Clinical and Translational Gastroenterology最新文献

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.

Methods: Results for the phase 3 LIBERTY EoE TREET study coprimary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.

Results: A steep initial relationship then plateau was observed between higher dupilumab steady-state trough concentrations and decreased eosinophilic infiltration at week 24, whereas a graded exposure-response relationship was observed for symptomatic improvement at week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation.

Discussion: The dupilumab 300 mg weekly regimen approved for adults and adolescents with EoE weighing ≥ 40 kg is supported by dose- and exposure-response relationships.

Introduction: The impact of pelvic bone structure on fecal incontinence (FI) is unclear. We assessed the association between weight-adjusted pelvic area and FI.

Methods: This was a population-based analysis of the National Health and Nutrition Examination Survey in 2005-2006. Participants who completed the bowel health survey and dual-energy x-ray absorptiometry were included.

Results: On multivariable analysis of 2,772 participants, the lowest pelvic area quartile predicted increased FI compared with the third (odds ratio [OR]: 2.05, confidence interval [CI]: 1.18-3.56, P = 0.014) and fourth (OR: 1.94, CI: 1.02-3.70, P = 0.045) quartiles. Sex-stratified analyses found similar association among female patients only.

Discussion: Small pelvic area on dual-energy x-ray absorptiometry is a potential risk factor of FI.

Introduction: The utility of serial procalcitonin (PCT) measurements in cirrhotic patients with systemic inflammatory response syndrome (SIRS) is not well understood. The aim of this study was to assess the effectiveness of serial PCT measurements for diagnosing bacterial infections and predicting 30-day mortality in this population.

Methods: We prospectively studied 120 cirrhotic patients with SIRS, 64.2% of whom had bacterial infections. Serial PCT levels were measured within the first 72 hours of admission.

Results: Patients with bacterial infections had significantly higher PCT levels at admission, 24 hours, and 72 hours compared with those without infections. PCT values >0.5 ng/mL within 72 hours demonstrated high sensitivity (81.8-87.5%) but moderate specificity (27.9-44.2%) for diagnosing bacterial infections. Serial PCT monitoring, including the 72-hr/baseline ratio and changes in PCT over 72 hours, provided insights into the evolution of bacterial infections and short-term mortality. Patients with a PCT 72-hour/baseline ratio >0.8 had higher 30-day mortality than those with a ratio <0.5 (50.0% vs 25.6%; odds ratio 3.91, 95% CI 1.40-10.97). Patients whose PCT levels decreased by >50% had lower 30-day mortality than those with increasing levels (23.3% vs 46.7%; odds ratio 0.25, 95% CI 0.08-0.74). Patients with Model for End-Stage Liver Disease scores >15 and bacterial infections who experienced a PCT decrease of <50% had higher 30-day mortality than those with greater reductions (57.7% vs 25.0%, P = 0.021).

Discussion: Serial PCT measurements within 72 hours of admission are useful for determining bacterial infections and mortality in cirrhotic patients with SIRS. PCT monitoring may optimize antibiotic use and enhance early risk stratification, potentially improving patient outcomes.

Introduction: Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, with delayed diagnosis often limiting effective treatment options. This study introduces a novel, noninvasive radiomics-based approach using [18F] FDG PET/CT (fluorodeoxyglucose positron emission tomography/computed tomography) to predict vascular endothelial growth factor (VEGF) status and survival in patients with GC. The ability to noninvasively assess these parameters can significantly influence therapeutic decisions and outcomes.

Methods: We conducted a retrospective study involving patients diagnosed with GC, stratified into training, validation, and test groups. Each patient underwent a [18F] FDG PET/CT scan, and radiomic features were extracted using dedicated software. A Radiomics Score (RS) was calculated, serving as a predictor for VEGF status. Statistical analyses included logistic regression and Cox proportional hazards models to evaluate the predictive power of RS on survival outcomes.

