Anticuerpos antimúsculo liso sin hepatitis autoinmune / Positive smooth muscle antibody without autoimmune hepatitis

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Utilidad de la entero-resonancia magnética en el estudio de la enfermedad de Crohn pediátrica / MRI enterography in the assessment of paediatric Crohn’s disease

Objetivo: Evaluar la utilidad de la resonancia magnética intestinal con contraste oral (RMI) para el estudio de extensión y actividad de la enfermedad de Crohn (EC) pediátrica, comparando los hallazgos con índices clínicos, tests biológicos, endoscopia y otras técnicas de imagen. Pacientes y métodos: Fueron valoradas las RMI efectuadas en pacientes menores de 18 años diagnosticados de EC. Para la preparación se administró 500-1000ml de polietilenglicol una hora antes de las imágenes (1,5-TMR). Se realizaron secuencias T2 HASTE con o sin Fat SAT, T2 true-FISP, T1 Fat-SAT VIBE pre/posgadolinio, HASTE dinámico y difusión. Se valoraron el engrosamiento de pared intestinal, la hipercaptación mucosa y las complicaciones extraintestinales. Se establecieron 5 patrones de RMI: normal, fibrosis, actividad leve, moderada y severa-transmural. Los hallazgos se compararon con PCDAI, parámetros inflamatorios, resultados endoscópicos e histológicos. Resultados: Incluimos para la evaluación 22 estudios. El 82% presentaba una distensión intestinal óptima. Observamos efectos secundarios leves en el 12% de los pacientes. Encontramos una relación significativa entre los patrones de RMI versus PCDAI (p=0,002), VSG (p=0,006) y PCR (p=0,047); no hallamos relación estadísticamente significativa (p=0,571) con la histología. La RMI valoró correctamente la extensión de la enfermedad a nivel ileal (80%) y a nivel cólico (66%). Un 86,4% de los estudios mostraron complicaciones extraintestinales, sin presentar relación estadística con la clasificación de RMI (p=0,274). Conclusiones: Existe una relación estadísticamente significativa entre nuestros patrones de RMI y PCR, VSG y PCDAI. La RMI presenta excelente concordancia con las ileoscopias. La RMI valora zonas no accesibles mediante endoscopia y permite el diagnóstico de complicaciones extraintestinales sin irradiación (AU)

Objective: To determine the usefulness of MRI enterography for assessing the extension and activity of paediatric Crohn's disease. MRI findings were compared with clinical, biological, endoscopic and other imaging data. Patients and methods: Studies of MRI enterography use in patients younger than 18 years of age were reviewed. Patients received 500-1000mL of polyethylene glycol one hour before examination (1.5-TMR). T2 HASTE sequences with or without fat saturation, T2 true-FISP, T1 with fat saturation, pre- and post gadolinium-enhanced VIBE sequences, and dynamic and diffusion HASTE were acquired. Thickening of the bowel wall, mucosal enhancement, and extra-luminal complications were evaluated. Five MRI patterns (normal, fibrosis, mild, moderate, and severe transmural activity) were defined. Findings were compared with PCDAI scores, inflammatory parameters, and endoscopic and histological results. Results: Twenty-two studies were reviewed. Optimal intestinal distension was present in 82% of the cases. Mild side effects were observed in 12% of patients. There was a significant relationship between MRI patterns and PCDAI scores (P=0.002), sedimentation rate (P=0.006) and serum PCR levels (P=0.047) and a non-significant relationship with the histology (P=0.571). MRI enterography correctly assessed the ileal (80%) and colonic (66%) extension. Extra-luminal complications unrelated to MRI classification (P=0.274) were reported in 86.4% of studies. Conclusions: There was a significant relationship between MRI patterns and PCR, sedimentation rate, and PCDAI scores. MRI enterography showed excellent agreement with ileoscopies, and allowed endoscopically non-accessible areas to be assessed, as well as the diagnosis of extra-luminal complications without irradiation (AU)

[MRI enterography in the assessment of paediatric Crohn's disease]. / Utilidad de la entero-resonancia magnética en el estudio de la enfermedad de Crohn pediátrica.

