Clinical and Translational Gastroenterology最新文献

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.

Introduction: Hypoalgesic inflammatory bowel disease (IBD) may provide critical insights into human abdominal pain. This condition was previously associated with homozygosity for a polymorphism (rs6795970, A1073V; 1073 val/val ) related to Na v 1.8, a voltage-gated sodium channel preferentially expressed on nociceptors. It was unclear whether this relationship existed for both Crohn's disease (CD) and ulcerative colitis (UC). This study evaluated a larger, carefully phenotyped IBD cohort to investigate this question.

Methods: Allelic and genotypic frequencies of rs6795970 were compared among study cohorts characterized by concomitant assessment of intestinal inflammatory status and abdominal pain experience. Visceral sensory perception was performed in healthy individuals using rectal balloon distension.

Results: We analyzed 416 patients with IBD (261CD:155UC) and 142 healthy controls. In the IBD cohort, 84 individuals (43CD:41UC) were determined to have hypoalgesic disease. The allelic frequency of rs6795970 was significantly higher in patients with hypoalgesic IBD when compared with other patients with IBD and healthy controls. Patients with hypoalgesic IBD were also more likely to be homozygous for this polymorphism when compared with other patients with IBD and healthy controls. Hypoalgesic CD (30% vs 12%, P = 0.004) and hypoalgesic UC (32% vs 15%, P = 0.036) were each significantly more likely to be associated with homozygosity for the rs6795970 polymorphism. In a cohort of healthy individuals (n = 50), rs6795970 homozygotes (n = 11) also demonstrated reduced abdominal discomfort to rectal balloon distension.

Discussion: These findings indicate that Na v 1.8 plays a key role in human visceral pain perception, and could serve as a novel diagnostic target in the management of hypoalgesic CD and UC, and potential therapeutic target for conditions associated with chronic abdominal pain.

Introduction: Liver stiffness measurement is principal for staging liver fibrosis but not included in routine examinations. We investigated whether comparable diagnostic performance can be achieved by mining ultrasound images and developing a novel serum index (NSI).

Methods: Texture features were extracted from ultrasound images. Spearman correlation and logistics regression selected independent variables for significant (F ≥ 2) and advanced (F ≥ 3) fibrosis. We compared the diagnostic performance of transient elastography (TE), ultrasound image biomarker, conventional serum indices (aspartate aminotransferase-to-platelet ratio index, fibrosis-4 index, gamma-glutamyl transpeptidase-to-platelet ratio), and NSI in 365 patients with chronic hepatitis B.

Results: Among patients, 52.1% had significant fibrosis and 24.2% had advanced fibrosis. PLT, gamma-glutamyl transferase, prealbumin, and globulin were incorporated into NSI. In the validation group, TE achieved the best performance (area under the curve [AUC]: 0.765 [0.690-0.849] for significant fibrosis; 0.812 [0.745-0.878] for advanced fibrosis), followed by ultrasound image biomarker (AUC: 0.712 [0.629-0.795]; 0.678 [0.595-0.763]) and NSI (AUC: 0.630 [0.534-0.725]; 0.659 [0.572-0.745]), outperforming conventional indices.

Discussion: Texture analysis enhances ultrasound's diagnostic utility, but TE remains superior. When TE is unavailable, ultrasound image analysis and NSI, incorporating prealbumin, can serve as alternative tools for fibrosis staging.

Introduction: Failure to document colonoscopy follow-up needs postpolypectomy can lead to delayed detection of colorectal cancer (CRC). Automating the update of a unified follow-up date in the electronic health record (EHR) may increase the number of patients with guideline-concordant CRC follow-up screening.

Methods: Prospective pre-post design study of an automated rules engine-based tool using colonoscopy pathology results to automate updates to documented CRC screening due dates was performed as an operational initiative, deployed enterprise-wide May 2023. Participants were aged 45-75 years who received a colonoscopy November 2022 to November 2023. Primary outcome measure is rate of updates to screening due dates and proportion with recommended follow-up < 10 years. Multivariable log-binomial regression was performed (relative risk, 95% confidence intervals).

Results: Study population included 9,824 standard care and 19,340 intervention patients. Patients had a mean age of 58.6 ± 8.6 years and were 53.4% female, 69.6% non-Hispanic White, 13.5% non-Hispanic Black, 6.5% Asian, and 4.6% Hispanic. Postintervention, 46.7% of follow-up recommendations were updated by the rules engine. The proportion of patients with a 10-year default follow-up frequency significantly decreased (88.7%-42.8%, P < 0.001). The mean follow-up frequency decreased by 1.9 years (9.3-7.4 years, P < 0.001). Overall likelihood of an updated follow-up date significantly increased (relative risk 5.62, 95% confidence intervals: 5.30-5.95, P < 0.001).

Discussion: An automated rules engine-based tool has the potential to increase the accuracy of colonoscopy follow-up dates recorded in patient EHR. The results emphasize the opportunity for more automated and integrated solutions for updating and maintaining EHR health maintenance activities.

Introduction: We aimed to compare pregnancy outcomes of women with inflammatory bowel disease using biosimilar vs originator infliximab (IFX).

Methods: In a prospective cohort of pregnant women with inflammatory bowel disease, we collected characteristics, medications, pregnancy outcomes, and developmental milestones. We compared outcomes by IFX biosimilar or originator use via bivariate statistics.

Results: A total of 100 pregnant women on originator IFX and 20 on biosimilar IFX were included. There were no differences in pregnancy complications between groups (48% vs 35%, P = 0.29). Infant developmental milestones were comparable at 12 months.

Discussion: Biosimilar IFX is not associated with adverse pregnancy or infant outcomes.

Introduction: A straightforward, reliable, and noninvasive method for predicting the development of liver-related events (LRE) in primary biliary cholangitis (PBC) has not been attained thus far. This study investigated whether serum autotaxin (ATX) could predict LRE in patients with PBC.

Methods: This retrospective multicenter investigation included 190 biopsy-proven untreated patients with PBC. All subjects were followed for at least 1 year, during which time the prevalence of LRE, including newly developing hepatocellular carcinoma, esophagogastric varices, ascites, and hepatic encephalopathy, was investigated in relation with ATX levels at the time of liver biopsy.

Results: During the median follow-up period of 9.7 years, LRE were observed in 22 patients (11.6%). The area under the receiver operating characteristic curve and cutoff value of serum ATX for predicting LRE were 0.80 and 1.086 mg/L, respectively. Patients with serum ATX ≥1.086 had a significantly higher cumulative incidence of LRE compared with patients with ATX < 1.086 (33.3% vs 3.6%, P < 0.00001). Notably, the predictive capability of ATX for LRE in patients with PBC surpassed that of FIB-4, ALBI, APRI, and Mac-2-binding protein glycan isomer. A multivariate Cox proportional hazards model revealed ATX as an independent associated factor for LRE (hazard ratio 6.24, 95% confidence interval 1.87-20.80, P = 0.003) along with Nakanuma stage (hazard ratio 2.75, 95% confidence interval 1.52-4.99, P < 0.001). These results were closely replicated in a serologically diagnosed PBC validation cohort (n = 32).

Discussion: Serum ATX levels may serve as a predictive marker for LRE in patients with PBC.