Therapeutic Advances in Gastroenterology最新文献

Background: Intraepithelial eosinophils have been described in patients with esophageal motor disorders. Conversely, motor disorders and even achalasia have been reported in patients with eosinophilic esophagitis (EoE).

Objectives: This prospective study aimed to further investigate the association between eosinophilia and achalasia.

Design: This is a prospective study.

Methods: A series of 30 consecutive treatment-naïve achalasia patients (mean age: 45.5 years, 53% female) undergoing laparoscopic myotomy were prospectively enrolled. Preoperative demographic and clinical data, radiological findings, and high-resolution manometry (HRM) features were collected. Patients underwent upper endoscopy with biopsy sampling before surgery, and two samples of distal esophageal muscle were obtained during myotomy. Histopathologic findings were analyzed, and clinical characteristics were compared based on the presence and absence of eosinophils on biopsy samples.

Results: Intraepithelial eosinophils were found in seven patients (23%; mean 8 eos/high-power field, 95% CI 0-15), but only one patient demonstrated >15 eos/high-power field, and one had eosinophilic infiltration of the esophageal muscle. Patients with intraepithelial eosinophilia had a narrower esophageal diameter on barium radiography (2.4 vs 3.6 cm without eosinophilia, p < 0.05). There were no additional differences in histopathology or preoperative and postoperative data between patients with and without intraepithelial eosinophilia.

Conclusion: Our study confirmed that intraepithelial and intramuscular eosinophils are present in some patients with achalasia, but seldom meet the criteria for EoE. Only a narrower esophagus was found in patients with intraepithelial eosinophils as compared to those without, possibly reflecting an earlier stage of the disease.

Background: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection (CDI) and shows promise for other dysbiosis-related conditions such as inflammatory bowel disease (IBD). Awareness and acceptance remain underexplored in the Middle East, where cultural and social factors may influence adoption.

Objectives: To evaluate awareness, perceptions, willingness, and acceptance of FMT among the Lebanese population.

Design: A nationwide cross-sectional survey with nonprobability sampling was conducted between April and November 2024.

Methods: A total of 725 participants were recruited through mixed sampling across Lebanon's governorates: 379 from the general population, 109 healthcare workers, 155 physicians, and 82 IBD or CDI patients. A structured bilingual questionnaire assessed awareness, perceptions, treatment preferences, and willingness to disclose or undergo FMT. Analyses included Chi-square tests, logistic regression, and false discovery rate-adjusted comparisons.

Results: Overall, 31% of participants had prior awareness of FMT, while 60.1% reported positive perception. Awareness and perception were significantly associated (p = 0.0017) and were highest among physicians (59.4% and 70.2%) and lowest among patients (17.1% and 52.4%). Sources varied by group: universities for the general population, media for patients, and professional networks for healthcare workers and physicians. Logistic regression identified physician status, younger age, and prior awareness as predictors of favorable perception. Capsules were the preferred delivery route across groups. Willingness to disclose (81.4%) and to donate stool (68.4%) were high, while 17.2% expressed stigma-related concerns. Major concerns included hygiene, infection risk, and psychological discomfort.

Conclusion: FMT awareness in Lebanon remains limited, particularly among patients and the public. Although perceptions are generally positive, misconceptions, stigma, and unrealistic expectations persist. These findings stem from a nonprobability sample that overrepresents younger, female, and highly educated participants and is not nationally representative. Targeted education, stronger physician-patient communication, and culturally sensitive approaches are needed to promote FMT acceptance and integration into practice.

Objectives: This study investigated temporal changes in resistance patterns among treatment-refractory Helicobacter pylori infections in Taiwan.

Background: Antibiotic resistance in H. pylori is a growing global concern.

Design: We retrospectively analyzed adult patients at Linkou Chang Gung Memorial Hospital (2018-2024) with ⩾2 prior eradication failures and confirmed active infection via [13C]-urea breath test.

