Prediction of peritoneal soiling in acute appendicitis with simple clinical and laboratory data. Prospective, multicenter, cohort study of 2,645 adult patients nationwide.

BACKGROUND AND AIMS: In order to facilitate the preoperative prediction of complicated appendicitis, we propose a complementary approach by selecting an endpoint defined by the intraoperative finding of peritoneal soiling (PS). METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending emergency general surgery patients on a 24-h, 7-days a week basis, enrolled consecutive adult patients requiring appendectomy. Patients were stratified according to the absence or the finding of PS during the surgical procedure. RESULTS: A total of 2645 patients were included; median age (IQR) was 35 (22-51) years, 44.3% were female. The laparoscopic approach was used in 70.8% of appendectomies. In a third of patients (31.7%), there was PS with pus around the appendix, or bowel contents, free pus, or blood in the peritoneal cavity. To develop the prediction model, 1764 patients were randomly selected for the derivation cohort and the remaining 881 patients were assigned to the validation cohort. On multivariable logistic regression analysis of all patients, two clinical variables (age, and pulse) and three laboratory variables (serum urea, serum sodium, and white blood cell count) were individually associated (P < .05) with a greater probability of having PS (Hosmer-Lemeshow chi, 1.63; P = .99; C-statistic, 0.7). Based on the multivariable regression model, both static and dynamic nomograms were developed for the prediction of PS in patients with acute appendicitis. CONCLUSIONS: The entry of simple clinical and laboratory variables in the dynamic nomogram may be useful in guiding the initial management of patients with acute appendicitis in resource-limited settings.

Simplified risk-prediction for benchmarking and quality improvement in emergency general surgery. Prospective, multicenter, observational cohort study.

BACKGROUND AND AIMS: Emergency General Surgery (EGS) conditions account for millions of deaths worldwide, yet it is practiced without benchmarking-based quality improvement programs. The aim of this observational, prospective, multicenter, nationwide study was to determine the best benchmark cutoff points in EGS, as a reference to guide improvement measures. METHODS: Over a 6-month period, 38 centers (5% of all public hospitals) attending EGS patients on a 24-h, 7-days a week basis, enrolled consecutive patients requiring an emergent/urgent surgical procedure. Patients were stratified into cohorts of low (i.e., expected morbidity risk <33%), middle and high risk using the novel m-LUCENTUM calculator. RESULTS: A total of 7258 patients were included; age (mean ± SD) was 51.1 ± 21.5 years, 43.2% were female. Benchmark cutoffs in the low-risk cohort (5639 patients, 77.7% of total) were: use of laparoscopy ≥40.9%, length of hospital stays ≤3 days, any complication within 30 days ≤ 17.7%, and 30-day mortality ≤1.1%. The variables with the greatest impact were septicemia on length of hospital stay (21 days; adjusted beta coefficient 16.8; 95% CI: 15.3 to 18.3; P < .001), and respiratory failure on mortality (risk-adjusted population attributable fraction 44.6%, 95% CI 29.6 to 59.6, P < .001). Use of laparoscopy (odds ratio 0.764, 95% CI 0.678 to 0.861; P < .001), and intraoperative blood loss (101-500 mL: odds ratio 2.699, 95% CI 2.152 to 3.380; P < .001; and 500-1000 mL: odds ratio 2.875, 95% CI 1.403 to 5.858; P = .013) were associated with increased morbidity. CONCLUSIONS: This study offers, for the first time, clinically-based benchmark values in EGS and identifies measures for improvement.

Perineal body anatomy seen by three-dimensional endovaginal ultrasound of asymptomatic nulliparae.

