Clinical and Translational Gastroenterology最新文献

Introduction: Acute variceal bleeding (AVB) is a severe complication of cirrhosis, with a 6-week mortality rate of up to 15%-20%. Early risk prediction is essential for guiding management. Model for End-Stage Liver Disease (MELD) 3.0, a refined version of the original MELD score, incorporates additional variables (sex, sodium, albumin, capped creatinine) to improve short-term mortality prediction. This study assessed MELD 3.0's use in predicting 6-week mortality in cirrhotic patients with AVB, in comparison with MELD, Glasgow-Blatchford Score (GBS), and Albumin, INR, Mental status, Systolic blood pressure, Age ≥ 65 (AIMS65).

Methods: A prospective cohort of cirrhotic patients with AVB admitted to Cho Ray Hospital (November 2023-May 2024) was studied. The primary outcome was 6-week mortality; in-hospital mortality was secondary. The predictive performance of MELD 3.0, MELD, GBS, and AIMS65 was evaluated using area under the receiver operating characteristic (AUROC).

Results: Among 212 patients, in-hospital and 6-week mortality rates were 4.7% and 19.8%, respectively. For in-hospital mortality, MELD 3.0 showed the highest AUROC (0.88), followed by MELD (0.80), AIMS65 (0.74), and GBS (0.59). For 6-week mortality, MELD 3.0 again outperformed others (AUROC: 0.81), vs MELD (0.75), AIMS65 (0.66), and GBS (0.61) (all P < 0.05). A MELD 3.0 cutoff ≥ 20 predicted >25% 6-week mortality (sensitivity 69.1%, specificity 83.5%).

Discussion: MELD 3.0 is a strong predictor of early mortality in cirrhotic patients with AVB. A cutoff ≥20 may help identify high-risk patients requiring prompt intensive care.

Introduction: Patients with inflammatory bowel disease (IBD) are at increased risk of herpes zoster and should receive the recombinant herpes zoster vaccine (RZV). We sought to assess the immunogenicity and safety of RZV series in patients receiving anti-tumor necrosis factor (TNF) therapy compared with those receiving vedolizumab.

Methods: This single-center prospective study enrolled patients with IBD on vedolizumab or anti-TNF monotherapy receiving RZV. Primary outcome assessed cell-mediated immunity (CMI) differences between groups postvaccination. Secondary outcomes included humoral response, sustained immunity, and safety monitoring for adverse events and IBD flares. Assessments occurred at baseline, 30, 240, and 425 days postvaccination. Statistical analyses included nonparametric Mann-Whitney U tests for between-group comparisons and Wilcoxon signed-rank tests for within-group changes, with significance set at P < 0.05.

Results: Thirty-three patients enrolled (16 vedolizumab, 17 anti-TNF). CMI responses increased postvaccination in both groups (median 56 cells/million [interquartile range {IQR} 21-102] vs 33 cells/million [IQR 11-73]; P = 0.13), with no significant difference between treatment groups. Both groups showed strong antibody responses to vaccination (preimmunization median: 349.9 mIU/mL [IQR 276.8-402.5] vs 90-day median: 605.0 mIU/mL [IQR 525.6-641.0]; P < 0.001). CMI responses remained elevated at both day 240 and 425 assessments. Antibody levels remained elevated through day 425 (549.1 mIU/mL, IQR 516.1-585.6), substantially higher than prevaccination levels. No IBD flares occurred; most adverse events were mild and transient.

Discussion: RZV demonstrated robust immunogenicity and favorable safety profile in patients with IBD receiving either vedolizumab or anti-TNF therapy. Both cellular and humoral immune responses persisted through 425 days postvaccination.

Introduction: Patients with immunoglobulin G4-related disease (IgG4-RD) have risk factors of metabolic bone disease (MBD), yet data are lacking on the prevalence of MBD in IgG4-RD. We assessed screening frequency and prevalence of MBD in patients with IgG4-RD with and without pancreatic involvement.

Methods: Using an IgG4-RD registry, we extracted details from medical records related to MBD in patients who actively followed in our system. Living patients with contact information available were invited to complete surveys detailing MBD and associated characteristics.

Results: Seventy patients met criteria for medical records review (n = 17 with pancreatic involvement). Fifty-one percent had taken proton-pump inhibitors, and 30% had investigator-determined MBD. Compared with the US population, the age-standardized prevalence of osteoporosis in the IgG4-RD cohort was higher among both female patients (28.1% vs 19.6%, P = 0.40) and male patients (8.3% vs 4.4%, P = 0.48), though this did not achieve statistical significance. Mean T-scores at all sites were numerically lower in patients with pancreatic involvement than those without (all P > 0.1). In patient-reported data (n = 105), despite 62% of patients reporting ≥3 months of glucocorticoid exposure, only 36% had a dual-energy x-ray absorptiometry performed. Of 15 patients for whom pharmacologic MBD treatment was recommended, 8 (53%) reported adherence to this recommendation.

