Clinical and Translational Gastroenterology最新文献

Background: Opioids are used to treat pain in chronic pancreatitis (CP), but little is known about current use patterns. The aims of this study were to characterize the utilization of opioids, and associations with clinical characteristics in adult patients with CP.

Methods: This cross-sectional analysis utilized baseline data from participants with definite CP enrolled in a cohort study in the US (PROCEED). Data on demographics, pain medication use, health care utilization, disability, and pain patterns were systematically collected in case report forms while quality of life (QOL) was assessed with patient-reported outcome instruments. Opioid use was classified according to strength (weak or strong) and frequency (scheduled or as-needed).

Results: A total of 681 participants (n=364, 53% male) were included: 299 (44%) were current opioid users (22% only weak opioids and 22% at least one strong opioid). Increasing frequency and severity of pain was associated with increase of weak, strong, as-needed, or scheduled opioids. Neuromodulators were used by ∼40% of participants; increasing use was associated with increasing frequency and severity of pain. On multivariate analysis, independent predictors associated with strength and frequency of current opioid use were pain patterns (ORs 1.84-8.32 and ORs 1.92-8.52, respectively, p<0.001) and prior celiac plexus block (OR 3.54, 95% CI 1.82-6.87) and (OR 3.42, 95% CI 1.76-6.64), respectively. Participants using opioids had higher prevalence of disability, healthcare utilization and poorer QOL.

Conclusions: Opioid use in CP is common and associated with increased pain severity and constancy. These data provide foundational estimates for future trials that can elucidate the complex interactions between patient factors, pain, and interventions.

Objectives: To assess strategies for optimizing participation of underserved minorities in a blood-based early CRC detection test study (PREEMPT CRC; NCT04369053) at a hospital serving primarily Black patients.

Methods: Culturally sensitive, racially congruent research staff approached patients undergoing average-risk screening colonoscopy. Consent/study procedures were synchronized with clinical appointments. Enrolled and not-enrolled patient characteristics were compared. Recruitment was compared with other study sites.

Results: 247/509 eligible participants enrolled; most identified as Black (88.7%). No baseline characteristics were associated with participation. Recruitment was high compared to other sites (11th centile).

Conclusions: Recruitment barriers for Black individuals can be overcome when easy, culturally sensitive access is facilitated.

Objectives: 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 versus standard management impacted clinical outcomes in a large prospective cohort.

Method: We analyzed patients consecutively admitted to the Los Angeles General Medical Center between June 2015 to November 2022 whose course was richly characterized by capturing more than 100 clinical variables. We inputted this data into the ADAPT system to generate resuscitation fluid recommendations. and compared to 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 (>500cc)- versus adequately (within 500cc) resuscitated with respect to the ADAPT fluid recommendation. Additional outcomes included ICU admission, SIRS at 48 hours, local complications, and pancreatitis severity.

Results: Among the 1083 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%CI 1.06, 7.03]) as well as ICU admission (OR 2.40 [1.41, 4.11]), more than 48 hours of hospital length of stay (OR 1.87 [1.19, 2.94]), SIRS at 48 hours (OR 1.73 [1.08, 2.77]) and local pancreatitis complications (OR 2.93 [1.23, 6.96]).

Conclusions: Adherence to ADAPT fluid recommendations reduces respiratory failure and other adverse outcomes compared to 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 versus 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/day, n=31), high-dose X842 (100 mg/day, n=31), or lansoprazole (30 mg/day, n=30) for 4 weeks. The main efficacy endpoint was the EE healing rate, which was the proportion of patients who achieved endoscopic healing after 4 weeks of treatment.

Results: For ITT 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 PP analysis, the EE healing rates at 4 weeks were 93.6% (29/31), 80.8% (21/26), and 82.1% (23/28) in the three groups, respectively. The EE healing rate did not significantly differ among the three groups in either the ITT (p = 0.2351) or PP (p = 0.3320) analysis. The incidence of drug-related treatment-emergent adverse events (TEAEs) did not differ among groups. No severe drug-related TEAEs occurred in the X842 group.

Conclusions: Our findings confirmed that X842 had efficacy and a favourable safety profile similar to those of lansoprazole. Therefore, X842, a novel P-CAB, 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.

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

Results: Of 23 patients who started treatment, 22 (95.6%) completed follow-up. Bloating severity on IBS-SSS and PAGI-SYM showed reduction in bloating with large effect sizes (Cohen's d of ∼0.8) at the end of treatment, as did VSI bloating-related anxiety. At end of treatment, 16 patients (69.6 %) were IBS-SSS 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 3-month follow-up.

Conclusions: 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.

Background: Lugol's chromoendoscopy (LCE) is valuable, cost-effective, and widely used in early esophageal cancer (EEC) screening, yet it suffers from low compliance due to 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 (RCT), 204 patients were randomized into the DC and No-DC groups. The primary endpoint was the difference in the incidence of positive starch reagent reaction (iodine solution reflux) between the two groups. The secondary endpoints were the comparisons of the incidence of other adverse events following LCE between the two 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 two groups were 1.0% and 9.8% (P =0.005). LCE satisfaction rates were respectively 78.4% and 76.5% in the DC and No-DC groups (P =0.363). 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).

Conclusion: 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 EEC screening.