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Breaking Therapeutic Inertia in Type 2 Diabetes : Active Detection of In-Patient Cases Allows Improvement of Metabolic Control at Midterm

  • Lucas Martín, Anna M.
  • Guanyabens, Elena
  • Zavala-Arauco, R.
  • Chamorro, Joaquín
  • Granada, Maria Luisa
  • Mauricio, Didac Puig-Domingo, Manuel
  • Universitat Autònoma de Barcelona. Departament de Medicina
Type 2 diabetes (T2D) exists in 25-40% of hospitalized patients. Therapeutic inertia is the delay in the intensification of a treatment and it is frequent in T2D. The objectives of this study were to detect patients admitted to surgical wards with hyperglycaemia (HH; fasting glycaemia > 140 mg/dL) as well as those with T2D and suboptimal chronic glycaemic control (SCGC) and to assess the midterm impact of treatment modifications indicated at discharge. A total of 412 HH patients were detected in a period of 18 months; 86.6% (357) had a diagnosed T2D. Their preadmittance HbA was 7.7 ± 1.5%; 47% (189) had HbA ≥ 7.4% (SCGC) and were moved to the upper step in the therapeutic algorithm at discharge. Another 15 subjects (3.6% of the cohort) had T2D according to their current HbA. Ninety-four of the 189 SCGC patients were evaluated 3-6 months later. Their HbA before in-hospital-intervention was 8.6 ± 1.2% and 7.5 ± 1.2% at follow-up (P < 0.004). Active detection of hyperglycaemia in patients admitted in conventional surgical beds permits the identification of T2D patients with SCGC as well as previously unknown cases. A shift to the upper step in the therapeutic algorithm at discharge improves this control. Hospitalization is an opportunity to break therapeutic inertia.

ASSURE-CSU : a real-world study of burden of disease in patients with symptomatic chronic spontaneous urticaria

  • Weller, Karsten
  • Maurer, Marcus
  • Grattan, Clive
  • Nakonechna, Alla
  • Abuzakouk, Mohamed
  • Bérard, Frédéric
  • Sussman, Gordon
  • Giménez-Arnau, Ana M.
  • Ortiz de Frutos, Javier
  • Knulst, André
  • Canonica, G. Walter
  • Hollis, Kelly
  • McBride, Doreen
  • Balp, Maria Magdalena
  • Universitat Autònoma de Barcelona. Departament de Medicina
Chronic spontaneous urticaria (CSU) formerly known as chronic idiopathic urticaria (CIU) is a severe and distressing skin condition that remains uncontrolled in approximately one half of patients, despite the use of licensed, recommended doses of modern, second-generation H-antihistamines. So far, the humanistic, societal and economic burden of CSU/CIU has not been well quantified. Therefore it is important to broaden our understanding of how CSU/CIU impacts patients, society, and healthcare systems, by determining the disease burden of CSU/CIU and the associated unmet need; as well as to further guide the use of new treatments in an efficient and cost-effective manner. ASSURE-CSU is an observational, multicenter study being conducted in the UK, Germany, Canada, France, Italy, Spain, and The Netherlands. The study comprises a retrospective medical chart review in conjunction with patient surveys (including validated tools for assessment of disease impact) and an 8-day patient diary. The primary objectives of the study are to describe patient demographics, medical history, treatments, and healthcare resource utilization based on medical-record data and to assess the impact of disease, healthcare resource utilization, work days missed, and productivity loss based on patient-reported data. Approximately 700 patients (aged ≥18 years) will be enrolled who have CSU/CIU despite currently receiving treatment, and have had persistent symptoms for at least 12 months. Data will be collected retrospectively for the 12 months (±1 month) prior to enrolment wherever possible, and prospectively for the week following enrolment. ASSURE-CSU will be the first study to examine the economic and humanistic burden of disease in patients diagnosed with CSU/CIU who are symptomatic despite treatment. By combining retrospective evaluation of medical records with prospective patient surveys and 8-day diaries, across seven different countries, the ASSURE-CSU study will contribute to a better understanding and acknowledgement of the burden of disease in patients with symptomatic chronic spontaneous urticaria.

