Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that poses a significant health concern. Although its etiology remains unknown, there is growing evidence that gut dysbiosis is involved in the development and exacerbation of IBS. Previous studies have reported altered microbial diversity, abundance, and composition in IBS patients when compared to controls. However, whether dysbiosis or aberrant changes in the intestinal microbiota can be used as a hallmark of IBS remains inconclusive. We reviewed the literatures on changes in and roles of intestinal microbiota in relation to IBS and discussed various gut microbiota manipulation strategies. Gut microbiota may affect IBS development by regulating the mucosal immune system, brain–gut–microbiome interaction, and intestinal barrier function. The advent of high-throughput multi-omics provides important insights into the pathogenesis of IBS and promotes the development of individualized treatment for IBS. Despite advances in currently available microbiota-directed therapies, large-scale, well-organized, and long-term randomized controlled trials are highly warranted to assess their clinical effects. Overall, gut microbiota alterations play a critical role in the pathophysiology of IBS, and modulation of microbiota has a significant therapeutic potential that requires to be further verified.
Objectives: Postponed open necrosectomy or minimally invasive intervention has become the treatment option for necrotizing pancreatitis. Nevertheless, several studies point to the safety and efficacy of early intervention for necrotizing pancreatitis. Therefore, we conducted a systematic review and meta-analysis to compare clinical outcomes of acute necrotizing pancreatitis between early and late intervention.
Methods: Literature search was performed in multiple databases for articles that compared the safety and clinical outcomes of early (<4 weeks from the onset of pancreatitis) versus late intervention (≥4 weeks from the onset of pancreatitis) for necrotizing pancreatitis published up to August 31, 2022. The meta-analysis was performed to determine pooled odds ratio (OR) of mortality rate and procedure-related complications.
Results: Fourteen studies were included in the final analysis. For open necrosectomy intervention, the overall pooled OR of mortality rate with the late intervention compared with early intervention was 7.09 (95% confidence interval [CI] 2.33–21.60; I2 = 54%; P = 0.0006). For minimally invasive intervention, the overall pooled OR of mortality rate with the late intervention compared with early intervention was 1.56 (95% CI 1.11–2.20; I2 = 0%; P = 0.01). The overall pooled OR of pancreatic fistula with the late minimally invasive intervention compared with early intervention was 2.49 (95% CI 1.75–3.52; I2 = 0%; P < 0.00001).
Conclusion: These results showed the benefit of late interventions in patients with necrotizing pancreatitis in both minimally invasive procedures and open necrosectomy. Late intervention is preferred in the management of necrotizing pancreatitis.
Objectives: Drug-induced liver injury (DILI) is an increasing etiology of liver dysfunction, with various incidence worldwide. To better understand the disease burden and establish appropriate preventive and treatment strategies, a systematic review and meta-analysis was conducted.
Methods: PubMed, EMBASE, Web of Science, and Cochrane Library were searched for studies on the incidence of DILI published up to June 1, 2022. According to the predefined criteria, only population-based studies were included. Incidence was presented as cases per 100 000 person-years with 95% confidence interval (CI) using a random-effects model.
Results: A total of 14 studies were included. The overall incidence of DILI was 4.94 per 100 000 person-years (95% CI 4.05–5.83). Time-based cumulative meta-analysis suggested that the incidence of DILI increased over time since 2010. The incidence varied by regions, with Asia having the highest incidence of 17.82 per 100 000 person-years (95% CI 6.26–29.38), while North America having the lowest incidence of 1.72 per 100 000 person-years (95% CI 0.48–2.95). All studies reported a higher incidence of DILI in the elderly but comparable incidences between male and female (3.42 per 100 000 person-years vs 4.64 per 100 000 person-years).
Conclusions: The global incidence of DILI has been increasing since 2010, with the highest incidence in Asia. Understanding the epidemiological characteristics of DILI helps establish specific strategies to deal with this emerging health problems.
Objective: To evaluate the relationship between gastric cancer and its precancerous lesions and gastric xanthoma.
