Digestive Diseases and Sciences最新文献

Introduction: Inflammatory bowel disease (IBD) is associated with an increased risk of major adverse cardiovascular events (MACE). Janus kinase inhibitors (JAKi) are approved to treat IBD, but there are concerns over whether they increase the risk of MACE or venous thromboembolism (VTE) in patients with IBD. We aimed to compare the incidence risk of MACE and VTE in patients with IBD treated with JAKi agents versus anti-TNFs.

Methods: We conducted a retrospective cohort study using the TriNetX database to identify patients  ≥ 18 years with IBD and treated with JAKi or anti-TNF therapy. Patients in the JAKi cohort were matched with patients treated with anti-TNF by using 1:1 propensity score matching. Patients with a history of a prior cardiovascular event were excluded from the analysis. Co-primary outcomes were MACE and VTE within 1-year after medication initiation. Additional subgroup analyses were performed based on age, sex, and IBD type. Kaplan-Meier analysis with adjusted hazard ratios (HRs) and 95% CIs were used to compare time-to-event rates.

Results: In total, there were 8942 patients in the JAKi cohort matched with 8942 patients in the anti-TNF cohort. There was no difference between the two cohorts in the development of MACE (aHR: 1.08; 95% CI: 0.87-1.33; p = 0.49) or VTE (aHR: 1.06; 95% CI: 0.84-1.36; p = 0.61). In patients aged ≥ 65 years, there was no statistically significant difference between the two cohorts in MACE outcomes (aHR: 0.95; 95% CI: 0.69-1.31; p = 0.75). Consistent findings were observed when comparing ulcerative colitis to Crohn's disease, upadacitinib to tofacitinib, or JAKi to infliximab.

Conclusion: Our results suggest that patients with IBD, including patients ≥ 65 years, who are treated with JAKi, were not at increased risk of MACE or VTE over a 12-month period as compared to those treated with anti-TNF therapy. Further prospective studies are warranted to confirm these findings.

Background: Better ways to predict and prevent delayed post-polypectomy-induced ulcer hemorrhage (DPPIUH) are needed.

Aims: (1) To correlate Doppler endoscopic probe (DEP) detection of PPIU blood flow with polyp artery size on histology. (2) To report risk factors which predict DPPIUH and prevent it.

Methods: 96 high-risk patients with benign colon polyps and 10-40 mm PPIUs were included in this cohort study which analyzed prospectively collected data. Coded polyps were analyzed by expert GI pathologists to report artery size at resection margins. 28 patients with severe DPPIUH's all DEP positive (+) for arterial blood flow including 15 with prior empiric hemoclip (HC) closure were compared with 68 similar high-risk patients without DPPIUHs: 34 DEP+ treated to obliterate blood flow; 22 DEP negative not treated; and 12 DEP+ not treated. 16 potential risk factors for DPPIUH were simultaneously assessed using multivariable logistic analysis and a classification tree model.

Results: The odds ratio (95% CI's) of DEP positivity predicting medium or large polyp arteries was 23.4 (5.73, 11.0)-p < 0.001. Risk factors predicting DPPIUH were DEP positivity, medium, or large size polyp artery, right colon polyp location, and empiric HC closure. DEP-guided treatment predicted the absence of DPPIUH.

Conclusions: (1) DEP positivity and medium or large artery size on polyp histology highly correlated and were new risk factors predicting DPPIUH. (2) Other significant risk factors predicting DPPIUH were right colon polyp location and empiric PPIU HC closure. (3) DEP-guided treatment prevented DPPIUH.

Background: Colorectal cancer (CRC) is a significant health challenge with high incidence and mortality rates. While SERPINE1 is overexpressed in CRC and linked to poor patient outcomes, the detailed mechanisms by which it promotes tumor progression remain poorly understood.

Methods: SERPINE1 was identified as a cuproptosis-related angiogenic protein using the GEO database. Expression and prognostic impact of SERPINE1 in CRC were analyzed with the TCGA database. To forecast the pathways SERPINE1 might enrich, we deployed gene set enrichment analysis. SERPINE1 mRNA levels were quantified via qPCR. Co-immunoprecipitation (Co-IP) assay was performed to analyze the interaction between SERPINE1 and uPA/uPAR. Western blot (WB) was conducted to gauge protein expression of MAPK signaling components, cuproptosis markers, and SERPINE1 itself. Changes in cell viability were assessed using CCK-8. Angiogenesis assays probed how SERPINE1 may impact the angiogenic ca of CRC cells. Xenograft tumor models were established in adult nude mice to track tumor growth and volume changes.

Results: SERPINE1 was highly expressed in CRC, with substantial enrichment in the MAPK signaling pathway, and this overexpression is associated with unfavorable prognoses. CRC cells overexpressing SERPINE1 showed increased cell viability and angiogenic capacity, while expression of cuproptosis-related genes was markedly reduced. Mechanistically, SERPINE1 activates p38/MAPK pathway, thereby enhancing angiogenesis and cuproptosis resistance in CRC. This process may be associated with the interaction between SERPINE1 and uPA/uPAR.