Evaluation of dose reduction versus standard dosing for maintenance of remission in patients with spondyloarthritis and clinical remission with anti-TNF (REDES-TNF) : study protocol for a randomized controlled trial

  • Pontes García, Caridad
  • Gratacós Masmitjà, Jordi
  • Torres, Ferran
  • Avendaño, Cristina
  • Sanz, Jesús
  • Vallano, Antoni
  • Juanola, Xavier
  • de Miguel, Eugenio
  • Sanmartí, Raimon
  • Calvo, Gonzalo
  • Universitat Autònoma de Barcelona. Departament de Medicina
Dose reduction schedules of tumor necrosis factor antagonists (anti-TNF) as maintenance therapy in patients with spondyloarthritis are used empirically in clinical practice, despite the lack of clinical trials providing evidence for this practice. To address this issue the Spanish Society of Rheumatology (SER) and Spanish Society of Clinical Pharmacology (SEFC) designed a 3-year multicenter, randomized, open-label, controlled clinical trial (2 years for inclusion and 1 year of follow-up). The study is expected to include 190 patients with axial spondyloarthritis on stable maintenance treatment (≥4 months) with any anti-TNF agent at doses recommended in the summary of product characteristics. Patients will be randomized to either a dose reduction arm or maintenance of the dosing regimen as per the official labelling recommendations. Randomization will be stratified according to the anti-TNF agent received before study inclusion. Patient follow-up, visit schedule, and examinations will be maintained as per normal clinical practice recommendations according to SER guidelines. The study aims to test the hypothesis of noninferiority of the dose reduction strategy compared with standard treatment. The first patients were recruited in July 2012, and study completion is scheduled for the end of April 2015. The REDES-TNF study is a pragmatic clinical trial that aims to provide evidence to support a medical decision now made empirically. The study results may help inform clinical decisions relevant to both patients and healthcare decision makers. EudraCT (21 December 2011) The online version of this article (doi:10.1186/s13063-015-0828-5) contains supplementary material, which is available to authorized users.

Profile of omalizumab in the treatment of chronic spontaneous urticaria

  • Labrador-Horrillo, Moises
  • Ferrer, Marta
  • Universitat Autònoma de Barcelona. Departament de Medicina
Chronic spontaneous urticaria (CSU) is a disease with significant morbidity and relative prevalence that has important effects on the quality of life (QoL) of those who suffer from it. Omalizumab is a recombinant humanized anti-immunoglobulin E (IgE) antibody that binds to the Cε3 domain of the IgE heavy chain and prevents it from binding to its high-affinity receptor FcεRI. It has been largely studied in the field of asthma and is currently approved for the treatment of both adult and pediatric (children; >6-year-old) patients. In addition, in recent, well-controlled clinical trials in patients with CSU resistant to antihistamines, add-on therapy with subcutaneous omalizumab significantly reduced the severity of itching, and the number and size of hives, and increased patients' health-related QoL and the proportion of days free from angioedema compared with placebo, with an excellent tolerance. Thus, omalizumab is an effective and well-tolerated add-on therapy for patients with CSU who are symptomatic despite background therapy with H1 antihistamines. In this review, we cover the following points: epidemiology, pathogenesis, assessment of activity, impact on QoL, and treatment of CSU, and finally, we focus on omalizumab in the treatment of CSU including the pharmacokinetic properties and mechanism of action, and use in pregnant women, nursing infants, and children.

The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

  • Gayarre, Javier
  • Kamieniak, Marta M.
  • Cazorla-Jiménez, Alicia
  • Muñoz-Repeto, Ivan
  • Borrego, Salud
  • García-Donas, Jesús
  • Hernando, Susana
  • Robles-Díaz, Luis
  • García-Bueno, José M.
  • Ramón y Cajal, Teresa
  • Hernández-Agudo, Elena
  • Heredia Soto, Victoria
  • Márquez-Rodas, Ivan
  • Echarri, María José
  • Lacambra-Calvet, Carmen
  • Sáez, Raquel
  • Cusidó, Maite
  • Redondo, Andrés
  • Paz-Ares, Luis
  • Hardisson, David
  • Mendiola, Marta
  • Palacios, José
  • Benítez, Javier
  • García, María José
  • Universitat Autònoma de Barcelona. Departament de Medicina
We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5- silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5 -silenced ovarian cancer cells. Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization.

