Metabolic and Bariatric Endoscopy: A Mini-Review

We are currently in a worldwide obesity pandemic, which is one of the most significant health problems of the 21st century. As the prevalence of obesity continues to rise, new and innovate treatments are becoming available. Metabolic and bariatric endoscopic procedures are exciting new areas of gastroenterology that have been developed as a direct response to the obesity crisis. These novel interventions offer a potentially reversible, less invasive, safer, and more cost-effective method of tackling obesity compared to traditional bariatric surgery. Minimally invasive endoscopic treatments are not entirely novel, but as technology has rapidly improved, many of the procedures have been proven to be extremely effective for weight loss and metabolic health, based on high-quality clinical trial data. This mini-review examines the existing evidence for the most prominent metabolic and bariatric procedures, followed by a discussion on the future trajectory of this emerging subspecialty

Effect of gastro-esophageal reflux symptoms on the risk of Barrett's esophagus: A systematic review and meta-analysis

Background and Aim Gastro-esophageal reflux (GER) is the main predisposing factor for Barrett's esophagus (BE). A more precise estimate of the association of GER symptoms with the risk of BE would be important to prioritize endoscopic screening. We conducted a systematic review and meta-analysis to examine this issue. Methods MEDLINE, EMBASE, and EMBASE Classic were searched to identify cross-sectional studies that reported the prevalence of BE based on presence of GER symptoms. The prevalence of BE was compared according to presence or absence of GER symptoms using an odds ratio (OR), with a 95% confidence interval (CI). Specificity and sensitivity of GER symptoms for predicting BE was calculated. Results Of 10,463 citations evaluated, 19 studies reported the prevalence of BE in 43,017 subjects. The pooled OR among individuals with weekly GER symptoms compared with those without was 1.67 (95% CI 1.30-2.15) for endoscopically suspected BE, and 2.42 (95% CI 1.59-3.68) for histologically confirmed BE. No significant association was found between weekly GER symptoms and the presence of short segment BE (OR 1.30; 95% CI 0.86-1.97), whereas a strong association was present with long segment BE, with an OR of 6.30 (95% CI 2.26-17.61). Conclusions Gastro-esophageal reflux symptoms are associated with an increased odds of BE, with a further increase when weekly symptoms are present. Overall, GER symptoms showed low sensitivity and specificity for predicting BE; however, a strong association was found between weekly GER symptoms and long segment BE, but not short segment BE, suggesting that it may be worth considering screening individuals with weekly GER symptoms to rule out long segment BE

Synthesis of Novel Tryptamine Derivatives and Their Biological Activity as Antitumor Agents

We synthesized five novel tryptamine derivatives characterized by the presence of an azelayl chain or of a 1,1,1-trichloroethyl group, in turn connected to another heterocyclic scaffold. The combination of tryptamin-, 1,1,1-trichloroethyl- and 2-aminopyrimidinyl- moieties produced compound 9 identified as the most active compound in hematological cancer cell lines (IC50 = 0.57–65.32 M). Moreover, keeping constant the presence of the tryptaminic scaffold and binding it to the azelayl moiety, the compounds maintain biological activity. Compound 13 is still active against hematological cancer cell lines and shows a selective effect only on HT29 cells (IC50 = 0.006 M) among solid tumor models. Compound 14 loses activity on all leukemic lines, while showing a high level of toxicity on all solid tumor lines tested (IC50 0.0015–0.469 M)

Distribution of Exonic Variants in Glycogen Synthesis and Catabolism Genes in Late Onset Pompe Disease (LOPD)

Pompe disease (PD) is a monogenic autosomal recessive disorder caused by biallelic pathogenic variants of the GAA gene encoding lysosomal alpha-glucosidase; its loss causes glycogen storage in lysosomes, mainly in the muscular tissue. The genotype-phenotype correlation has been extensively discussed, and caution is recommended when interpreting the clinical significance of any mutation in a single patient. As there is no evidence that environmental factors can modulate the phenotype, the observed clinical variability in PD suggests that genetic variants other than pathogenic GAA mutations influence the mechanisms of muscle damage/repair and the overall clinical picture. Genes encoding proteins involved in glycogen synthesis and catabolism may represent excellent candidates as phenotypic modifiers of PD. The genes analyzed for glycogen synthesis included UGP2, glycogenin (GYG1-muscle, GYG2, and other tissues), glycogen synthase (GYS1-muscle and GYS2-liver), GBE1, EPM2A, NHLRC1, GSK3A, and GSK3B. The only enzyme involved in glycogen catabolism in lysosomes is alpha-glucosidase, which is encoded by GAA, while two cytoplasmic enzymes, phosphorylase (PYGB-brain, PGL-liver, and PYGM-muscle) and glycogen debranching (AGL) are needed to obtain glucose 1-phosphate or free glucose. Here, we report the potentially relevant variants in genes related to glycogen synthesis and catabolism, identified by whole exome sequencing in a group of 30 patients with late-onset Pompe disease (LOPD). In our exploratory analysis, we observed a reduced number of variants in the genes expressed in muscles versus the genes expressed in other tissues, but we did not find a single variant that strongly affected the phenotype. From our work, it also appears that the current clinical scores used in LOPD do not describe muscle impairment with enough qualitative/quantitative details to correlate it with genes that, even with a slightly reduced function due to genetic variants, impact the phenotype