Discussion: The burden of MBD and its risk factors is high in patients with IgG4-RD, yet screening and treatment is low. Although our study was underpowered to detect statistical differences, there may be a greater burden of MBD in patients with pancreatic involvement. Screening and treatment of MBD should be emphasized in these patients.

Introduction: Pharmacological therapies for chronic idiopathic constipation (CIC) are useful, but many patients report dissatisfaction from a lack of efficacy and occurrence of adverse events. The vibrating capsule (VC) is a US Food and Drug Administration approved nonpharmacologic treatment of CIC. However, its long-term usefulness in a community setting is unknown. The goal of this study was to assess the long-term efficacy and safety of VC treatment in a real-world community setting.

Methods: We conducted a postmarketing analysis of CIC patients prescribed VC who completed at least 3 or 6 months of treatment. The clinical utility was assessed by patient reported symptoms in an electronic stool diary. Safety data were also collected.

Results: One thousand seven hundred twenty-two patients were prescribed VC, and 491 and 298 took the VC and kept stool diaries for 3 and 6 months, respectively. Approximately 46% of patients were older than 55 years of age and 85% were women. Compared with baseline, complete spontaneous bowel movement rates increased significantly throughout the 3 and 6-month periods (average increase of >1 complete spontaneous bowel movement per week; P < 0.0001). Mean stool consistency (Bristol Stool Form Scale) improved from 2.9 (baseline) to 4.1 during treatment ( P < 0.0001), mean straining effort (1-4) decreased from 2.9 to 1.6 ( P < 0.0001), and toileting time also significantly decreased ( P < 0.0001). Safety analysis revealed that 4.6% of patients reported feeling a sensation of vibration, 1.8% reported abdominal pain and 0.64% reported diarrhea.

Discussion: In a community setting, the VC seems both effective and safe for long-term treatment of chronic constipation with diarrhea being notably uncommon.

Introduction: Intrapancreatic fat deposition is related to insulin resistance and type 2 diabetes mellitus. However, the association between intrapancreatic fat deposition and coronary artery disease has not been well studied. In this study, we investigated the associations between intrapancreatic fat deposition alone or in combination with triglyceride-glucose (TYG) index and the risk of coronary artery calcification (CAC) in a general population.

Methods: A total of 9,479 participants who underwent CT scans for lung cancer screening from 2018 to 2020 were included in this study. The TYG index was calculated through the following equation: Ln (fasting glucose [mg/dL] × fasting TG [mg/dL]/2). Pancreatic CT attenuation was used as a marker of intrapancreatic fat deposition. CAC was evaluated on noncardiogram-gated chest CT.

Results: CAC was detected in 2,447 of 9,479 participants. The prevalence of CAC was significantly lower in subjects with high pancreatic CT attenuation (37.8% in the first quartile [Q1] vs 17.8% in the fourth quartile [Q4], P < 0.001). Pancreatic CT attenuation was associated with the occurrence of CAC (odds ratio 0.82, 95% confidence interval 0.69-0.97, Q4 vs Q1). The area under the curve of the combination of pancreatic CT attenuation and the TYG index was significantly greater than that of TYG and pancreatic CT attenuation alone in identifying CACs (0.646 vs 0.596 and 0.612, P < 0.001).

Discussion: Intrapancreatic fat deposition was associated with CAC, and the combination of pancreatic CT attenuation and the TYG index performed better than TYG or pancreatic CT attenuation alone in identifying CACs.

Introduction: We examined whether the symptom expression of depression as assessed using the Patient Health Questionnaire-9 (PHQ-9) depression screening tool differs between patients with decompensated cirrhosis (DC) compared with primary care patients.

Methods: Study included 218 patients with DC (91% Child-Pugh Class B/C) recruited from a liver transplant center and a real-world cohort of 436 outpatients from 4 primary care clinics in a large tertiary academic health system who completed the PHQ-9. We calculated positive screening rates for depression (PHQ-9 cutoff score of 10) for both cohorts. We evaluated PHQ-9 items for differential item functioning (DIF) in both cohorts within an Item Response Theory framework. We compared DIF-adjusted and unadjusted Item Response Theory scores to characterize the impact of DIF on PHQ-9 total scores.

Results: Positive screening rates using a PHQ-9 cutoff score of 10 were 39% and 29% for DC and primary care patients, respectively. Three PHQ-9 somatic symptom items (sleep problems, low energy, psychomotor agitation, or retardation) showed significant DIF, with DC more likely than primary care patients with similar levels of depression severity to endorse these symptoms. DIF-adjusted scores suggested a 1-point increase (PHQ-9 cutoff score of 11) in the screening threshold for patients with DC.