Salivary Secretory Disorders, Inducing Drugs, and Clinical Management

  • Miranda-Rius, Jaume
  • Brunet-Llobet, Lluís
  • Lahor -Soler, Eduard
  • Farré Albaladejo, Magí
  • IMIM: Institut Hospital del Mar d'Investigacions Mèdiques
  • Universitat Autònoma de Barcelona. Departament de Medicina
Background: Salivary secretory disorders can be the result of a wide range of factors. Their prevalence and negative effects on the patient's quality of life oblige the clinician to confront the issue. Aim: To review the salivary secretory disorders, inducing drugs and their clinical management. Methods: In this article, a literature search of these dysfunctions was conducted with the assistance of a research librarian in the MEDLINE/PubMed Database. Results: Xerostomia, or dry mouth syndrome, can be caused by medication, systemic diseases such as Sjögren's Syndrome, glandular pathologies, and radiotherapy of the head and neck. Treatment of dry mouth is aimed at both minimizing its symptoms and preventing oral complications with the employment of sialogogues and topical acting substances. Sialorrhea and drooling, are mainly due to medication or neurological systemic disease. There are various therapeutic, pharmacologic, and surgical alternatives for its management. The pharmacology of most of the substances employed for the treatment of salivary disorders is well-known. Nevertheless, in some cases a significant improvement in salivary function has not been observed after their administration. Conclusion: At present, there are numerous frequently prescribed drugs whose unwanted effects include some kind of salivary disorder. In addition, the differing pathologic mechanisms, and the great variety of existing treatments hinder the clinical management of these patients. The authors have designed an algorithm to facilitate the decision making process when physicians, oral surgeons, or dentists face these salivary dysfunctions.

Modelos experimentales de peritonitis bacteriana inducida en ratas con cirrosis y nuevas estrategias terapéuticas

  • Sánchez Ardid, Elisabet
  • Universitat Autònoma de Barcelona. Departament de Medicina
INTRODUCCIÓN: Los pacientes cirróticos tienen una elevada susceptibilidad a las infecciones, siendo la peritonitis bacteriana espontánea especialmente grave. Pese a que el tratamiento antibiótico es eficaz, la mortalidad todavía es elevada. Los modelos experimentales descritos hasta el momento son modelos de cirrosis que pueden llegar a desarrollar ascitis y peritonitis bacteriana espontánea, aunque con dificultades metodológicas. Para validar nuevos tratamientos es imprescindible disponer de un modelo experimental que se asemeje al máximo a la patología humana a estudiar. OBJETIVOS: Desarrollar modelos experimentales de peritonitis bacteriana inducida en ratas con cirrosis que permita evaluar nuevas estrategias terapéuticas MATERIAL Y MÉTODOS: Para el desarrollo del modelo experimental de peritonitis bacteriana inducida se utilizó ratas Sprague-Dawley con cirrosis inducida mediante la administración orogástrica de CCl4 con o sin ascitis. Recibieron una inyección intraperitoneal de diferentes concentraciones de E. coli diluido en 1 ml de agua estéril y diferentes volúmenes de agua estéril. Un subgrupo de animales sin ascitis recibió ceftriaxona 4 horas después de la inoculación de E. coli. En el segundo protocolo se utilizaron ratas a las que se les indujo PBI mediante una inyección intraperitoneal de 109 ufc de E. coli diluido en 20 ml de agua estéril. Fueron aleatorizados a recibir por vía subcutánea: placebo, ceftriaxona, anti-TNFα y ceftriaxona, o anti-TNFα solo. RESULTADOS: Las ratas con ascitis mostraron una menor mortalidad que las ratas sin ascitis a las que se les inyectó 108 o 109 ufc de E. coli (p 0.05). La mortalidad fue mayor con 109 ufc respecto 108 ufc de E. coli tanto en ratas con ascitis (pNS) como en las ratas sin ascitis (p 0.01). Se observó una tendencia a una menor mortalidad en las ratas inoculadas con 108 ufc de E. coli y mayor volumen