AIM: The perineal body (PB) plays an important role in supporting the pelvic floor and the posterior vaginal wall, but its attachments and relationships are still debated. This study aimed to assess the normal anatomy of the PB using high-resolution three-dimensional endovaginal ultrasound (3D-EVUS) in asymptomatic nulliparae. METHOD: To validate the identification of perineal structures, 3D-EVUS was initially performed on nulliparous cadavers. Fresh frozen pelves were prepared and echogenic structures thought to be the PB, the external anal sphincter, the superficial and deep transverse perineii, pubovaginalis, puboperinealis, puboanalis, puborectalis and iliococcygeus muscles were tagged with biopsy needles, and marked with indigo carmine dye for localization during dissection. In the second part of the study, consecutive asymptomatic nulliparae were prospectively imaged with the same ultrasound modality. Interrater reproducibility was assessed off-line from stored 3D US volumes using a standardized technique. RESULTS: Five fresh frozen pelves and 44 asymptomatic nulliparae were assessed with 3D-EVUS. The PB was seen as an ovoid structure of mixed echogenicity between the rectum and vagina. It appeared to be divided into a superficial level, in contact with the external anal sphincter, the bulbospongiousus and the superficial transverse perineii muscle and a deep level, in contact with puboperinealis and puboanalis muscles. Interobserver repeatability was excellent for the measurements of PB height [intraclass correlation coefficient (ICC) 0.927], PB depth (ICC 0.969) and PB width (ICC 0.932). CONCLUSION: The PB is divided into two levels with different anatomical relationships with the pelvic floor muscles. 3D-EVUS yields reproducible assessment of this complex structure.

Variations of pharmacokinetics of drugs in patients with cirrhosis.

Liver cirrhosis is the end stage of many different chronic liver diseases and is becoming an important cause of mortality and morbidity across the world. In theory, the numerous physiopathological changes suffered by these patients warrant relevant pharmacokinetic changes in most drugs. However, the influence of these changes on the efficacy and toxicity responses of patients with cirrhosis have been evaluated by few clinical trials and observational studies. As a consequence, therapeutic decisions in these patients are usually complex and subject to uncertainties. In this article, we review the regulatory guidelines to study responses to drugs according to pharmacokinetic variability and the published information that is useful for guiding the dosage adjustment of frequently used drugs in patients with cirrhosis (antivirals, antibiotics, analgesics, etc.) to obtain the best risk-benefit ratio.

Dual-specificity phosphatase 6 regulates CD4+ T-cell functions and restrains spontaneous colitis in IL-10-deficient mice.

Mitogen-activated protein kinase (MAPK) phosphatases are dual-specificity phosphatases (DUSPs) that dephosphorylate phosphothreonine and phosphotyrosine residues within MAPKs. DUSP6 preferentially dephosphorylates extracellular signal-regulated kinases 1 and 2 (ERK1/2) rendering them inactive. Here, we study the role of DUSP6 in CD4(+) T-cell function, differentiation, and inflammatory profile in the colon. Upon T-cell receptor (TCR) stimulation, DUSP6 knockout (Dusp6(-/-)) CD4(+) T cells showed increased ERK1/2 activation, proliferation, T helper 1 differentiation, and interferon-γ production, as well as a marked decrease in survival, interleukin- 17A (IL-17A) secretion, and regulatory T-cell function. To analyze the role of DUSP6 in vivo, we employed the Il10(-/-) model of colitis and generated Il10(-/-)/Dusp6(-/-) double-knockout mice. Il10(-/-)/Dusp6(-/-) mice suffered from accelerated and exacerbated spontaneous colitis, which was prevented by ERK1/2 inhibition. ERK1/2 inhibition also augmented regulatory T-cell differentiation in vitro and in vivo in both C57Bl/6 and Dusp6(-/-) mice. In summary, DUSP6 regulates CD4(+) T-cell activation and differentiation by inhibiting the TCR-dependent ERK1/2 activation. DUSP6 might therefore be a potential intervention target for limiting aberrant T-cell responses in T-cell-mediated diseases, such as inflammatory bowel disease.

Extracto de Polypodium leucotomos en dermatitis atópica: Ensayo multicéntrico, aleatorizado, doble ciego y controlado con placebo / Polypodium leucotomos Extract in Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial

