Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice.

BACKGROUND: Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. AIMS: To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). METHODS: We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. RESULTS: Of 255 patients, median follow-up was 35.1 months (IQR: 20.2-53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. CONCLUSION: Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension.

Clinical and genetic factors involved in Porto-sinusoidal vascular disorder after oxaliplatin exposure.

BACKGROUND AND AIMS: Oxaliplatin (OX) has been described as a potential etiologic agent for porto-sinusoidal vascular disorder (PSVD). Our aim was to describe the natural history of PSVD due to OX in colon cancer (CRC) and identify risk factors for its development. METHODS: We made a multicenter retrospective case-control (ratio 1:3) study with patients diagnosed of PSVD-OX. Baseline data, end of treatment, years of follow-up and diagnosis of PSVD were collected and compared to controls (without PSVD). Besides, 16 different SNPs were selected from bibliography and analyzed by genotyping in the case group to identify potential genetic risk factors. RESULTS: 41 cases were identified, with a median time to PSVD diagnosis after the end of OX of 34 months. Spleen diameter was the strongest predictor of PSVD during treatment (OR 43.94 (14.48-133.336); p < 0.0001). Additionally, thrombocytopenia (<150 × 10^9) at one year was a significant disease risk marker (OR 9.35; 95% CI: 3.71-23.58; p = 0.001). We could not establish any significant association between the selected SNPs and PSVD diagnosis. CONCLUSION: The increase of spleen diameter is the strongest predictor of PSVD in patients treated with OX for CRC. These patients could be candidates for a specific follow-up of portal hypertension-related complications.

Are liver contour and bone fusion comparable to fiducials for IGRT in liver SBRT?

Introduction: Liver stereotactic body radiotherapy (SBRT) is increasingly being used to treat tumours. The purpose of this study was to compare the differences in patient positioning when using implanted fiducials as surrogates compared to alternative methods based on liver contour or bone registration. Material and methods: Eighteen patients treated with SBRT who underwent a fiducial placement procedure were included. Fiducial guidance was our gold standard to guide treatment in this study. After recording the displacements, when fusing the planning CT and CBCT performed in the treatment unit using fiducials, liver contour and bone reference, the differences between fiducials and liver contour and bone reference were calculated. Data from 88 CBCT were analyzed. The correlation between the displacements found with fiducials and those performed based on the liver contour and the nearest bone structure as references was determined. The mean, median, variance, range and standard deviation of the displacements with each of the fusion methods were obtained. µ, Æ©, and σ values and margins were obtained. Results: Lateral displacements of less than 3 mm with respect to the gold standard in 92% vs. 62.5% of cases using liver contour and bone references, respectively, with 93.2% vs. 65.9% in the AP axis and SI movement in 69.3% vs. 51.1%. The errors µ, σ and Æ© of the fusions with hepatic contour and bone reference in SI were 0.26 mm, 4 mm and 3 mm, and 0.8 mm, 5 mm and 3 mm respectively. Conclusion: Our study showed that displacements were smaller with the use of hepatic contour compared to bone reference and comparable to those obtained with the use of fiducials in the lateral, AP and SI motion axes. This would justify that hepatic contouring can be a guide in the treatment of patients in the absence of fiducials.

Pre-surgical risk assessment in patients with cirrhosis.

Over the last decades, significant improvements in the clini- cal management of patients with cirrhosis have increased their life expectancy. Thus, indications for surgical procedures other than liver transplantation are becoming more frequent. However, patients with advanced liver disease are at high risk of perioperative morbidity and mortality. This is the consequence of multiple factors that include the presence of portal hypertension, alterations on hemostasis and coagulation, the immune dysfunction that entails an increased risk of infections, and the impaired synthesis of proteins that impacts on the nutritional status and the wound healing. Surgical outcomes are not only determined by the severity of the liver disease, but also by the type of surgery and the presence of other comorbidities. Different models to predict mortality have been proposed, including the MELD score, the Child-Pugh classification, the hepatic venous pressure gradient, and the Mayo postoperative mortality risk calculator, among others. Multidisciplinary committees including surgeons, anesthesiologists, hepatologists, critical care physicians and other specialties involved in each case, should assess individually the risk-benefit of the surgical procedure, also considering patient`s expectations and will.