Conclusion: Our study illuminates how SERPINE1, often overexpressed in CRC, leverages the p38/MAPK pathway to bolster cuproptosis resistance and angiogenesis, offering a promising avenue for anti-angiogenic strategies in CRC treatment.

Background: Endoscopic full-thickness resection (EFTR) can effectively remove extraluminal tumors, overcoming limitations of endoscopic submucosal dissection (ESD). However, optimal post-EFTR feeding timing lacks standardized guidelines for patients with gastric tumors. This study aims to assess the safety of early feeding after EFTR.

Methods: Retrospective analysis was conducted on patients who underwent EFTR at our hospital between January 2014 and January 2019. Based on actual fasting duration, patients were categorized: short fasting (≤ 2 days, n = 72) and long fasting (> 2 days, n = 431) group. Using 1:1 propensity score matching, postoperative complications and hospital stay were compared between balanced groups.

Results: A total of 503 patients were included in this study, among which 72 were in the short fasting group and 431 were in the long fasting group. After matching, the baseline characteristics of 68 patients in the short fasting group and 68 patients in the long fasting group reached equilibrium (P > 0.05). The average age was 53.82 ± 10.98 years old. There was no significant difference in clinicopathological conditions or lesion size between the two groups. There was no statistically significant difference in the rates of postoperative bleeding, fever and abdominal distension between the two groups of patients after EFTR. However, compared with the long fasting protocol, a trend of shorter hospitalization was observed in the short fasting group.

Conclusions: Compared with the long fasting protocol, early feeding after EFTR for gastric tumors did not increase the incidence of discomfort or postoperative complications. In addition, short fasting protocol has a tendency to shorten hospital stays, which represents potential clinical benefits.

Objective: Timed-barium esophagogram (TBE) is established test for assessing bolus clearance in achalasia post-treatment. However, radiation exposure is an important disadvantage. Esophageal bolus transit can be evaluated by HRIM. Previous studies comparing Impedance bolus height (IBH) using saline and TBE showed fair correlation. We compared bolus clearance by TBE versus HRIM using yogurt (viscosity matched to barium-calculated using Ostwald viscometer) in patients treated for achalasia.

Methods: HRIM was performed using solid-state system (MMS, Netherlands). Twenty patients (age 45.1 years; 8 men) treated with pneumatic dilatation (Rigiflex, Boston Scientific) were evaluated with TBE (200 ml Barium) and HRIM (200 ml yoghurt) two weeks after dilation. Both tests were performed in upright position. Barium column height and impedance bolus height (IBH) were measured at 0, 1 and 5 min. Analysis of IBH was performed with spatial impedance variation plot overlayed on esophageal pressure topography. All patients gave consent, and protocol was approved by the IRB.

Results: At baseline, 5, 11 and 4 patients had type I, II and III achalasia, respectively. Eckardt score showed an improvement of 5 (range 1-9) points. The mean column height as measured by IBH and TBE at 5 min was similar (4.6 [range 0-12.5] cm vs. 4.25 [0-16] cm). Pearson correlation between the TBE column and IBH was 0.73 at 5 min. Bland Altman plot for bolus clearance as measured by TBE and HRIM showed good agreement between the modalities.

Conclusions: There is good agreement between HRIM (performed using yoghurt) and TBE for evaluation of bolus clearance after therapy in achalasia patients. Single HRIM study done with viscosity matched liquid to barium can give information about bolus clearance and motor function in treated achalasia patients, avoiding radiation exposure.

Purpose: Achalasia is an uncommon primary esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter and esophageal body peristalsis, with a rising prevalence among the elderly due to global population aging. This review summarizes the current evidence on the clinical presentation, diagnostic algorithm, and management of achalasia in geriatric patients.

Methods: A literature search was conducted focusing on age-related differences in symptoms, endoscopic and functional testing, and outcomes of available therapeutic modalities.

Results: Clinical presentation of achalasia differs among younger and geriatric patients, with the latter presenting less pronounced symptoms. Geriatric patients experience a higher risk of malnutrition and aspiration and exhibit more often advanced disease stages, including sigmoid esophagus. High-resolution manometry represents the gold standard for diagnosis, and upper gastrointestinal endoscopy should precede it in order to exclude causes of mechanical obstruction. The treatment remains non-causative and encompasses botulinum toxin injection, pneumatic dilation, peroral endoscopic myotomy, and laparoscopic Heller's myotomy with fundoplication.

Conclusion: Considering the evolving potential of minimally invasive techniques, advanced age should not be regarded as a contraindication for the definitive treatment of achalasia, and evidence-based, age-specific recommendations should be developed for optimizing clinical outcomes.