OBJECTIVE: To determine the usefulness of MRI enterography for assessing the extension and activity of paediatric Crohn's disease. MRI findings were compared with clinical, biological, endoscopic and other imaging data. PATIENTS AND METHODS: Studies of MRI enterography use in patients younger than 18 years of age were reviewed. Patients received 500-1000mL of polyethylene glycol one hour before examination (1.5-TMR). T2 HASTE sequences with or without fat saturation, T2 true-FISP, T1 with fat saturation, pre- and post gadolinium-enhanced VIBE sequences, and dynamic and diffusion HASTE were acquired. Thickening of the bowel wall, mucosal enhancement, and extra-luminal complications were evaluated. Five MRI patterns (normal, fibrosis, mild, moderate, and severe transmural activity) were defined. Findings were compared with PCDAI scores, inflammatory parameters, and endoscopic and histological results. RESULTS: Twenty-two studies were reviewed. Optimal intestinal distension was present in 82% of the cases. Mild side effects were observed in 12% of patients. There was a significant relationship between MRI patterns and PCDAI scores (P=.002), sedimentation rate (P=.006) and serum PCR levels (P=.047) and a non-significant relationship with the histology (P=.571). MRI enterography correctly assessed the ileal (80%) and colonic (66%) extension. Extra-luminal complications unrelated to MRI classification (P=.274) were reported in 86.4% of studies. CONCLUSIONS: There was a significant relationship between MRI patterns and PCR, sedimentation rate, and PCDAI scores. MRI enterography showed excellent agreement with ileoscopies, and allowed endoscopically non-accessible areas to be assessed, as well as the diagnosis of extra-luminal complications without irradiation.

Seguridad y eficacia del polietilenglicol 3350 con electrolitos en el tratamiento del estreñimiento funcional en niños / Safety and efficacy of polyethylene glycol 3350 plus electrolytes for the treatment of functional constipation in children

Introducción: El objetivo del trabajo ha sido evaluar la seguridad del PEG 3350 con electrolitos (PEG+E) a nivel renal y digestivo. Objetivo secundario: valorar su eficacia y dosis de efectividad. Pacientes y métodos: Quince pacientes con estreñimiento funcional (criterios de Roma III) y función renal normal fueron evaluados. La mediana de edad fue de 6,2 años (r=2-9). Sobres pediátricos de PEG+E fueron administrados durante 4 semanas (4ST) La dosis media administrada fue de 0,44g/kg/día. La natruria y osmolaridad urinaria se midieron al inicio y a las 4ST. La determinación de principios inmediatos en heces mediante FENIR (análisis de reflexión de infrarrojos) y una prueba de hidrógeno espirado fueron efectuadas a las 4ST. La eficacia del tratamiento fue evaluada mediante el cambio en el número de deposiciones por semana y la consistencia de las heces (escala de Bristol). Resultados: A las 4ST el número de deposiciones por semana fue de 5,29±1,68 vs 2,46±0,71 al inicio (p<0,001). La puntuación de la escala de Bristol fue de 4,5±0,91 tras 4TS vs 2,47±1,24 al inicio (p<0,001). No se encontraron diferencias estadísticas entre los valores de sodio y osmolalidad en orina al inicio vs 4ST. Los valores de FENIR fueron normales en todos los pacientes. La prueba del aliento de hidrógeno fue normal con una mediana de 7ppm. Conclusiones: No se observaron efectos adversos renales ni alteraciones digestivas. El PEG+E puede ser recomendado para el tratamiento del estreñimiento funcional en los niños (AU)

Introduction: Polyethylene glycol 3350 plus electrolytes (PEG+E) efficacy has been validated in some studies, but not many have evaluated its safety in children. The aim of our study was to evaluate the safety; renal, malabsorption or excessive production of gas and efficacy of PEG+E treatment in our paediatric population. Patients and methods: Fifteen patients who suffered functional constipation (Rome III criteria) were evaluated. Median age was 6.2 years (r 2-9). All patients had normal renal function. PEG+E were administered for 4weeks (4WP). The mean dose was 0.44g/kg/day, titrated according to age, weight and response. Urine screens (sodium and osmolality) were performed at the beginning and 4WP. Stool sample NIRA (near-infrared reflectance analysis) and hydrogen breath test analysis samples were performed at 4WP. To analyse the efficacy of the treatment, the number of stools per week and stool form type (Bristol stool scale) were recorded. Results: The number of stools per week was higher after 4weeks (2.46±0.71 vs 5.29±1.68, P<0.001), as well as the stool form score (2.47±1.24 vs 4.5±0.91, P<0.001). No statistical differences were obtained between urine sodium and urine osmolality values at the beginning and 4WP. After 4WP the NIRA median values were normal in all patients [fat 4.45% (range (r) 3.6-7.09); nitrogen 0.78% (r 0.4-1); sugars 1.4% (r 0.47-2.35) and water 68% (r 59-74)]. Median breath hydrogen test was 7ppm (r 2-18). Conclusions: No adverse effects on biochemistry values or gastrointestinal disturbances were observed. PEG+E can be recommended for the treatment of functional constipation in children (AU)

[Safety and efficacy of polyethylene glycol 3350 plus electrolytes for the treatment of functional constipation in children]. / Seguridad y eficacia del polietilenglicol 3350 con electrolitos en el tratamiento del estreñimiento funcional en niños.