de líquido inoculado. Se observó una marcada respuesta de las células polimorfonucleares peritoneales 4 horas después de la inyección de E. coli tanto en ratas con o sin ascitis. La terapia con antibióticos redujo significativamente la mortalidad en las ratas infectadas con 108 ufc de E. coli (p 0.01). En el segundo protocolo la mortalidad en las ratas tratadas con ceftriaxona y anti-TNFα fue menor que en los animales que recibieron placebo (53% vs 100%, p 0.01). Los niveles TNFα en suero se redujeron significativamente en las ratas que sobrevivieron tratadas con ceftriaxona y anti-TNFα pero no en aquellas tratadas con antibiótico solo. CONCLUSIONES: Hemos desarrollado un nuevo modelo experimental de peritonitis bacteriana inducida en ratas cirróticas con o sin ascitis, que es fácilmente reproducible, mediante la inoculación intraperitoneal de E. coli y que podría ser de gran utilidad para evaluar nuevas estrategias terapéuticas, como la administración de anti-TNFα asociada a antibióticos., INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a common and severe infection in patients with cirrhosis. Although antibiotic treatment is effective, mortality is still high. The experimental model of cirrhosis induced by carbon tetrachloryde administration has been used to study the pathogenesis of ascites formation, renal dysfunction and bacterial translocation and to evaluate the effect of administration of different drugs on portal pressure and water and sodium renal excretion. However, this model has not been used to evaluate spontaneous bacterial peritonitis and the effect of different therapies. It is very important to design an experimental model of bacterial peritonitis in cirrhotic rats that remembers the outcome of the disease in cirrhotic patients. AIM: To develop an available experimental model of induced bacterial peritonitis in cirrhosis and to evaluate the efficacy of new therapeutic interventions in this model of induced bacterial peritonitis (IBP). MATERIAL AND METHODS: We used Sprague-Dawley rats with carbon-tetrachloride-induced cirrhosis with or without ascites. Rats were randomized to receive an intraperitoneal administration of different concentrations of Escherichia coli (E. coli) diluted in 1 ml of sterile water in ascitic rats and in different volumes in nonascitic rats. A subgroup of nonascitic animals received ceftriaxone 4 h after E. coli inoculation. In the second protocol cirrhotic rats without ascites were infected with an intraperitoneal injection of 109 cfu of E. coli diluted in 20 ml of sterile water to induce bacterial peritonitis and then were randomized to receive placebo, ceftriaxone, anti-TNFα and ceftriaxone, or anti-TNFα alone administered subcutaneously. RESULTS: Ascitic rats showed a lower mortality rate than nonascitic rats infected with 108 or 109 cfu of E. coli (p 0.05). Mortality was higher with 109 cfu than with 108 cfu of E. coli in ascitic (pNS) and nonascitic (p 0.01) rats. A trend was noted to ward higher mortality in nonascitic rats inoculated with 108 cfu with increasing water volumes. A marked peritoneal polymorphonuclear cell response was observed 4 h after E. coli injection in both ascitic and nonascitic rats. Antibiotic therapy significantly reduced the mortality rate of rats infected with 108 cfu (p 0.01). In the second protocol mortality in rats treated with ceftriaxone and anti-TNFα was significantly lower than in animals receiving placebo (53% vs. 100%, p 0.01). Serum TNFα decreased significantly in surviving rats treated with ceftriaxone plus anti-TNFα but not in treated with antibiotics alone. CONCLUSIONS: We have developed a new experimental model of induced bacterial peritonitis in cirrhotic rats with or without ascites, which is easily reproducible by intraperitoneal inoculation of E. coli and may represent a useful tool for the study of pathogenic events postinfection and for the design of new therapeutic strategies to treat patients with SBP such as the administration of anti-TNFα associated with antibiotics.

