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Celiac disease has been associated with abnormal liver function tests at diagnosis that usually resolve with a gluten-free diet (GFD). The aim of this study was to assess the evolution of liver involvement and possible long-term complications in patients on a GFD.Retrospective and single-center study, which included all individuals with Celiac disease followed in specialized consultation in a tertiary referral hospital.A total of 162 patients were included, most of them female (77.8%) with a median age of 24 years (IQR, 7-39). Seventy-four (45.7%) patients had abnormal liver function tests at diagnosis. These individuals had higher anti-tissue transglutaminase IgA (tTG-IgA) antibody titers (126 vs. 29 IU/L; P = 0.003). There were no significant differences in the Marsh classification ( P = 0.599). During follow-up, most celiac hepatitis patients had normalization of liver function tests and tTG-IgA antibodies. At the last follow-up, all the patients had fibrosis-4 indexlt;2.4 and an aspartate aminotransferase-to-platelet ratio index scorelt;0.6. Vibration-controlled transient elastography showed valueslt;6.4 kPa in all cases. On the other hand, it was found that 42.9% of the individuals had a controlled attenuation parametergt;206.5 db/m.In our cohort, liver function tests normalized in the vast majority of celiac hepatitis patients on a GFD, with no progression to chronic liver disease. It should be noted the high number of individuals who present hepatic steatosis during follow-up, which may be related to a diet that tends to be hyperlipidemic and hypercaloric.

Coronavirus disease 2019 (COVID-19) is an infection caused by a novel coronavirus (SARS-CoV-2) originated in China in December 2020 and declared pandemic by WHO. This coronavirus mainly spreads through the respiratory tract and enters cells through angiotensin-converting enzyme 2 (ACE2). The clinical symptoms of COVID-19 patients include fever, cough, and fatigue. Gastrointestinal symptoms (diarrhea, anorexia, and vomiting) may be present in 50% of patients and may be associated with worst prognosis. Other risk factors are older age, male gender, and underlying chronic diseases. Mitigation measures are essential to reduce the number of people infected. Hospitals are a place of increased SARS-CoV-2 exposure. This has implications in the organization of healthcare services and specifically endoscopy departments. Patients and healthcare workers safety must be optimized in this new reality. Comprehension of COVID-19 gastrointestinal manifestations and implications of SARS-CoV-2 in the management of patients with gastrointestinal diseases, under or not immunosuppressant therapies, is essential. In this review, we summarized the latest research progress and major societies recommendations regarding the implications of COVID-19 in gastroenterology, namely the adaptations that gastroenterology/endoscopy departments and professionals must do in order to optimize the provided assistance, as well as the implications that this infection will have, in particularly vulnerable patients such as those with chronic liver disease and inflammatory bowel disease under or not immunosuppressant therapies.

Individuals within specific risk groups for pancreatic ductal adenocarcinoma (PDAC) [mucinous cystic lesions (MCLs), hereditary risk (HR), and new-late onset diabetes mellitus (NLOD)] represent an opportunity for early cancer detection. Endoscopic ultrasound (EUS) is a premium image modality for PDAC screening and precursor lesion characterization. While no specific biomarker is currently clinically available for this purpose, glypican-1 (GPC1) is overexpressed in the circulating exosomes (crExos) of patients with PDAC compared with healthy subjects or those harboring benign pancreatic diseases.To evaluate the capacity of GPC1This cross-sectional study with a prospective unicentric cohort included 88 subjects: 40 patients with MCL, 20 individuals with HR, and 20 patients with NLOD. A control group (CG) was submitted to EUS for other reasons than pancreatic pathology, with normal pancreas and absence of hereditary risk factors (Half of MCLs harbored worrisome features (WF) or high-risk stigmata (HRS). Pancreatic abnormalities were detected by EUS in 10.0% and 35.0% in HR and NLOD individuals, respectively, all considered non-malignant and "harmless." Median levels of GPC1GPC1

Gastrointestinal involvement occurs in approximately 4% of cases of systemic amyloidosis. The most common site of amyloid deposition is small bowel, followed by stomach, colorectum and esophagus. Although rare, gastrointestinal amyloidosis may be associated with severe complications including gastrointestinal bleeding or perforation and may be mistaken for malignancy.

BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).

Immune-mediated inflammatory diseases share several pathogenic pathways and this pushes sometimes to extrapolate from one disease or indication to others. A biosimilar can be defined as a biotherapeutic product which is similar in terms of quality, safety, and efficacy to an already licensed reference biotherapeutic product. We review the substrate for extrapolation, the current approval process for biosimilars and the pioneering studies on biosimilars performed in rheumatoid arthritis patients. A biosimilar has the same amino acid sequence as its innovator product. However, post-translational modifications can occur and the current analytical techniques do not allow the final structure. To test the efficacy in one indication, a homogeneous population should be chosen and immunogenicity features are essential in switching and interchangeability. CT-P13 (Remsima™; Inflectra™) is a biosimilar of reference infliximab (Remicade®). It meets most of the requirements for extrapolation. Nevertheless, in inflammatory bowel diseases (IBD) we need more studies to confirm the postulates of extrapolation from rheumatoid arthritis and ankylosing spondylitis to IBD. Furthermore, an effective pharmacovigilance schedule is mandatory to look for immunogenicity and side effects.

BACKGROUND AND AIMS Pancreatic ductal adenocarcinoma (PDAC) diagnosis can be difficult in a chronic pancreatitis (CP) background, especially in its mass forming presentation. We aimed to assess the accuracy of glypican-1-positive circulating exosomes (GPC1+crExos) to distinguish PDAC from CP versus the state-of-the-art CA 19-9 biomarker. METHODS This was a unicentric prospective cohort. Endoscopic ultrasound with fine-needle aspiration or biopsy and blood tests (GPC1+crExos and serum CA 19-9) were performed. RESULTS The cohort comprised 60 PDAC and 29 CP (7 of which mass forming - MF) patients. Median levels of GPC1+crExos were significantly higher in PDAC (99.7%) versus CP (28.4%; p

Diazepam is commonly used in the management of epileptic seizures, although it has limitations that can be overcome by using formulations that are easier to administer and capable of directing the drug to the brain. In this field, it has been reported that the use of nanostructured lipid carriers (NLC) via intranasal (or via nose-to-brain) promotes the targeting of drugs to the brain, improving the effectiveness of therapy. The aim of this work was to optimize two diazepam-loaded NLC formulations for nose-to-brain delivery, one with positive surface charge and one with negative surface charge. The quality by design (QbD) approach was used to design the experiments, where the quality target product profile (QTPP), the risk assessment and the critical quality attributes (CQAs) were defined to ensure safety, efficacy and quality of the final formulations. The experiments started with the optimization of critical material attributes (CMAs), related to the ratios of lipids and emulsifiers, followed by the selection of critical process parameters (CPPs), related to the production methods of the diazepam-loaded NLC formulation (ultrasound technique and high-pressure homogenization - HPH). Afterwards, the positive surface charge of the diazepam-loaded NLC was optimized. Finally, the biocompatibility with human neuronal cells of the formulation with a negative surface charge and of the formulation with a positive surface charge was evaluated. The results of the optimization of the CMAs showed that the ratios of lipids and emulsifiers more adequate were 6.7:2.9 and 4.2:0.3 (% w,w), respectively. Regarding the CPPs, HPH was considered the most suitable production method, resulting in an optimized diazepam-loaded NLC formulation (F1C15) with negative surface charge, showing particle size of 69.59 ± 0.22 nm, polydispersity index (PDI) of 0.19 ± 0.00, zeta potential (ZP) of −23.50 ± 0.24 mV and encapsulation efficiency (EE) of 96.60 ± 0.03 %. The optimized diazepam-loaded NLC formulation (F2A8) with positive surface charge had particle size of 124.40 ± 0.84 nm, PDI of 0.17 ± 0.01, ZP of 32.60 ± 1.13 mV and EE of 95.76 ± 0.24 %. In addition, the incorporation of diazepam in NLC resulted in a sustained release of the drug. No significant changes in particle size, PDI, ZP and EE were observed for the formulation F1C15, after 3 months of storage, whereas for formulation F2A8, particle size increased significantly. Biocompatibility studies showed that the formulation F2A8 was more cytotoxic than the formulation F1C15. Thereby, we conclude that the formulation F1C15 is more suitable for targeting the brain, when compared with the formulation F2A8. From the results of these studies, it can be confirmed that the QbD approach is an adequate and central tool to optimize NLC formulations.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) is a technically demanding procedure with a high risk for adverse events (AEs). Aim: evaluate patient- and procedure-related risk factors for ERCP-related AEs and develop an online app to estimate risk of AEs. Methods: retrospective study of 1,491 consecutive patients who underwent 1,991 ERCPs between 2012 and 2017 was conducted. AEs definition and severity were classified according to most recent ESGE guidelines. Each variable was tested for association with occurrence of overall AEs, post-ERCP pancreatitis (PEP) and cholangitis. For each outcome, 2 regression models were built, from which an online Shiny-based app was created. Results: Overall AE rate was 15.3%; in 19 procedures, >1 AE occurred. Main post-ERCP AE was PEP (7.5%), followed by cholangitis (4.9%), bleeding (1.3%), perforation (1%), cardiopulmonary events (0.9%), and cholecystitis (0.3%). Seventy-eight percent of AEs were mild/moderate; of severe (n = 55) and fatal (n = 20) AEs, more than half were related to infection, cardiac/pulmonary AEs, and perforation. AE-related mortality rate was 1%. When testing precannulation, procedural covariates, and ERCP findings, AE occurrence was associated with age (odds ratio [OR] 0.991), previous PEP (OR 2.198), ERCP complexity grade III/IV (OR 1.924), standard bile duct cannulation (OR 0.501), sphincterotomy (OR 1.441), metal biliary stent placement (OR 2.014), periprocedural bleeding (OR 3.024), and biliary duct lithiasis (OR 0.673). Conclusion: Our app may allow an optimization of the patients’ care, by helping in the process of decision-making, not only regarding patient or endoscopist’s selection but also definition of an adequate and tailored surveillance plan after the procedure.

