American Journal of Gastroenterology最新文献

Background: Rapid symptom control is critical in managing ulcerative colitis (UC), especially in patients with severe disease. While multiple advanced therapies (AT) are approved for moderate to severe UC, data comparing their speed of onset are limited. We compared the onset and induction efficacy of ATs for UC among biologic-naïve patients with severe endoscopic disease (Mayo endoscopic subscore [MES] of 3) and explored differential responses in patients with moderate (MES 2) versus severe endoscopic disease.

Methods: This was a post-hoc analysis using individual participant-level data from 11 randomized controlled trials. Biologic-naïve patients with MES 3 disease receiving standard induction regimens of infliximab, adalimumab, golimumab, vedolizumab, ustekinumab, mirikizumab, tofacitinib, or upadacitinib were included. The primary outcome was early PRO-2 response, defined as ≥50% reduction in stool frequency and rectal bleeding scores at two weeks post-baseline. Secondary outcomes included post-induction clinical remission and PRO-2 remission. Logistic regression models adjusted for baseline covariates were used.

Results: A total of 1781 biologic-naïve patients with MES 3 disease were included. Infliximab (35.1%) and upadacitinib (32.4%) demonstrated the highest early PRO-2 response rates. Compared to placebo, the highest odds of response were observed with upadacitinib [adjusted odds ratio (aOR): 6.38 (95% CI: 2.11-19.23), p=0.001] and infliximab [aOR 4.49 (95% CI: 2.05-9.85), p<0.001]. At post-induction, infliximab (72.2%) and upadacitinib (59.5%) again demonstrated superior PRO-2 response rates. In comparison to MES 2 patients, those with MES 3 had reduced odds of early and post-induction response for several therapies, particularly ustekinumab, tofacitinib, vedolizumab, and mirikizumab.

Conclusions: Among biologic-naïve UC patients with severe endoscopic disease, infliximab and upadacitinib had the highest rates of week 2 and post-induction PRO-2 response. Baseline disease activity may help to better inform treatment choices.

Introduction: Type 2 diabetes mellitus (T2DM) can lead to structural pancreatic changes potentially predisposing to acute pancreatitis (AP), increasing morbidity and mortality. Scarce data exist on the outcomes of AP in patients with T2DM who are taking glucagon-like peptide-1 receptor agonists (GLP-1 RAs). The study aim was to evaluate AP outcome and all-cause mortality in patients with T2DM using GLP-1 RAs.

Methods: A retrospective cohort study was performed using population-based data from the TriNetX platform. Patients with T2DM receiving GLP-1 RAs drugs (semaglutide, liraglutide, dulaglutide, and tirzepatide) between January 1, 2015, and October 31, 2023, were included. This patient cohort was matched with patients with T2DM who did not receive GLP-1 RAs according to age, demographics, comorbidities, and medication by using 1:1 propensity matching. To avoid confounding, etiologies of AP including alcohol-induced, trauma, biliary, class Ia drug-induced, hypertriglyceridemia, and postendoscopic retrograde cholangiopancreatography were excluded from both cohorts. Primary outcomes were risk of developing AP, need for parenteral nutrition, systemic complications (sepsis, systemic inflammatory response syndrome, shock, mechanical ventilation, acute kidney injury), and local pancreatic complications. The secondary outcome was all-cause mortality. Cox proportional hazards models were used to estimate hazard ratios (HRs).

Results: A total of 740,370 patients with T2DM were identified with 29,423 on GLP-1 RAs; 20,459 of those 29,423 (mean [SD] age, 58.1 [11.9] years; 10,190 [49.85%] female) were matched with 20,459 individuals (mean [SD] age, 57.5 [13.9] years; 10,301 [50.35%] female) who did not take GLP-1 RAs. The GLP-1 RAs group had lower risk of complicated pancreatitis (HR 0.32; 95% confidence interval [CI] 0.14-0.74), parenteral nutrition needs (HR 0.28; 95% CI 0.09-0.83), sepsis (HR 0.71; 95% CI 0.59-0.84), acute kidney injury (HR 0.54; 95% CI 0.49-0.60), shock (HR 0.52; 95% CI 0.36-0.75), and mechanical ventilation support during admission (HR 0.23; 95% CI 0.16-0.33) compared with the non-GLP-1 RAs group. In addition, all-cause mortality was decreased in the GLP-1 agonist group compared with the non-GLP-1 agonist group (HR 0.45; 95% CI 0.41-0.49). Important to note that the GLP-1 RAs group had a tendency of lower risk of uncomplicated pancreatitis (HR 0.71; 95% CI 0.49-1.01) but without statistically significant result. No difference was found between the groups in risk of developing systemic inflammatory response syndrome if it occurs.

Discussion: GLP-1 RAs use does not increase AP risk is associated with lower complications in those who developed AP and linked with lower all-cause mortality in patients with T2DM. Prospective studies are needed to determine the mechanisms behind these findings.

Introduction: Owing to the therapeutic ceiling associated with inflammatory bowel disease (IBD) therapies, some patients may require 2 advanced therapeutic agents, known as advanced combination treatment (ACT) to control disease or treat associated extraintestinal manifestations (EIMs).