Activación del sistema del complemento en la insuficiencia renal aguda y su relacion con otras vías inflamatorias

  • Rodríguez García, Eva
  • Universitat Autònoma de Barcelona. Departament de Medicina
El objetivo principal de este estudio de investigación es determinar si existe activación del sistema del complemento en la Insuficiencia Renal Aguda (IRA) humana, como sugieren estudios preclínicos. Como objetivos secundarios hemos estudiado si existe activación de otras vías inflamatorias representadas por la interleuquina-6 (IL-6), interleuquina-10 (IL-10) y NGAL o Lipocalina-2, como marcador de activación de los neutrófilos. Con el objetivo de estudiar la activación del sistema del complemento determinamos la fracción lítica del sistema de complemento ó Complejo Ataque de Membrana (MAC) tanto en plasma, mediante técnicas de ELISA-HS, como en tejido renal, mediante técnicas de tinción por inmunohistoquímica. Se incluyeron en el estudio 156 pacientes, el 52,6% de ellos presentaban IRA y el resto son homólogos respecto a las condiciones clínicas, pero mantuvieron función renal normal. Se incluyeron pacientes con IRA de distintas etiologías (séptica, nefrotoxicidad, isquemia-reperfusión y multifactorial). Las concentraciones plasmáticas de MAC son significativamente más elevadas en pacientes con IRA y se relacionan con parámetros clínicos de gravedad utilizados en la práctica clínica habitual, de tal manera que los pacientes con niveles plasmáticos más elevados de MAC son aquellos que requerirán tratamiento renal sustitutivo durante el ingreso hospitalario y que presentarán una recuperación más lenta de la función renal. Además, las concentraciones de MAC durante el episodio de IRA pueden influir a medio plazo en la función renal, de tal manera que los pacientes que evolucionaron a insuficiencia renal crónica o bien presentaron nuevos episodios de IRA en un período de tres años, son aquellos con los niveles más altos de MAC. Por otro lado, en los pacientes con IRA existe una elevación plasmática significativa de IL-6 y Lipocalina-2, que se relacionan con los mismos parámetros de gravedad de MAC. Ambos biomarcadores muestran distintos grados de correlación con el MAC plasmático e IL-10 en los pacientes más graves, aquellos que fallecerán en el episodio agudo. Los resultados en tejido renal, tanto procedente de autopsia clínica como de biopsia renal, muestran un depósito lineal en la membrana basal tubular de MAC de aquellas muestras de pacientes con IRA, que no se objetiva en pacientes con función renal normal. En las muestras de tejido renal en pacientes con IRA se observa una mayor tinción citoplasmática de Factor H, regulador de la vía alternativa, especialmente en formas histológicas IRA de mayor gravedad, aunque no hemos objetivado diferencias en las concentraciones plasmáticas de Factor H., The main objective of this study is to establish if complement pathway is activated in human Acute Kidney Injury (AKI), as suggested by pre-clinical studies. Secondary objectives are to determine if other inflammatory pathways are activated, represented by interleukin-6, interleukin-10 and NGAL or Lipocalin-2 as a marker of the neutrophil activation. For this purpose, we evaluated the lytic complex of the complement pathway or Membrane Attack Complex (MAC) in plasma, using ELISA-HS techniques or in kidney tissue by immunochemistry staining. We included 156 patients, 52.6% of them with AKI and 47,4% under the same clinical conditions but with normal kidney function. The study enrolled different AKI etiologies (septic, nephrotoxic, ischemia-reperfusion and multifactorial). Plasma results show that MAC concentrations are significant higher in AKI patients. Furthermore, plasmatic MAC concentrations are related with clinical parameters of severity, AKI patients with higher MAC plasmatic levels need renal replacement therapy during hospitalization and show delayed recovery of renal function. Our data suggest that MAC concentrations during AKI episode could have influence in mid-term renal function, in such a way that the patients developing chronic kidney disease or those suffering new AKI episodes during 3-years follow up, show higher MAC concentrations in the first AKI episode. AKI patients show significantly higher plasmatic IL-6 and Lipocalin-2 concentrations than those with normal kidney function. These concentrations are related with clinical severity parameters and show different degrees of correlation with MAC plasmatic levels. IL-10 is significant higher in critically ill patients who die during an AKI episode. Immunohistochemistry staining results show linear deposits of MAC in tubular basal membranes of AKI patients. Immunohistochemistry staining for Factor H, the main regulator of alternative pathway, shows cytoplasmic pattern with high intensity in AKI patients, displaying a correlation between intensity of staining and histologic patterns of acute tubular necrosis. Plasmatic concentrations of Factor H do not show differences between AKI patients and patients with a normal renal function.