This guideline presents recommendations for the management of coeliac disease (CD) and other gluten-related disorders both in adults and children. There has been a substantial increase in the prevalence of CD over the last 50 years and many patients remain undiagnosed. Diagnostic testing, including serology and biopsy, should be performed on a gluten-containing diet. The diagnosis of CD is based on a combination of clinical, serological and histopathological data. In a group of children the diagnosis may be made without biopsy if strict criteria are available. The treatment for CD is primarily a gluten-free diet (GFD), which requires significant patient education, motivation and follow-up. Slow-responsiveness occurs frequently, particularly in those diagnosed in adulthood. Persistent or recurring symptoms necessitate a review of the original diagnosis, exclude alternative diagnoses, confirm dietary adherence (dietary review and serology) and follow-up biopsy. In addition, evaluation to exclude complications of CD, such as refractory CD or lymphoma, should be performed. The guideline also deals with other gluten-related disorders, such as dermatitis herpetiformis, which is a cutaneous manifestation of CD characterized by granular IgA deposits in the dermal papillae. The skin lesions clear with gluten withdrawal. Also, less well-defined conditions such as non-coeliac gluten sensitivity (NCGS) and gluten-sensitive neurological manifestations, such as ataxia, have been addressed. Newer therapeutic modalities for CD are being studied in clinical trials but are not yet approved for use in practice.

Background and aims:Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis. Methods:Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification. Results:Mean age at IBD diagnosis: 42 +/- 16 years;at dysplasia diagnosis: 56 +/- 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation ofIGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation ofMSH6, TIMP3was significantly associated to IBD-related dysplasia/cancer. Promoter methylation ofMSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1,BCL2genes was significantly associated to active IBD. Conclusions:Methylation analysis, namely ofMSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies. Grupo de Estudos em Doenca Inflamatoria Intestinal (GEDII), Portugal, a non-profit Portuguese research organization info:eu-repo/semantics/publishedVersion