Enfermedad de Wilson en adolescente con hipertransaminasemia asintomática / Wilson's disease in adolescent with asymptomatic hypertransaminasemia

La hipertransaminasemia en la edad pediátrica es un hallazgo relativamente frecuente en niños asintomáticos; suele ser un indicador sensible de daño hepático, aunque poco específico. Se considera crónica cuando persiste más de 6 meses. En esos casos puede ser el primer indicador de enfermedades que requieren tratamiento precoz para mejorar el pronóstico. Presentamos el caso de una niña preadolescente que presenta hipertransaminasemia crónica en el contexto de un estudio inicial de dolor abdominal inespecífico, cuyo diagnóstico final fue enfermedad de Wilson

Hypertransaminasemia in the pediatric age is a relatively common finding in asymptomatic children, which is usually a sensitive indicator of liver damage, although not very specific. It is considered prolonged when hypertransaminasemia persists for more than 6 months. In those cases, it may be the first indicator of diseases that require early treatment to improve prognosis. We present the case of a preadolescent girl who presented hypertransaminasemia detected during the study of nonspecific abdominal pain, whose final diagnosis was Wilson's disease

Manejo actual de la pancreatitis aguda idiopática y la pancreatitis aguda recurrente / Current management of acute idiopathic pancreatitis and acute recurrent pancreatitis

La pancreatitis aguda es una entidad de notable importancia debido a su elevada incidencia y a su no desdeñable morbimortalidad. Se conoce como pancreatitis aguda idiopática aquella en la que no se consigue determinar la causa del cuadro tras un estudio básico inicial. Conocer la etiología subyacente permite plantear un tratamiento dirigido para así disminuir el riesgo de recurrencia. La ecoendoscopia y la colangiografía por resonancia magnética son las pruebas de elección para profundizar en el estudio etiológico. La principal causa es la enfermedad litiásica no diagnosticada en el estudio inicial, cuyo tratamiento de elección es la colecistectomía. Por otra parte, la pancreatitis aguda recurrente se diagnostica tras la existencia de 2 o más episodios de pancreatitis aguda. El objetivo de esta revisión es proporcionar una aproximación actualizada de estas 2 entidades, repasando aspectos de su epidemiología, diagnóstico y alternativas terapéuticas disponibles

Acute pancreatitis is an entity of notable importance due to its high incidence and its non-negligible morbidity and mortality. Idiopathic acute pancreatitis is that in which the cause of the clinical condition cannot be determined after an initial basic study. Understanding the underlying aetiology enables clinicians to propose a targeted treatment to reduce the risk of recurrence. Endoscopic ultrasonography and magnetic resonance cholangiopancreatography are the tests of choice to deepen the aetiological study. The main cause is undiagnosed lithiasic disease in the initial study, whose treatment of choice is cholecystectomy. Moreover, recurrent acute pancreatitis is diagnosed after 2 or more episodes of acute pancreatitis. The objective of this review is to provide an updated approach for these 2 entities, reviewing aspects of their epidemiology, diagnosis and available alternative therapies

Current management of acute idiopathic pancreatitis and acute recurrent pancreatitis. / Manejo actual de la pancreatitis aguda idiopática y la pancreatitis aguda recurrente.

Acute pancreatitis is an entity of notable importance due to its high incidence and its non-negligible morbidity and mortality. Idiopathic acute pancreatitis is that in which the cause of the clinical condition cannot be determined after an initial basic study. Understanding the underlying aetiology enables clinicians to propose a targeted treatment to reduce the risk of recurrence. Endoscopic ultrasonography and magnetic resonance cholangiopancreatography are the tests of choice to deepen the aetiological study. The main cause is undiagnosed lithiasic disease in the initial study, whose treatment of choice is cholecystectomy. Moreover, recurrent acute pancreatitis is diagnosed after 2 or more episodes of acute pancreatitis. The objective of this review is to provide an updated approach for these 2 entities, reviewing aspects of their epidemiology, diagnosis and available alternative therapies.

