Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

BACKGROUND AND AIMS: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Correction: Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885.

The authors wish to make the following corrections to this paper [...].

Early predictors of corticosteroid response in acute severe autoimmune hepatitis: a nationwide multicenter study.

BACKGROUND AND AIMS: To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. METHODS: This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan-Meier and Cox regression methods were used for data analysis. RESULTS: Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4-67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2-0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8-0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0-75.8]; specificity 95.2% [95% CI: 89.9-97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3-2.1). CONCLUSION: Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided.

Characteristics and outcome of incidental hepatocellular carcinoma after liver transplantation: a cohort study

Introduction: despite advances in imaging diagnosticmodalities, hepatocellular carcinoma is sometimes incidentally diagnosed on histological examination of the liver explant. The objectives of the study were: a) to compare the characteristics between incidental and known hepatocellular carcinoma; and b) to estimate survival and tumor recurrence after liver transplantation.Material and methods: a retrospective, single-center study was performed. The inclusion criteria were: a) cirrhotic patients, age ≥ 18 years; b) liver transplantation between 1998 and 2018; and c) hepatocellular carcinoma diagnosed via histopathologic examination of the explanted liver. Cholangiocarcinoma and patients with early retransplantation were excluded. Multivariate analysis was performed using binomial logistic regression to assess the factors associated with incidental hepatocellular carcinoma. Kaplan-Meier curves were plotted to explore the impact on overall survival and recurrence free survival.Results: two hundred and sixty-nine patients were enrolled. The prevalence of incidental hepatocellular carcinoma was 4.18 % (95 % CI: 2.89-6.01 %) of all liver transplants performed in cirrhotic patients. The median diameter of the main nodule was smaller in incidental hepatocellular carcinoma (20 vs 27 mm, p = 0.004), although they were more likely to be beyond the Up-to-Seven criteria on explant examination (22.2 % vs 7.5 %, p = 0.001), with no differences in any other histological features. No differences were found in overall survival rates (incidental 70.2 % vs 70.4 %, p = 0.87) or recurrence-free survival (incidental 100 % vs 83.8 %, p = 0.07) at five years. Conclusion: incidental hepatocellular carcinoma are smaller in size and are more frequently found to be beyond the Up-to-Seven criteria. However, no differences were found in overall survival rates or recurrence-free survival, although there was no tumor recurrence in the incidental hepatocellular carcinoma group. (AU)

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients.

BACKGROUND: Previous studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. METHODS: Prospective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. RESULTS: We included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. CONCLUSIONS: Compared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.

Management and Long-term Outcomes of Crohn's Disease Complicated with Enterocutaneous Fistula: ECUFIT Study from GETECCU.

BACKGROUND AND AIMS: Crohn's disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. METHODS: Clinical information from all adult patients with CD and at least one ECF-excluding perianal fistulae-were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. RESULTS: A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, p = 0.001, and HR 1.49, 95% CI 1.07-2.06, p = 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. CONCLUSIONS: ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.

Polypharmacy in Patients With Inflammatory Bowel Disease: Prevalence and Outcomes in a Single-center Series.

BACKGROUND: Polypharmacy can complicate the course and management of chronic diseases, and has been little explored in patients with inflammatory bowel disease (IBD) to date. AIM: The aim of this study was to determine the prevalence of polypharmacy in a series of IBD patients, describing associated factors and its correlation with poor disease outcomes. MATERIALS AND METHODS: Retrospective study of a single-center series. Polypharmacy was defined as the simultaneous use of 5 or more drugs. Disease outcomes, IBD treatment nonadherence and undertreatment were evaluated at 1 year. RESULTS: A total of 407 patients were included [56% males, median age: 48 y (interquartile range, 18 to 92 y)], of whom 60.2% had Crohn's disease; Chronic comorbidity and multiple comorbidities were present in 54% and 27% of patients, respectively. Median number of prescriptions per patient was 3 (range: 0 to 15). Polypharmacy was identified in 18.4% of cases, inappropriate medication in 10.5% and use of high-risk drugs in 6.1% (mainly opioids). In multivariate analysis, polypharmacy was associated with chronic comorbidity [odds ratio (OR)=10.1, 95% confidence interval (CI): 2.14-47.56; P˂0.003], multiple comorbidities (OR=3.53, 95% CI: 1.46-8.51; P=0.005) and age above 62 years (OR=3.54, 95% CI: 1.67-7.51; P=0.001). No association with poor disease outcomes was found at 12 months. However, polypharmacy was the only factor associated with IBD treatment nonadherence (OR=2.24, 95% CI: 1.13-4.54, P=0.02). CONCLUSIONS: Polypharmacy occurs in around 1 in 5 patients with IBD, mainly in older adults and those with comorbidity. This situation could interfere with adherence to IBD treatment and therapeutic success.

