Gastroenterology Research最新文献

Background: Ubiquitin-specific protease 34 (USP34) is a deubiquitinase that has been shown to play a critical role in the process of tumor drug-resistance. The objective of this study was to investigate the role of USP34 in cisplatin resistance in hepatocellular carcinoma (HCC).

Methods: Firstly, we analyzed the USP34 levels in cisplatin-sensitive and -resistant patients using The Cancer Genomic Atlas (TCGA) data from Gene Expression Profiling Interactive Analysis (GEPIA2). The cell viability and half-maximal inhibitory concentration (IC₅₀) were measured by Cell Counting Kit-8 (CCK-8) assay. The cell apoptosis of HepG2 and HepG2/DDP cells was detected by annexin V-fluorescein isothiocyanate/propidium iodide (FITC/PI) double staining. The expression levels of USP34, multidrug resistance-associated protein 1 (MRP1), p-glycoprotein (p-gp), pan-lysine lactylation (Pan-Kla), histone H3 lysine 18 lactylation (H3K18la), lactate dehydrogenase A (LDHA) and lactate dehydrogenase B (LDHB) were measured by Western blot. HCC samples from the GEPIA2 database were used to determine the correlation between USP34 with LDHA and LDHB expression.

Results: USP34 was significantly upregulated in cisplatin-resistant HCC tissues and cells. Functional studies found that knockdown of USP34 inhibited HepG2 and HepG2/DDP cell proliferation and survival. Importantly, knockdown of USP34 enhanced cisplatin sensitivity in HepG2 and HepG2/DDP cells. Mechanistically, lactylation of histones promoted the expression level of USP34 in HepG2/DDP cells.

Conclusion: USP34 promotes the progression of HCC by regulating histone lactylation levels and cisplatin resistance in HCC.

Background: Endoscopic ultrasound (EUS)-guided lumen-apposing metal stent (LAMS) placement is increasingly being used in lieu of surgery for multiple procedures, including transmural fluid drainage. However, few studies have evaluated adverse events (AEs) associated with LAMS placement. Our aim was to characterize the rates of AEs associated with several LAMS placement strategies across different procedures and indications.

Methods: A single-center retrospective cross-sectional study was conducted on patients who underwent EUS-guided LAMS placement between 2015 and 2023 at a single institution. Technical and clinical success rates and rates of early and late AEs were analyzed. Comparisons of AE rates were determined for patients who had LAMS dilation versus those without dilation, patients who had plastic stent placement in addition to LAMS placement versus those with no plastic stents, and patients who had combined dilation and plastic stent procedures versus those with LAMS dilation only.

Results: A total of 243 patients underwent EUS-guided LAMS interventions: 110 (45.3%) women and 133 (54.7%) men (mean age 53.7 ± 15.9 years). There were 96 (39.5%) patients who had at least one AE. Abdominal pain was the most common early and late AE. Plastic stent placement alongside LAMS placement was associated with a significantly higher rate of overall AEs (48.3% vs 29.9%; P = 0.009), late AEs (33% vs 17.9%; P = 0.021), and stent occlusion (5.7% vs 0%; P = 0.046). LAMS dilation was associated with higher rates of late AEs (34.2% vs 20.6%; P = 0.022) and stent occlusion (6.2% vs 1.0%; P = 0.049).

Conclusions: LAMS placement showed high technical and clinical success rates across different indications with mostly mild AEs, suggesting that LAMSs may be safe and effective for pancreatic and biliary drainage.

Background: Irritable bowel syndrome (IBS) is the major form of functional bowel disorders, where the diagnosis is based on set criteria and characterized by abdominal pain and changes in bowel habits. Epidemiological data, alongside self-reported outcomes, are of interest with regard to IBS, as these factors may need to be addressed to optimize underlying IBS. This study aims to examine the effect of IBS on certain aspects of life, including sleep quality alongside some epidemiological aspects with regards to the presence of IBS in the Jazan region of Saudi Arabia.

Methods: Individuals were invited to participate in the study by replying to a validated questionnaire, whereby respondents self-identified as having IBS or not. Non-parametric comparisons using Fisher's exact test, between those with self-reported IBS versus those without IBS, were performed, with P < 0.05 considered significant.