Enfermedades vasculares del hígado. Guías Clínicas de la Sociedad Catalana de Digestología y de la Asociación Española para el Estudio del Hígado / Vascular diseases of the liver. Clinical Guidelines from the Catalan Society of Digestology and the Spanish Association for the Study of the Liver

Las enfermedades vasculares hepáticas, a pesar de su relativamente baja prevalencia, representan un problema de salud importante en el campo de las enfermedades hepáticas. Una característica común a muchas de estas enfermedades es que pueden causar hipertensión portal, con la elevada morbimortalidad que ello conlleva. Con frecuencia estas enfermedades se diagnostican en pacientes jóvenes y el retraso en su diagnóstico y/o un tratamiento inadecuado pueden reducir de forma importante la esperanza de vida. El presente artículo revisa la evidencia actual en el síndrome de Budd-Chiari, la trombosis venosa portal en pacientes no cirróticos, la hipertensión portal idiopática, el síndrome de obstrucción sinusoidal, las malformaciones vasculares hepáticas en la telangiectasia hemorrágica hereditaria, la trombosis portal en la cirrosis, otras patologías vasculares menos frecuentes como las fístulas arterioportales, así como un apartado sobre el diagnóstico por imagen de las enfermedades vasculares hepáticas y su tratamiento desde el punto de vista hematológico (estudio de la diátesis trombótica y tratamiento anticoagulante). Las recomendaciones se han realizado de acuerdo a los estudios publicados extraídos de Pubmed. La calidad de la evidencia y la intensidad de las recomendaciones fueron graduadas de acuerdo al sistema Grading of Recommendations Assessment Development and Evaluation (GRADE). Cuando no existían evidencias suficientes, las recomendaciones se basaron en la opinión del comité que redactó la guía.

Despite their relatively low prevalence, vascular diseases of the liver represent a significant health problem in the field of liver disease. A common characteristic shared by many such diseases is their propensity to cause portal hypertension together with increased morbidity and mortality. These diseases are often diagnosed in young patients and their delayed diagnosis and/or inappropriate treatment can greatly reduce life expectancy. This article reviews the current body of evidence concerning Budd-Chiari syndrome, non-cirrhotic portal vein thrombosis, idiopathic portal hypertension, sinusoidal obstruction syndrome, hepatic vascular malformations in hereditary haemorrhagic telangiectasia, cirrhotic portal vein thrombosis and other rarer vascular diseases including arterioportal fistulas. It also includes a section on the diagnostic imaging of vascular diseases of the liver and their treatment from a haematological standpoint (study of thrombotic diathesis and anticoagulation therapy). All recommendations are based on published studies extracted from PubMed. The quality of evidence and strength of recommendations were rated in accordance with the GRADE system (Grading of Recommendations, Assessment Development and Evaluation). In the absence of sufficient evidence, recommendations were based on the opinion of the committee that produced the guide.

Initial immunosuppression with or without basiliximab: a comparative study.

BACKGROUND: Following liver transplantation, acute kidney injury (AKI) and chronic kidney disease occur in 20%-50% and 30%-90% of patients, respectively. Basiliximab, a chimeric monoclonal antibody, is highly effective to prevent rejection in organ transplant recipients, particularly among patients with renal dysfunction who benefit from delayed introduction of calcineurin inhibitors. OBJECTIVE: The objective of this study was to measure the immunosuppressive effect of basiliximab and its impact on renal failure, lengths of hospital and intensive care unit (ICU) stays and prevalence of infection. METHODS: From January 2010 through December 2011, we performed a controlled, nonrandomized study comparing two different immunosuppressive regimens: Group I, 36 transplantation on 34 patients, tacrolimus and corticosteroids de novo with mycophenolate mofetil in cases of renal failure; and Group II, 33 transplantation in 33 patients, corticosteriods and mycophenolate mofetil de novo with basiliximab on day 0 and day 4, and inception of tacrolimus on day 3. RESULTS: Basiliximab patients (Group II) showed a significantly lower incidence of renal failure requiring replacement therapy (3.03% vs 25%; P = .014). The incidence of acute cellular rejection episodes treated with corticosteriod boluses was also significantly lower (3.03% vs 25%; P = .014). Bacterial, fungal, and cytomegalovirus infection rates were lower in Group II, although the differences were not significant. Similarly, Group II patients had an insignificantly shorter average stay in the hospital (25.9 vs 40.06 days) and the ICU (5.9 vs 8.17 days). CONCLUSIONS: Basiliximab administration with delayed introduction of calcineurin inhibitors may be an effective strategy to reduce post-liver transplantation AKI requiring renal replacement therapy.

Endoscopic follow-up of gastric ulcer in a population at intermediate risk for gastric cancer.

