Clinical and Translational Gastroenterology最新文献

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.

Introduction: The aim of treat-to-target (T2T) algorithms in inflammatory bowel disease was to maximize the benefit of medical therapies by establishing a framework for disease activity assessment to guide therapeutic decisions. There are limited data on adoption rates of T2T monitoring in real-world practice. We aimed to describe rates of T2T monitoring, predictors of completion, and associations with clinical outcomes.

Methods: A retrospective cohort study was conducted from 2015 to 2021 of individuals with inflammatory bowel disease starting new biologic or small molecule therapy within a multistate healthcare system. The completion of biochemical monitoring including fecal calprotectin or C-reactive protein and structural monitoring including endoscopy or enterography, or both, was assessed between 3 and 6 months and 6 and 12 months, respectively. Healthcare utilization (HCU), defined as emergency department visits, hospitalizations, prednisone prescriptions, or abdominal surgery within 2 years, was also assessed.

Results: A total of 823 patients were included in the cohort, and 127 (15.4%) completed some form of T2T monitoring. Twenty-two patients (2.7%) completed both biochemical and structural monitoring. The completion of T2T was not associated with lower HCU. The completion of only biochemical T2T, but not structural or both biochemical and structural T2T, was associated with decreased 12-month medication persistence (hazard ratio 0.36, 95% confidence interval 0.17-0.75). The completion of just structural T2T (hazard ratio 1.59, 95% confidence interval 1.05-2.39) was associated with higher HCU.

Discussion: In this retrospective cohort of individuals initiating new therapy, the rates of T2T monitoring were low. The completion of all T2T was not associated with lower HCU. The completion of only biochemical T2T monitoring was associated with lower 12-month medication persistence and only structural T2T with higher HCU.

Introduction: Indomethacin is often used experimentally to induce intestinal hyperpermeability, enabling evaluation of interventions targeting barrier function.

Methods: We conducted a randomized, double-blind, placebo-controlled study (NCT05538247) in healthy volunteers to assess whether a supplement could mitigate indomethacin-induced hyperpermeability. Participants received 150 mg/d of indomethacin for 6 days, either before or during placebo/supplement administration. Permeability was measured using 13 C-mannitol and lactulose urinary excretion.

Results: Contrary to expectations, indomethacin failed to increase 13 C-mannitol excretion in either group. No meaningful elevations in serum (zonulin, claudins) or fecal (calprotectin) biomarkers were observed.

Discussion: Our findings suggest that the expected increase in intestinal permeability after indomethacin administration may not be consistently observed in healthy volunteers. These results highlight the need to carefully consider the reproducibility and sensitivity of this model in future clinical studies aiming to investigate gut barrier function.

Introduction: Over one-third of people are not up-to-date with colorectal cancer (CRC) screening, and blood-based tests offer a promising alternative to existing options. We used conjoint analysis to quantify the proportion of people who would prefer a hypothetical blood test over current methods (e.g., fecal immunochemical test, multitarget stool DNA test, colonoscopy).

Methods: We conducted a conjoint analysis survey in a US nationally representative sample of average risk individuals aged 40-75 years who were not up-to-date with CRC screening. We performed latent class analysis to identify groups with similar decision-making profiles and estimated the proportion who would prefer a blood test every 3 years over existing methods.

Results: Overall, 1,009 participants completed the survey. Using latent class analysis, we identified 2 distinct groups: (i) prioritized how the test is performed-39.4%, and (ii) prioritized the accuracy of detecting CRC and advanced adenomas-60.6%. Through simulations using the conjoint data, most individuals in the first group preferred a blood test every 3 years (65.1%), whereas 53.0% of the second group also favored the blood test. In additional simulations that incorporated test accuracy for CRC and advanced adenoma detection, these performance characteristics emerged as important drivers of screening preferences across the different testing options.

Discussion: Among individuals not up-to-date with CRC screening, our findings suggest that many would generally prefer a blood-based screening test over other options, but preference may depend on test accuracy. Offering a blood test option may improve CRC screening uptake, particularly among individuals who are unscreened or overdue for screening.

Introduction: Elexacaftor-tezacaftor-ivacaftor (ETI) is a highly effective therapy for over 70% of people with cystic fibrosis (pwCF), improving lung disease, quality of life, and survival. The aim of this prospective study was to explore ETI's effects on the gastrointestinal manifestations of cystic fibrosis.

Methods: In this prospective cross-sectional study, performed in a single tertiary referral center for cystic fibrosis, clinical and laboratory data, intestinal ultrasound (IUS) findings, and pancreatic stiffness (2D-SWE) were assessed at baseline (T0) and during ETI treatment at 6 and 12 months (T6, T12). Abdominal pain, alterations in stool frequency, form, and consistency (diarrhea, constipation) were monitored.

Results: The participants were 86 pwCF (57% male, mean age 21.6 years) and 22 healthy controls enrolled for pancreatic stiffness comparison. IUS abnormalities (e.g., bowel wall thickening, inspissated intestinal contents, lymph node hypertrophy), and abdominal pain (63% at T0 to 2% at T12) significantly decreased ( P < 0.05). Constipation dropped from 7% at T0 to 0% at T12 and recurrent diarrhea from 77% to 9% ( P < 0.0001). Pancreatic stiffness normalized after 1-year treatment (T0: 4.21 vs T12: 5.7 kPa, P < 0.05). Body mass index increased (T0: 21.0 vs T12: 22.4 kg/m 2 , P < 0.001), and glycemic control improved, with reduced fasting glucose (T0: 97.8 vs T12: 86 mg/dL, P < 0.001) and hemoglobin A1c (38 vs 36 mmol/mol, P < 0.001). High-density lipoproteins cholesterol increased, whereas low density lipoprotein and triglycerides remained stable.

Discussion: ETI normalized IUS parameters and significantly improved pancreatic stiffness, gastrointestinal symptoms, glycemic control, and cholesterol metabolism in pwCF.