Results: Of 728 respondents, 244 (33.5%) had self-reported IBS, and 484 (66.5%) did not. Respondents with IBS were more likely female (P < 0.001), younger age (P = 0.002), city-dwelling (P = 0.028), divorced (P = 0.028) and smokers (P = 0.003). Overall, education level did not differ amongst the groups (P = 0.093). A minority (13.5%) of those with self-reported IBS were diagnosed by a gastroenterology specialist. Abdominal pain, distension, constipation and diarrhea were all more prevalent (P < 0.001) in the IBS group compared to the non-IBS group. The IBS group had poorer sleep quality compared to the non-IBS group (P = 0.006), although no difference in medications for sleep was present between the two groups (P = 0.271).

Conclusions: Self-reported IBS was highly prevalent in our region, with risk factors for its presence being similar to those reported in previous studies. Sleep deprivation was highly prevalent in IBS patients, albeit not leading to increased prescription of relevant therapies for aid of sleep in these patients. However, marital separation and city-dwelling seemed to confer a higher self-reported IBS status. These issues should be investigated using more robust, Rome IV criteria-centered questionnaires in the future.

Background: Gastrointestinal stromal tumors (GISTs) are associated with a substantial economic burden to the healthcare system despite their relatively low incidence and prevalence compared to other more common malignancies. This study aimed to evaluate trends in GIST-related hospitalizations, inpatient mortality, and the financial burden of GISTs in the United States.

Methods: The National Inpatient Sample (NIS) database from 2016 to 2020 was used to identify adult hospitalizations (age > 18 years) with a primary diagnosis of GIST. A multivariate logistic regression along with Chi-square and t-tests was performed using SAS 9.4 software to analyze inpatient GIST-associated mortality, inflation-adjusted total hospital charge (THC), and length of stay (LOS) during the study period.

Results: The study analyzed 48,690 hospitalizations (49.2% female, mean age 64.2 years, 38.2% elective admissions) with a primary diagnosis of GIST between 2016 and 2020. Annual GIST-related hospitalizations increased from 2,645 in 2016 to 11,565 in 2020 (P = 0.1208). The most common tumor location was stomach (48.5%), followed by small intestine (18.7%), large intestine (3.6%), and rectum (1.6%). There was a non-significant reduction in inpatient mortality from 4.16% in 2016 to 3.29% in 2020 (P = 0.807). Overall, 36.2% of patients had THC between $10,000 and $20,000 (36.5% in 2016 vs. 34.7% in 2020, P = 0.0001), and 9.8% of patients had a THC > $40,000 (8.3% in 2016 vs. 12.6% in 2020, P = 0.0001). Furthermore, 61.5% of patients had LOS of fewer than 5 days (59.16% in 2016 vs. 61.39% by 2020, P = 0.0001), and 38.5% had LOS of 5 days or more (40.84% in 2016 vs. 38.61% in 2020, P = 0.0001). The proportion of GISTs treated with endoscopic resection has remained stable with 13.02% in 2016 and 13.01% in 2020 (P = 0.08). Additionally, the proportion of surgical excisions decreased from 26.8% in 2016 to 21.4% in 2020 with a statistically significant trend (P = 0.004).

Conclusions: GIST-related inpatient mortality between 2016 and 2020 has remained stable, and endoscopic and surgical interventions have become more common for the management of GISTs. This has been accompanied by a significant rise in overall inflation-adjusted hospitalization costs in the study period. These findings highlight the need for continued optimization of care and resource allocation for GIST management.

Background: Immune checkpoint inhibitors (ICIs) have moved to the frontline in recent years to manage upper gastrointestinal (UGI) tumors, such as esophageal and gastric cancers. This retrospective review sheds light on real-world data on ICI-treated UGI tumors to identify risk factors (clinical and pathological) impacting the outcome other than traditional biomarkers (programmed cell death ligand 1 (PD-L1) or microsatellite instability status).

Methods: Patients with UGI tumors who received at least one dose of ICI for stage IV or recurrent disease between January 1, 2015, and July 31, 2021, at The Ohio State University were included in the study. The patients' baseline characteristics, labs, and blood counts (even at disease progression) were extracted with survival outcomes (progression-free survival (PFS) and overall survival (OS)). Descriptive statistics, log-rank test and Cox proportional hazard model for survival outcomes, Fisher exact test for categorical variables, were conducted using JMP Pro 16 (SAS Institute Inc., Cary, NC).

