Clinical and Translational Gastroenterology最新文献

Introduction: Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is an artificial intelligence tool using mathematical algorithms to predict severity and manage fluid resuscitation needs based on the physiologic parameters of individual patients. Our aim was to assess whether adherence to ADAPT fluid recommendations vs standard management impacted clinical outcomes in a large prospective cohort.

Methods: We analyzed patients consecutively admitted to the Los Angeles General Medical Center between June 2015 and November 2022 whose course was richly characterized by capturing more than 100 clinical variables. We inputted these data into the ADAPT system to generate resuscitation fluid recommendations and compared with the actual fluid resuscitation within the first 24 hours from presentation. The primary outcome was the difference in organ failure in those who were over-resuscitated (>500 mL) vs adequately resuscitated (within 500 mL) with respect to the ADAPT fluid recommendation. Additional outcomes included intensive care unit admission, systemic inflammatory response syndrome (SIRS) at 48 hours, local complications, and pancreatitis severity.

Results: Among the 1,083 patients evaluated using ADAPT, 700 were over-resuscitated, 196 were adequately resuscitated, and 187 were under-resuscitated. Adjusting for pancreatitis etiology, gender, and SIRS at admission, over-resuscitation was associated with increased respiratory failure (odd ratio [OR] 2.73, 95% confidence interval [CI] 1.06-7.03) as well as intensive care unit admission (OR 2.40, 1.41-4.11), more than 48 hours of hospital length of stay (OR 1.87, 95% CI 1.19-2.94), SIRS at 48 hours (OR 1.73, 95% CI 1.08-2.77), and local pancreatitis complications (OR 2.93, 95% CI 1.23-6.96).

Discussion: Adherence to ADAPT fluid recommendations reduces respiratory failure and other adverse outcomes compared with conventional fluid resuscitation strategies for acute pancreatitis. This validation study demonstrates the potential role of dynamic machine learning tools in acute pancreatitis management.

Background: Cholelithiasis is influenced by various factors, including genetic elements identified in genome-wide association studies (GWAS), but their biological functions are not fully understood.

Methods: Analyzing data from the Finngen database with 37,041 cholelithiasis cases and 330,903 controls, this study combined SNP data from GTEx v8 and linkage disequilibrium data from the 1000 Genomes Project. Using the TWAS FUSION protocol and SMR analysis, it investigated the relationship between gene expression and cholelithiasis, employing colocalization tests and conditional analyses to explore causality.

Results: The study identified genes associated with cholelithiasis in the liver and whole blood, such as LINC01595, TTC39B, UGT1A3, with several showing colocalization traits. Notably, RP11-378A13.1 and ADAR were significantly associated with the disease in both tissues.

Conclusion: This research provides insights into the genetic underpinnings of cholelithiasis, highlighting the significant role of gene expression in its development. It establishes new gene associations and identifies potential genetic markers for the disease.

Introduction: X842 is a new type of gastric acid-suppressing agent with a rapid onset of action and a long duration of effect. We aim to investigate the efficacy and safety of different doses of X842 vs lansoprazole in the treatment of patients with erosive esophagitis (EE).

Methods: This phase 2 study included 90 patients with EE (Los Angeles grades A-D) who were randomized (1:1:1) to receive oral low-dose X842 (50 mg/d, n = 31), high-dose X842 (100 mg/d, n = 31), or lansoprazole (30 mg/d, n = 30) for 4 weeks. The main efficacy end point was the EE healing rate, which was the proportion of patients who achieved endoscopic healing after 4 weeks of treatment.

Results: For intention-to-treat analysis, the EE healing rates at 4 weeks were 93.6% (29/31), 79.3% (23/29), and 80.0% (24/30) for the X842 50 mg, the X842 100 mg, and the lansoprazole 30 mg groups. For per-protocol analysis, the EE healing rates at 4 weeks were 93.6% (29/31), 80.8% (21/26), and 82.1% (23/28) in the 3 groups, respectively. The EE healing rate did not significantly differ among the 3 groups in either the intention-to-treat ( P = 0.2351) or per-protocol ( P = 0.3320) analysis. The incidence of drug-related treatment-emergent adverse events did not differ among groups. No severe drug-related treatment-emergent adverse events occurred in the X842 group.

Discussion: Our findings confirmed that X842 had efficacy and a favorable safety profile similar to those of lansoprazole. Therefore, X842, a novel potassium-competitive acid blocker, is expected to become a promising therapeutic agent for EE.

