Nationwide COVID-19-EII Study: Incidence, Environmental Risk Factors and Long-Term Follow-Up of Patients with Inflammatory Bowel Disease and COVID-19 of the ENEIDA Registry

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March-July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged >= 60 years (OR 7.1, 95% CI: 1.8-27 and 4.5, 95% CI: 1.3-15.9), while having >= 2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3-11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD.This study is funded by the Carlos III Health Institute (COV20/00227: Co-IP Dra. Maria Esteve and Dra. Yamile Zabana), FEDER (Fondo Europeo de Desarrollo Regional) and supported by GETECCU. The ENEIDA Registry of GETECCU is supported by Takeda, Pfizer, Galapagos, AbbVie and Biogen

Pancreatic Cancer in Lynch Syndrome Patients

Although colorectal cancer (CRC) is the most common cancer type in Lynch syndrome (LS) families, patients have also increased lifetime risk of other types of tumors. The accumulated risk of pancreatic cancer (PC) in LS patients is around 3.7% and developed tumors often present a characteristically medullary appearance with prominent lymphocytic infiltration. LS patients are considered in high risk for PC development as they present 8.6-fold increase compared with the general population. Here we review PC cases reported in LS patients and current management guidelines. Literature data show that LS is clearly associated with PC and recent publications also demonstrated a connection with pancreatic neoplasic precursor lesions such as intraductal papillary mucinous neoplasms (IPMN) in these patients. While screening techniques are well established for CRC detection, clear strategies are not yet uniform for PC. Magnetic resonance imaging (MRI) and/or endoscopic ultrasound every 1-2 years in MMR mutation carriers with PC in a first or second-degree relative is recommended. Better pancreatic cancer detection strategies should be urgently defined due to the importance of early diagnosis in this disease

Inflammatory Mediators of Hepatic Steatosis

Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming a world-wide public health problem. NAFLD represents a spectrum of disease ranging from “simple steatosis”, which is considered relatively benign, to nonalcoholic steatohepatitis and to NAFLD-associated cirrhosis and end-stage liver disease. The etiology of NAFLD and its progression is complex and remains incompletely understood. The progression of the disease involves many factors. Apart from the two hits, the accumulation of TG and the development of fibrosis and necroinflammatory processes, exit numerous molecules associated with these two hits. Among them we can highlight the pro-inflammatory molecules and adiponectins. This review focuses on the growing evidence from both experimental and human studies suggesting a central role of cytokines in the pathogenesis of NAFLD. We review the role of cytokines as key regulators of insulin sensitivity and hepatic lipid overloading, liver injury and inflammation, and fibrosis with an emphasis on potential therapeutic implications

Relationship between IGF-1 and body weight in inflammatory bowel diseases: Cellular and molecular mechanisms involved

[EN] Inflammatory bowel diseases (IBD), represented by ulcerative colitis (UC) and Crohn's disease (CD), are characterized by chronic inflammation of the gastrointestinal tract, what leads to diarrhea, malnutrition, and weight loss. Depression of the growth hormone-insulin-like growth factor-1 axis (GH-IGF-1 axis) could be responsible of these symptoms. We demonstrate that long-term treatment (54 weeks) of adult CD patients with adalimumab (ADA) results in a decrease in serum IGF-1 without changes in serum IGF-1 binding protein (IGF1BP4). These results prompted us to conduct a preclinical study to test the efficiency of IGF-1 in the medication for experimental colitis. IGF-1 treatment of rats with DSS-induced colitis has a beneficial effect on the following circulating biochemical parameters: glucose, albumin, and total protein levels. In this experimental group we also observed healthy maintenance of colon size, body weight, and lean mass in comparison with the DSS-only group. Histological analysis revealed restoration of the mucosal barrier with the IGF-1 treatment, which was characterized by healthy quantities of mucin production, structural maintenance of adherers junctions (AJs), recuperation of Ecadherin and beta-catenin levels and decrease in infiltrating immune cells and in metalloproteinase-2 levels. The experimentally induced colitis caused activation of apoptosis markers, including cleaved caspase 3, caspase 8, and PARP and decreases cell-cycle checkpoint activators including phosphorylated Rb, cyclin E, and E2F1. The IGF-1 treatment inhibited cyclin E depletion and partially protects PARP levels. The beneficial effects of IGF-1 in experimental colitis could be explained by a re-sensitization of the IGF-1/IRS-1/AKT cascade to exogenous IGF-1. Given these results, we postulate that IGF-1 treatment of IBD patients could prove to be successful in reducing disease pathology.Authors would like to thank the Radioactive facility, the Chemical and Microbiological analysis Centre and the Animal facility of the University of Alcalá for their technical help. This research has been funded by grants from: Asociación Española de Gastroenterologia (AEG), Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU), Instituto de Salud Carlos III (FIS12/02557 and PI13/00041) and Universidad de Alcalá (32/2013, 22/2014, 26/2015) and B2017/BMD-3804 MITIC-CM (Comunidad de Madrid) and Halekulani S. L. We thank Miguel Pérez Toledano "in memoriam" for his valuable work in the management of laboratory animals