Background: Several studies have reported an association between tumor necrosis factor Introducción: Para el control de la lesión inflamatoria de la dermatitis atópica, y secundariamente del prurito, se utilizan corticosteroides tópicos, pero su empleo está limitado por las reacciones adversas. Objetivos: El objetivo primario del estudio fue evaluar si el tratamiento diario con extracto de Polypodium leucotomos permitiría reducir el uso de corticosteroides tópicos en niños y adolescentes con dermatitis atópica. Secundariamente se valoró el consumo de antihistamínicos orales, así como la evolución de la enfermedad. Pacientes y métodos: Se ha realizado un ensayo clínico en fase IV , multicéntrico, aleatorizado y doble ciego de extracto de Polypodium leucotomos, controlado con placebo, en 105 pacientes de 2 a 17 años de edad, con dermatitis atópica de intensidad moderada e indicación de corticosteroides tópicos. Los pacientes recibieron durante 6 meses extracto de Polypodium leucotomos o placebo por vía oral añadidos al protocolo terapéutico habitual, y se calculó el porcentaje de días en que se utilizaban corticosteroides tópicos u otros tratamientos para la dermatitis atópica. Resultados: El extracto de Polypodium leucotomos redujo de modo no significativo el uso de corticosteroides tópicos (11±12% de días), comparado con placebo (12±11%). El porcentaje de días en los que los pacientes requirieron antihistamínicos orales fue significativamente menor con extracto de Polypodium leucotomos (mediana de 4,5% días) que con placebo (13,6%) (p=0,038). También se redujo el porcentaje de pacientes que tomaron antihistamínicos orales. Conclusiones: El tratamiento prolongado con extracto de Polypodium leucotomos aporta beneficios relevantes para los pacientes en edad pediátrica con dermatitis atópica que precisan tratamiento farmacológico para controlar la lesión inflamatoria y reducir el prurito (AU)

Introduction: Topical corticosteroids are used to treat inflammation and relieve itching in atopic dermatitis, but their use is limited by adverse reactions. Objectives: The main aim of this study was to investigate whether daily treatment with Polypodium leucotomos extract would reduce the use of topical corticosteroids in children and adolescents with atopic dermatitis. We also analyzed oral antihistamine use and changes in disease severity. Patients and methods: We performed a phase IV randomized, double-blind, placebo-controlled, multicenter trial involving 105 patients aged between 2 and 17 years who were receiving topical corticosteroids to treat moderate atopic dermatitis. The patients were randomized to receive, in addition to their standard treatment, Polypodium leucotomos extract or placebo (both in capsule form) for 6 months. The percentage of days on which topical corticosteroids and other atopic dermatitis treatments were used was calculated. Results: Use of Polypodium leucotomos extract did not significantly reduce the mean (SD) percentage of days on which topical corticosteroids were used (11% [12%] vs 12% [11%] for placebo). A significant reduction was, however, observed for oral histamine use (median percentage of days, 4.5% in the Polypodium leucotomos group and 13.6% in the placebo group [P= 0.038]). The percentage of patients who used oral antihistamines was also lower in the Polypodium leucotomos group. Conclusion: Long-term treatment with Polypodium leucotomos extract has benefits for children and adolescents with atopic dermatitis who require pharmacologic treatment to reduce inflammation and relieve itching (AU)

Eficacia de la administración precoz de levosimendán en urgencias en pacientes con insuficiencia cardiaca aguda: un ensayo clínico piloto aleatorizado / Efficacy of early administration of levosimendan in emergency department in patients with acute heart failure: a randomized pilot clinical trial

Objetivo: Comparar la eficacia y la seguridad de la administración precoz de levosimendán junto con la terapia convencional en pacientes con síntomas graves de insuficiencia cardiaca aguda (ICA) atendidos en un servicio de urgencias (SU).Método: Estudio piloto de intervención controlado con placebo, aleatorizado, tripleciego, unicéntrico, y que incluyó 45 pacientes con ICA avanzada atendidos en un SU. Los pacientes fueron aleatorizados 1:1 para recibir levosimendán o placebo añadido al tratamiento convencional. El objetivo primario fue la mejoría de la disnea basal las primeras 24 horas. También se registró la mejoría de la ortopnea, la ingurgitación yugular, el edema periférico, la diuresis acumulada, las modificaciones en la presión arterial sistólica y diastólica y en la frecuencia respiratoria y cardiaca. Se recogió los eventos adversos durante la administración del tratamiento. Se realizó un seguimiento de todos los pacientes a los 7 días, y en el primer y sexto mes tras el alta hospitalaria, y se registró la mortalidad y los reingresos hospitalarios por cualquier causa o su combinación. Resultados: La disnea mejoró más rápido y en más pacientes con la administración delevosimendán (p < 0,05). Resultados similares se encontraron con la ortopnea(p < 0,05), sin diferencias significativas en el resto de las variables. Aparecieron efectos adversos en el 20% y en el 25% de los pacientes con levosimendán y placebo respectivamente (p = NS), pero en ningún caso motivó la retirada del paciente del estudio. No se observó diferencias respecto al reingreso, la mortalidad o la variable combinada .Conclusiones: El tratamiento precoz con levosimendán no produce diferencias estadísticamente significativas respecto el reingreso o la mortalidad, aunque sí se asocia con un beneficio clínico significativo en términos de mejoría de la disnea y la ortopnea comparado con placebo (AU)

