Digestive Diseases and Sciences最新文献

Background: The incidence of obesity in patients with inflammatory bowel disease (IBD) is increasing and there are limited data on the impact of obesity on perianal fistulas in Crohn's disease (CD).

Aims: We aim to examine the relationship between obesity and the prevalence and complications of Crohn's perianal fistulas.

Methods: We conducted a cross-sectional study of CD patients treated at a tertiary care center from 2012 to 2022. Obesity was defined as maximum BMI > 30 kg/m² and further subdivided into 5 BMI categories. The prevalence of perianal fistulas was defined by any history of perianal fistula. The complications of perianal fistulas were measured by five variables including complex fistulas, history of perianal fistula surgery, number of perianal surgeries, history of fecal diversion, and median time to first anal surgery.

Results: In all, 704 patients with CD were included; 31.1% were obese. There was no significant association between obesity and prevalence of perianal fistulas (p = 0.719), complex fistulas (p = 0.144), history of perianal surgery (p = 0.146), ≥ 1 perianal surgeries (p = 0.220), fecal diversion (p = 0.705), or median time to first perianal surgery (p = 0.192). Increasing BMI category was not associated with the prevalence of perianal fistulas (p = 0.944), complex fistulas (p = 0.089), perianal surgery (p = 0.583), ≥ 1 perianal surgeries (p = 0.114), fecal diversion (p = 0.542), or median time to first perianal surgery (p = 0.486). When comparing those with perianal fistulas to those without, there was no significant difference in rates of obesity (p = 0.876).

Conclusion: There was no association between obesity and the prevalence and complications of Crohn's perianal fistulas.

Background: Emerging evidence indicates a robust association between internal RNA N7-methylguanosine (m7G) modification and hepatocarcinogenesis. However, the precise implications of altered internal m7G modifications within mRNA on the progression of Hepatitis B Virus (HBV)-induced Hepatocellular Carcinoma (HCC) remain inadequately elucidated.

Methods: This study utilized a previously published dataset from the Gene Expression Omnibus (GEO) that includes samples of normal liver tissue, HBV positive (HP) liver tissue, and HP HCC tissue to investigate the profiling of mRNA internal m7G methylation. The STRING database and in vitro experiments were employed for the screening and validation of key m7G-related genes. The Cancer Genome Atlas cohorts were utilized to analyze the association of these key genes with the prognosis of HCC patients.

Results: Comparative analyses revealed internal m7G modification alterations in 1546 mRNAs between HP liver and normal liver tissues, and in 3424 mRNAs between HP HCC and HP liver tissues. Following Protein-Protein Interaction (PPI) network analyses, validation experiments confirmed sustained high levels of internal m7G methylation modifications in EZH2, SMARCA4, and YY1. Furthermore, these genes were found to exhibit m7G modification-dependent expression changes during the transition from HBV infection to HCC, and were closely associated with the prognosis of HCC patients.

Conclusions: This study provides validation of substantial dynamic alternations in mRNA internal methylation profiles during the HBV infection to HCC. EZH2, SMARCA4, and YY1 emerge as promising molecular targets within this intricate regulatory landscape, offering avenues for further research and potential therapeutic exploration.

Background: The proportion of early onset colorectal cancer (EOCRC) is alarming in adults, including in African Americans (AA).

Aim: To investigate differences between EOCRC compared to late-onset colorectal cancer (LOCRC) among AA patients.

Methods: This retrospective study reviewed demographic, clinical presentations, colonoscopy, and pathology reports of patients at Howard University Hospital from 1959 to 2023. The study included 176 EOCRC cases (< 45 years) and 2034 LOCRC cases (> 45 years).

Results: Both EOCRC and LOCRC groups were predominantly AA (> 80%) with slightly more females (53%) than males. The mean age was 38 years for EOCRC and 66 years for LOCRC cases. EOCRC cases increased as a proportion of total detected CRC cases since 2010 (over 13%) after several decades of just above 6%. Family history of CRC in first degree relatives was higher among EOCRC (15.5% vs.3.4% in LOCRC patients, p < 0.01). Symptoms at presentation were prevalent in both EOCRC (93.8%) and LOCRC (92.6%). EOCRC patients exhibited higher incidence of abdominal pain (23.3% vs. 17.2%, p = 0.05) and changes in bowel habits (24.4% vs. 14%, p < 0.01) compared to LOCRC patients. Other symptoms such as melena, hematochezia, and weight loss were less prevalent in EOCRC patients. Comorbidities like hypertension (HTN), diabetes mellitus (DM), and inflammatory bowel disease (IBD) were less frequent among EOCRC patients. EOCRC was primarily observed in the sigmoid and rectosigmoid regions (p = 0.02). Metastasis at index colonoscopy was more prevalent with EOCRC compared to LOCRC (p = 0.04), with a higher proportion of patients at stage 3 cancer (p < 0.05). Significant differences were noted in the timeline for undergoing surgery after the diagnosis of colorectal cancer, with EOCRC patients taking longer than LOCRC patients (p = 0.03).

