Language Summary: In this observational study, we investigated the association of proton pump inhibitors with fatigue and health-related quality of life among kidney transplant recipients. Our data showed that proton pump inhibitors were independently associated with fatigue severity, severe fatigue, and lower physical and mental health-related quality of life. These associations were present among all individually assessed proton pump inhibitor types and were dose dependent. While we await future studies on this topic, proton pump inhibitor use might be an easily accessible target for alleviating fatigue and improving health-related quality of life among kidney transplant recipients.</p

Reversal of secondary protein-losing enteropathy after surgical revision of a jejunal Roux-en-Y loop in a patient after liver transplantation

Secondary protein-losing enteropathy (PLE) is a rare complication following pediatric liver transplantation (LT), mostly related to venous outflow obstruction of the liver. Here, we discuss a thus far unknown cause of secondary PLE following pediatric LT. A 7-month-old boy underwent LT with biliary anastomosis using a Roux-en-Y jejunal loop. Eleven months later he developed PLE. Routine diagnostic workup was negative. No hepatic outflow obstruction was detected during catheterization. Although the hepatic venous pressure gradient was slightly increased (10 mm Hg), there were no clinical signs of portal hypertension. Albumin scintigraphy with specific early recordings suggested focal albumin intestinal entry in the jejunal Roux-en-Y loop. Local bacterial overgrowth or local lymphangiectasia, possibly due to (venous) congestion, was considered. Treatment with metronidazole did not improve albumin loss. Next, surgical revision of the jejunal Roux-en-Y loop was performed. The explanted loop contained a small abnormal area with a thin hyperemic mucosa, near the former anastomosis. Histopathological analysis showed changes both in the blood vessels and the lymphatic vessels with focal deeper chronic active inflammation resulting in congestion of vessels, hampering lymphatic outflow leading to lymphangiectasia and patchy distortion of lymphatic vessels. Following surgical revision, secondary PLE disappeared, up to now, 1.5 year post revision

First report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion

One of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ machine perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation. We here report the first successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion. The full-size liver graft was derived from a 13-year-old, female DCD donor and was end-ischemic pretreated with dual hypothermic oxygenated machine perfusion. Arterial and portal pressures were set at 18 and 4 mm Hg, slightly lower than protocolized settings for adult livers. During 2 hours of machine perfusion, portal and arterial flows increased from 100 to 210 mL/min and 30 to 63 mL/min, respectively. The pretreated liver graft was implanted in a 16-year-old girl with progressive familial intrahepatic cholestasis type 2. Postoperative AST, ALT, and prothrombin time normalized within a week. The recipient quickly recovered and was discharged from the hospital after 18 days. One year after transplantation, she is in excellent condition with a completely normal liver function and histology. This case is the first report of successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion and illustrates the potential role of ex situ machine perfusion in expanding the donor pool and improving outcome after pediatric liver transplantation

Característica do ambiente comunitário nos níveis de atividade física de adolescentes de Curitiba, PR

