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The prevalence of the non-alcoholic fatty liver disease (NAFLD) in developed countries is up to 30% of the general population, and 50% of patients present type 2 diabetes mellitus (DM2). Fibrosis is the most important prognostic factor in NAFLD. The aim of this study was to search evidence for an early diagnosis of liver fibrosis in subjects with DM2 and to evaluate potential risk and protective factors. This study was conducted among 160 diabetic patients with NAFLD proven biopsy. Anthropometric assessments, laboratory test, liver histological features and follow-up of a Mediterranean diet were evaluated. Diabetic patients with liver fibrosis showed a greater number of positive metabolic criteria than diabetic patients without liver fibrosis. Patients with hepatic fibrosis have a lower score on the PREDIMED test (9.0 (2.4) vs. 6.2 (2.3); p

BACKGROUND There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. AIM To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) METHODS: Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. RESULTS Three hundred and five patients were analysed (≥2 previous anti-TNFα therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (

Gluten-free breads have been characterised by a weak aroma. In this study, different mixtures of gluten-free flours (teff and quinoa) and starches (wheat and corn) were investigated by SPME-GC/QTOF with the aim of providing flours that potentially improve the aroma of gluten-free bread. Bread with the highest proportion of corn starch (60%) was discarded for its higher content in rancid volatile compounds from lipid oxidation, while bread with the highest level of wheat starch (60%) was discarded for its lower content of the key aroma 2-acetyl-1-pyrroline. Thus, the bread composed of 40% of each starch, 15% of quinoa flour and 5% of teff flour was chosen due to the higher proportion of pleasant volatiles from fermentation, 2-acetyl-1-pyrroline and pyrazines as well as the lower levels in rancid volatile compounds from lipid oxidation. Moreover, it exhibited relatively dark crust, high volume and superior textural properties.

Methotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited.To assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti-tumour necrosis factor (anti-TNFα) drugs.A retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti-TNFα started on methotrexate monotherapy. Short-term effectiveness was assessed at 12-16 weeks based on Harvey-Bradshaw index (HBI): clinical remission as HBI ≤ 3 points and clinical response as HBI drop of ≥ 3 points over baseline. Long-term effectiveness was defined as steroid-free methotrexate persistence from 12 to 16 weeks until maximum follow up. Adverse events were recorded.Data were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti-TNFα agents. Short-term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long-term effectiveness was achieved in 82% and 74% at 12 and 24 months respectively. In the multivariate analysis, non-remission at short term (vs remission) was associated with long-term failure (HR 2.58, 95%CI 1.95-3.68, P = 0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation.The benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti-TNFα.

Background Data on the long-term administration of ustekinumab in recommended doses are limited. Aim To assess the real-world, long-term effectiveness of ustekinumab in refractory Crohn's disease (CD). Methods Multicenter study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey-Bradshaw Index (HBI), endoscopic activity, C-reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined. Results A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti-TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission. Conclusion After 52 weeks, ustekinumab demonstrated effectiveness to induce clinical and endoscopic remission with safety in patients with refractory CD.

Prevalence of non-alcoholic fatty liver disease (NAFLD) in developed countries is 30% in the general population and 50% in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to compare the severity of NAFLD, as assessed by liver biopsy and using the non-invasive index NAFLD Fibrosis Score (NFS), in subjects with and without T2DM.The study sample consisted of 217 patients with biopsy-proven NAFLD. Anthropometric assessments, laboratory tests, histological criteria established by the Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN), and the NFS were recorded.Patients with T2DM (n=36; 16.5%) had higher HOMA-IR values (6.3±3.6 vs. 3.3±2.4; p0.0001), GGT levels (125.2±102.3 vs. 82.5±70.6IU/l; p005), and NFS index (-0.6±0.2 vs. -1.8±0.1; p0.001) than subjects with no T2DM. Patients with T2DM were found higher rates of NASH (72.2% vs. 48.6%; p0.05), advanced steatosis (80.6% vs. 63%; p0.05), and liver fibrosis (75% vs. 43.1%, p0.05) than patients with no T2DM. Patients with T2DM also had higher NFS values (-0.6±1.2 vs. -1.8±1.8: p=0.01). A logistic regression analysis adjusting for age, gender and BMI showed a significant independent association between NASH and presence of T2DM (OR=4.2: 95% CI: 1.4-12.1; p=0.007). A second model adjusting for the same covariates showed T2DM to be an independent factor associated to advanced fibrosis (OR=4.1; 95% CI: 1.7-9.7).Patients with T2DM have more advanced degrees of NAFLD and advanced fibrosis as assessed by liver biopsy and the NFS index. Particular attention should be paid to the study and monitoring of NASH in patients with T2DM.