Conclusion: Presentation of EOCRC over LOCRC increased proportionally in our cohort since 2010 and is associated with family history, and symptoms such as abdominal pain and change in bowel habits. Likely because of age at presentation, there are less comorbidities among EOCRC patients who predominantly present in the outpatient setting, and more likely diagnosed with advanced stage lesions that are predominantly sigmoid or rectosigmoid. These findings are similar to observations seen in the general population with EOCRC, albeit African American patients have commonly had earlier age presentation of CRC than White American patients.

Background and aims: Although a relevant animal model is essential for studying human diseases, one has yet to be established for mouse pancreatitis. Early non-invasive models of mouse pancreatitis have serious limitations.

Methods: In this study, we compared the efficiency, consistency, and reproducibility of inducing pancreatitis in 3 non-invasive mouse models of pancreatitis in Wistar albino mice: (1) L-arginine-induced model (2 intraperitoneal injections of 4 g/kg body weight of L-arginine spaced 1 h apart), (2) caerulein-induced model (6 intraperitoneal injections of 50 µg/kg body weight of caerulein at hourly intervals), and (3) caerulein + LPS (lipopolysaccharide)-induced model (6 intraperitoneal doses of 50 µg/kg body weight of caerulein at hourly intervals, along with an LPS [10 mg/kg body weight] injection immediately after the last caerulein injection).

Results: Our findings showed that the L-arginine-induced model was inconsistent. The levels of the pancreatic enzymes, amylase and lipase, were higher in the caerulein and caerulein + LPS groups. Histological examination showed tissue destruction in the induced groups, with varying degrees of fibrosis in the caerulein + LPS group.

Conclusions: The caerulein + LPS model was the most reliable model in Wistar albino mice. Our findings may be useful in helping investigators choose the most appropriate animal model for pancreatitis research.

Background and aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) and resultant steatohepatitis (MASH) have been linked to psychiatric comorbidities. The treatment of MASLD/MASH primarily relies upon weight loss, where achieving a 7% total body weight loss is recommended to improve steatohepatitis. We aimed to determine whether achieving a 7% total body weight loss (TBWL) in MASLD/MASH patients was significantly different in the presence of a mood and/or anxiety disorder in an interdisciplinary clinic that integrates weight management and hepatology care.

Methods: We conducted a single center retrospective cohort study of MASLD/MASH patients segregated into those with an ICD-10 diagnosis of a mood and/or anxiety disorder to those without. The primary outcome was reaching a 7% TBWL at 12 months with univariable and multivariable logistic regression models used to identify treatments predicting a 7% TBWL. Secondary outcomes were noninvasive assessment of steatohepatitis improvement, including change in ALT and FIB-4 scores.

Results: Of 567 patients with MASLD/MASH, 366 (64.6%) had a mood and/or anxiety disorder. The presence of psychiatric disease was not a significant predictor of weight loss or any secondary outcome measures at 12 months. Significant predictors of achieving 7% TBWL at 12 months among all patients with MASLD/MASH included semaglutide, phentermine-topiramate, and bariatric surgery. Significant predictors of achieving 7% TBWL at 12 months in patients with MASLD/MASH and a psychiatric comorbidity included semaglutide, topiramate, phentermine-topiramate, and bariatric surgery. Both groups experienced similar improvements in hepatic outcomes.

Conclusions: Our findings suggest that obesity management in patients with MASLD/MASH performs similarly in the presence of comorbid mood and/or anxiety disorders. Topiramate and phentermine may be particularly effective in this patient population, yet are underutilized in routine hepatology practice.

Background: To advance personalized medicine in pediatric Crohn's disease (CD), we aimed to explore the utility of serological biomarkers in predicting response to anti-tumor necrosis factor (TNF).