Discussion: Equating for depression severity, we found differences in the symptom expression of depression for patients with DC relative to primary care patients. Our findings highlight the need for future clinical and basic research into the diagnostic performance of depression screening tests and the phenomenology of depression in patients with DC.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with poor prognosis and limited treatment options. Electroporation-based therapies, such as electrochemotherapy (ECT) and irreversible electroporation (IRE), could be promising alternatives. ECT combines reversible electroporation with chemotherapy, enhancing intracellular drug uptake, while IRE leads to nonthermal tumor ablation. Both have been suggested as immunotherapy potentiators (electroimmunotherapy) in some tumor locations. We conducted a systematic review to evaluate the efficiency and safety of ECT, IRE, and immunoelectroporation in PDAC treatment.

Methods: We searched Medline, Embase, Cochrane, and Google-Scholar for ECT, IRE, and electroimmunotherapy following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. For ECT and electroimmunotherapy, regarding the scarcity of the data, we described independently each study protocol and results. For IRE, we collected protocol, efficiency, and safety data to provide a global analysis.

Results: Fifteen studies described the effects of ECT for PDAC treatment: Safety and efficiency were promising in both preclinical and human models. Thirty-eight clinical studies including 2,245 patients were analyzed for IRE, with patients mostly treated for locally advanced pancreatic cancer and a median overall survival of 17.2 months at the expanse of a 36% adverse event rate, half of which severe. Seven (preclinical and clinical) studies investigated electroimmunotherapy suggesting significant potentiation of immunotherapy in both preclinical and human models.

Discussion: In the largest systematic review to date regarding electroporation in PDAC treatment, analysis of study results plead against the use of IRE but highlight the potential benefits of ECT and electroimmunotherapy.

Introduction: Gastric cancer (GC) is a lethal malignant tumor necessitating high-sensitivity detection to improve diagnostic accuracy and the prognosis of patients. Alterations in long noncoding RNAs can influence cancer progression through various mechanisms. Our study tried to explore the potential of STARD4 antisense RNA 1 (STARD4-AS1) as a GC biomarker and its mechanism of action in GC development.

Methods: Pan-cancer analysis using The Cancer Genome Atlas database identified STARD4-AS1. Serum STARD4-AS1 levels in patients with GC were measured by quantitative real-time PCR, and diagnostic efficiency was assessed using receiver operating characteristic curves. Functional inactivation experiments and western blotting evaluated the biological role of STARD4-AS1 in GC cells. Bioinformatics analysis explored its potential role in GC immunotherapy and underlying mechanisms.

Results: Pan-cancer analysis revealed lower overall survival in GC patients with higher STARD4-AS1 expression. Quantitative real-time PCR confirmed the reproducibility and stability of STARD4-AS1 as a marker. Serum STARD4-AS1 levels in patients with GC were significantly higher than those in healthy subjects and gastritis patients. Receiver operating characteristic analysis demonstrated that STARD4-AS1 outperformed carcinoembryonic antigen, carbohydrate antigen 199 , and carbohydrate antigen 724 in differentiating GC from gastritis, with optimal diagnostic power when combined with these markers. Knockdown of STARD4-AS1 inhibited GC cell proliferation and metastasis and inhibited the epithelial-mesenchymal transition process. Biosignature prediction indicated that higher STARD4-AS1 expression could evaluate prognosis, as well as regulate GC progression through phosphatidylinositol-mediated signaling, and transmembrane receptor protein tyrosine phosphatase signaling pathway.

Discussion: Serum STARD4-AS1 may serve as a diagnostic biomarker and oncogene function for GC for improving diagnosis, monitoring progression, and evaluating prognosis of GC.

Introduction: Serrated polyposis syndrome (SPS) is clinically defined by the presence of multiple serrated polyps in the colon and rectum, and is associated with increased colorectal cancer risk. SPS is the most prevalent polyposis condition; however, its genetic basis remains poorly characterized. The British Society of Gastroenterology recommends gene panel testing for all patients with SPS to rule out other polyposis conditions. The aim of this study was to evaluate the diagnostic yield of genetic testing in patients with SPS.

Methods: We conducted a retrospective, cross-sectional analysis using the Polyposis Registry from St. Mark's Hospital, London, a national referral center in the United Kingdom. Patients with SPS who underwent genetic testing between April 4, 2009 and February 9, 2024, and met the SPS WHO criteria were included. Genetic variants were identified from test reports, and clinical data were extracted from medical records.

Results: In total, 573 people with SPS were identified in our registry, of whom 258 underwent genetic testing. Of these, 119 underwent target gene testing and 139 underwent multigene panel testing. No pathogenic variants were detected through targeted genetic testing. On multigene panel testing, pathogenic germline variants were found in 4 patients (2.9%), including 3 with Lynch syndrome (2 with PMS2 , one with MSH2 ) and one with an RNF43 variant.

Discussion: Genetic testing demonstrated a low diagnostic yield in this SPS cohort, suggesting undefined genetic risk or involvement of other pathophysiological factors. Therefore, genetic testing seems to have limited utility in patients with SPS and may primarily identify those with an incidental diagnosis of Lynch syndrome.