INTRODUCTION: Polyethylene glycol 3350 plus electrolytes (PEG+E) efficacy has been validated in some studies, but not many have evaluated its safety in children. The aim of our study was to evaluate the safety; renal, malabsorption or excessive production of gas and efficacy of PEG+E treatment in our paediatric population. PATIENTS AND METHODS: Fifteen patients who suffered functional constipation (Rome III criteria) were evaluated. Median age was 6.2 years (r 2-9). All patients had normal renal function. PEG+E were administered for 4 weeks (4WP). The mean dose was 0.44 g/kg/day, titrated according to age, weight and response. Urine screens (sodium and osmolality) were performed at the beginning and 4WP. Stool sample NIRA (near-infrared reflectance analysis) and hydrogen breath test analysis samples were performed at 4WP. To analyse the efficacy of the treatment, the number of stools per week and stool form type (Bristol stool scale) were recorded. RESULTS: The number of stools per week was higher after 4 weeks (2.46 ± 0.71 vs 5.29 ± 1.68, P<.001), as well as the stool form score (2.47 ± 1.24 vs 4.5 ± 0.91, P<.001). No statistical differences were obtained between urine sodium and urine osmolality values at the beginning and 4WP. After 4WP the NIRA median values were normal in all patients [fat 4.45% (range (r) 3.6-7.09); nitrogen 0.78% (r 0.4-1); sugars 1.4% (r 0.47-2.35) and water 68% (r 59-74)]. Median breath hydrogen test was 7 ppm (r 2-18). CONCLUSIONS: No adverse effects on biochemistry values or gastrointestinal disturbances were observed. PEG+E can be recommended for the treatment of functional constipation in children.

[Optimising azathioprine treatment: determination of thiopurine methyltransferase activity and thiopurine metabolites]. / Optimización del tratamiento con azatioprina: determinación de la actividad de tiopurina metiltransferasa y las concentraciones de metabolitos tiopurínicos.

INTRODUCTION: Individualised doses of azathioprine (AZA) may be prescribed by monitoring the levels of the enzyme thiopurine methyltransferase (TPMT). The measurements of thiopurine metabolites of AZA, 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP), have also been reported as new markers of AZA activity. OBJECTIVES: To describe TPMT phenotype in our population and to establish a relationship between thiopurine metabolites,and therapeutic activity and adverse effects. MATERIAL AND METHODS: Data on TPMT were retrospectively collected from 107 patients, and 6-TGN and 6-MMP levels in 18 patients currently on treatment with AZA (Crohn's disease 5, ulcerative colitis 5, autoimmune hepatitis 5). RESULTS: Mean value of TPMT was 20.19U/ml. None of the patients had a TPMT activity<5U/ml. Of the 18 patients on treatment, 13 showed sub-therapeutic levels of 6-TGN (<235pmol/8x10(8) red blood cells). Clinical remission was maintained in 45% of patients. Mean levels of 6-TGN in patients with clinical remission were 259pmol/8x10(8) red blood cells versus 209pmol/8x10(8) red blood cells in non-responders (p=0.37). There was an inverse relationship (r=-0.28) between TPMT and 6-TGN levels. Toxic effects occurred in 6 of 18 patients, with leukopenia in 5 and hyperamylasemia in 1. CONCLUSIONS: Determination of TPMT and monitoring of thiopurine metabolites allows AZA treatment to be optimised, although further studies are necessary to establish therapeutic effectiveness and toxicity ranges.