Objective: To compare the efficacy and safety of early levosimendan administration in addition to standard treatment in patients with severe symptoms of decompensated heart failure attended in the emergency department (ED).Methods: A single-center, prospective, third-party blinded, randomized, placebo controlled, pilot study was performed in 45 patients with advanced heart failure attended in the ED. Patients were randomized 1:1 to receive intravenous levosimendan or placebo in addition to standard care. The primary endpoint was improvement in baseline dyspnea over24 hours. Improvement of orthopnea, jugular ingurgitation and peripheral edema, cumulated diuresis and changes insystolic and diastolic blood pressure and in heart and respiratory rates were also registered. Adverse events during treatment were recorded. Patients were followed for 7 days and at 1 and 6 months after hospital discharge for all causes of hospital readmission, mortality or both. Results: Dyspnea improved faster and in more patients with the use of levosimendan (P<0.05). Similar findings were found for orthopnea (P<0.05), with no differences for the remaining variables. Adverse effects were observed in 20% and25% of patients in the levosimendan and placebo groups, respectively (P=NS), with no patients withdrawn from the protocol. No differences were seen with respect to readmission, mortality or both outcomes in combination. Conclusion: Early treatment with levosimendan produces no significant differences in readmission or mortality rates, although it is associated with a significant clinical benefit in terms of improvement in dyspnea and orthopnea compared with placebo (AU)

Polypodium leucotomos extract in atopic dermatitis: a randomized, double-blind, placebo-controlled, multicenter trial.

INTRODUCTION: Topical corticosteroids are used to treat inflammation and relieve itching in atopic dermatitis, but their use is limited by adverse reactions. OBJECTIVES: The main aim of this study was to investigate whether daily treatment with Polypodium leucotomos extract would reduce the use of topical corticosteroids in children and adolescents with atopic dermatitis. We also analyzed oral antihistamine use and changes in disease severity. PATIENTS AND METHODS: We performed a phase IV randomized, double-blind, placebo-controlled, multicenter trial involving 105 patients aged between 2 and 17 years who were receiving topical corticosteroids to treat moderate atopic dermatitis. The patients were randomized to receive, in addition to their standard treatment, Polypodium leucotomos extract or placebo (both in capsule form) for 6 months. The percentage of days on which topical corticosteroids and other atopic dermatitis treatments were used was calculated. RESULTS: Use of Polypodium leucotomos extract did not significantly reduce the mean (SD) percentage of days on which topical corticosteroids were used (11% [12%] vs 12% [11%] for placebo). A significant reduction was, however, observed for oral histamine use (median percentage of days, 4.5% in the Polypodium leucotomos group and 13.6% in the placebo group [P= .038]). The percentage of patients who used oral antihistamines was also lower in the Polypodium leucotomos group. CONCLUSION: Long-term treatment with Polypodium leucotomos extract has benefits for children and adolescents with atopic dermatitis who require pharmacologic treatment to reduce inflammation and relieve itching.

Ketanserin potentiates morphine-induced antinociception mediated by kappa-receptor activation.

How can we treat patients with reduced morphine doses without loosing the pain killing effect or morphine antinociceptive effects (MAE)? To address this question, we hypothesized that serotonin (5-HT2) receptor antagonism could enhance MAE mediated by kappa-opioid receptors. We pretreated mice with ketanserin, a 5-HT2 receptor antagonist, and measured the morphine dose required to observe analgesia. The morphine dose effective in 50% of animals (ED(50)) was reduced from 4.7 to 1.3mg/kg, and the morphine dose effective in 100% of animals (ED(max)) from 13.7 to 2.5mg/kg. Ketanserin has a similar enhancer effect when morphine, which has a dual role via mu and kappa receptors, was substituted by the antinociceptive spiradoline, a selective κ-opioid agonist. At a morphine dose of 3.5mg/kg, 30% of the mice showed antinociceptive behaviour, rising to 100% when ketanserin was co-administered and then reduced to 20% in the presence of nor-binaltorphimine, a kappa-opioid receptor antagonist. Our data strongly suggests a serotonergic inhibition of the kappa-opioid component of MAE and the possibility that this serotonergic inhibition could be reversed through 5-HT2 receptor antagonism.

