Clinical and Translational Gastroenterology最新文献

Background: Neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker studied in several autoimmune diseases including inflammatory bowel diseases (IBD) in adults, but poorly characterized in pediatric IBD (pIBD). We aimed to primarily investigate the relationship between NLR and pIBD endoscopic disease severity. We also examined whether NLR predicted hospitalization, surgery, and therapy response by 52 weeks.

Methods: We used the Canadian children IBD Network (CIDsCaNN) prospective inception cohort including patients<18 years old with baseline data from 2013-2022. We excluded patients with concurrent diseases affecting NLR. Both Mayo endoscopic score (MES) and simple endoscopic scale for Crohn Diseases (SES-CD) were dichotomized as low (quiescent-mild), and high activity (moderate-severe). For therapy responses, we examined year-1 steroid- and biologic-free remission. We used logistic regression for binary outcomes.

Results: 580 UC and 1081 CD patients were included. High NLR was associated with high activity MES and SES-CD in both univariate and multivariable analyses (OR=1.45, 95%CI= 1.07-1.97, p-value=0.016; and OR=1.42, 95%CI= 1.04-1.94, p-value=0.026, respectively). We also calculated the best NLR cutoff point to predict MES (1.90, sensitivity=68%, specificity=67%, AUC=0.67, AUC 95%CI= 0.59-0.74) and SES-CD (2.50, sensitivity=63%, specificity=69%, AUC=0.66, AUC 95%CI= 0.59-0.75) high activity. NLR did not predict therapy response in either UC or CD.

Conclusion: pIBD patients with high baseline NLR are more probable to have worse endoscopic disease at diagnosis. This highlights NLR potential as a reliable non-invasive biomarker of disease activity. The predictive power of NLR is based mostly on neutrophils and the balance between neutrophils and lymphocytes.

Background/aims: Delayed postpolypectomy bleeding occurs in approximately 1% to 2% of all patients undergoing colonoscopic polypectomy, and this rate increases to 6% in patients with large (>2 cm) colon polyps. Sucralfate can protect the mucosa and promote its healing. This study was conducted to investigate whether colonoscopic spraying of sucralfate powder on polypectomy wounds can prevent delayed postoperative bleeding.

Methods: This randomized controlled trial included patients with polyps (size≥0.5cm) who had undergone colonoscopic polypectomy at our hospital between May 2023 and January 2024. After polypectomy, the patients received standard treatment for immediate bleeding. Then, they were randomly allocated to either a sucralfate group (prophylactic spraying of sucralfate powder [3g] on polypectomy wounds) or a control group. All patients were monitored for delayed bleeding within 28 days after colonoscopy.

Results: A total of 160 patients were divided into the sucralfate and control groups (80 per group). The baseline characteristics were balanced between the groups. The rate of delayed postpolypectomy bleeding (0% vs 6.3%, respectively; P=0.029) and postpolypectomy overt bloody stool (2.4% vs 18.8%, respectively; P=0.001) were lower in the sucralfate group than in the control group. The duration of freedom from delayed bleeding was longer in the sucralfate group than in the control group (P=0.024). Multivariate Cox regression analysis confirmed the additional sucralfate spray as an independent factor against postpolypectomy overt bloody stool (RR, 0.03; 95% CI, 0.003-0.43; P=0.009).

Conclusion: Colonoscopic spraying of sucralfate powder is a safe approach with potential to reduce the risk of delayed postpolypectomy bleeding.

Bile acid diarrhea (BAD) is a chronic and socially debilitating disease characterized by abdominal pain, diarrhea, urgency, and fecal incontinence. Recently, in a 6-week randomized controlled trial, we showed that the glucagon-like peptide 1 receptor agonist (GLP-1RA) liraglutide is superior to bile acid sequestration (considered standard-of-care) using colesevelam in reducing BAD symptoms. The emergence of new, more potent, and longer-acting GLP-1RAs has spurred an interest in these treatments in BAD management. Here, we review the literature on different GLP-1RAs in BAD treatment and outline their potential mode of actions, highlight knowledge gaps, and outline the need for further clinical evidence generation.