New devices for endoscopic treatments in gastroenterology: a narrative review

Endoscopy is living period of continuous innovations in terms of image quality, endoscopes, post-processing software and lastly, application of Artificial Intelligence. Therapeutic boundaries have expanded widening the grey zone between endoscopy and surgery, increasing endoscopic approaches in clinical scenarios where, until a few years ago, surgery was the only option New scopes and accessories have made easier to access critical districts such as the biliary tree and the small bowel intestine. In the field of hepato-pancreato-biliary endoscopy (HPB), it is now possible to directly access the biliary ducts or cystic lesions though dedicated stents and scopes, rather than having to rely only on fluoroscopy and ultrasound, increasing the diagnostic and therapeutic options by applying a three-dimensional approach. This narrative review will give an overview of some of most relevant emerging fields in luminal and HPB endoscopy, highlighting advantages and main limitations of the techniques, and providing considerations for future development

Applications of Artificial Intelligence for the Diagnosis of Gastrointestinal Diseases

The development of convolutional neural networks has achieved impressive advances of machine learning in recent years, leading to an increasing use of artificial intelligence (AI) in the field of gastrointestinal (GI) diseases. AI networks have been trained to differentiate benign from malignant lesions, analyze endoscopic and radiological GI images, and assess histological diagnoses, obtaining excellent results and high overall diagnostic accuracy. Nevertheless, there data are lacking on side effects of AI in the gastroenterology field, and high-quality studies comparing the performance of AI networks to health care professionals are still limited. Thus, large, controlled trials in real-time clinical settings are warranted to assess the role of AI in daily clinical practice. This narrative review gives an overview of some of the most relevant potential applications of AI for gastrointestinal diseases, highlighting advantages and main limitations and providing considerations for future development

Systmatic review with meta-analysis: Risk factors for Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms

Background: Gastro-oesophageal reflux is considered the main risk factor for Barrett's oesophagus. The role of other potential risk factors for the development of Barrett's oesophagus in patients with gastro-oesophageal reflux symptoms is controversial. Aims: To perform a systematic review and meta-analysis examining risk factors in development of Barrett's oesophagus. Methods: Medline, Embase and Embase Classic were searched (until December 2020) to identify cross-sectional studies reporting prevalence of Barrett's oesophagus based on presence of one or more proposed risk factors in individuals with gastro-oesophageal reflux symptoms. Prevalence of Barrett's oesophagus was compared according to presence or absence of each risk factor in individuals with gastro-oesophageal reflux symptoms. Results: Of 7164 citations evaluated, 13 studies reported prevalence of BO in 11 856 subjects. Pooled prevalence of histologically confirmed Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms in all studies was 7.0% (95% CI 4.8% to 9.6%). Prevalence was higher in subjects with hiatal hernia (OR 2.74; 95% CI 1.58 to 4.75) and in those who drank alcohol (OR 1.51; 95% CI 1.17 to 1.95). Other features including non-steroidal anti-inflammatory drugs and/or aspirin use (OR 1.19; 95% CI 1.00 to 1.42), smoking (OR 1.14; 95% CI 0.96 to 1.35) or obesity (OR 1.10; 95% CI 0.92 to 1.33) were not significantly associated with Barrett's oesophagus. Conclusions: The prevalence of Barrett's oesophagus in individuals with gastro-oesophageal reflux symptoms was higher in those who drank alcohol, although this association was modest. The strongest association found was between hiatal hernia and Barrett's oesophagus. Other potential risk factors assessed in this study did not appear to be associated with presence of Barrett's oesophagus among individuals with gastro-oesophageal symptoms

Transcription regulation by the adaptor protein Fe65 and the nucleosome assembly factor SET

Fe65 protein interacts with the cytosolic domain of the amyloid precursor APP. Its possible involvement in gene regulation is suggested by numerous observations, including those demonstrating that it activates transcription. Here, we show that the Fe65 transcription activation domain overlaps with the WW domain of Fe65 and binds to the nucleosome assembly factor SET. This protein is required for the Fe65-mediated transactivation of a reporter gene. Two-step chromatin immunoprecipitation experiments demonstrate that a complex including Fe65/AICD/Tip60 and SET is associated with the KAI1 gene promoter. Suppression of SET levels by RNA interference shows that this protein is required for full levels of basal transcription of the KAI1 gene. These results further support the function of Fe65 and APP in gene regulation and show a new role for the SET factor