Update of the Atlanta Classification of severity of acute pancreatitis: should a moderate category be included?

BACKGROUND: Persistent and multiple organ failure (POF and MOF) are predictive of death in acute pancreatitis (AP). Local complications without organ failure are associated with morbidity but a low risk of mortality. AIM: To design a three-category classification of AP severity and to compare it with the Atlanta Classification (AC) in terms of morbidity and mortality. METHOD: Severe AP was defined as death, POF (>48 h) or MOF. Moderate AP was defined as the presence of acute collections and/or pancreatic necrosis. Mild AP was defined by exclusion. We compared this classification with AC in 144 episodes of AP. RESULTS: In the three-category classification, severe AP was associated with significantly more frequent intensive care unit admission, invasive treatment and mortality than moderate and mild AP (p < 0.01). Severe AP patients required longer hospital stay and more nutritional support than mild AP patients (p < 0.01). Patients with moderate AP had significantly longer hospital stay and more need for nutritional support than patients with mild AP (p < 0.01). Five patients died, all of them with MOF and/or POF. CONCLUSIONS: A three-category classification distinguishes three homogeneous groups of severity.

The existence of a relationship between increased serum alanine aminotransferase levels detected in premarketing clinical trials and postmarketing published hepatotoxicity case reports.

BACKGROUND: Drug-induced liver injury (DILI) profile in most drugs' available information is based on both the incidence of alanine aminotansferase (ALT) elevations in clinical trials and published case reports. AIM: To assess the relationship between ALT elevations in clinical trials and the number of published case reports in the postmarketing setting. METHODS: Hepatotoxic drugs were identified from product labelling and classified in high-medium risk (Black Box Warning or Precautions section) or low risk (a statement in the Adverse Reactions section). Incidence of ALT elevations (> or = 3 x ULN) for drug (I(D)) and placebo (I(C)) treated patients in premarketing clinical trials and DILI published case reports were retrieved from product labelling and MEDLINE. RESULTS: The median I(C) was 10/1000. The high-medium-risk drugs' median I(D) was significantly higher compared with low-risk drugs (17/1000 vs. 10/1000; P = 0.046). Chi-squared test, absolute difference and odds ratio comparing I(D) and I(C) identified 35%, 51% and 77% of high-medium-risk drugs respectively. Less number of case reports were associated with low- than high-medium-risk drugs (1 vs. 7; P = 0.001). A high odds ratio in clinical trials (I(D) vs. I(C)) was the strongest predictor of published DILI case reports. CONCLUSION: A relationship between increased ALT incidence in premarketing clinical trials and postmarketing published case reports exists.

Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding.

OBJECTIVE: to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. MATERIAL AND METHODS: prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. RESULTS: median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age >= 65 years, presence of HCC, CTP score >=10, and MELD score >= 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). CONCLUSION: MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding.

Valoración del pronóstico a corto y largo plazo de pacientes con cirrosis y hemorragia digestiva por hipertensión portal / Assessing the short- and long-term prognosis of patients with cirrhosis and acute variceal bleeding

