World Journal of Gastroenterology最新文献

Background: Chronic biliary disease, including cholangitis and cholecystitis, is attributed to ascending infection by intestinal bacteria. Development of a mouse model for bile duct inflammation is imperative for the advancement of novel therapeutic approaches. Current models fail to replicate the harmful bacterial influx to the biliary tract observed in humans and spread of inflammation to the liver. Therefore, we aimed to establish an animal model of biliary disease that faithfully replicates the mechanisms of human diseases.

Aim: To establish a cholecystoduodenal anastomosis model capable of mimicking the mechanisms of ascending infection and inflammation observed in human biliary diseases.

Methods: We established a mouse biliary disease model by directly connecting the gallbladder and duodenum, enabling ascending infection into the biliary tract without traversing the sphincter of Oddi.

Results: In the cholecystoduodenal anastomosis mouse model, we observed impaired epithelial structure, wall thickening, and macrophage recruitment in the gallbladder. Despite the absence of postoperative antibiotics, we detected no changes in serum proinflammatory cytokine levels, indicating no systemic inflammation. Moreover, patency between the gallbladder and duodenum was confirmed via common bile duct ligation. Injection of patient-derived pathogenic bacteria into bile duct-ligated mice led to ascending infection, which significantly increased proinflammatory cytokine mRNA expression in the liver, duodenum, and ileum. These results indicate that our mouse model exhibited a direct connection between the gallbladder and duodenum, leading to ascending infection and closely mimicking the clinical features of biliary diseases observed in humans.

Conclusion: The cholecystoduodenal anastomosis mouse model is an effective chronic biliary disease model with significant relevance in the development of microbiome-based therapies for the prevention and treatment of biliary disease.

Background: Emphysematous pancreatitis (EP) is a rare, severe form of acute necrotizing pancreatitis characterized by gas in pancreatic or peripancreatic tissue, with a high mortality rate.

Aim: To assess the diagnosis, treatment, and outcomes of EP through a series of case studies.

Methods: This case series was conducted in intensive care units at the Second Affiliated Hospital of Anhui Medical University. Patients were included if they were diagnosed with pancreatic necrosis and gas via computed tomography from June 2018 to June 2024. Patients were categorized into early and late EP groups based on the timing of the appearance of the bubble sign and into extensive and common types based on the distribution range of the bubble sign. The data recorded included sex, age, aetiology, Acute Physiology and Chronic Health Evaluation II score, Sequential Organ Failure Assessment score, Bedside Index for Severity in Acute Pancreatitis score, subtype, gas distribution extent, aetiological diagnostic basis, pathogen categories, intervention measures, and prognosis.

Results: Among the 15 patients, 66.7% had a biliary aetiology and extensive type of EP, 47.1% had early-onset EP, and 73.3% had confirmed aetiological evidence [6 based on bacterial culture, 4 based on both routine culture and next-generation sequencing (NGS), and 1 solely based on NGS]. The common pathogens were Escherichia coli and Klebsiella pneumoniae. Six patients survived. Among the 2 patients who did not undergo percutaneous drainage or surgical treatment, 1 survived. Of the 6 patients who underwent percutaneous drainage, 2 survived, 2 survived after subsequent surgery, and 2 died without surgery. Among the 6 patients who underwent surgery alone, 5 died and 1 survived. Among the early-onset EP patients, 4 survived; among the late-onset EP patients, 2 survived. Among the common EP types, 4 survived; among the extensive EP types, only 1 survived.

Conclusion: The mortality rate among patients with EP is considerable, and NGS enhances pathogen identification accuracy. Despite the debate on conservative vs surgical management, the STEP-UP strategy remains viable. Aggressive antimicrobial therapy, early percutaneous catheter drainage, and other minimally invasive interventions, along with delayed surgical intervention, may improve patient prognosis.

The feasibility of population screening for colorectal cancer has been demonstrated in several studies. Most of these studies have considered individual characteristics, diagnostic approaches, epidemiological data, and socioeconomic factors. In this article, we comment on an editorial by Metaxas et al published in the recent issue of the journal. The authors emphasized the need to raise public awareness through health education programs and the possibility of using easily accessible non-invasive screening methods. Here, we focus on non-invasive molecular genetic approaches that can aid in colorectal cancer screening. On the one hand, we highlighted the use of tumor DNA/RNA markers directly for screening and, on the other hand, underline the use of polygenic risk assessment and hereditary predisposition to select individuals for more thorough cancer screening.