Búsqueda de nuevas dianas terapéuticas en la encefalopatía hepática

  • Simón-Talero Horga, Macarena
  • Universitat Autònoma de Barcelona. Departament de Medicina
La encefalopatía hepática (EH) es una complicación frecuente e invalidante de la cirrosis hepática. Su fisiopatología aún no está bien establecida, aunque el amoníaco desempeña un papel clave. Los tratamientos disponibles se basan en la reducción del amoníaco plasmático. Actualmente, el tratamiento de un episodio agudo consiste en intentar corregir el factor precipitante y en la administración de disacáridos no absorbibles (lactulosa o lactitol). Como segundo escalón, en casos de recidiva, se emplean antibióticos como la rifaximina. Sin embargo, a pesar de los tratamientos disponibles, la EH es una descompensación frecuente, que merma la calidad de vida de los pacientes y que se asocia a una elevada morbimortalidad. Por ello, consideramos necesaria la búsqueda de nuevas dianas terapéuticas. En el primer estudio se valora la eficacia de la administración de albúmina (proteína con múltiples funciones, cuya concentración y capacidad funcional se encuentran disminuidas en la cirrosis) en el episodio agudo de EH. Para ello, se llevó a cabo un ensayo clínico multicéntrico doble ciego controlado con placebo, en el que se administró albúmina (a dosis equivalentes a la administrada en la peritonitis bacteriana espontánea) o suero fisiológico a pacientes con un episodio de EH grado II o superior. El objetivo principal del estudio fue valorar la eficacia en reducir la duración del episodio de EH. Se incluyeron 56 pacientes, de los cuales 26 fueron aleatorizados a recibir albúmina y 30, placebo. La administración de albúmina no demostró una disminución en la duración del episodio de EH. Sin embargo, dentro de los objetivos secundarios, el grupo que recibió albúmina sí que presentó una mayor supervivencia libre de trasplante hepático a los 90 días (69.2% en el grupo albúmina vs. 40% en el grupo placebo; p = 0.02), con un Hazard Ratio de 0.37 (IC 95% 0.16-0.89). Es posible que la EH identifique un grupo de pacientes graves que se beneficien de la administración de dicho tratamiento. En el segundo estudio, se plantea si la embolización de colaterales portosistémicas de gran tamaño es un tratamiento eficaz para la EH recurrente. La experiencia relativa a este procedimiento se basa en casos aislados o en series pequeñas. Para responder esta cuestión llevamos a cabo un estudio retrospectivo multicéntrico, en el que se incluyeron 37 pacientes. En el seguimiento a corto plazo (100 días tras el procedimiento), 59.5% de los pacientes (22 de 37) no volvieron a presentar un episodio de EH (p 0.001). En el seguimiento a largo plazo (697 ± 157 días), el 48.6% de los pacientes (18 de 37, p 0.001) permanecía libre de EH respecto a antes de la embolización. En el análisis estadístico, fue la función hepática determinada mediante la escala MELD, la que permitió predecir la recurrencia tras el procedimiento. Mediante la realización de una curva ROC se estableció un punto de corte de 11 puntos, que permitía identificar a los pacientes que se beneficiarían de la embolización. Respecto a la seguridad, el 24.3% (9 de 37) presentó efectos adversos relacionados con el procedimiento, siete de ellos leves. A largo plazo, no observamos un incremento significativo en el número de pacientes con varices gastroesofágicas ni ascitis. Las conclusiones de este estudio son que la embolización de colaterales portosistémicas de gran tamaño es un procedimiento seguro y eficaz en pacientes con buena función hepática., Hepatic encephalopathy (HE) is a frequent and impairment complication of liver cirrhosis. Its pathophysiology is not well established, although ammonia plays an important role. Current treatments are based on reducing plasma ammonia. Treatment of an acute episode consists in correcting the precipitating factors and the administration of nonabsorbable disaccharides (lactulose or lactitol). As a second step, in case of relapse, antibiotics as rifaximin are used. However, despite available treatments, HE is a frequent decompensation, which affects patients' quality of life and that is associated with high morbidity and mortality. Therefore, we consider necessary the search for new therapeutic targets. In the first study the effectiveness of the administration of albumin (a protein with multiple functions, which concentration and functional capacity are decreased in cirrhosis) in an acute episode of HE is evaluated. For this purpose, we conducted a double blind placebo-controlled multicenter trial in which albumin (at doses similar to those recommended for spontaneous bacterial peritonitis) or saline was administered to patients with an episode of HE grade II or more. The main objective was to assess the effectiveness in reducing the duration of the episode of HE. Fifty-six patients were included, 26 randomized to albumin and 30 to placebo. Albumin administration did not show any clinical benefit on HE. However, as a secondary objective, the group receiving albumin had a higher transplant-free-survival at day 90 (69.2% in the albumin group vs. 40% in the placebo group; p = 0.02), with a Hazard Ratio of 0.37 (95% CI 0.16-0.89). HE may identify a group of patients that benefits from the administration of albumin. In the second study, we verify whether the embolization of large portosystemic shunts is an effective treatment for recurrent HE. The experience with this procedure is based on anecdotal cases or short series. To answering this question we conducted a retrospective multicenter study in which 37 patients were included. In the short-term follow-up (100 days after the procedure), 59.5% of the patients (22 of 37) did not present any new episode of HE (p 0.001). In the long-term follow-up (697 ± 157 days), 48.6% (18 of 37, p 0.001) remained free of HE. In the statistical analysis, the MELD score was identified as a predictor of recurrence after the procedure. By performing a ROC curve, a cutoff of 11 points allowed to identify patients who would benefit from embolization. Regarding safety, 24.3% (9 of 37) had adverse effects related to the procedure, 7 of them mild. In the long-term, we did not observe a significant increase in the number of patients with gastroesophageal varices or ascites. Embolization of large portosystemic shunts is a safe and effective procedure in patients with good liver function.

Epidemiologia molecular de Legionella

  • García Núñez, Marian
  • Sabriá-Leal, M
  • Universitat Autònoma de Barcelona. Departament de Medicina

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