Results: We had 64 patients (84% males) included in the study, with the racial distribution as follows: 88% Caucasian, 5% African American, 1% Asian, and 6% from other racial groups. Men and the use of ICI in third lines or more had a positive impact on PFS and OS. For OS, 1) history of surgery positively impacted the outcome, while bone metastases worsened it; 2) baseline red blood cell count (RBC), hemoglobin, and thyroid-stimulating hormone (TSH) negatively impacted the OS. For PFS, 1) PD-L1 positivity, baseline lymphocyte count, and aspartate transferase levels had a positive impact; 2) human epidermal growth factor receptor 2 (HER2) positivity, baseline RBC, TSH, alkaline phosphatase, and alanine transferase (AST) levels had a negative impact. A slight increase in white blood cell (WBC) count (by 1.54, P = 0.02) and a drop in lymphocyte count (by 0.1907, P = 0.003) was significantly associated with disease progression.

Conclusions: Baseline risk factors and monitoring blood counts can help predict outcomes in ICI-treated UGI tumors. We need larger studies to confirm this.

Background: As mental health awareness increases, healthcare professionals must understand the interplay between chronic gastrointestinal (GI) conditions and psychological well-being, particularly regarding healthcare utilization. This study uniquely aggregates various chronic GI disorders, such as inflammatory bowel disease, celiac disease, and eosinophilic esophagitis, to examine their impact on depression and anxiety.

Methods: Utilizing a retrospective observational design, we analyzed data from 34,876 patients admitted to HCA national hospitals from January 2016 to December 2022.

Results: We found that patients with GI conditions and comorbid psychiatric disorders had significantly higher readmission rates and longer hospital stays compared to those without mental health diagnoses. Results indicated that patients with GI disorders and depression or anxiety were 1.29 times more likely to be readmitted within 90 days and had 1.50 times longer hospital stay.

Conclusion: These findings underscore the importance of integrated care approaches addressing physical and mental health in managing chronic GI conditions. Future research should focus on targeted interventions to enhance mental health management and improve outcomes in this vulnerable patient population.

A 23-year-old man was diagnosed with Crohn's disease (CD) of the large intestine after colonoscopy revealed longitudinal ulcers, and pathology revealed non-caseating epithelioid cell granulomas and anal fistulas. The CD relapsed, and therefore prednisolone (PSL) and infliximab (IFX) treatment was initiated. The PSL was gradually tapered. Steroid-free remission was maintained with IFX. The patient subsequently developed a high fever and headache, while CD-related symptoms did not worsen. Laboratory data showed white blood cells at 14,200/µL and C-reactive protein at 17.2 mg/dL. Contrast-enhanced computed tomography revealed thoracoabdominal aortitis, and the patient was consequently diagnosed with Takayasu's arteritis (TA). We therefore again initiated PSL treatment that immediately reduced the fever and headache. The PSL dose was again tapered and the administration of IFX was resumed to maintain CD remission. No further episodes of aortitis relapse were noted after restarting IFX, and the CD currently remains in remission. This is a rare case of TA onset during IFX treatment for CD, and, as such, contributes to the limited literature on such cases. More specifically, this case highlights that when patients with CD present with symptoms such as fever or headache, it is necessary to investigate the possibility of vasculitis.

Background: Alcohol dependence remains a significant global health issue, exacerbated by the coronavirus disease 2019 (COVID-19) pandemic. Phosphatidylethanol (PEth), a direct biomarker of recent alcohol consumption, offers improved specificity, sensitivity, and a longer detection window of 2 - 4 weeks compared to traditional biomarkers. This study evaluates the association between PEth testing and hospital outcomes in hospitalized patients by comparing outcomes among patients with positive PEth and negative PEth test results.

Methods: This retrospective cohort study used data from the TriNetX database, comprising de- identified medical records from 66 US healthcare organizations from 2015 to 2024. The study population included patients with documented PEth test results. Patients were divided into two groups: positive PEth test results (≥ 20 ng/mL) and negative PEth test results (≤ 19 ng/mL). Propensity score matching was performed to minimize bias, balancing for age, sex, race, ethnicity, and comorbidities such as cirrhosis, diabetes mellitus, hypertension, coronary artery disease, and chronic obstructive pulmonary disease (COPD). Key hospital outcomes assessed included mortality, delirium tremens, endoscopy/colonoscopy, liver transplant status, liver transplant rejection, liver transplant complications, hepatorenal syndrome, intensive care unit (ICU) admission, hepatic encephalopathy, and sarcopenia. These outcomes were chosen based on their prevalence in patients with alcohol use.