Introduction splenomegaly and/or focal splenic lesions (FSL) have limited histopathologic studies due to the risk posed by splenic punctures. Percutaneous biopsies with a fine needle are difficult, especially due to interposition of gases, ascites, obesity or a history of abdominal surgery. On the other hand, endoscopic ultrasound (EUS) takes advantage of the proximity of the gastric wall to the spleen in order to puncture and visualize the needle and its movements in real time. Objective to describe the initial experience and results obtained with EUS-FNA in patients with splenomegaly or FSL. Materials and methods this was a descriptive observational study. EUS-FNA of the spleen was performed with a slow-pull technique, which avoided fanning with an average of 3 needle passes. Biopsies were sent in Cytorich RedTM solution for analysis by cytology and cell block. Results punctures were performed in 15 patients (9 females) and the median age was 67 years (range 44-86). Patients studied due to an enlarged spleen or splenic FSL, in the context of fever of an unknown origin, adenopathies and abnormal weight loss were included. A conclusive diagnosis was achieved by EUS-FNA in 10 patients (66.7 %), 4 were large cell type B non-Hodgkin's lymphoma and one Hodgkin's lymphoma. There were no immediate or delayed complications related to the procedure. Conclusions EUS-guided splenic punctures appear to be safe, effective and may be necessary in some clinical settings in order to complete the etiologic filiation of splenomegaly of an uncertain origin or FSL and to rule out malignancy.

This work was partially funded by Junta de Castilla y León (SAN/673/2008 and grant to E.M.) and the University of Valladolid (grant to C.E.H. FPI-UVa).

The cat scratch esophagus is an uncommon entity. The first case described in the literature of this type of lesions was published in 2007 and was located in the colon. There are two cases described in the esophagus, this has been the first detected by endoscopic capsule. It is defined by the presence of linear, erythematous, shiny and superficial breaks of the mucosa without significant hemorrhage associated. The diagnosis is morphological. Even though the etiology is unknown, it has been postulated that the main pathogenic mechanism is barotrauma secondary to insufflation. It has also been described association with other processes that can affect the esophageal elasticity as well as the previous use of NSAIDs.

Background and Aims Primary sclerosing cholangitis [PSC] is usually associated with inflammatory bowel disease [IBD]. An increased risk of malignancies, mainly colorectal cancer [CRC] and cholangiocarcinoma [CCA], has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies. Methods PSC-IBD patients were identified from the Spanish ENEIDA registry of GETECCU. Additional data were collected using the AEG-REDCap electronic data capture tool. Results In total, 277 PSC-IBD patients were included, with an incidence rate of 61 PSC cases per 100 000 IBD patient-years, 69.7% men, 67.5% ulcerative colitis and mean age at PSC diagnosis of 40 ± 16 years. Most patients [85.2%] were treated with ursodeoxycholic acid. Liver transplantation was required in 35 patients [12.6%] after 79 months (interquartile range [IQR] 50–139). It was more common in intra- and extrahepatic PSC compared with small-duct PSC (16.3% vs 3.3%; odds ratio [OR] 5.7: 95% confidence interval [CI] = 1.7–19.3). The incidence rate of CRC since PSC diagnosis was 3.3 cases per 1000 patient-years [95% CI = 1.9–5.6]. Having symptoms of PSC at PSC diagnosis was the only factor related to an increased risk of CRC after IBD diagnosis [hazard ratio= 3.3: 95% CI = 1.1–9.9]. CCA was detected in seven patients [2.5%] with intra- and extrahepatic PSC, with median age of 42 years [IQR 39–53], and presented a lower life expectancy compared with patients without CCA and patients with or without CRC. Conclusions PSC-IBD patients with symptoms of PSC at PSC diagnosis have an increased risk of CRC. CCA was only diagnosed in patients with intra- and extrahepatic PSC and was associated with poor survival.