Background: Classical-like Ehlers Danlos Syndrome type 1 (clEDS1) is a very rare form of Ehlers Danlos Syndrome (EDS) caused by tenascin-X (TNX) deficiency, with only 56 individuals reported. TNX is an extracellular matrix protein needed for collagen stability. Previous publications propose that individuals with clEDS1 might be at risk for gastrointestinal (GI) tract perforations and/or tracheal ruptures.

Aim: To characterize complications resulting from perforations of the GI tract and/or tracheal rupture in an international case series of individuals with clEDS1 due to disease-related tissue fragility.

Methods: This case series includes individuals with confirmed clEDS1 and GI perforations and/or tracheal ruptures from participating centres. Researchers who previously reported such individuals were contacted for additional information. A retrospective assessment of clinical features was performed.

Results: Fifteen individuals were included. Ten had spontaneous GI perforations, seven of whom had multiple GI perforations. Almost all had severe diverticulosis. Three individuals experienced iatrogenic tracheal ruptures.

Conclusion: Severe GI complications, such as perforation, and tracheal rupture were observed in a substantial number of individuals with clEDS1. As these features seem significantly more common in clEDS1 than in the average population, we advise vigilance during intubation and GI endoscopic interventions of individuals with clEDS1. Routine referrals to clinical geneticists are recommended for patients with symptoms indicative of clEDS1, especially with unexplained GI perforations and connective tissue symptoms. Our findings offer valuable insights for the clinical management of clEDS1 and underscore the importance of specialized care, providing a foundation for improved clinical guidelines and preventive strategies.

Introduction: Disorders of gut-brain interaction, such as functional dyspepsia (FD), are prevalent and challenging conditions. In other gastrointestinal (GI) disorders, individuals from underserved areas (UAs) have difficulty accessing care. Little is known about UA FD patient perspectives of their care, especially in those with limited English proficiency. We aimed to characterize patients' experiences with FD management with the goal of informing future studies targeting disorders of gut-brain interaction management in potentially vulnerable communities residing in UAs.

Methods: Participants meeting FD criteria were identified in 2 community health centers affiliated with a large academic medical center in the Northeastern United States. Semistructured interviews were conducted in English and Spanish. Transcripts were reviewed by a bilingual panel of investigators using the constant comparative method of iterative data acquisition. Psychosocial stressors and GI symptom severity were assessed.

Results: A total of 26 participants were interviewed (12 English-speaking and 14 Spanish-speaking). Broadly, GI symptoms were mild and there was mild-to-moderate psychological distress present. Adverse social determinants of health were highly prevalent. Despite mild symptom severity on objective scales, FD severely affected quality of life and interfered with physical, psychological, and social well-being, including avoidance of certain foods and professional/social situations. Study participants (particularly those with limited English proficiency status) reported difficulty in receiving care. Thematic saturation was achieved.

Discussion: Even when symptoms were mild, interviewees from UAs reported significant FD-related impairment, along with psychological distress. Education interventions targeting FD-related care in UAs should be designed to improve shared decision making in FD, sensitive to the burden of social determinants of health.

Introduction: Disaccharidases produced by the small intestinal brush border facilitate digestion of dietary carbohydrates. If deficient, they can cause carbohydrate malabsorption, resulting in several abdominal symptoms. Our aim was to examine the prevalence of disaccharidase deficiency and correlate this with abdominal symptoms in adult patients with chronic abdominal symptoms.

Methods: In a retrospective study, patients with gas and bloating and normal endoscopy and computed tomography scan were assessed for lactase, sucrase, maltase, palatinase, and glucoamylase activity. Nine common symptoms such as pain, cramping, constipation, belching, bloating, fullness, indigestion, nausea, diarrhea, vomiting, and gas were assessed for their frequency, intensity, and duration using a validated scale, and a total symptom index was calculated and compared. K-means cluster analysis was performed on lactase-deficient and pandeficient patients with deficiency in 3 or more enzymes.