OBJECTIVES: Primary: to assess the necessity of a second endoscopy with a pathology study to confirm the healing of all gastric ulcers previously diagnosed through endoscopy in a population at intermediate risk for gastric cancer. Secondary: to assess correlation between endoscopic findings and pathology diagnosis. PATIENTS AND METHODS: a prospective analysis of patients diagnosed with gastric ulcer through endoscopy at Hospital General de Ciudad Real (Spain) over three years. We collected demographic, clinical, endoscopic, and pathological data for the first and subsequent endoscopies. We collected at least six biopsies obtained from ulcer margins, and assessed H. pylori infection. RESULTS: Three hundred and two patients were included in this study. H. pylori infection was diagnosed in 173 (57%), and 113 (37%) patients had used NSAIDs. The positive and negative predictive value for malignancy of endoscopic diagnosis regarding ulcer fold, base, and margins were 34 and 97%, respectively. Only one patient was diagnosed with a tumor during the second endoscopy. At the end of follow-up, the etiology of the ulcer was considered as peptic in 276 patients; Crohn s disease-related in one, and neoplastic in 25 patients (21 adenocarcinomas, 4 lymphomas). CONCLUSIONS: in an intermediate-risk population for gastric cancer a second endoscopy is not justified for gastric ulcer patients when endoscopy and biopsy results do not suggest malignancy.

Seguimiento endoscópico de la úlcera gástrica en una población de riesgo intermedio de cáncer gástrico / Endoscopic follow-up of gastric ulcer in a population at intermediate risk for gastric cancer

Objetivos: Primario: valorar la necesidad de una segunda endoscopia con estudio anatomopatológico para confirmar la curación de todas las úlceras gástricas diagnosticadas previamente mediante endoscopia, en una población de riesgo intermedio de cáncer gástrico. Secundario: correlacionar el juicio diagnóstico del endoscopista y el diagnóstico anatomopatológico. Pacientes y métodos: análisis prospectivo de todos los pacientes diagnosticados de úlcera gástrica mediante endoscopia en el Hospital General de Ciudad Real durante tres años. Se recogieron datos demográficos, clínicos, endoscópicos y anatomopatológicos de la primera y sucesivas endoscopias. Se tomaron al menos seis muestras de biopsia del nicho y se valoró la presencia de H. pylori. Resultados: se incluyeron 302 pacientes. Se diagnosticó infección por H. pylori en 173 (57%) y se documentó la toma de AINE en 113 (37%). El valor predictivo positivo y negativo para malignidad del diagnóstico endoscópico atendiendo a los pliegues, fondo y bordes del nicho fue de 34 y 97%, respectivamente. La segunda endoscopia sólo diagnosticó un paciente. Al final del seguimiento, el diagnóstico etiológico fue de 276 casos de úlcera péptica, 1 de úlcera por enfermedad de Crohn y 25 de úlcera neo-plásica (21 adenocarcinomas, 4 linfomas). Conclusiones: en una población de riesgo intermedio de cáncer gástrico, no está indicada la realización sistemática de una segunda endoscopia en pacientes con úlcera gástrica en los que la visión endoscópica y la biopsia del nicho no indican malignidad(AU)

Objectives: Primary: to assess the necessity of a second endoscopy with a pathology study to confirm the healing of all gastric ulcers previously diagnosed through endoscopy in a population at intermediate risk for gastric cancer. Secondary: to assess correlation between endoscopic findings and pathology diagnosis. Patients and methods: a prospective analysis of patients diagnosed with gastric ulcer through endoscopy at Hospital General de Ciudad Real (Spain) over three years. We collected demographic, clinical, endoscopic, and pathological data for the first and subsequent endoscopies. We collected at least six biopsies obtained from ulcer margins, and assessed H. pylori infection. Results: Three hundred and two patients were included in this study. H. pylori infection was diagnosed in 173 (57%), and 113 (37%) patients had used NSAIDs. The positive and negative predictive value for malignancy of endoscopic diagnosis regarding ulcer fold, base, and margins were 34 and 97%, respectively. Only one patient was diagnosed with a tumor during the second endoscopy. At the end of follow-up, the etiology of the ulcer was considered as peptic in 276 patients; Crohn's disease-related in one, and neoplastic in 25 patients (21 adenocarcinomas, 4 lymphomas). Conclusions: in an intermediate-risk population for gastric cancer a second endoscopy is not justified for gastric ulcer patients when endoscopy and biopsy results do not suggest malignancy(AU)

Nadolol plus isosorbide mononitrate alone or associated with band ligation in the prevention of recurrent bleeding: a multicentre randomised controlled trial.