Methods: Gastric biopsy specimens were cultured, and antimicrobial susceptibility testing was performed using the Epsilometer test for amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, rifabutin, ciprofloxacin, and moxifloxacin. Breakpoints were defined according to the European Committee on Antimicrobial Susceptibility Testing.

Results: Among 144 patients (mean age 57.1 ± 10.8 years; 27.8% male), 88 were culture positive (61.1%), yielding 109 isolates. Resistance rates were high for clarithromycin (89.9%), levofloxacin (86.2%), metronidazole (71.6%), and ciprofloxacin (87.2%), while tetracycline resistance was 15.6%. A temporal trend analysis revealed a marked and statistically significant increase in amoxicillin resistance (odds ratio per year, 1.60; 95% confidence interval, 1.31-1.96; p < 0.001), while resistance to other key antimicrobials remained persistently high but stable.

Conclusion: In refractory H. pylori infection, there is persistently high resistance to clarithromycin, fluoroquinolones, and metronidazole, with a notable surge in amoxicillin resistance. These findings underscore the need for strengthened antimicrobial stewardship and reconsideration of empiric treatment strategies in high-resistance regions.

Background: Gastric intraepithelial neoplasia (GIN) is a key precancerous lesion of gastric cancer, and discrepancies between preoperative endoscopic forceps biopsy (EFB) pathology and postoperative pathology after endoscopic submucosal dissection (ESD) pose significant challenges for accurate diagnosis and treatment planning.

Objective: To analyze the risk factors for pathological upgrade in patients with GIN after an ESD procedure.

Design: Retrospective study.

Methods: A retrospective analysis was conducted on 682 patients diagnosed with GIN by gastric EFB pathology at the Digestive Endoscopy Center of Wuxi People's Hospital from January 2018 to December 2024 (490 with low-grade intraepithelial neoplasia (LGIN) and 192 with high-grade intraepithelial neoplasia (HGIN)). Demographic characteristics (gender, age, BMI, chronic disease history, fecal occult blood), endoscopic features of lesions (location, morphology, size), and pathology data after the ESD procedure were collected. Univariate, multivariate, and stepwise logistic regression analyses were performed to identify independent risk factors for pathological upgradation.

Results: The total pathological upgrade rate after ESD was 59.4% (51.2% in the LGIN group and 80.2% in the HGIN group). Stepwise regression analysis revealed that a maximum lesion diameter ⩾2 cm (odds ratio (OR) = 2.49) was the most significant risk factor for pathological upgrade. Meanwhile, age ⩾70 years, comorbid hypertension, Paris classification type IIc lesion, and a lesion location at the gastric angle or cardia were independent risk factors for pathological upgrade, whereas a type IIb lesion demonstrated a protective effect (OR = 0.61).

Conclusion: Advanced age (⩾70 years), hypertension, lesion size ⩾2 cm, type IIc morphology, and lesions in the gastric angle/cardia significantly increase the risk of pathological upgrade after ESD. These findings provide a basis for preoperative risk assessment and individualized treatment strategies for GIN patients.

Background: Eosinophilic esophagitis (EoE) is characterized by eosinophil infiltration into the esophageal tissue and esophageal dysfunction. In the United States, EoE has an estimated prevalence of 26-163 cases per 100,000 people. Real-world data concerning the clinical burden of EoE and treatment patterns in the United States are limited.

Objectives: To describe the demographics, clinical characteristics, symptoms, comorbidities, treatment pathways, and healthcare resource utilization (HCRU) and costs among patients with EoE in the United States.

Design: Retrospective analysis.

Methods: A study of pediatric and adult patients diagnosed with incident EoE (full incident EoE cohort) using Merative™ MarketScan^® health insurance claims data between January 1, 2017, and June 30, 2020. A subset of patients (matched incident EoE cohort) was matched with patients without EoE for age, sex, and payor (matched control cohort). Follow-up was 12 months after the EoE diagnosis date. All statistics are descriptive.