Results: Four hundred ninety-six patients (78.4% female) were enrolled of whom 143 (28.8%) had single enzyme deficiency, 9 (1.8%) had double enzyme deficiency, and 48 (9.7%) were pandeficient. The mean symptom prevalence and its severity were not significantly different between those with or without disaccharidase deficiency. Patients with pandeficiency did not have worse symptoms than those with single or double enzyme deficiency. No single symptom was more prevalent in patients with confirmed enzyme deficiency than those without. Three groups were identified in cluster analysis of pandeficient patients with one group demonstrating significantly lower average symptoms of cramping, indigestion, and nausea.

Discussion: Disaccharidase deficiency is common in adults presenting with gas, bloating, distention, and pain. Because these deficiencies are treatable with enzyme supplements or diet, an evaluation for disaccharidase deficiency should be routinely considered.

Introduction: Vidofludimus calcium (VidoCa) is a dihydroorotate dehydrogenase inhibitor that demonstrated efficacy in immune-related diseases. This study assessed the safety and efficacy of VidoCa in patients with active ulcerative colitis (UC).

Methods: This placebo-controlled, phase 2 trial randomized adults with moderate-to-severe UC to receive once-daily VidoCa (10, 30, or 45 mg) or placebo for 10 weeks (induction); patients with symptomatic remission were rerandomized to VidoCa 10, 30 mg, or placebo once daily for an additional 40 weeks (maintenance). The primary endpoint was clinical remission at week 10. Secondary endpoints included symptomatic remission, endoscopic healing, and symptomatic response. The study is registered with ClinicalTrials.gov (NCT03341962) and EudraCT (2017-003703-22).

Results: Two hundred sixty-three patients were randomized to induction treatment with VidoCa (10 mg [n = 67], 30 mg [n = 66], and 45 mg [n = 66]) or placebo (n = 64). Sixteen (14%) patients treated with VidoCa (30 mg or 45 mg) achieved the primary endpoint compared with 8 (14%) with placebo. In patients without concomitant corticosteroids, 7 (12%) treated with VidoCa achieved clinical remission at week 10 vs 1 (4%) with placebo. At week 50, dose-dependent increases in the rate of clinical remission ( P = 0.0358), steroid-free clinical remission, and endoscopic healing were observed. Common adverse events (AEs) were headache (4 [6%]), anemia (3 [6%]), vomiting (3 [5%]), and hypertension (3 [5%]) with incidence similar between placebo and VidoCa. Hematuria (4 [6%]) was a treatment-related AE with VidoCa 45 mg only. The incidence of serious AEs was low.

Discussion: VidoCa was safe, well-tolerated, and demonstrated proof-of-concept for dihydroorotate dehydrogenase inhibition to treat UC.

Background: Gastrointestinal ultrasound (GIUS) is recommended for monitoring Crohn's disease (CD). GIUS scores are used to quantify CD activity. Among them, IBUS-SAS (International Bowel Ultrasound Segmental Activity Score), BUSS (Bowel Ultrasound Score), Simple-US (Simple Ultrasound Score), and SUS-CD (Simple Ultrasound Score for Crohn's Disease) are most commonly used. This study aimed to compare and correlate the performance of such indicators with endoscopic activity and to calculate interobserver agreement.

Methods: Consecutive CD patients at our hospital between June 2015 and July 2021 were retrospectively enrolled. All patients underwent ileocolonoscopy after medical treatment. GIUS was performed within 2 weeks and four GIUS scores were independently calculated. Receiver operating characteristic (ROC) curve analyses were used to determine a cut-off value. Cohen's kappa(κ) coefficient was calculated to estimate the agreement between GIUS findings.