Methods: Medical records of 47 736 patients who underwent gastroscopy in our center from January 2020 to December 2021 were reviewed. Patients’ age, sex, endoscopic and histopathological findings, and the presence, number and location of gastric xanthoma were recorded. To investigate the detection rate of gastric xanthoma at different stages of gastric lesions, the participants were further divided into the chronic gastritis group (n = 42 758), the precancerous lesion group (n = 3672), and the gastric cancer group (n = 1306), respectively.
Results: The overall detection rate of gastric xanthoma was 2.85%, and it was most commonly observed in the gastric antrum (52.50%). In addition, gastric xanthoma was more common in men and more likely to be single lesion. It was most detected in the precancerous lesion group (8.39%), followed by the gastric cancer group (5.44%), and least in the chronic gastritis group (2.29%). Multivariate analysis showed that gastric xanthoma was closely related to precancerous lesions (odds ratio [OR] 3.197, 95% confidence interval [CI] 2.791–3.662,P < 0.001) and gastric cancer (OR 1.794, 95% CI 1.394–2.309,P < 0.001).
Conclusion: Gastric xanthoma is closely related to gastric precancerous lesions and gastric cancer.
Objectives: Percutaneous electrical nerve field stimulation (PENFS) has documented efficacy for irritable bowel syndrome (IBS) via plausible vagal neuromodulation effects. The vagus nerve may affect gut microbiome composition via brain–gut–microbiome signaling. We aimed to investigate gut microbiome alterations by PENFS therapy in adolescent IBS patients.
Methods: A prospective study of females with IBS aged 11–18 years receiving PENFS therapy for 4 weeks with pre- and post-intervention stool sampling was conducted. Outcome surveys completed pre-therapy, weekly, and post-therapy included IBS-Severity Scoring System (IBS-SSS), Visceral Sensitivity Index (VSI), Functional Disability Inventory (FDI), and the global symptom response scale (SRS). Bacterial DNA was extracted from stool samples followed by 16S rRNA amplification and sequencing. QIIME 2 (version 2022.2) was used for analyses of α and β diversity and differential abundance by group.
Results: Twenty females aged 15.6 ± 1.62 years were included. IBS-SSS, VSI, and FDI scores decreased significantly after PENFS therapy (P < 0.0001,P = 0.0003,P = 0.0004, respectively). No intra- or interindividual microbiome changes were noted pre- versus post-therapy or between responders and non-responders. When response was defined by 50-point IBS-SSS score reduction, α diversity was higher in responders compared with non-responders at week 4 (P = 0.033). There was higher abundance of Blautia in excellent responders versus non-responders.
Conclusions: There were no substantial microbial diversity alterations with PENFS. Subjects with excellent therapeutic response showed an enrichment of relative abundance of Blautia, which may indicate that patients with specific microbial signature have a more favorable response to PENFS.
Objectives: Severe acute pancreatitis (SAP) is characterized by pancreatic and systemic inflammation and persistent organ failure. Neutrophil extracellular traps (NETs) are considered to play an important role in the development of SAP. We aimed to explore the effect of disulfiram (DSL), a newly developed anti-inflammatory drug, on NETs in SAP.
Methods: A mouse model of SAP was induced by caerulein and lipopolysaccharide, and the mice were divided into the normal control group, the DSL group, the SAP group, and the SAP treated with 50 mg/kg (50DSLSAP) and 100 mg/kg DSL (100DSLSAP) groups, respectively. The severity of SAP was evaluated based on the morphological and biochemical changes. Gasdermin D (GSDMD) expression was evaluated in vivo and in vitro to verify the effect of DSL. Additionally, the expressions of NETs were also evaluated in vivo and in vitro in SAP with and without DSL treatment to explore the possible mechanism of DSL on SAP.
Results: Pancreatic inflammatory injury increased in the SAP group, which was alleviated by DSL. GSDMD, a protein related to the formation of NETs, increased in SAP. Expressions of NETs were also promoted in the in vivo SAP model and by phorbol myristate acetate (PMA) in vitro. Moreover, DSL inhibited the expressions of GSDMD and NETs in vivo. The results were further confirmed in the in vitro experiment.
Conclusions: NETs are highly associated with inflammatory injury in SAP. DSL inhibits NETs formation by downregulating GSDMD, which in turn relieves the inflammation of SAP. Our study may provide a possible therapeutic target for SAP.