Results: The full incident EoE cohort included 20,290 patients (62.61% were male; median (range) age was 38 (1-93) years); 13,710 patients (matched incident EoE cohort) were matched to 54,727 patients without EoE (matched control cohort). During baseline in the full incident EoE cohort, the most common comorbidities within the Charlson Comorbidity Index (CCI) were chronic pulmonary disease (19.79%), hypertension (15.77%), and depression (9.71%); the most common non-CCI comorbidities were reflux esophagitis (38.84%), allergic rhinitis (19.14%), and depression/anxiety (19.07%). During follow-up, the most frequently reported symptoms were acid reflux/heartburn (56.02%), dysphagia (51.89%), and abdominal pain (30.50%). The most common medications first observed were proton pump inhibitors (42.51%) and oral corticosteroids (12.26%). Overall, a larger proportion of the matched incident EoE cohort had visits to any healthcare setting during baseline and follow-up than the matched control cohort. Correspondingly, the annualized, all-cause healthcare costs per patient were higher in the matched incident EoE cohort than in the matched control cohort at baseline (mean (standard deviation), $10,185 ($29,455); median, $3248 vs $4906 ($20,601); $632) and during follow-up ($15,103 ($35,484); $6708 vs $5200 ($21,314); $651).

Conclusion: Considerable disease burden is experienced by patients with EoE (before and after diagnosis), which contributes to a high level of HCRU and increased costs.

Background: Proton pump inhibitors (PPIs) use has been linked to adverse outcomes in patients with inflammatory bowel disease (IBD). However, it remains unknown whether this is due to protopathic bias (i.e., when the outcome precedes exposure).

Objectives: We aimed to conduct a propensity-weighted study of the association between PPI use and IBD-related hospitalizations and surgery in patients with IBD.

Design: Historical propensity score (PS)-weighted cohort study.

Methods: We identified all Danish residents diagnosed with IBD in 2000-2022 in the Danish National Patient Registry. We analyzed separate PPI treatment episodes allowing an individual to contribute with more than one PPI episode. We used PS-weighted Cox regression to estimate the hazard ratio (HR) for IBD-related hospitalization and surgery for current PPI-users compared with current nonusers.

Results: We identified 50,460 patients with IBD (67% with ulcerative colitis, 33% with Crohn's disease). Five years after their diagnosis, two-thirds of patients with IBD had used PPI at some point and 10% were in current treatment. The weighted HR for IBD-related hospitalizations was 1.45 (95% confidence interval (CI): 1.38-1.52) during the first year after PPI prescription, and 1.16 (95% CI: 1.05-1.28) thereafter. The weighted HR for IBD-related surgery was 1.21 (95% CI: 1.11-1.32) the first year and 1.35 (95% CI: 1.18-1.54) thereafter.

Conclusion: We observed a 20%-40% higher rate of IBD-related hospitalization and surgery, the first year after PPI prescription in patients with IBD which most likely represents a protopathic bias, yet the rate of IBD-related surgery remained elevated more than 1 year after PPI prescription.

Background: A combination of immune checkpoint inhibitors and chemotherapy has emerged as standard therapy in advanced human epidermal growth factor receptor 2-negative advanced gastric cancer (AGC). However, the clinical benefit in patients with a low combined positive score (CPS) of 1-4 remains controversial.

Objectives: To evaluate the efficacy and safety of nivolumab plus chemotherapy in AGC patients with low CPS (1-4) in a real-world clinical setting.

Design: A retrospective single-center study conducted at Samsung Medical Center.

Methods: We analyzed outcomes in AGC patients with CPS 1-4 who received nivolumab in combination with capecitabine and oxaliplatin (XELOX) or fluorouracil, oxaliplatin, and leucovorin (FOLFOX) as first-line therapy between April 2021 and December 2024. Tumor response was assessed using Response Evaluation Criteria in Solid Tumor version 1.1. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods.