Objetivo: evaluar la eficacia de los diferentes indicadores pronósticosde supervivencia a corto y largo plazo en pacientes concirrosis y hemorragia digestiva alta por hipertensión portal (HTP).Material y métodos: calculamos los indicadores pronósticosen una cohorte de 201 pacientes con cirrosis y hemorragia digestivapor HTP ingresados en el Hospital General Universitario deAlicante. Las variables a estudio fueron: edad, sexo, etiología de lacirrosis, hallazgos endoscópicos, episodios previos de hemorragiadigestiva por HTP. Infección por el virus de la inmunodeficienciahumana (VIH), hepatocarcinoma (HCC), infección bacteriana duranteel episodio de hemorragia digestiva y clasificación de Child-Turcotte-Pugh (CTP) y el modelo para enfermedades terminalesdel hígado (MELD score) calculados dentro de las primeras 24 horasdel inicio de la hemorragia. Los pacientes fueron seguidos almenos 6 meses hasta su muerte, trasplante hepático o final del seguimiento.Resultados: la mediana de seguimiento fue de 66,85 semanas(rango 0-432,4). La mortalidad a las 6 semanas, 3 meses, 12meses y 36 meses fue de 22,9, 24,9, 34,3 39,8%, respectivamente.La edad ≥ 65 años, la presencia de HCC, una clasificaciónde CTP ≥ 10 y un MELD score ≥ 18 fueron las variables asociadasa la mortalidad en el estudio multivariante. La precisión delMELD score como predictor de mortalidad a las 6 semanas, 3meses, 12 meses y 36 meses fue superior a la de la clasificaciónde CTP (valor c-estadístico: 6 semanas MELD 0,804, CTP 0,762;3 meses MELD 0,794, CTP 0,760; 12 meses MELD 0,766, CTP0,741; 36 meses MELD 0,737, CTP 0,717).Conclusión: el MELD score y la clasificación de CTP, juntocon la edad y la presencia de HCC, son marcadores útiles en lavaloración pronóstica de supervivencia a corto y largo plazo de lospaciente con cirrosis y hemorragia digestiva por HTP(AU)

Objective: to evaluate the efficacy of various indicators in predicting short- and long-term survival in patients with cirrhosis and acute variceal bleeding. Material and methods: prognostic indicators were calculated for a cohort of 201 cirrhotic patients with acute variceal bleeding hospitalized in our center, a third-level teaching hospital. The studied variables were: age, sex, etiology of cirrhosis, endoscopic findings, previous variceal bleeding episodes, human immunodeficiency virus (HIV) infection, hepatocellular carcinoma (HCC), infection during episode, and Child-Turcotte-Pugh (CTP) and Model for End-stage Liver Disease (MELD) scores within 24 hours of bleeding onset. Patients were followed up for at least 6 months until death, liver transplantation, or end of observation. Results: median follow-up was 66.85 weeks (range 0-432.4). The 6-week, 3-month, 12-month and 36-month mortality rates were 22.9, 24.9, 34.3, and 39.8%, respectively. Age ≥ 65 years, presence of HCC, CTP score ≥ 10, and MELD score ≥ 18 were the variables associated with mortality in the multivariate analysis. The accuracy of MELD scores as predictors of 6-week, 3-month, 12-month, and 36-month mortality was better than that of CTP scores (c-statistics: 6 week MELD 0.804, CTP 0.762; 3-month MELD 0.794, CTP 0.760; 12-month MELD 0.766, CTP 0.741; 36 month MELD 0.737, CTP 0.717). Conclusion: MELD and CTP scores together with age and a diagnosis of hepatocellular carcinoma are useful indicators to assess the short- and long-term prognosis of patients with acute variceal bleeding(AU)

Pharmacogenetic relevance of the CYP2C9*3 allele in a tenoxicam bioequivalence study performed on Spaniards.

We performed a study to quantify CYP2C9 and CYP2C8 alleles influence on the variability observed in tenoxicam pharmacokinetic (PK) and implication in a bioequivalence study design performed on Spaniards. Eighteen healthy volunteers were included in an open, randomized, crossover, phase I bioequivalence study. Significant increases were found in CYP2C9*3 alleles vs. *1 and *2 in AUC(0-infinity) (median (min-max)): 256 (230-516) vs. 150 (100-268) and 169 (124-197) microg h/mL (p<0.01) and half-life time (t1/2) 102 (79-36) vs. 56 (45-94) and 64 (60-80)h (p<0.01). Non-significant differences were observed in C(max) 1.9 (1.8-2.9) vs. 2.4 (1.7-3.4), 2.5 (1.6-2.9) microg/mL or in according to CYP2C8 alleles presence. CYP2C9*3 allele is associated to a longer elimination time of tenoxicam. PK parameters calculated in bioequivalence studies (AUC(0-infinity), t1/2) may be influenced by the presence of CYP2C9*3 allele resulting in a high variability. Thus, bioequivalence studies of tenoxicam formulations should be designed considering genotype profile.