BACKGROUND AND AIMS: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes METHODS: 158 patients with cirrhosis, admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n = 78) or combined with EBL (Drug+EBL; n = 80). HVPG measurements were performed at randomisation and after 4-6 weeks on medical therapy. RESULTS: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p = 0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction >or=20% or

[Hepatitis C virus in populations at risk for infection. Venezuela]. / Virus de hepatitis C en poblaciones de riesgo a adquirir la infección. Venezuela.

OBJECTIVE: The aim of this study was to establish the prevalence of hepatitis C virus infection in different populations at risk for infection. METHODS: This was a descriptive, transversal study whose variables were evaluated by Pearson s correlation analysis. Different populations were selected: 100 drug users, 47 sex workers, and 50 hemodialysis patients for a total of 197 individuals. The only inclusion criterion was the apparent risk of acquiring this viral infection. The presence of antibodies against virus was examined by ELISA IV (Innotest HCV Ab IV). Reactive samples were then tested using a recombinant assay (INNO-LIA HCV Ab III), both from Innogenetics N. V. (Belgium). The presence of viral RNA was determined in all ELISA and immunoblot-reactive samples by a nested polymerase chain reaction method (HCV-fast of Pharma Gen). RESULTS: A prevalence of 1% was found in drug users, and absence of infection or previous contact with the virus in sex workers and hemodialysis patients. CONCLUSIONS: This study shows a very low prevalence of infection with hepatitis C virus in populations at risk for acquiring the infection, and considered that this infection is not a public health problem in these populations in Maracaibo, Venezuela.

Virus de hepatitis C en poblaciones de riesgo a adquirir la infección. Venezuela / Hepatitis C virus in populations at risk for infection. Venezuela

Objetivo: conocer la prevalencia del virus de hepatitis C en diferentes poblaciones de riesgo a adquirir la infección de la ciudad de Maracaibo, Venezuela. Método: la presente investigación comprendió un estudio de tipo descriptivo y transversal, cuyas variables fueron evaluadas por el análisis de correlación de Pearson. Se seleccionaron 100 drogadictos, 47 trabajadoras sexuales y 50 hemodializados, para un total de 197 individuos. Como único criterio de inclusión se tomó el hecho de presentar riesgo de contraer la infección por el virus de hepatitis C. Para la detección de anticuerpos contra el virus se utilizó la técnica de inmunoensayo enzimático de cuarta generación (Innotest HCV Ab IV). Toda muestra reactiva se confirmó por el método de inmunoblot recombinante de tercera generación (INNO-LIA HCV Ab III ), ambos de Innogenetics Lab (Bélgica). La detección del genoma viral (ARN) se realizó en aquellas muestras reactivas por ELISA e INNO-LIA por la técnica de reacción en cadena de la polimerasa, HCV-fast de Pharma Gen. Resultados: se encontró uno por ciento de prevalencia de hepatitis C en la población de drogadictos y ausencia de infección o contacto previo con el virus en trabajadoras sexuales y pacientes en hemodiálisis. Conclusiones: en el presente estudio se señala la baja prevalencia de la infección por el virus de hepatitis C en poblaciones de riesgo a adquirir la infección, por lo que se considera que esta infección no representa un problema de salud en estas poblaciones de la ciudad de Maracaibo, Venezuela

Objective: the aim of this study was to establish the prevalence of hepatitis C virus infection in different populations at risk for infection. Method: this was a descriptive, transversal study whose variables were evaluated by Pearson’s correlation analysis. Different populations were selected: 100 drug users, 47 sex workers, and 50 hemodialysis patients for a total of 197 individuals. The only inclusion criterion was the apparent risk of acquiring this viral infection. The presence of antibodies against virus was examined by ELISA IV (Innotest HCV Ab IV). Reactive samples were then tested using a recombinant assay (INNO-LIA HCV Ab III), both from Innogenetics N. V. (Belgium). The presence of viral RNA was determined in all ELISA and immunoblot-reactive samples by a nested polymerase chain reaction method (HCV-fast of Pharma Gen). Results: a prevalence of 1% was found in drug users, and absence of infection or previous contact with the virus in sex workers and hemodialysis patients. Conclusions: this study shows a very low prevalence of infection with hepatitis C virus in populations at risk for acquiring the infection, and considered that this infection is not a public health problem in these populations in Maracaibo, Venezuela

[Serological and genetic markers in the diagnosis and follow-up of coeliac disease]. / Marcadores serológicos y genéticos en el diagnóstico y seguimiento de la enfermedad celíaca.