The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has increased significantly in recent decades and is projected to increase further due to the rising obesity rates. MASLD patients are at higher risk of developing advanced liver diseases "cirrhosis and hepatocellular carcinoma" as well as liver- or cardiovascular-related mortality. Existing lipid-lowering therapies failed to reduce the risk of mortality in these patients. Therefore, there is an urgent need for pharmacotherapies that can control and even reverse this disease. Fanlian Huazhuo Formula (FLHZF) is a combination herbal preparation, and its various individual constituents regulate hepatic lipid metabolism, adipose tissue inflammation, and gut microbiota. Despite, these useful effects, limited information is available on its benefits in diet-induced hepatosteatosis. In this article, we discuss the research findings recently published about the therapeutic effects of FLHZF in suppressing MASLD development and underlying mechanisms. Utilizing a series of in vitro and in vivo experiments, the authors demonstrated for the first time that FLHZF suppresses MASLD in male mice possibly by inhibiting hepatic de novo lipogenesis pathways and reducing hepatocyte death. This study paves the way for future investigations aimed at investigating FLHZF's role in inhibiting lipogenesis particularly using radioactively-labeled glucose and acetate, and governing hepatocyte mitochondrial function, gut microbiome profile, and its effects in other models of MASLD, and female mice.

Background: Over the last decade, the treatment options for inflammatory bowel disease (IBD) have significantly progressed with the emergence of new medications designed to target various immune pathways and mitigate inflammation. Adalimumab (ADA) is a tumor necrosis factor alpha antagonist and stands as an effective treatment for IBD. In April 2021, the province of British Columbia implemented a mandatory non-medical switch policy of the ADA originator Humira^® to ADA biosimilars. Biosimilars offer a potential cost-effective, safe, and efficacious alternative to the originator, yet there remains limited real-world evidence on long-term outcomes of ADA non-medical switching in IBD.

Aim: To assess the long-term outcomes of non-medical switching from the ADA originator Humira^® to an ADA biosimilar among IBD patients.

Methods: A retrospective observational chart review study was conducted on IBD patients eligible for the provincially mandated non-medical switch to an ADA biosimilar. The primary outcome was treatment persistence at 30 months post-switch. Secondary outcomes included the proportion of and reasons for therapy alteration or ADA discontinuation, loss of response (LOR) rates, adverse events (AE), and clinical and biochemical remission status. Patients who remained on the originator throughout the switch period, through compassionate support or private pay, constituted the comparison group.

Results: Patients in the originator (n = 43) and biosimilar switch (n = 228) groups displayed similar demographics and baseline disease characteristics. By the study endpoint of 30 months, there was no difference in the rate of treatment persistence in either group (n = 36, 83.7% originator group vs n = 201, 88.2% biosimilar group, P = 0.451). Treatment persistence demonstrated similar rates of discontinuation between both study groups (log-rank P = 0.543). There was a numerical but not statistically significant difference in rates of adverse outcomes between either group (39.5% originator vs 28.9% biosimilars, P = 0.206). This included comparable rates of LOR (27.9% vs 17.5%) or AE (11.6% vs 11.4%) between the originator and biosimilar cohorts, respectively. C-reactive protein and fecal calprotectin levels were similar one year pre- and post-switch.

Conclusion: These data support the long-term efficacy and safety of non-medical ADA switching in IBD and will help inform patients and physicians in jurisdictions currently undergoing biosimilar switching.

This article delved into the comprehensive study by Jiang et al, which meticulously examined the bidirectional relationships among gallstone disease, non-alcoholic fatty liver disease, and kidney stone disease through a multicenter study, systematic review, and meta-analysis. The study provides significant evidence supporting these associations, offering valuable insights into the etiology and potential prevention strategies for these interconnected conditions. The clinical significance of these bidirectional relationships is profound, as they underscore the importance of recognizing these conditions not only as isolated diseases but as part of a complex network that can influence each other. These results highlight the critical need for thorough screening and personalized prevention strategies for individuals with these interconnected conditions. Explicit implications for prevention strategies and early screening practices are crucial, as they can lead to early detection and intervention, significantly altering disease progression and outcomes. Furthermore, identifying potential therapeutic targets within these shared pathways may enhance treatment efficacy and patient outcomes, making this research highly relevant to clinical practice. By comprehending the common pathophysiological mechanisms and applying specific interventions, healthcare professionals can greatly enhance patient care and lessen the impact of these widespread diseases on global health.