Results: Of 336 patients receiving first-line nivolumab plus XELOX or FOLFOX, 63 had a CPS of 1-4. Median age was 61 years, and the most common CPS was 1, found in 26 patients (41%). One patient achieved a complete response (2%), and 25 patients achieved partial response (40%), for an overall response rate of 42%. Stable disease was observed in 23 patients, a disease control rate of 76%. Median PFS was 5.8 months (95% confidence interval (CI), 4.9-6.7), and median OS was 15.0 months (95% CI, 13.2-18.7). Any-grade adverse events were reported in 92% of patients, while grade 3 or 4 treatment-related adverse events occurred in 61% of patients, most commonly anemia and neutropenia.

Conclusion: This real-world retrospective study suggests modest efficacy of AGC patients with low CPS treated with nivolumab with chemotherapy. Further studies are needed to determine the optimal treatment strategy and to identify predictive biomarkers for therapy selection in patients with low-CPS AGC.

Background: Patients with ulcerative colitis (UC) usually experience anxiety symptoms that seriously affect their quality of life, treatment, and prognosis. Dysbiosis of the gut microbiota plays an important role in UC and mental illness. However, little is known about the role of the gut microbiota in UC patients with anxiety.

Objectives: To identify the gut-microbiome and fecal metabolome profiles uniquely associated with comorbid anxiety in UC patients and to explore potential biomarkers for diagnosis.

Design: A cross-sectional, two-group comparative study.

Methods: To study the underlying association between them, we recruited 126 UC patients in this study, including 78 with anxiety and 48 without anxiety. A total of 102 fecal samples were collected for metagenomic sequencing and metabolome sequencing. Microbial diversity, differential gut microbiota, functional pathways, and metabolites were analyzed. Multivariable logistic regression was used to identify independent risk factors associated with anxiety in UC patients, while Spearman correlation was employed to explore microbe-metabolite interactions and the performance of potential biomarkers.

Results: We found that disease severity, steroid usage, and abdominal pain may promote the occurrence of anxiety. Compared to UC patients without anxiety, UC patients with anxiety had low fecal microbial community diversity, with an increase in the species Haemophilus sp. HMSC71H05 and Corynebacterium durum, and a decrease in the species Roseburia intestinalis (RI), Bifidobacterium longum (BL), and Enterococcus hirae. The metabolic pathways driven by the gut microbiota were disrupted. Moreover, the levels of most metabolites (such as L-kynurenine) were increased in the feces, while the levels of a few metabolites decreased, including indole-2-carboxylic acid, N-demethylmirtazapine, and tauroursodeoxycholic acid.

Conclusion: Our research further revealed that these gut microbiota and metabolites are highly correlated. This study provides a new perspective for understanding the occurrence and development of anxiety in UC patients, suggesting that RI and BL may serve as potential candidate biomarkers to diagnose UC patients with anxiety.

Background: Clostridioides difficile infection (CDI) is a significant complication in patients with acute severe ulcerative colitis (ASUC).

Objectives: To assess the clinical outcomes of hospitalized ASUC patients with CDI.

Design: Retrospective, single-center study.

Methods: Medical records of ASUC patients admitted from December 1, 2008, to June 1, 2018, were reviewed. Primary outcomes included hospital duration, in-hospital colectomy rates, and escalation of immunosuppression at discharge. Secondary outcomes included readmission rates and use of salvage therapy.

Results: Among 410 ASUC patients, 67 tested positive for CDI. No significant differences in hospital duration, colectomy rates, or readmission rates were found between CDI-positive and CDI-negative groups. CDI-positive patients were less likely to receive intravenous corticosteroids.

Conclusion: A positive CDI test in ASUC patients does not correlate with worse clinical outcomes. Based on these results, CDI should be ruled out and treated in hospitalized patients with severe ulcerative colitis without delaying ASUC management.