Optimización del tratamiento con azatioprina: determinación de la actividad de tiopurina metiltransferasa y las concentraciones de metabolitos tiopurínicos / Optimising azathioprine treatment: determination of thiopurine methyltransferase activity and thiopurine metabolites

Introducción: la determinación de la enzima tiopurina metiltransferasa (TPMT) nos permite pautar la dosis inicial individualizada de azatioprina (AZA). Las determinaciones de los metabolitos tiopurínicos de la AZA, la 6-tioguanina (6-TGN) y la 6-metilmercaptopurina (6-MMP) se han descrito como nuevos marcadores de la actividad del fármaco. Objetivos: describir el fenotipo de TPMT en nuestra población y relacionar los valores de los metabolitos tiopurínicos con la actividad terapéutica y los efectos adversos. Material y métodos: se recogieron retrospectivamente los valores de TPMT de 107 pacientes y de 6-TGN y 6-MMP de 18 pacientes en tratamiento con AZA (8 con enfermedad de Crohn, 5 con colitis ulcerosa y 5 con hepatitis autoinmune). Resultados: la media de determinación de TPMT fue 20,19U/ml. Ninguno presentó actividad de TPMT menor que 5U/ml. De los 18 pacientes, 13 mostraron concentraciones subterapéuticas de 6-TGN (<235pmol/8×108 hematíes). El 45% de los pacientes mantuvieron remisión clínica. La media de concentración de 6-TGN en los pacientes en remisión fue 259pmol/8×108 hematíes frente a 209pmol/8×108 hematíes en los no respondedores (p=0,37). Hay una relación inversa (r=−0,28) entre los valores de TPMT y los de 6-TGN. En 6/18 pacientes encontramos toxicidad: 5 con leucocitopenia y uno con hiperamilasemia. Conclusiones: la determinación de TPMT y la monitorización de los metabolitos tiopurínicos nos permite optimizar tratamiento con AZA, aunque son necesarios nuevos estudios que permitan el correcto conocimiento de los intervalos de efectividad terapéutica y toxicidad (AU)

Introduction: Individualised doses of azathioprine (AZA) may be prescribed by monitoring the levels of the enzyme thiopurine methyltransferase (TPMT). The measurements of thiopurine metabolites of AZA, 6-thioguanine (6-TGN) and 6-methylmercaptopurine (6-MMP), have also been reported as new markers of AZA activity. Objectives: To describe TPMT phenotype in our population and to establish a relationship between thiopurine metabolites,and therapeutic activity and adverse effects. Material and methods: Data on TPMT were retrospectively collected from 107 patients, and 6-TGN and 6-MMP levels in 18 patients currently on treatment with AZA (Crohn’s disease 5, ulcerative colitis 5, autoimmune hepatitis 5). Results: Mean value of TPMT was 20.19U/ml. None of the patients had a TPMT activity<5U/ml. Of the 18 patients on treatment, 13 showed sub-therapeutic levels of 6-TGN (<235pmol/8×108 red blood cells). Clinical remission was maintained in 45% of patients. Mean levels of 6-TGN in patients with clinical remission were 259pmol/8×108 red blood cells versus 209pmol/8×108 red blood cells in non-responders (p=0.37). There was an inverse relationship (r=−0.28) between TPMT and 6-TGN levels. Toxic effects occurred in 6 of 18 patients, with leukopenia in 5 and hyperamylasemia in 1. Conclusions: Determination of TPMT and monitoring of thiopurine metabolites allows AZA treatment to be optimised, although further studies are necessary to establish therapeutic effectiveness and toxicity ranges (AU)

Levofloxacin in the treatment of ventilator-associated pneumonia.

The use of levofloxacin in critically ill patients has progressively increased since commercial marketing of the drug in 1999, despite the fact that few studies have been designed to assess the use of levofloxacin in this population. Pharmacological characteristics, broad spectrum of activity, and tolerability account for the high interest in the drug for the treatment of different infectious diseases, including ventilator-associated pneumonia (VAP), and the recommendation of levofloxacin in guidelines developed by a number of scientific societies. According to pharmacokinetic-pharmacodynamic data, it seems reasonable to assume that an increase in activity follows from a larger dose, so that 500 mg/12 h is adequate in patients with VAP. In critically ill patients with VAP, levofloxacin monotherapy is indicated for empirical treatment of patients with early onset pneumonia without risk factors for multiresistant pathogens, and in combination therapy for late onset VAP or for patients at risk for multiresistant pathogens. The use of levofloxacin in combination therapy is supported by multiple reasons, including: increased empirical coverage in infections with suspected intracellular pathogens; substitution for more toxic antimicrobial agents (e.g., aminoglycosides) in patients with renal dysfunction and in those at risk for renal insufficiency; and severity of systemic response to infection (septic shock) that justifies multiple treatment with better tolerated antibiotics. The availability of the oral formulation allows sequential therapy, switching from the intravenous route to the oral route. Levofloxacin is well tolerated by critically ill patients, with few adverse events of mild to moderate severity.