Background and aims: non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in the western world. Although NAFLD prevalence is higher in patients with a BMI > 25 kg /m2, it is unclear if there are differences between overweight and obese patients. The associated biochemical, dietary and genetic parameters were compared between overweight and obese patients with NAFLD. Methods: patients with biopsy-proven NAFLD (n = 203) were enrolled in a cross-sectional study. The MEDAS questionnaire was used to assess adherence to the Mediterranean diet. Biochemical, anthropometrical parameters and the I148M variant (rs738409) of the PNPLA3 gene and rs180069 of the TNF-α gene were evaluated. Results: overweight patients had higher serum adiponectin levels (22.5 ± 21.9 vs 11.2 ± 18.1 ng/ml; p < 0.05) and lower resistin (3.3 ± 1.7 vs 8.1 ± 8 ng/ml; p < 0.001) and leptin concentrations (22.9 ± 21.9 vs 55.8 ± 45 ng/ml; p < 0.001) than obese patients. Non-alcoholic steatohepatitis (NASH) was more frequent in the obese group (59.3% vs 41.3%; p = 0.02). The multivariate analysis showed adherence to the Mediterranean diet to be an independent protective factor for NASH and liver fibrosis in overweight patients (OR 0.7, 95% CI 0.5-0.8). Conclusions: NASH was more prevalent in obese patients than in overweight subjects. HOMA-IR and adherence to the Mediterranean diet provided protection against fibrosis in overweight patients. Adherence to the Mediterranean diet was the only independent factor associated with NASH in these patients.

Introduccion: la esplenomegalia y/o las lesiones ocupantes de espacio (LOE) esplenicas, han tenido limitaciones en su estudio histopatologico por el riesgo que suponen las punciones esplenicas. Las biopsias percutaneas con aguja fina, son dificiles en especial por interposicion de gases, ascitis, obesidad o por antecedentes de cirugia abdominal. En cambio, el ultrasonido endoscopico (USE) aprovecha la proximidad de la pared gastrica con el bazo, para puncionar con visualizacion de la aguja y de sus movimientos en tiempo real. Objetivo: describir la experiencia inicial y resultados obtenidos con USE-PAAF en pacientes con esplenomegalia o LOE esplenica. Materiales y metodos: estudio observacional descriptivo. Se realizo USE-PAAF del bazo, con tecnica de slow-pull, evitando fanning, con 3 pases de aguja en promedio. Las biopsias se enviaron en solucion Cytorich RedTM para analisis mediante citologia y bloque celular. Resultados: se realizaron punciones en 15 pacientes (9 mujeres), con mediana de 67 anos (rango 44-86) en pacientes estudiados por esplenomegalia o LOE esplenica, en contexto de fiebre de origen desconocido, adenopatias, perdida anormal de peso. Se logro un diagnostico concluyente mediante USE-PAAF en 10 pacientes (66,7 %), de los cuales 4 fueron linfomas no Hodgkin tipo B de celula grande y un linfoma de Hodgkin. No se presentaron complicaciones inmediatas, ni diferidas relacionadas al procedimiento. Conclusiones: las punciones esplenicas USE-guiadas parecen ser seguras, eficaces y podrian ser necesarias en algunos escenarios clinicos para completar la filiacion etiologica de esplenomegalia de origen incierto o LOE esplenica y descartar malignidad.