[A cost-effectiveness study of hepatic venous pressure gradient measurement in the secondary prevention of variceal bleeding]. / Estudio coste-efectividad sobre la medición del gradiente de presión venosa hepática en la profilaxis secundaria de la hemorragia digestiva varicosa.

OBJECTIVE: variceal rebleeding is common following a first episode of hemorrhage in cirrhotic patients. The objective of this study was to determine the cost-effectiveness of monitoring hepatic venous pressure gradient (HVPG) to guide secondary prophylaxis. METHODS: we created a Markov decision model to calculate cost-effectiveness for two strategies: Group 1: HVPG monitoring to decide treatment -when portal pressure was reduced by at least 20 percent or HVPG was less than 12 mmHg after beta-blocker administration, patients received beta-blockers; when portal pressure did not meet these criteria therapy was endoscopic band ligation. Group 2: in this group there was no monitoring of HVPG. Patients with large varices received treatment with beta-blockers combined with EBL; patients with small varices received beta-blockers plus isosorbide mononitrate. RESULTS: there was no recurrent variceal bleeding in group 1 for good responders, and for 17% of poor responders. In group 2 a 25% rebleeding rate was detected in patients with small varices and 13% for those with big varices. Overall cost in group 1 was 14,100.49 euros, and 14,677.16 in group 2. CONCLUSIONS: HVPG measurement is cost-effective for the secondary prophylaxis of variceal bleeding.

Estudio coste-efectividad sobre la medición del gradiente de presión venosa hepática en la profilaxis secundaria de la hemorragia digestiva varicosa / No disponible

Objetivo: la hemorragia digestiva es una complicación frecuenteen pacientes con cirrosis hepática. La tasa de recidiva trasun primer episodio oscila en torno al 60%, motivo por el cual laprofilaxis está recomendada. Esta puede realizarse mediante fármacos(betabloqueantes y nitratos) combinados o no con ligaduraendoscópica con bandas. El objetivo de este estudio es valorar elcoste-efectividad de la medición del gradiente de presión venosahepática (GPVH) previo a la elección de la profilaxis secundaria.Métodos: creamos un árbol de decisión para calcular el costeefectividadde dos estrategias: grupo 1: pacientes a los que se les determinóel GPVH; cuando tras la administración de propranolol hubouna disminución del gradiente >= al 20% respecto al inicial o disminuyópor debajo de 12 mmHg, los pacientes fueron tratados con propranolol.Si no hubo tal variación del GPVH, se realizó ligadura endoscópicade las varices. Grupo 2: en este grupo no se monitorizó elGPVH. Los pacientes con varices grado I recibieron tratamiento conbetabloqueantes más nitratos y los que presentaban varices grandes(II, III, IV) fueron tratados con betabloqueantes y LEB.Resultados: en el grupo del estudio hemodinámico respondióun 36%, estos recibieron tratamiento betabloqueante, la tasa de resangradofue del 0%. En los no respondedores la tasa de resangradofue de un 17%. En el grupo sin estudio se trató con propranololmás nitratos al 28,42% y resangraron un 25%; la tasa de resangradoen el grupo que recibió tratamiento con betabloqueantes más ligaduraendoscópica fue de un 13%. El coste total en el grupo al quese realizó el estudio hemodinámico fue de 14.100,49 euros y de14.677,16 euros para el grupo sin estudio hemodinámico.Conclusiones: la realización del estudio hemodinámico es unaherramienta coste-efectiva en la profilaxis de la hemorragia digestivavaricosa en pacientes cirróticos y mantiene una relación costeefectiva favorable comparado con la no realización del mismo

Objective: variceal rebleeding is common following a firstepisode of hemorrhage in cirrhotic patients. The objective of thisstudy was to determine the cost-effectiveness of monitoring hepaticvenous pressure gradient (HVPG) to guide secondary prophylaxis.Methods: we created a Markov decision model to calculatecost-effectiveness for two strategies: Group 1: HVPG monitoringto decide treatment –when portal pressure was reduced by at least20 percent or HVPG was less than 12 mmHg after beta-blockeradministration, patients received beta-blockers; when portal pressuredid not meet these criteria therapy was endoscopic band ligation.Group 2: in this group there was no monitoring of HVPG.Patients with large varices received treatment with beta-blockerscombined with EBL; patients with small varices received betablockersplus isosorbide mononitrate.Results: there was no recurrent variceal bleeding in group 1for good responders, and for 17% of poor responders. In group 2a 25% rebleeding rate was detected in patients with small varicesand 13% for those with big varices. Overall cost in group 1 was14,100.49 euros, and 14,677.16 in group 2.Conclusions: HVPG measurement is cost-effective for thesecondary prophylaxis of variceal bleeding