Results: The developed radiomics model demonstrated high predictive accuracy, with the RS formula achieving an area under the receiver operating characteristic curve of 0.861 in the training cohort and 0.857 in the validation cohort for predicting VEGF status. The model also identified RS as an independent prognostic factor for survival, where higher RS values correlated with poorer survival rates.

Discussion: The findings underscore the potential of [18F] FDG PET/CT radiomics in transforming the management of GC by providing a noninvasive means to assess tumor aggressiveness and prognosis through VEGF status. This model could facilitate earlier and more tailored therapeutic interventions, potentially improving survival outcomes in a disease marked by typically late diagnosis and limited treatment success.

Background: Because biologic and small molecule therapy is expensive, payors have mandated pre-authorizations for these medications, often resulting in a lengthy approval process. The aims of this study are to assess the frequency of and risk factors for delays in starting advanced therapies assessing insurance, care team, and patient-related factors.

Methods: Retrospective, multi-center study of adult inflammatory bowel disease patients with prescriptions for an advanced therapy in two geographically distinct academic gastroenterology practices; one with and the other without a dedicated pharmacist. A priori we defined a delay in starting therapy as >14 days between prescription and first dose. Logistic regression analysis was performed to assess for risk factors for delay.

Results: A total of 388 patients were prescribed advanced therapies with 46.6% receiving their first dose within 14 days. Patients who were on time vs delayed were similar in baseline demographics, disease characteristics, and disease activity. After adjusting for confounders, three independent risk factors remained significant as predictors for delay; study site (OR=5.2, 95% CI 2.894, 9.333), intravenous drug delivery as opposed to subcutaneous or oral (OR=3.07, 95% CI 1.845, 5.099), and insurance denial (OR=2.72, 95% CI 1.082, 6.825).

Conclusions: In a multicenter study, we found that a delay between prescription and administration of first dose of an advanced therapy is common, with >50% of patients having the first dose delayed by >2 weeks. Delays in starting therapy were significantly more likely if denied by insurance, given via IV induction, or at a study site without a dedicated pharmacist.

Introduction: We assessed potential mechanisms behind the requirement for more frequent dupilumab dosing in eosinophilic esophagitis (EoE) compared with other approved indications.

Methods: Results for the phase 3 LIBERTY EoE TREET study co-primary endpoints (proportion of patients achieving a peak intraepithelial eosinophil count of ≤6 eosinophils per high-power field and absolute change from baseline in Dysphagia Symptom Questionnaire total score) were pooled in exposure-response analyses.

Results: A steep initial relationship then plateau was observed between higher dupilumab steady state trough concentrations (Ctrough) and decreased eosinophilic infiltration at Week 24, while a graded exposure-response relationship was observed for symptomatic improvement at Week 24. Patients with the highest exposures were more likely to achieve greater symptomatic benefit, independent of strictures or history of dilation.

Conclusions: The dupilumab 300 mg qw regimen approved for adults and adolescents with EoE weighing ≥40 kg is supported by dose- and exposure-response relationships.

Introduction: United States Multi-Society Task Force colonoscopy surveillance intervals are based solely on adenoma characteristics, without accounting for other risk factors. We investigated whether a risk model including demographic, environmental, and genetic risk factors could individualize surveillance intervals under an "equal management of equal risks" framework.

Methods: Using 14,069 individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnostic colonoscopy following an abnormal flexible sigmoidoscopy, we modeled the risk of colorectal cancer, considering the diagnostic colonoscopy finding, baseline risk factors (e.g., age and sex), 19 lifestyle and environmental risk factors, and a polygenic risk score for colorectal cancer. Ten-year absolute cancer risks for each diagnostic colonoscopy finding (advanced adenomas [N = 2,446], ≥3 non-advanced adenomas [N = 483], 1-2 non-advanced adenomas [N = 4,400], and no adenoma [N = 7,183]) were used as implicit risk thresholds for recommended surveillance intervals.