Introduction: "Healthcare contact days" is a patient-centered quantitative proxy for time toxicity, which can be informative for liver transplant (LT) decision-making. We aimed to (i) quantify contact days in patients with cirrhosis pre-LT and post-LT and (ii) identify clinical and demographic features associated with contact days.

Methods: Using a national health system database, we calculated healthcare contact days (inpatient, outpatient hospital [e.g. observation], ambulatory, emergency, mental health, other) for patients with cirrhosis before and after LT.

Results: Between 2008 and 2023, 2,708 patients underwent LT (median age 59 years [interquartile range 52-65], 66% male, 68% non-Hispanic White). Total mean contact days were 76.0 (SD, 58.6) 1 year pre-LT, increasing to 92.3 (SD, 63.2) 1 year post-LT, then decreasing to 39.7 (SD, 43.3) and 30.9 (SD, 35.6) 2 years and 3 years post-LT, respectively. The mean inpatient contact days were 33.6 (SD, 47.5) 1 year pre-LT, increasing to 49.6 (SD, 59.1) 1 year post-LT, then decreasing to 11.9 (SD, 32.0) and 6.7 (SD, 19.8) 2 years and 3 years post-LT, respectively. In multivariable analysis, pre-LT contact days were not associated with post-LT days (incidence rate ratio [IRR] 1.00 [1.00-1.00]). Post-LT, female gender (IRR 1.09 [1.03-1.15]), Black race (IRR 1.11 [1.00-1.23]), and pre-LT dialysis (IRR 1.21 [1.10-1.34]) were associated with increased total contact days.

Discussion: Healthcare contact days provide interpretable prognostic information to inform expectations regarding LT for cirrhosis and can be useful for patients, providers, and policymakers alike.

Introduction: Abdominal bloating is a difficult symptom to treat. Hypnotherapy and diaphragmatic intervention have separately shown benefit on bloating in prior work but have not been united into a single intervention. We aimed to obtain data on the potential therapeutic impact of a novel audio-recorded bloating treatment for bloating integrating hypnosis and diaphragmatic breathing, with proposed synergistic effect.

Methods: Patients with nonorganic bowel disorders with predominant bloating symptoms completed a digitally delivered 7-session audio-recorded hypnotherapy program without clinician involvement. The intervention combined bloating-targeted hypnotic suggestions and guided diaphragmatic breathing delivered under hypnosis, and was supplemented with interval self-guided breathing exercises. Participants completed online REDCap assessments at baseline, midtreatment, at end of treatment, and 3-month follow-up, evaluating symptom severity, gastrointestinal symptom-specific anxiety, overall anxiety/depression, and quality of life. Outcomes were assessed in an intention-to-treat manner with repeated measures analysis of variances (ANOVAs) with Bonferroni-adjusted pairwise post hoc tests.

Results: Of 23 patients who started treatment, 22 (95.6%) completed follow-up. Bloating severity on Irritable Bowel Syndrome-Symptom Severity Scale and Patient Assessment of Upper Gastrointestinal Symptom Severity Index showed reduction in bloating with large effect sizes (Cohen d of ∼0.8) at the end of treatment, as did Visceral Sensitivity Index bloating-related anxiety. At the end of treatment, 16 patients (69.6%) were Irritable Bowel Syndrome-Symptom Severity Scale treatment responders (≥30% symptom reduction) on bloating and 17 (73.9%) on overall bowel symptom severity. Anxiety, depression, and quality-of-life scores were unchanged. Outcome measures were fully maintained at the 3-month follow-up.

Discussion: Results suggest the therapeutic utility of a new cost-effective self-administered bloating intervention. A randomized controlled trial is planned to confirm these therapeutic effects.

Introduction: Patients with primary sclerosing cholangitis (PSC) are at increased risk for acute cholangitis. The epidemiological risks for cholangitis are poorly studied despite the high morbidity associated with this infection. This study's aim was to understand the impact of statins on acute cholangitis in PSC.

Methods: This multicenter, retrospective cohort study assessed data from 294 patients with PSC at Stanford Medical Center, Baylor Medical Center, and Valley Medical Center. Clinical factors associated with development of cholangitis were identified using multivariable Cox regression.

Results: The patients were predominantly male (68.7%) with a median age at enrollment of 48 years [IQR: 31.0-60.8]. Fifty patients (17.0%) were prescribed statins. Median follow-up time was 6 years [IQR: 2.0-12.0], in which 29.6% (n=87) developed cholangitis.In multivariable analysis, statins were associated with an 81% reduction in cholangitis (HR 0.19, 95% CI 0.03-0.64). Statins were associated with a lower incidence of cholangitis at 36 months compared with patients not on statin therapy (incidence of 11.9% vs 34.7%, p<0.001). Statins were also associated with increased time-to-stricture (p=0.004), an outcome known to be associated with PSC complications1,2.