In this letter, we commented on the article by Wu et al. We examined the interactions between mesenteric adipose tissue, creeping fat, and gut microbiota in Crohn's disease (CD), a condition marked by chronic gastrointestinal inflammation with a rising global incidence. The pathogenesis of CD involves complex genetic, environmental, and microbial factors. Dysbiosis, which is an imbalance in gut microbial communities, is frequently observed in CD patients, highlighting the pivotal role of the gut microbiota in disease progression and the inflammatory response. Recent studies have shown that mesenteric adipose tissue and creeping fat actively contribute to inflammation by producing proinflammatory cytokines. The relationship between creeping fat and altered microbiota can shift from a potentially protective role to one that encourages bacterial translocation, further complicating disease management. Recent research has suggested that fecal microbiota transplantation could help restore microbial balance, offering a promising therapeutic strategy to improve clinical disease response.

Background: A body of evidence has suggested bidirectional relationships among gallstone disease (GSD), non-alcoholic fatty liver disease (NAFLD), and kidney stone disease (KSD). However, the results are inconsistent, and studies on this topic in China are relatively few. Our goal is to explore the bidirectional associations among these three diseases through a multicenter study, systematic review, and meta-analysis.

Aim: To explore the bidirectional associations among these three diseases through a multicenter study, systematic review, and meta-analysis. The results may help to investigate the etiology of these diseases and shed light on the individualized prevention of these three diseases.

Methods: Subjects who participated in physical examinations in Beijing, Tianjin, Chongqing in China were recruited. Multivariable logistic regression was employed to explore the bidirectional relationships among GSD, KSD, and NAFLD. Systematic review and meta-analysis were initiated to confirm the epidemiologic evidence from previous observational studies. Furthermore, trial sequential analysis (TSA) was conducted to evaluate whether the evidence was sufficient and conclusive.

Results: Significant bidirectional associations were detected among the three diseases, independent of potential confounding factors. The pooled results of the systematic review and meta-analysis also corroborated the aforementioned results. The combined evidence from the multicenter study and meta-analysis was significant [pooled odds ratio (OR) = 1.42, 95%CI: 1.16-1.75, KSD → GSD; pooled OR = 1.48, 95%CI: 1.31-1.67, GSD → KSD; pooled OR = 1.31, 95%CI: 1.17-1.47, GSD → NAFLD; pooled OR = 1.37, 95%CI: 1.26-1.50, NAFLD → GSD; pooled OR = 1.28, 95%CI: 1.08-1.51, NAFLD → KSD; pooled OR = 1.21, 95%CI: 1.16-1.25, KSD → NAFLD]. TSA indicated that the evidence was sufficient and conclusive.

Conclusion: The present study presents relatively sufficient evidence for the positive bidirectional associations among GSD, KSD, and NAFLD. The results may provide clues for investigating the etiology of these three diseases and offer a guideline for identifying high-risk patients.

The presence of Helicobacter pylori (H. pylori) infection has been indicated to have a protective influence on esophageal cancer (EC) in some studies, but its specific impact on the risk of esophageal squamous cell carcinoma and esophageal adenocarcinoma remains inconclusive. This manuscript comment addresses the recent study by López-Gómez et al. Despite it was a retrospective observational study without a control group, this study revealed a notably low prevalence of H. pylori infection among EC patients, indicating a potential association between H. pylori and EC in Spain. It is important to note that the relationship between H. pylori and the risk of EC varies geographically. We also conducted a meta-analysis focusing on this association in Asian populations to offer precise clinical insights. However, no significant correlation between H. pylori infection and EC was identified, suggesting that the perceived protective effect of H. pylori against EC may have been overestimated in the Asian population.

Diabetic gastrointestinal neuropathy is a diabetes-related complication, associated with a complex interplay of hyperglycemic damage, autoimmune responses, oxidative stress, gastrointestinal hormones, and vascular insufficiency. Patients with diabetes should be monitored and therapeutic intervention introduced to prevent neuropathy due to diabetes prior to "the point of no return". Determining gastric bioelectrical activity by body surface gastric mapping may be a promising option to monitor diabetic gastrointestinal neuropathy.