Results: The area under the curve for the model including colonoscopy findings, baseline characteristics, and polygenic risk score was 0.658. Applying the equal management of equal risks framework, 28.2% of individuals with no adenoma and 42.7% of those with 1-2 non-advanced adenomas would be considered high risk and assigned a significantly shorter surveillance interval than currently recommended. Among individuals who developed cancer within 10 years, 52.4% with no adenoma and 48.3% with 1-2 non-advanced adenomas would have been considered high risk and assigned a shorter surveillance interval.

Discussion: Using a personalized risk-based model has the potential to identify individuals with no adenoma or 1-2 non-advanced adenomas, who are higher risk and may benefit from shorter surveillance intervals.

Introduction: The morphology of the major papilla plays a crucial role in the selection of the cannulation method for the common bile duct during endoscopic retrograde cholangiopancreatography. Nevertheless, there is limited evidence available that compares the efficacy and safety of cannulation approaches in certain papilla morphologies. The aim of this study was to assess the safety and effectiveness of 2 cannulation methods, including primary needle-knife fistulotomy (pNKF) and standard transpapillary (STP), in patients with long-size papilla.

Methods: A total of 260 patients with intact long-size papilla were enrolled and were randomly assigned to the pNKF or STP groups (n = 130 in each group). The primary endpoint was the rate of postendoscopic retrograde cholangiopancreatography pancreatitis. Biliary cannulation success rates, the duration of cannulation and the overall procedure, and the incidence of adverse events were also compared between the groups. All of the patients were hospitalized for at least 24 hours after the procedure.

Results: A total of 125 (96.2%) patients in the pNKF and 114 (87.7%) patients in the STP groups had successful primary biliary cannulation ( P = 0.01) and were included in the final analysis. Postendoscopic retrograde cholangiopancreatography pancreatitis occurred in 11 patients in the STP group and 3 patients in the pNKF group (9.6% vs 2.4%, P = 0.02; number needed to treat [95% confidence interval] = 13.9 [7.5-83.2]). Moreover, compared with the pNKF, STP was associated with more cannulation attempts (3.4 vs 2.5, P < 0.001) and longer cannulation time (258 vs 187 seconds, P < 0.001).

Discussion: In patients with long-size papilla, pNKF is a safer, easier, and more efficient approach to gain primary biliary access than the STP technique.

Introduction: Several studies suggest that new-onset diabetes mellitus is an early manifestation of pancreatic ductal adenocarcinoma (PDAC). Therefore, the International Cancer of the Pancreas Screening Consortium recommends glucose and hemoglobin A1c (HbA1c) monitoring in high-risk individuals (HRIs) undergoing surveillance. However, evidence that such monitoring improves PDAC detection is lacking. Our aim was to investigate the association between serum glucose and HbA1c values and the development of PDAC in HRIs undergoing surveillance.

Methods: Participants were recruited from the familial pancreatic cancer surveillance cohort, which follows hereditary predisposed HRIs yearly by magnetic resonance imaging and/or endoscopic ultrasound and blood sampling. Those who underwent fasting glucose and/or HbA1c monitoring at least once were eligible candidates.

Results: Four hundred four HRIs met the inclusion criteria. During a median follow-up of 41 months (range 14-120), 9 individuals developed PDAC and 4 (without PDAC) were diagnosed with new-onset diabetes mellitus. Glucose levels ranged from 3.4 to 10.7 mmol/L (mean 5.6 ± 0.7) and HbA1c levels from 25 to 68 mmol/mol (mean 37.7 ± 4.1). The mean values did not differ significantly between PDAC cases and controls. The percentage of individuals with at least one elevated value were comparable between PDAC cases and controls for glucose (33% and 27%, P = 0.707) and HbA1c (22% and 14%, P = 0.623). No consistent glucose or HbA1c trends over time suggested a correlation with PDAC development.

Discussion: In this HRI surveillance cohort, measuring glucose and HbA1c values did not contribute to PDAC detection. Larger and longer-term studies are needed to determine the final role of glucose and HbA1c monitoring in PDAC surveillance.