Fried battered foods are widely consumed worldwide. In this study, the influence of the replacement of native wheat flour by extruded flours (7.5 and 15%) subjected to different extrusion severities on chicken nuggets was assessed. Microstructure, pick-up, moisture and fat content, texture, colour, volatile profile, and consumer acceptability were evaluated. Extruded flour replacement resulted in batters with improved pick-up with increasing percentage and severity of extrusion treatment. Extruded flour also contributed to a moisture increase, while oil remained practically unchanged. Textural properties highlighted a higher crispness of batters made with high-severity treatment extruded flours. Volatile compounds analyses revealed lower amount of lipid oxidation (lower rancidity notes) and higher furfuryl alcohol content (pleasant aroma and darker crust) in fried batters containing extruded flour. Consumers testing showed that batters made with intermediate-severity treatment extruded flour presented the best acceptability. These results confirm that extruded flour inclusion improves the quality of deep-fried batters.

The aroma of bread crust, as one of the first characteristics perceived, is essential for bread acceptance. However, gluten-free bread crusts exhibit weak aroma. A SPME-GC/QTOF methodology was optimised with PCA and RSM and validated for the quantification of 44 volatile compounds in bread crust, extracting 0.75 g of crust at 60 °C for 51 min. LODs ranged between 3.60 and 1760 μg Kg−1, all the R2 were higher than 0.99 and %RSD for precision and %Er for accuracy were lower than 9% and 12%, respectively. A commercial wheat bread crust was quantified, and furfural was the most abundant compound. Bread crusts of wheat starch and of japonica rice, basmati rice and teff flours were also quantified. Teff flour and wheat starch crusts were very suitable for improving gluten-free bread crust aroma, due to their similar content in 2-acetyl-1-pyrroline and 4-hydroxy-2,5-dimethyl-3(2H)-furanone compared to wheat flour crust and also for their high content in pyrazines.

Objectives Nonalcoholic fatty liver disease (NAFLD) includes a spectrum of histological phenotypes including steatosis, steatohepatitis (NASH) and fibrosis. While liver biopsy is the reference for diagnosis, it is invasive and associated with procedural risks and sampling variability. There is urgent need for a noninvasive diagnostic procedure. Recently, we have described a serum-based lipidomic signature associated with NAFLD able to fulfill these unmet diagnostic needs by: differentiating NAFLD from healthy cohort; discriminating between steatosis and NASH. The aim of this study is to validate this non-invasive assay using blind-histology as a reference standard and apply it in the follow-up of the patients. Method Thirty patients were enrolled as a blind, biopsy-proven NAFLD cohort, collecting serum at the time of liver biopsy. Patients were prescribed hypocaloric diet (1500kcal/day) and aerobic exercise (30-60min/day), monitored for 2-5 years, when a serum sample was collected. Metabolic syndrome was assessed based on the presence of at least three of the conditions listed by the NCEP ATPIII. The lipidomic test was based on 467 biopsy-proven patients and two BMI-dependent logistic regression algorithms discriminating between: NAFLD-healthy liver (assay name: OWLiver Care); and NASH-steatosis (OWLiver). The diagnostic performances of both assays were assessed by the ROC curve: 0.90±0.02 and 0.95±0.01, respectively. Results Applied to the independent biopsy-proven cohort (33%female, weight=86±15kg; BMI=32±5kg/m 2 ), the test diagnosed correctly 28 out of 30 patients, misclassifying one patient having NASH with NAS score=2, but presenting metabolic syndrome; and one patient as having steatosis with NAS score=5, although without ballooning. Once validated, the test was applied to the follow-up of the patients (weight=84±14kg; BMI=31±4kg/m 2 ). 31% of the patients lose at least 5% of baseline body weight. Among those responders, 50% improved their diagnosis presenting positive post-interventional shifts from NASH to steatosis or steatosis to healthy liver. The original diagnosis remained unchanged for the 95% of the non-responder patients. Conclusions The results obtained in the independent cohort support the feasibility of these lipidomic tests as a noninvasive tool for NAFLD diagnosis and to monitor the disease progression/regression while circumventing the need for repeat liver biopsy.