INTRODUCTION: Understanding of celiac disease has changed with the advent of serological markers (antigliadin IgA, anti-endomysial IgA and anti-transglutaminase IgA antibodies) and with the identification of major susceptibility genes (HLA-DQA1*05-DQB1*02). Reports of the efficacy of these diagnostic tests have varied, depending on the methodology used and the population investigated. OBJECTIVES: To determine the clinical utility of genetic and serological markers in the diagnosis of celiac disease, their relationship with histological lesions and their changes during treatment, in order to establish an optimal diagnostic algorithm in our environment. PATIENTS AND METHODS: We performed a retrospective study of 590 patients from the health area of Badajoz referred to the Immunology Laboratory for screening or follow-up of celiac disease. The results of intestinal histology, serological markers (antigliadin IgA, anti-endomysial IgA and anti-transglutaminase IgA antibodies), and genomic typing (HLA-DQA1*05-DQB1*02) were analyzed. RESULTS: The sensitivity and specificity of serological tests were greater than 90 %, with a negative predictive value of 98-100 %. HLA-DQA1*05-DQB1*02 was detected in 97 % of celiac patients, with a very high negative predictive value (99 %). On biopsy, 95 % of the patients with some grade of intestinal lesion were positive for antigliadin and/or anti-endomysial antibodies. CONCLUSION: To avoid missed diagnoses, the diagnostic algorithm of celiac disease should include at least two serological markers (antigliadin antibodies and anti-endomysial and/or anti-transglutaminase antibodies) and IgA quantification. Genomic typing should be carried out if one or more markers are positive or if the subject belongs to any of the risk groups. The physician should decide on the advisability of intestinal biopsy on the basis of the patient's clinical and immunological history.

Marcadores serológicos y genéticos en el diagnóstico y seguimiento de la enfermedad celíaca / Serological and genetic markers in the diagnosis and follow-up of coeliac disease

Introducción: El conocimiento de la enfermedad celíaca ha cambiado con la aparición de marcadores serológicos: anticuerpos antigliadina IgA (AAG), antiendomisio IgA (AAE) y antitransglutaminasa tisular IgA (ATGt-IgA) y con la identificación de genes asociados a la enfermedad: HLA-DQA1*05-DQB1*02. Los estudios de eficacia de estas pruebas diagnósticas varían dependiendo de la metodología utilizada y de la población investigada. Objetivos: Estudiar la rentabilidad clínica de los marcadores genéticos y serológicos, su relación con el grado de lesión intestinal y con el tratamiento de la enfermedad, para así poder establecer el algoritmo diagnóstico de enfermedad celíaca más adecuado en nuestro medio. Pacientes y métodos: Estudio retrospectivo de 590 pacientes del Área Sanitaria de Badajoz remitidos al Laboratorio de Inmunología para el diagnóstico o seguimiento de la enfermedad celíaca. Se analizan los resultados del examen histológico, marcadores serológicos (anticuerpos AAG, AAE y ATGt de isotipo IgA) y tipificación genómica (HLA-DQA1*05-DQB1*02). Resultados La sensibilidad y especificidad de los marcadores serológicos son superiores al 90 %, y el valor predictivo negativo (VPN) es del 98-100 %. El HLA-DQA1*05-DQB1*02 se detecta en el 97 % de los enfermos celíacos, destacando su elevado VPN (99 %). En el momento de la biopsia intestinal, el 95 % de los pacientes con algún grado de atrofia tienen serología positiva (AAG y/o AAE). Conclusión: Para evitar la pérdida de casos, los algoritmos diagnósticos de enfermedad celíaca deben de incluir la determinación de, al menos, dos marcadores serológicos (AAG y AAE y/o ATGt) y la cuantificación de IgA. La tipificación genómica, se realizará si algún marcador es positivo, o por pertenecer a grupos de riesgo. Con los datos clínicos e inmunológicos el gastroenterólogo infantil decidirá en cada caso la realización de la biopsia intestinal