Results: A total of 106 CD patients were enrolled. 80.2% (85/106) were endoscopic active (SES-CD≥3), and 8.49% (9/106) were severe cases (SES-CD≥9). All GIUS features (bowel wall thickness, color doppler signs, bowel wall stratification, inflammatory signals at the mesentery) were statistically significant in assessing CD activity (p<0.05). IBUS-SAS showed the highest AUC (0.98; 95% CI:0.96-1.00) and specificity (95.2%) for a cut-off value of 46.50. However, IBUS-SAS had only moderate agreement (Cohen's κ=0.427; p<0.001). BUSS had substantial interobserver agreement (Cohen's κ=0.947; p< 0.001), with a similar diagnostic value [sensitivity, 100.0%; accuracy, 95.3%; AUC of 0.96(95% CI:0.91-1.00) for a cut-off value of 4.58].

Conclusions: GIUS score is an efficient and reliable method to assess CD activity. BUSS achieved a high accuracy and excellent interobserver agreement, which is more suitable for treatment assessment.

Introduction: Our study aimed to explore whether hepatitis B surface antigen (HBsAg) levels affected the role of nucleot(s)ide analog treatment (entecavir [ETV] and tenofovir disoproxil fumarate [TDF]) in improving the prognosis of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) after liver resection.

Methods: A total of 865 patients with HBV-related HCC after hepatectomy treated with TDF or ETV were included in our study. Patients were divided into the high HBsAg cohort (n = 681) and the low HBsAg cohort (n = 184). Propensity score matching (PSM) analysis was used to reduce the impact of potential confounding factors. Kaplan-Meier method and competing risk analysis were used to compare the survival outcomes.

Results: In the high HBsAg cohort, patients in the TDF group had better recurrence-free survival (RFS) and overall survival (OS) compared with patients in the ETV group both before (RFS: P < 0.001; OS: P < 0.001) and after (RFS: P = 0.005; OS: P = 0.035) PSM. TDF treatment was a favorable factor independently associated with RFS (hazard ratio: 0.58, 95% confidence interval: 0.45-0.75, P < 0.001) and OS (hazard ratio: 0.43, 95% confidence interval: 0.28-0.66, P < 0.001). In the low HBsAg cohort, no difference was observed in RFS and OS between the TDF group and the ETV group both before (RFS: P = 0.140; OS: P = 0.640) and after (RFS: P = 0.480; OS: P = 0.920) PSM. TDF treatment remained superiority after controlling for competing events by competing risk analysis in the high HBsAg cohort.

Discussion: TDF treatment was superior to ETV treatment in improving RFS and OS of HBV-related HCC patients with high HBsAg level after liver resection. Even after controlling for survival competing events, the advantage of TDF treatment remained. Our findings may better help clinicians to assign individualized antiviral regimens to patients with HBV-related HCC after liver resection.

Introduction: Pediatric Crohn's disease (CD) easily progresses to an active disease compared with adult CD, making it important to predict and minimize CD relapses. However, prediction of relapse at various time points (TPs) during pediatric CD remains understudied. We aimed to develop a real-time aggregated model to predict pediatric CD relapse in different TPs and time windows (TWs).

Methods: This retrospective study was conducted on children diagnosed with CD between 2015 and 2022 at Severance Hospital. Laboratory test results and demographic data were collected starting at 3 months after diagnosis, and cohorts were formed using data from 6 different TPs at 1-month intervals. Relapse-defined as a pediatric CD activity index ≥ 30 points-was predicted, and TWs were 3-7 months with 1-month intervals. The feature importance of the variables in each setting was determined.

Results: Data from 180 patients were used to construct cohorts corresponding to the TPs. We identified the optimal TP and TW to reliably predict pediatric CD relapse with an area under the receiver operating characteristic curve score of 0.89 when predicting with a 3-month TW at a 3-month TP. Variables such as C-reactive protein levels and lymphocyte fraction were found to be important factors.

Discussion: We developed a time-aggregated model to predict pediatric CD relapse in multiple TPs and TWs. This model identified important variables that predicted relapse in pediatric CD to support real-time clinical decision making.