Methods: Children with CD were enrolled at initiation of anti-TNF and followed prospectively at 4 and 12 months thereafter, as well as at last follow-up. At baseline, 10 serological markers of the "PROMETHEUS® IBD sgi Diagnostic test" were measured, including pANCA, ASCA IgG and IgA, anti-CBir1, anti-OmpC, anti-A4-Fla2, anti-Fla-X, SAA, ICAM-1 and VCAM-1. The primary outcome was sustained steroid-free remission (SSFR, i.e. clinical remission without steroids at both 4 and 12 months) and the secondary outcome was primary non-response (PNR).

Results: Of the 72 included children (mean age, 12.8 ± 3.1 years; median disease duration, 6.4 months [IQR 2.5-17.3]), 42 (58%) were treated with adalimumab and 30 (42%) with infliximab. PNR was noted in 20 (28%) children and failure to achieve SSFR in 36 (50%). The most common positive serological markers were SAA (86%) and ICAM-1 (82%). In univariate analyses, none of the serological markers achieved statistical significance in association with SSFR or with PNR. In multivariable analysis, positivity of ASCA IgG (OR 3.3 [95%CI 0.8-14.4]) and pANCA (OR 5.3 [95%CI 0.9-48]) were the closest to achieving significance in predicting SSFR, with fair predictive performance for the model (AUC 0.67 [95%CI 0.55-0.80]).

Conclusion: The serological markers tested here have limited utility in predicting response to anti-TNF treatment. Further studies with larger sample sizes are needed to confirm the utility of ASCA IgG and pANCA.

Inflammatory bowel disease refers to a group of non-specific inflammatory illnesses affecting the gastrointestinal tract. According to pathogenic characteristics, it is divided into Ulcerative colitis and Crohn's disease. The exact cause and pathogenic mechanism of these disorders are not yet fully understood. In addition, there is currently no definitive diagnostic method for inflammatory bowel disease, which mainly depends on clinical symptoms, blood testing, imaging investigations, and endoscopic examination, which includes histology. Endoscopic Ultrasonography is a digestive tract examination technique that combines endoscopy and ultrasound. Compared to conventional endoscopy, it can visualize surface and deep lesions of the gastrointestinal wall, as well as provide information on the characteristics of the surrounding layers and nearby lymph nodes. Due to these advantages, Endoscopic Ultrasonography has played a significant role in the evaluation of inflammatory bowel disease in recent years. Through this work, we aim to identify the applications of this method in the case of patients with inflammatory bowel disease.

Background: Irritable bowel syndrome symptoms are associated with diverse pathophysiological mechanisms including small intestinal bacterial overgrowth and food intolerance. Small intestinal bacterial overgrowth leads to the decreased activity of several digestive enzymes, including lactase.

Aims: To assess the efficacy of rifaximin-alpha on the symptoms and lactase activity of patients with irritable bowel syndrome without constipation.

Methods: This was a prospective, pilot study. The recruited patients had irritable bowel syndrome without constipation (Rome IV criteria), a positive lactulose-Hydrogen Breath Test for small intestinal bacterial overgrowth, low urinary D-Xylose levels measured using the Lactest® test, and self-reported lactose intolerance. In addition, lactose HBT was performed. All patients received 400 mg rifaximin-alpha every 8 h for 2 weeks. Four weeks after the intervention, lactose and lactulose HBT were performed, and the symptoms and urinary D-Xylose levels were evaluated.

Results: After treatment with rifaximin-alpha, 60% of the patients reported improvement in abdominal pain, 44% in bloating, 36% in flatulence, 60% in borborygmi, and 72% in stool consistency. A negative lactulose-Hydrogen Breath Test result for SIBO was documented in 32% of patients, and lactose maldigestion by lactose-Hydrogen Breath Test was reduced from 88 to 52% of the studied subjects. The median D-Xylose levels before and after treatment were 7.6 (IQR 4.34-13.7) mg/dL vs. 10.4 (IQR 7.1-17.3) mg/dL, p = 0.002.

Conclusions: Rifaximin-alpha caused symptomatic improvement, reduced lactose maldigestion, and reduced positive Hydrogen Breath Test results for small intestinal bacterial overgrowth in patients with irritable bowel syndrome without constipation.

A 79-year-old man with fatigue and melena was diagnosed with severe iron-deficiency anemia. Capsule endoscopy revealed submucosal vascular lesions in the jejunum and active bleeding in the ileum, consistent with Blue Rubber Bleb Nevus Syndrome (BRBNS). Exploratory laparoscopy led to the resection of a 120 cm intestinal segment, confirming the diagnosis. Figures show the resected section and vascular anomalies.