Comparison Between Real-time Ammonium and pH Measurement, Immunohistochemistry, and Histochemistry for the Diagnosis of Helicobacter pylori.

BACKGROUND: Helicobacter pylori (HP) infection has been implicated in several malignant and nonmalignant conditions. The confirmatory diagnosis of HP requires an endoscopic biopsy, followed by a rapid urease test, culture, and/or histopathologic examination using hemotoxylin and eosin, histochemical stains, or immunohistochemistry against HP. EndoFaster is a novel device that can perform real-time ammonium and pH measurements in gastric juice, allowing a diagnosis of HP during gastroduodenal endoscopy. GOAL: This study aimed to validate the accuracy of EndoFaster and to compare different histochemical and immunohistochemical techniques for the diagnosis of HP infection. STUDY: Consecutive patients who underwent upper endoscopy at our center were prospectively enrolled. During the endoscopy procedure, gastric juice was aspirated to perform an automatic analysis by EndoFaster and gastric biopsies were taken. Histologic sections were reviewed to assess the histopathologic features. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for the EndoFaster test, Diff-Quick (DQ), and immunohistochemistry against HP (anti-HP) using Warthin-Starry as the gold standard for HP detection. RESULTS: Overall, 80 patients were enrolled. In 19 cases (23,75%), histology was normal. In the remaining cases, varying degrees of inflammation were found. The sensitivity, specificity, positive predictive value, and negative predictive value were 73.33%, 86.00%, 75.86%, and 84.31% for the EndoFaster test using 67 ppm/mL as the positive threshold; 73.33%, 100%, 100%, and 86.21% for DQ; and 79.31%, 88.00%, 79.31%, and 88.00% for anti-HP, respectively. CONCLUSIONS: The EndoFaster test has good sensitivity and specificity for the diagnosis of HP during the gastroscopy procedure. DQ and anti-HP are excellent alternatives to Warthin-Starry for the detection of HP.

Characteristics and outcome of incidental hepatocellular carcinoma after liver transplantation: a cohort study.

INTRODUCTION: despite advances in imaging diagnostic modalities, hepatocellular carcinoma is sometimes incidentally diagnosed on histological examination of the liver explant. The objectives of the study were: a) to compare the characteristics between incidental and known hepatocellular carcinoma; and b) to estimate survival and tumor recurrence after liver transplantation. MATERIAL AND METHODS: a retrospective, single-center study was performed. The inclusion criteria were: a) cirrhotic patients, age ≥ 18 years; b) liver transplantation between 1998 and 2018; and c) hepatocellular carcinoma diagnosed via histopathologic examination of the explanted liver. Cholangiocarcinoma and patients with early retransplantation were excluded. Multivariate analysis was performed using binomial logistic regression to assess the factors associated with incidental hepatocellular carcinoma. Kaplan-Meier curves were plotted to explore the impact on overall survival and recurrence free survival. RESULTS: two hundred and sixty-nine patients were enrolled. The prevalence of incidental hepatocellular carcinoma was 4.18 % (95 % CI: 2.89-6.01 %) of all liver transplants performed in cirrhotic patients. The median diameter of the main nodule was smaller in incidental hepatocellular carcinoma (20 vs 27 mm, p = 0.004), although they were more likely to be beyond the Up-to-Seven criteria on explant examination (22.2 % vs 7.5 %, p = 0.001), with no differences in any other histological features. No differences were found in overall survival rates (incidental 70.2 % vs 70.4 %, p = 0.87) or recurrence-free survival (incidental 100 % vs 83.8 %, p = 0.07) at five years. CONCLUSION: incidental hepatocellular carcinoma are smaller in size and are more frequently found to be beyond the Up-to-Seven criteria. However, no differences were found in overall survival rates or recurrence-free survival, although there was no tumor recurrence in the incidental hepatocellular carcinoma group.

Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study.

(1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery.