Methods: We included adult patients with IBD from 9 Canadian centers treated with either 2 biological therapies, a biological plus an oral small molecule, or 2 small molecules. Indications for ACT were the following: (i) refractory IBD, (ii) uncontrolled immune mediated diseases, and (iii) uncontrolled EIMs. Primary outcomes were cumulative rates of clinical and endoscopic response and remission at 6 and 12 months. Secondary outcomes included serious adverse events and infections. Cox-proportional hazard analyses identified independent predictors of treatment effectiveness.

Results: We included 105 IBD patients (76 Crohn's disease, 29 ulcerative colitis) with median age 35 years (Interquartile Range 35.4-40.8). At baseline, 39% had perianal involvement, 58% had failed at least 3 advanced therapies, and 40% had previous surgery. The primary reason for ACT was refractory IBD (63.8%), with the add-on approach used in 97.1% cases. The most frequent combination was antitumor necrosis factor + anti-integrin. At 12 months, cumulative rates of clinical and endoscopic response were 60.0% and 32.4%, respectively, and remission rates were 29.5% and 28.6%. Perianal disease was associated with reduced clinical remission (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.17-0.65, P = 0.001) and endoscopic response (HR = 0.42, 95% CI: 0.12-0.50, P = 0.001). Longer disease duration (HR = 0.96, 95% CI: 0.92-0.99, P = 0.035) and baseline steroid use (HR = 0.39, P = 0.006) was associated with reduced clinical remission. Serious adverse events and infections occurred in 12.4% and 7.6% of patients, respectively.

Discussion: ACT was effective in achieving clinical and endoscopic outcomes in patients with refractory IBD or concomitant immune-mediated diseases/EIMs, with favorable safety profile.

Introduction: We aimed to explore the prevalence of carbohydrate (lactose and fructose) intolerance in patients with disorders of gut-brain interaction (DGBI) and to characterize those patients regarding gastrointestinal and nongastrointestinal symptoms.

Methods: Patients with DGBI who were referred to the physiology unit of our hospital between May 2022 and December 2023 for lactose (25 g) and fructose (25 g) breath tests were prospectively included. Patients were required to have a negative glucose breath test, before lactose and fructose breath tests, and to have completed the adult carbohydrate perception questionnaire during each breath test. Intolerance was defined as an increase of ≥20 mm in the Visual Analog Scale score from baseline in at least 1 of the 5 symptoms (pain, nausea, bloating, flatulence, and diarrhea) assessed with the adult Carbohydrate Perception Questionnaire.

Results: Among the 301 patients with DGBI included in our analysis, 178 (59.1%) had carbohydrate intolerance. Carbohydrate-intolerant patients were significantly more likely to be female ( P value < 0.001), to have 2 or more DGBI ( P value = 0.001), to have lactose maldigestion ( P value< 0.001) and fructose malabsorption ( P value = 0.023), higher irritable bowel syndrome and somatic symptom severity, and lower quality of life ( P value < 0.001) compared with patients without carbohydrate intolerance. The binary logistic regression showed that lactose maldigestion ( P value = 0.001), as well as somatic symptoms ( P value = 0.025), were independently associated with carbohydrate intolerance (Nagelkerke R Square = 0.206).

Discussion: Carbohydrate intolerance affects a substantial group of patients with DGBI, affecting their quality of life and symptom severity. Further research is needed to explore the underlying mechanisms in patients who do not have carbohydrate malabsorption/maldigestion.

Introduction: The term laryngopharyngeal reflux (LPR) is frequently applied to aerodigestive symptoms despite lack of objective reflux evidence. The aim of this initiative was to develop a modern care paradigm for LPR supported by otolaryngology and gastroenterology disciplines.

Methods: A 28-member international interdisciplinary working group developed practical statements within the following domains: definition/terminology, initial diagnostic evaluation, reflux monitoring, therapeutic trials, behavioral factors and therapy, and risk stratification. Literature reviews guided statement development and were presented at virtual/in-person meetings. Each statement underwent 2 or more rounds of voting per the RAND Appropriateness Method; statements reaching appropriateness with ≥80% agreement are included as recommendations.

Results: The term laryngopharyngeal symptoms (LPS) applies to aerodigestive symptoms with potential to be induced by reflux and include cough, voice change, throat clearing, excess throat phlegm, and throat pain. Laryngopharyngeal reflux disease (LPRD) refers to patients with LPS and objective evidence of reflux. Importantly, the presence of LPS does not equate to LPRD. Laryngoscopy has value in assessing for nonreflux laryngopharyngeal processes, but laryngoscopic findings alone cannot diagnose LPRD. LPS patients should be categorized as with or without concurrent esophageal reflux symptoms. While lifestyle modification and empiric trials of acid suppression ± alginates are appropriate when esophageal reflux symptoms coexist, upper endoscopy and ambulatory reflux monitoring are required for LPRD diagnosis when symptoms persist, when LPS is isolated, or when management needs to be escalated to include invasive antireflux management. The two recommended ambulatory reflux monitoring modalities, 24-hour pH-impedance and 96-hour wireless pH monitoring, are not mutually exclusive with distinct roles for the evaluation of LPS. Laryngeal hyperresponsiveness and hypervigilance commonly contribute to both LPS and LPRD presentations and are responsive to laryngeal recalibration therapy and neuromodulators.

Discussion: The San Diego Consensus represents the formal modern-day interdisciplinary care paradigm to evaluate and manage LPS and LPRD.