Translocation of bacterial DNA from Gram-positive microorganisms is associated with a species-specific inflammatory response in serum and ascitic fluid of patients with cirrhosis.

Translocation of bacterial-DNA in patients with cirrhosis and ascites triggers an innate immune response. Identification of characteristics to which this response is sensitive is relevant from a clinical standpoint. The aim of this study has been to determine if the proinflammatory immune response established in vivo in cirrhotic patients with ascites as a consequence of bacterial-DNA translocation is related to the identified bacterial species and their frequency of cytosine-guanosine content in serum and ascitic fluid. Patients with advanced cirrhosis and ascites were included in the study and distributed into groups I and II according to the absence or presence of bacterial-DNA translocation, respectively. Serum and ascitic fluid levels of proinflammatory cytokines after normalization of bacterial-DNA concentration and the activated form of nuclear factor-kappa B in ascitic fluid pellets were measured by enzyme-linked immunosorbent assay techniques. Translocation of bacterial-DNA with higher cytosine-guanosine content induced the highest cytokine response, which was higher than that in patients without bacterial-DNA translocation. The activated form of nuclear factor-kappa B in ascitic fluid pellets of patients with bacterial-DNA translocation was greater in patients with higher bacterial-DNA cytosine-guanosine content, whereas the amount of total nuclear factor-kappa B remained unaltered. Bacterial-DNA translocation induces a marked immune reaction in vivo in patients with advanced cirrhosis and ascites which is related, among other factors, to the bacterial-DNA cytosine-guanosine content. Therefore, the host's immune response to bacterial-DNA translocation constitutes a species-specific phenomenon.

Cross-reactivity among amide-type local anesthetics in a case of allergy to mepivacaine.

Among the various adverse reactions to local anesthetics, IgE-mediated reactions, particularly to the more commonly used amide group, are extremely rare. We report the case of a 39-year-old man who suffered itching and generalized urticaria with facial angioedema 15 minutes after administration of mepivacaine. Skin tests revealed a strong positive reaction to mepivacaine, lidocaine, and ropivacaine, but negative reactions to bupivacaine and levobupivacaine. Furthermore, double-blind placebo-controlled subcutaneous challenge with bupivacaine and levobupivacaine was well tolerated. We conclude that an extensive allergologic study must be carried out in rare cases of true allergic reaction to amide-type local anesthetics in order to rule out cross reactivity.

A comparison of two different dosages of somatostatin combined with sclerotherapy for the treatment of acute esophageal variceal bleeding: a prospective randomized trial.

BACKGROUND: the association of somatostatin (SMT) with endoscopic therapy in patients with cirrhosis and variceal bleeding significantly improves the control of the bleeding episode, and hemodynamic data have shown that a dosage of 500 mg/h allows a more marked reduction of portal pressure versus the usual dosage of 250 mg/h. AIM: to assess if the 500 mg/h dosage is associated with an improved outcome. METHODS: sixty-two patients with variceal bleeding were included in the study. Patients were randomized to receive the usual dosage of SMT (group I: 250 mg/h), or a double dosage (group II: 500 mg/h), together with emergency endoscopic sclerotherapy. RESULTS: the control of the bleeding episode was similar in both groups of patients. Early rebleeding was less frequent in patients receiving double vs. single dosage of SMT (p = 0.06). When considering patients with advanced liver disease (Child-Pugh B or C) early rebleeding was significantly less frequent in patients receiving the 500 mg/h dose of SMT (39 vs. 13%, p = 0.03). CONCLUSIONS: the perfusion of higher doses of SMT (500 mg/h) in association with emergency sclerotherapy in patients with cirrhosis and esophageal hemorrhage significantly decreases the rate of early rebleeding in patients with more advanced stages of liver disease.