Clinical and Translational Gastroenterology最新文献

Patients with cirrhosis are at risk of developing hepatic encephalopathy (HE), which can present with a wide range of symptoms, including confusion, lethargy, inappropriate behavior, and altered sleep patterns. In addition to HE, patients with cirrhosis are at risk of developing mild cognitive impairment, dementia, and delirium, which have features closely resembling HE. Given the similar presentation of these conditions, misdiagnosis can and does occur. Mild cognitive impairment is common in individuals aged 50 years and older and can progress to dementia in those affected. Dementia and HE are both characterized by sleep disturbance and cognitive dysfunction, thus differentiating these conditions can be difficult. Furthermore, delirium can disrupt sleep patterns, and liver disease is recognized as a risk factor for its development. As HE is a cirrhosis-related complication, determining if a patient has undiagnosed cirrhosis is critical, particularly given the large number of patients with asymptomatic, compensated cirrhosis. Separately, underdiagnosis of minimal HE can occur even in patients with diagnosed liver disease, related, in part, to lack of testing. Given the availability of effective therapies for managing symptoms and preventing future episodes, accurate diagnosis of HE is essential.

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: The increasing prevalence of clarithromycin (CLA)-resistant Helicobacter pylori(H. pylori) strains poses a significant challenge in the management of H. pylori infections. This systematic review and meta-analysis investigates the diagnostic accuracy of polymerase chain reaction (PCR) in identifying CLA-resistant H. pylori strains in stool.

Methods: A comprehensive literature search was conducted using PubMed, Embase, and Cochrane databases from database inception to April 30, 2023. Eligible studies evaluated the effectiveness of PCR stool tests in detecting CLA-resistant H. pylori strains in adults (>18-year-old). Studies of pediatric populations, alternative methods to PCR or stool samples, and reference tests other than gastric biopsy were excluded. The bivariate random-effects model was used to pool diagnostic accuracy from the included studies.

Results: The analysis of 11 prospective diagnostic studies with a total of 866 patients showed a pooled sensitivity of 0.97 (95% CI: 0.9-0.99) and a pooled specificity of 0.98 (95% CI: 0.81-1.00). Subgroup analysis based on the used technique demonstrated consistent findings without notable variations. The diagnostic odds ratio was calculated at 1843.92 (95% CI: 134.28-25,321.3). The positive likelihood ratio was determined as 51.02 (95% CI: 4.61-564.5), while the negative likelihood ratio was found to be 0.03 (95% CI: 0.01-0.1).

Discussion: PCR testing for clarithromycin-resistant H. pylori was highly sensitive and specific across studies with proven reliability in clinical practice, particularly in outpatient settings. Their implementation offers cost-effectiveness and the potential for tailored treatment strategies, holding promise for improved patient outcomes.

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.

Introduction: Trastuzumab deruxtecan (T-DXd) has been approved for human epidermal growth factor receptor 2-positive locally advanced or metastatic gastric and gastroesophageal junction (HER2+ mG/GEJ) cancer since July 2022 in France, through an accelerated approval. The aim of this study was to evaluate its real-world use.

Methods: We characterized T-DXd users treated for HER2+ mG/GEJ cancer using data from the French National Health Insurance database.

Results: The cohort included 196 patients, mostly men (78.1%), with a median age of 65 years. Median overall survival reached 7.7 months (95% CI: 6.2-9.0).

Discussion: Patients treated with T-DXd for HER2+ mG/GEJ cancer in the real world showed lower outcomes than those in pivotal clinical trials, consistent with previous reports on accelerated approvals.

Introduction: Esophageal lichen planus (ELP) is a rare inflammatory disease most seen in middle-aged White women, manifested by sloughing mucosa, thick exudate, and proximal strictures. Most case reports and small series highlight using steroids and other immunosuppressants. To the best of our knowledge, oral tablet tacrolimus has not been studied. We aimed to assess the change in ELP after oral tacrolimus treatment.

Methods: The primary outcome was the efficacy of tacrolimus objectively through our scoring system, ELP Severity Score (ELPSS). All consecutive adults with ELP who underwent more than one esophagogastroduodenoscopy by 2 esophagologists and being treated with tacrolimus or other treatment were eligible for inclusion in this retrospective cohort study. Inflammation and fibrostenotic disease were graded using the novel ELPSS.

Results: Twenty-two patients met the inclusion criteria. Half (11) received tacrolimus (dose 1-2 mg twice daily), and half (11) received other therapy (i.e., cyclosporine, topical steroids, or none). Mean ELPSS on the first esophagogastroduodenoscopy, extraesophageal manifestations of disease, presenting symptoms, and baseline characteristics were similar between groups. Among patients on Tac vs No-Tac, there was a statistically significant improvement in ELPSS (mean difference 1.8 pts; 95% confidence interval 0.25-3.38; P = 0.02). Response rate was 89% with Tac vs 30% with No-Tac ( P = 0.025). All 22 patients underwent bougie dilation safely with a mean diameter of 16 mm achieved. Patients on Tac also required less frequent dilation.

Discussion: Oral tablet tacrolimus reduced the inflammatory and fibrostenotic components of ELP. Thus, low-dose oral tacrolimus is safe and should be considered in patients with more severe disease.

Introduction: A link between inflammatory bowel disease (IBD), stressful life events, and psychological factors has previously been reported. Our objective was to examine the relationship between emotional, physical, and sexual abuse of childhood and risk of IBD using a large cohort of female health professionals.

Methods: We included participants in the Nurses' Health Study II who completed the Physical and Emotional Abuse Subscale of the Childhood Trauma Questionnaire and the Sexual Maltreatment Scale of the Parent-Child Conflict Tactics Scale in 2001. Diagnosis of IBD was determined by self-report and confirmed independently by 2 physicians through review of medical records. We used Cox proportional hazard modeling to estimate the risk of Crohn's disease (CD) and ulcerative colitis (UC) while adjusting for covariates.

Results: Among 68,167 women followed from 1989 until 2017, there were 146 incident cases of CD and 215 incident cases of UC. Compared with women with no history of abuse, the adjusted hazard ratios of CD were 1.16 (95% confidence interval [CI] 0.67-2.02) for mild, 1.58 (95% CI 0.92-2.69) for moderate, and 1.95 (95% CI 1.22-3.10) for severe abuse ( Ptrend = 0.002). We did not observe an association between childhood abuse and risk of UC.

Discussion: Women who reported early life severe abuse had an increased risk of CD. These data add to the growing body of evidence on the critical role of early life stressors in development of CD.