Orientador : Prof. Dr. Rodrigo Siqueira ReisDissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Educação Física. Defesa: Curitiba, 24/02/2017Inclui referências : f. 108-114Resumo: RESUMO As características ambientais tem se mostrado relacionadas aos hábitos da prática de atividade física da população. Grande parte da população mundial de adolescentes não atinge os níveis recomendados de atividade física. Recentemente tem sido estudado como as características ambientais podem auxiliar na melhoria destes indicadores. No entanto, a maior parte das evidências na literatura são de países de renda elevada, o que não permite representar as características de países de renda baixa e média. Além disso, as medidas são comumente avaliadas por Sistemas de Informações Geográficas. Mensurar as características ambientais a nível de microescala podem permitir compreender melhor as características do ambiente e a prática de atividade física e proporcionar mudanças com menor custo e maior rapidez. Portanto, o objetivo deste estudo foi avaliar a associação entre atributos físicos do ambiente construído capturados pela microescala e atividade física de adolescentes de Curitiba-PR, Brasil. Os dados são oriundos de dois projetos, IPEN Adolescent (Projeto ESPAÇOS) e MAPS Global, caracterizados estudos de delineamento transversal. Foram selecionados apenas adolescentes que apresentaram informações de acelerômetro e/ou GPS válidas (n=356). Os dados da prática dos deslocamentos para a escola e pelo bairro foram autoreportados e a atividade física moderada a vigorosa obtida com dados coletados por meio de acelerômetros. As informações do ambiente construído a nível de microescala foram coletadas no projeto MAPS Global por meio de observação sistemática. As rotas avaliadas pela rede de ruas, possuíam, no mínimo 400 metros e, no máximo, 720 metros a partir da residência do adolescente até um conglomerado comercial mais próximo, distribuídas em quatro quadrantes da combinação de walkability e renda do bairro. Locais de alto walkability se mostraram positivos com a presença de locais comerciais, estética e qualidade das calçadas. O contexto da atividade física do deslocamento, para a escola ou de lazer, se mostraram associadas com a presença de características de locais não residenciais e melhor qualidade dos segmentos e de forma inversa para transportes motorizados. A atividade física moderada à vigorosa se mostrou associada apenas com a presença de "semáforos". Conclui-se que as características do bairro a nível de microescala são mais importantes para o deslocamento do que atividades de maior intensidade, que aparentemente são realizadas em locais mais específicos. Estudos com amostra representativa de adolescentes e do entorno das residências devem ser desenvolvidos para identificar as reais condições da cidade e quais domínios da atividade física podem ser associados com a microescala. Palavras-chave: Atividade motora, ambiente construído, adolescenteAbstract:Environmental characteristics showed related to the habits of the physical activity of the population. Most of the adolescents' population does not reach recommended levels of physical activity. Recently has been studied how the environmental characteristics can help to improve of these indicators. However, most of the evidence in the literature is from high-income countries, which does not allow us to represent the characteristics of low- and middle-income countries. In addition, the measurements are commonly evaluated by Geographic Information Systems (GIS). Measuring the environmental characteristics at the microscale can allow better understanding of the characteristics of the environment and the practice of physical activity and provide changes with lower costs and faster. Therefore, the objective of this study was to evaluate the association between physical attributes of the built environment captured by the microscale and physical activity of adolescents from Curitiba-PR, Brazil. The data come from two projects, IPEN Adolescent (Projeto ESPAÇOS) and MAPS Global, characterized as cross-sectional design. Only adolescents presenting valid accelerometer and / or GPS information (n=356) were selected. The data of the practice of the trips to the school and the neighborhood were self-reported and the moderate to vigorous physical activity obtained with data collected through accelerometers. Information on the environment built at the microscale level collected in the MAPS Global project through systematic observation. The routes evaluated by the street network had at least 400 meters and a maximum of 720 meters from the adolescent's residence to a nearby commercial cluster, distributed in four quadrants of the combination of walkability and income. Places of high walkability were positive with the presence of commercial sites, aesthetics and quality of the sidewalks. The context of the physical activity of the displacement, for the school or of leisure, showed to be associated with the presence of characteristics of non-residential places and better quality of the segments and of inverse form for motorized transports. Moderate to vigorous physical activity was associated only with the presence of traffic lights. Characteristics of the neighborhood at the microscale level are more important for commuting than activities of greater intensity, which apparently are performed in specific places. Studies with a representative sample of adolescents and the surroundings of the residences to identify the real conditions of the city and which domains of physical activity can be associated with the microscale. Keywords: Motor activity, built environment, adolescen

Cystic Fibrosis-related Liver Disease:Research Challenges and Future Perspectives

Objectives: Hepatobiliary complications are a leading cause of morbidity and mortality in cystic fibrosis (CF) patients. Knowledge of the underlying pathological aspects and optimal clinical management is, however, sorely lacking. Methods: We provide a summary of the lectures given by international speakers at the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) monothematic conference on cystic fibrosis-related liver disease (CFLD) held in Paris in January 2016, to discuss the status of our current knowledge of liver disease in CF patients, to define the critical areas that need to be addressed, and to resolve actions to elucidate relevant mechanisms of disease to optimise future therapeutic options. Conclusions: The need for a universal consensus on the definition of CFLD to clarify disease stage and to identify relevant biomarkers to assess disease severity was highlighted. A deeper understanding of the pathophysiology and prognostic factors for the long-term evolution of CFLD is fundamental to move forward and has a strong bearing on identifying potential treatments. Novel experimental models and new treatment options under investigation are discussed and offer hope for the near future of CFLD