Background Cytomegalovirus (CMV) is frequently detected in patients with ulcerative colitis (UC). The impact of CMV infection on the outcome of UC exacerbation remains unclear. The benefit of combining antiviral with anti-inflammatory treatment has not been evaluated yet. The aim of this study was to compare the outcome of CMV-positive hospitalized patients with UC treated with antiviral therapy either alone or combined with salvage anti-inflammatory therapy (infliximab [IFX] or cyclosporine A [CsA]). Methods This was a multicenter retrospective study of hospitalized CMV-positive patients with UC. The patients were classified into 2 groups: antiviral-if treated with antivirals alone; combined-if treated with both antiviral and anti-inflammatory therapy. The outcomes included the rate of colectomy in both arms during the course of hospitalization and after 3/12 months. Results A total of 110 patients were included; 47 (42.7%) patients did not receive IFX nor CsA; 36 (32.7%) received IFX during hospitalization or within 1 month before hospitalization; 20 (18.1%) patients received CsA during hospitalization; 7 (6.4%) were exposed to both IFX and CsA. The rate of colectomy was 14.5% at 30 days, 20.0% at 3 months, and 34.8% at 12 months. Colectomy rates were similar across treatment groups. No clinical and demographic variables were independently associated with the risk of colectomy. Conclusions IFX or cyclosporine therapy is not associated with additional risk for colectomy over antiviral therapy alone in hospitalized CMV-positive patients with UC.

Smaller endoscopes and catheters have been developed that permit direct visualization of the bile and pancreatic ducts (cholangioscopy and pancreatoscopy, respectively). These endoscopes and catheters are passed through the working channel of a standard therapeutic duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). The SpyGlass Direct Visualization System (Boston Scientific Corp, Natick, MA, USA) is currently the most widely used and studied device. Cholangioscopy with intraductal lithotripsy has become an established modality in the treatment of difficult biliary lithiasis. When used in the evaluation of indeterminate biliary strictures by experienced endoscopists in recognizing intraductal pathology, it increases the diagnostic yield of tissue sampling. Pancreatoscopy is complementary to other imaging modalities in the evaluation of intraductal papillary mucinous neoplasms of the pancreas and is emerging as a sole or adjunctive therapy to extracorporeal shock wave lithotripsy for the treatment of main pancreatic duct stones. It remains investigational in the diagnosis of pancreatic adenocarcinoma. Complications specific to the performance of cholangiopancreatoscopy include cholangitis, which is related to intraductal fluid irrigation.Abbreviations: EHL: Electrohydraulic lithotripsy; ERCP: Endoscopic retrograde cholangiopancreatography; ESWL: Extracorporeal lithotripsy by shock waves; ET: Endoscopic therapy; EUS: Endoscopic ultrasound; IPMN: intraductal papillary mucinous neoplasm; LL: Laser lithotripsy; MDCT: Multi-detector computed conventional tomography; MPD: Main pancreatic duct; MRCP: Magnetic resonance cholangiopancreatography; MRI: Magnetic resonance imaging; POCPS: Peroral cholangiopancreatoscopy; PSC: Primary sclerosing cholangitis

Ischaemic colitis (IC) is the most common form of intestinal ischaemia with a wide spectrum of severity, with possible risk of death.The purpose of this study was to evaluate predictive factors of in-hospital and short-term mortality, in a cohort of patients with IC.Retrospective analysis of IC cases diagnosed between 2008-2013 in a single tertiary centre, with assessment of factors at the time of diagnosis associated with in-hospital and 90-day mortality.Of the 203 patients included (132 women), 47 (23%) died during the follow-up (median: 16 months). There were 21 patients (45%) who died during hospitalization and at 90 days there were 30 deaths (64% of total). In multivariate analysis, need for vasopressor support (odds ratio (OR) 11.21; 95% confidence interval (CI): 2.31-54.24;Most deaths in ischaemic colitis occur in the first 90 days after admission, sharing similar risk factors. Assessment of the presence of atrial fibrillation, need of vasopressor support or hospitalization in the intermediate/intensive care unit provides a useful tool to estimate in-hospital mortality and to establish the management for patients admitted for ischaemic colitis.