Discussion: Statin therapy is associated with reduced risk of cholangitis in PSC, possibly by delaying time to development of a dominant or high-grade strictures. In patients with PSC, use of statin therapy may be a beneficial modality to prevent the development of cholangitis and warrants further investigation.

Introduction: Describing cirrhosis and hepatic encephalopathy (HE) burden over time can inform clinical management and resource allocation. Using healthcare claims data, this observational study examined recent trends in the prevalence of cirrhosis and HE and associated healthcare resource utilization among commercially and Medicare-insured adults in the United States.

Methods: Data from the MarketScan Commercial Claims and Encounters Database and 100% Medicare Research Identifiable Files were analyzed (2007-2020). Annual prevalence of cirrhosis, HE, overt HE (OHE) hospitalizations, and rifaximin ± lactulose use, and costs per hospitalization per year were calculated. Average year-over-year changes in prevalence of cirrhosis, and HE were estimated. Trends were extrapolated to 2030 using ordinary least-squares regression.

Results: From 2007 to 2020, the prevalence of cirrhosis increased by an average of 4.6% year-over-year in the Commercial population and 8.1% in the Medicare population; the prevalence of HE increased by 4.3% and 2.5%, respectively. Rates of OHE hospitalizations decreased from 27.5% to 5.5% (Commercial) and from 26.2% to 9.5% (Medicare), and rates of liver transplantation increased. Average payer costs (Commercial) and provider charges (Medicare) per OHE hospitalization increased (from $40,881 to $77,699 and from $45,913 to $74,894, respectively). Use of rifaximin ± lactulose showed an increasing trend during the observation period, whereas lactulose use declined steadily.

Discussion: The healthcare burden of cirrhosis and HE in the United States is increasing. Trends are projected to continue unless action is taken, such as improving medication access and developing policies addressing the contributing factors.

Introduction: Lugol chromoendoscopy (LCE) is valuable, cost-effective, and widely used in early esophageal cancer screening, yet it suffers from low compliance because of adverse events after LCE. In addition, the reflux of iodine during iodine staining in the upper esophagus brings the risk of bucking and aspiration. We introduced a new model called distance countdown (DC) aimed to reduce reflux during iodine staining in upper esophageal LCE.

Methods: In this randomized controlled trial, 204 patients were randomized into the DC and No-DC groups. The primary end point was the difference in the incidence of positive starch reagent reaction (iodine solution reflux) between the 2 groups. The secondary end points were the comparisons of the incidence of other adverse events after LCE between the 2 groups.

Results: The rate of iodine solution reflux was 1.0% in the DC group and 26.5% in the No-DC group ( P < 0.001). Furthermore, the incidences of bucking between the 2 groups were 1.0% and 9.8% ( P = 0.005). LCE satisfaction rates were 78.4% and 76.5% in the DC and No-DC groups ( P = 0.363), respectively. Concerning symptoms after LCE, incidences of sore throat, pharyngeal discomfort or odor, bitter taste, and heartburn were also reduced in the DC group (all P < 0.05).

Discussion: Adding DC as an auxiliary effect during LCE would reduce the risk of iodine solution reflux, as well as other adverse events after LCE. Implementing this measure could be beneficial in improving the safety of LCE in early esophageal cancer screening.

Introduction: Neutrophil-to-lymphocyte ratio (NLR) is a novel biomarker studied in several autoimmune diseases including inflammatory bowel disease (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 prospective inception cohort including patients < 18 years old with baseline data from 2013 to 2022. We excluded patients with concurrent diseases affecting NLR. Both Mayo endoscopic score (MES) and simple endoscopic scale for Crohn's disease (SES-CD) were dichotomized as low activity (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: A total of 580 patients with ulcerative colitis and 1,081 patients with CD were included. High NLR was associated with high-activity MES and SES-CD in both univariate and multivariable analyses (odds ratio = 1.45, 95% CI = 1.07-1.97, P value = 0.016; and odds ratio = 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%, area under the curve [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 ulcerative colitis or CD.

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

Introduction: Delayed postpolypectomy bleeding occurs in approximately 1%-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 ≥0.5 cm) 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 [3 g] 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 (relative risk, 0.03; 95% confidence interval, 0.003-0.43; P = 0.009).

Discussion: Colonoscopic spraying of sucralfate powder is a safe approach with potential to reduce the risk of delayed postpolypectomy bleeding. Trial registration: NCT05817656.