Results: Patients with positive PEth results demonstrated significantly worse outcomes compared to patients in the negative PEth group. Positive PEth results were associated with higher mortality (odds ratio, 10.037; P < 0.001), ICU admissions, and rates of complications such as hepatorenal syndrome, hepatic encephalopathy, and sarcopenia. Postoperative liver transplant complications and rejection were also more frequent in the positive cohort.

Conclusions: This study highlights the association between recent alcohol use, as identified by PEth testing, and severe hospital outcomes. While PEth testing provides an objective measure of recent alcohol consumption, further research is needed to explore its role in improving clinical outcomes and guiding interventions for patients with alcohol use.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are prevalent conditions linked to obesity and metabolic disturbances, with potential complications such as cirrhosis and cardiovascular risks. This systematic review and meta-analysis aimed to evaluate the efficacy of pemafibrate, a drug targeting fat and sugar metabolism genes, in treating patients with MASLD/MASH.

Methods: Databases such as MEDLINE, Web of Science, Cochrane Library, and Scopus were searched until September 2023 to identify relevant studies. Selected studies underwent a thorough quality assessment using tools like Risk of Bias 2 tool (ROB-2) and the National Institutes of Health (NIH) Quality Assessment Tools. Comprehensive meta-analysis software was used for statistical evaluations, with a focus on lipid profiles, liver function tests, and fibrosis measurements.

Results: A total of 13 studies were included; 10 of them were included in the quantitative analysis. Our findings showed that pemafibrate significantly decreased low-density lipoprotein cholesterol (LDL-C) (effect size (ES) = -9.61 mg/dL, 95% confidence interval (CI): -14.15 to -5.08), increased high-density lipoprotein cholesterol (HDL-C) (ES = 3.15 mg/dL, 95% CI: 1.53 to 4.78), and reduced triglycerides (TG) (ES = -85.98 mg/dL, 95% CI: -96.61 to -75.36). Additionally, pemafibrate showed a marked reduction in liver enzyme levels, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), and alkaline phosphatase (ALP), with significant effect sizes and P values. For liver stiffness outcomes, pemafibrate decreased AST to platelet ratio index (APRI) (ES = -0.180, 95% CI: -0.221 to -0.138).

Conclusions: Pemafibrate, with its enhanced efficacy and safety profile, presents as a pivotal agent in MASLD/MASH treatment. Its lipid-regulating properties, coupled with its beneficial effects on liver inflammation markers, position it as a potentially invaluable therapeutic option.

Background: The aim of the study was to explore the clinical efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous microwave coagulation therapy (PMCT) for advanced hepatocellular carcinoma (HCC).

Methods: Eighty-three advanced HCC patients were divided into the experimental group (TACE + PMCT, 57 cases) and the control group (TACE alone, 26 cases). They received TACE treatment first, and computed tomography (CT) or hepatic artery angiography was performed 3 - 4 weeks after each treatment. Based on the comprehensive evaluation of iodine oil deficiency, fistula recanalization, residual lesions, and lesion progression, TACE or PMCT treatment was selectively performed, and three consecutive treatments were considered as one treatment cycle.

Results: The experimental group had a response rate (RR) of 49.1%, and the control group had a RR of 38.4%. The reduction rate of alpha-fetoprotein (AFP) in the experimental group was significantly higher than the control group (P < 0.05). The cumulative survival rates in the experimental at 1-, 1.5-, and 2-year post-treatment were higher than the control group. The cumulative recurrence and metastasis rates in the experimental at 1.5-, and 2-year post-treatment were significantly lower than those in the control group (P < 0.05). In addition, there were no significant differences in treatment-related complications in the two groups.

Conclusions: The combined treatment of TACE and PMCT for advanced HCC is a safe, feasible, and effective treatment method, prolonging the survival time, and reducing the recurrence and metastasis rate, without increased toxic and side effects.