Validación clínica del test Endofaster(R) como método diagnóstico rápido de la infección por Helicobacter pylori / No disponible

INTRODUCCIÓN: el objetivo fue evaluar la exactitud diagnóstica de Endofaster(R) para la detección de Helicobacter pylori. MÉTODOS: se realizó estudio histológico de biopsias gástricas (patrón oro) y aspirado del jugo gástrico para análisis por Endofaster(R) (negativo si la concentración de amonio fue < 57 ppm, positivo si > 67 ppm y débilmente positivo entre 57-67). RESULTADOS: ochenta y seis pacientes fueron incluidos y Endofaster(R) fue positivo en el 33,7%, débilmente positivo en el 11,6% y negativo en el 54,7%. Las biopsias fueron positivas en el 38,4%. Se alcanzó una precisión del 81,4% y Kappa = 0.57. CONCLUSIONES: Endofaster(R) permitiría un diagnóstico rápido de la infección con una buena precisión diagnóstica (AUROC = 0.81)

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Clinical validation of Endofaster® for a rapid diagnosis of Helicobacter pylori infection.

BACKGROUND: this study aimed to evaluate the diagnostic accuracy of the Endofaster® for the detection of Helicobacter pylori. METHODS: during upper gastrointestinal endoscopy, gastric juice was aspirated to perform an analysis using the Endofaster®. This test was considered as positive when the ammonium concentration was > 67 ppm, negative when < 57 ppm and weakly positive between 57 and 67. Biopsy specimens were also taken as the gold standard. RESULTS: among the 86 patients enrolled in the study, the Endofaster® result was positive in 23.7%, negative in 54.7% and weakly positive in 11.6%, whereas infection was detected via histology in 38.4% of patients. The accuracy was 81.4%, with a Kappa value of 0.57. CONCLUSIONS: the Endofaster® could be useful to perform a rapid diagnosis of Helicobacter pylori infection (area under the curve = 0.81).

Intraductal papillary mucinous neoplasm of the biliary tract: a lesion of the bile duct lumen

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Intraductal papillary mucinous neoplasm of the biliary tract: a lesion of the bile duct lumen.

Intraductal papillary neoplasm of the bile duct (IPNB) is a rare entity characterized by papillary growth within the bile duct lumen1, currently regarded as a biliary counterpart of intraductal papillary mucinous neoplasm of the pancreas. The most common clinical findings are abdominal pain, jaundice or cholangitis, although some patients are asyntomatic. The diagnosis requires careful assessment of imaging findings and cito-histological evaluation, with endoscopic ultrasound guided fine needle aspiration (EUS-FNA) playing a very important role. IPNB is a premalignant lesion which can evolve into invasive cholangiocarcinom. A radical treatment strategy should be planned accordingly.

Hemorragia digestiva tras una colecistoduodenostomía guiada por ecoendoscopia / Gastrointestinal bleeding following transduodenal endoscopic ultrasound-guided gallbladder drainage

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Genetic and flow cytometry analysis of seronegative celiac disease: a cohort study.

Background: Seronegative celiac disease (CD) poses a diagnostic challenge. Aims: Characterize and identify differences between seronegative and seropositive CD. Patients and methods: Retrospective cohort study examining adult patients diagnosed with CD (1980-2017). Clinical, analytical, histological, genetic and immunophenotypic data were compiled. Seronegative CD was defined as a anti-tissue transglutaminase type 2 IgA and endomysial antibodies (EMA) negative and HLA-DQ2 and/or DQ8 positive, showing clinical signs of CD plus an abnormal duodenal biopsy, and responding to a gluten-free diet (GFD). Factors associated with seronegative CD were identified through binomial logistic regression. Results: Of 315 CD patients, 289 were seropositive (91.7%) and 26 seronegative (8.3%). Among the seronegative patients, higher prevalence was observed for autoimmune thyroiditis (26.9% vs. 9.7%, p = .016), HLA-DQ8 heterozygosity (23.1% vs. 2.5%, p ˂ .001) and Marsh I lesion (34.6% vs. 3.7%, p ˂ .001). The two groups showed similar flow cytometry-determined duodenal immunophenotypes and rates of refractory CD. Conclusions: Seronegative CD differs mostly in genetic (more HLA-DQ8) and histologic (milder atrophy) features as compared with seropositive. Intestinal intraepithelial immunophenotype by flow cytometry, similar in both modalities, is a useful tool to diagnose seronegative CD.

Hepatic angiosarcoma in a patient with liver cirrhosis / Angiosarcoma hepático en un paciente con cirrosis hepática

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Metástasis adrenal como presentación de un hepatocarcinoma / Adrenal metastasis as presentation of hepatocellular carcinoma

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