Introduction: Understanding of celiac disease has changed with the advent of serological markers (antigliadin IgA, antiendomysial IgA and antitransglutaminase IgA antibodies) and with the identification of major susceptibility genes (HLA-DQA1*05-DQB1*02). Reports of the efficacy of these diagnostic tests have varied, depending on the methodology used and the population investigated. Objectives: To determine the clinical utility of genetic and serological markers in the diagnosis of celiac disease, their relationship with histological lesions and their changes during treatment, in order to establish an optimal diagnostic algorithm in our environment. Patients and methods: We performed a retrospective study of 590 patients from the health area of Badajoz referred to the Immunology Laboratory for screening or follow-up of celiac disease. The results of intestinal histology, serological markers (antigliadin IgA, antiendomysial IgA and antitransglutaminase IgA antibodies), and genomic typing (HLA-DQA1*05-DQB1*02) were analyzed. Results: The sensitivity and specificity of serological tests were greater than 90 %, with a negative predictive value of 98-100 %. HLA-DQA1*05-DQB1*02 was detected in 97 % of celiac patients, with a very high negative predictive value (99 %). On biopsy, 95 % of the patients with some grade of intestinal lesion were positive for antigliadin and/or antiendomysial antibodies. Conclusion: To avoid missed diagnoses, the diagnostic algorithm of celiac disease should include at least two serological markers (antigliadin antibodies and antiendomysial and/or antitransglutaminase antibodies) and IgA quantification. Genomic typing should be carried out if one or more markers are positive or if the subject belongs to any of the risk groups. The physician should decide on the advisability of intestinal biopsy on the basis of the patient’s clinical and immunological history

Mitochondrial calcium sequestration and protein kinase C cooperate in the regulation of cortical F-actin disassembly and secretion in bovine chromaffin cells.

Mitochondria play an important role in the homeostasis of intracellular Ca(2+) and regulate its availability for exocytosis. Inhibitors of mitochondria Ca(2+) uptake such as protonophore CCCP potentiate the secretory response to a depolarizing pulse of K(+). Exposure of cells to agents that directly (cytochalasin D, latrunculin B) or indirectly (PMA) disrupt cortical F-actin networks also potentiate the secretory response to high K(+). The effects of cytochalasin D and CCCP on secretion were additive whereas those of PMA and CCCP were not; this suggests different mechanisms for cytochalasin D and CCCP and a similar mechanism for PMA and CCCP. Mitochondria were the site of action of CCCP, because the potentiation of secretion by CCCP was observed even after depletion of Ca(2+) from the endoplasmic reticulum. CCCP induced a small increase in the cytosolic Ca(2+) concentration ([Ca(2+)](c)) that was not modified by the protein kinase C (PKC) inhibitor chelerythrine. Both CCCP and PMA induced cortical F-actin disassembly, an effect abolished by chelerythrine. In addition, rotenone and oligomycin A, two other mitochondrial inhibitors, also evoked cortical F-actin disassembly and potentiated secretion; again, these effects were blocked by chelerythrine. CCCP also enhanced the phosphorylation of PKC and myristoylated alanine-rich C kinase substance (MARCKS), and these were also inhibited by chelerythrine. The results suggest that the rapid sequestration of Ca(2+) by mitochondria would protect the cell from an enhanced PKC activation and cortical F-actin disassembly, thereby limiting the magnitude of the secretory response.

Multicenter randomized controlled trial comparing different schedules of somatostatin in the treatment of acute variceal bleeding.

BACKGROUND/AIMS: The dose of somatostatin used for variceal bleeding (250 microg/h) is lower than that proven to effectively decrease portal pressure and azygos blood flow (500 microg/h). Moreover, i.v. somatostatin boluses have greater effects than continuous infusions. The aim of this study was to investigate whether higher doses of somatostatin and repeated boluses may increase its efficacy in controlling variceal bleeding. METHODS: A total of 174 patients with acute variceal bleeding were randomized to receive for 48 h: (A) one 250 microg bolus +250 microg/h infusion; (B) three 250 microg boluses +250 microg/h infusion; (C) three 250 microg boluses +500 microg/h infusion. RESULTS: The three schedules of somatostatin were equally effective in controlling variceal bleeding (73, 75 and 81%, respectively, NS). Multivariate analysis showed active bleeding at endoscopy (n=75) as the only predictor of failure to control bleeding. In these patients, the 500 microg/h infusion dose achieved a higher rate of control of bleeding (82 vs. 60%, P<0.05), less transfusions (3.7 +/- 2.7 vs. 2.5 +/- 2.3 UU, P=0.07) and better survival (93 vs. 70%, P<0.05) than schedules A/B. CONCLUSIONS: Somatostatin is highly effective in controlling variceal bleeding. Patients with active bleeding at emergency endoscopy may benefit from higher doses of somatostatin infusion.