Role of Dairy Foods, Fish, White Meat, and Eggs in the Prevention of Colorectal Cancer: A Systematic Review of Observational Studies in 2018–2022

[EN] There is limited evidence to support the relationship between the consumption of animal-source foods other than red meat and processed meat and colorectal cancer (CRC) risk. We aimed to examine the recent available evidence from observational studies about the association between these food groups’ intake and CRC risk. For this systematic review, we searched the PubMed database for the last five years. A total of fourteen cohort studies and seven case–control studies comprising a total of >60,000 cases were included. The studies showed a consistent significant decrease in CRC risk, overall and by subsites, associated with a high consumption of total dairy products. Less strong effects associated with the consumption of any subtype of dairy product were observed. Fish consumption, overall and by subtypes (oily or non-oily and fresh or canned), showed a mild inverse association with CRC risk. The association between white meat and egg intake and CRC risk was low and based on a small number of studies; thus, these findings should be interpreted with caution. In conclusion, a high consumption of total dairy products was associated with a lower CRC risk. However, evidence for fish, white meat, and eggs and the CRC risk were not as strong.This research received no external funding. CIBERehd is funded by the Instituto de Salud Carlos III. BIOMICS Research Group, Microfluidics & BIOMICS Cluster of the UPV/EHU is funded by the Basque Government. Funding of article processing charges provided by the Spanish Gastroenterology Foundation

Natural history of liver disease in a large international cohort of children with Alagille syndrome: Results from the GALA study

Background and Aims: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers, and real‐world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international cohort of children with ALGS. Approach and Results: This was a multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born between January 1997 and August 2019. Native liver survival (NLS) and event‐free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. In total, 1433 children (57% male) from 67 centers in 29 countries were included. The 10 and 18‐year NLS rates were 54.4% and 40.3%. By 10 and 18 years, 51.5% and 66.0% of children with ALGS experienced ≥1 adverse liver‐related event (CEPH, transplant, or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and 10.0 mg/dl were associated with a 4.8 (95% CI, 2.4–9.7) and 15.6 (95% CI, 8.7–28.2) increased risk of transplantation relative to <5.0 mg/dl. Median TB <5.0 mg/dl were associated with higher NLS rates relative to ≥5.0 mg/dl, with 79% reaching adulthood with native liver (p < 0.001). Conclusions: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dl between 6 and 12 months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision‐making and in the evaluation of therapies.This study received funding support from the following agencies: The Alagille Syndrome Alliance, Mirum Pharmaceuticals, Inc., and Albireo Pharma, Inc., who provided unrestricted educational grants to the Hospital for Sick Children (SickKids Foundation). The study sponsors were not involved in the conduct of the research study or preparation of the manuscript

Current Approaches for Predicting a Lack of Response to Anti-EGFR Therapy in KRAS Wild-Type Patients

Targeting epidermal growth factor receptor (EGFR) has been one of the most effective colorectal cancer strategies. Anti-EGFR antibodies function by binding to the extracellular domain of EGFR, preventing its activation, and ultimately providing clinical benefit. KRAS mutations in codons 12 and 13 are recognized prognostic and predictive biomarkers that should be analyzed at the clinic prior to the administration of anti-EGFR therapy. However, still an important fraction of KRAS wild-type patients do not respond to the treatment. The identification of additional genetic determinants of primary or secondary resistance to EGFR targeted therapy for further improving the selection of patients is urgent. Herein, we review the latest published literature highlighting the most important genes that may predict resistance to anti-EGFR monoclonal antibodies in colorectal cancer patients. According to the available findings, the evaluation of BRAF, NRAS, PIK3CA, and PTEN status could be the right strategy to select patients who are likely to respond to anti-EGFR therapies. In the future, the combination of those biomarkers will help establish consensus that can be introduced into clinical practice.This study was supported by Grants from Kaohsiung Medical University Hospital (KMUH102-M207) and Ministry of Health and Welfare (MOHW103-TD-B-111-05). Marta Herreros-Villanueva is supported by Universidad del Pais Vasco, Instituto Biodonostia, San Sebastian, and CIBERehd (Red de Enfermedades Hepaticas y Digestivas)

Mediastinal abscess, an unusual way of presentation of eosinophilic esophagitis

Eosinophilic esophagitis (EoE) is one of the most prevalent esophageal diseases and the leading cause of dysphagia and food impaction in children and young adults. EoE represents a chronic, local immune-mediated esophageal disease, characterized clinically by symptoms related to esophageal dysfunction and histologically by eosinophil-predominant inflammation. Mediastinal abscess is an uncommon condition that typically appears after esophageal perforations or thoracic surgeries, usually requiring treatment for surgical intervention due to its high morbidity-mortality. Mediastinal abscess, outside these two contexts, is extremely rare. We present the case of a mediastinal abscess secondary to EoE. It is important to think about this entity when there is a mediastinal abscess without trauma or previous surgery