Clinical and Translational Gastroenterology最新文献

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant contributor to morbidity and mortality, linked to adverse cardiovascular outcomes. While extensive research highlights the cardiovascular burden in non-lean MASLD, lean MASLD remains comparatively understudied. To address this gap, our study evaluates cardiovascular outcomes in lean MASLD compared to non-lean MASLD.

Methods: This is a retrospective cohort study of patients with MASLD identified in the multi-institutional database, TriNetX. Lean MASLD was defined as a BMI <25 kg/m2. Leveraging 1:1 propensity score matching, we balanced baseline characteristics, including age, gender, comorbidities, laboratory values, and medication use. Cox proportional hazards models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular events, cerebrovascular outcomes, new onset heart failure, and all-cause mortality over 1-, 3-, 5-, and 7-year follow-up.

Results: After matching, there were 67,519 patients in both groups. At 7-year follow-up, lean patients with MASLD demonstrated significantly higher rates of new onset heart failure compared to non-lean patients with MASLD (HR: 1.23 (95% CI: 1.16-1.31, p<0.0001), composite cardiovascular events (HR: 1.21 (95% CI: 1.13-1.30, p<0.0001)), cerebrovascular events (HR: 1.33 (95% CI: 1.24-1.43, p<0.0001)), and all-cause mortality (HR: 1.48 (95% CI: 1.38-1.59, p<0.0001)). These increased risks were noted at 1-, 3-, and 5-year follow-up.

Conclusion: Patients with lean MASLD are at significantly higher risks of cardiovascular events and all-cause mortality compared to non-lean patients with MASLD. Further research is needed to clarify the underlying pathophysiology and develop tailored interventions to improve outcomes for this growing population.

Abstract: Gastric varices present a unique therapeutic challenge for endoscopists. While the use of direct endoscopic cyanoacrylate glue injection is superior to band ligation, it carries a risk of systemic adverse events. This led to the development of endoscopic ultrasound (EUS)-guided therapy. EUS enables accurate measurement and targeting of vessels, allowing for the precise intravascular delivery of cyanoacrylate and/or coils. Doppler imaging can be used to confirm obliteration in real time. In this review, we highlight recent literature on varying embolization techniques and detail the technical considerations required for a successful EUS-guided approach.

Introduction: Pancreatic cancer is among the most aggressive malignancies, with a 5-year survival rate of 10%. Most patients present with advanced disease, limiting curative treatment options. Endoscopic ultrasound with fine-needle biopsy (EUS-FNB) is the standard for diagnosis and staging. While early access to EUS may enable timely systemic therapy and improve resectability; uncertainty remains regarding how delays to EUS impact surgical resection rates and overall survival, particularly in older adults. We aimed to identify factors associated with delayed EUS and to evaluate its impact on surgical resection and overall survival.

Methods: Using national Medicare claims (2011-2020), we conducted a retrospective cohort study of beneficiaries aged ≥66 years with newly diagnosed pancreatic cancer The index date was the most recent claim for a pancreatic lesion or abnormal liver enzymes, serving as the indicator for EUS referral. Delay to EUS was defined as >30 days between the index date and the EUS procedure. Multivariable logistic regression identified sociodemographic and clinical factors associated with delayed EUS. Cox proportional hazards models estimated the associations between delayed EUS and two outcomes: (1) pancreatic surgical resection and (2) all-cause mortality.

Results: Among 2,843 patients, 586 (20.6%) experienced a delay in EUS, 774 (27.2%) underwent surgery, and 1,591 (56.0%) died. Black patients were more likely to experience delay (aOR 1.65, 95%CI 1.09-2.51), while those with more comorbidities were less likely (aOR 0.95, 95%CI 0.90-0.99). Delayed EUS was associated with a lower likelihood of surgery (HR 0.73, 95%CI 0.61-0.88) but lower mortality (HR 0.58, 95%CI 0.50-0.66). Mortality increased with older age (HR 1.43, 95%CI 1.27-1.61) and comorbidity (HR 1.04, 95%CI 1.02-1.07).

Conclusions: Timely EUS was associated with higher surgical resection rates, suggesting earlier access to curative treatment. Lower mortality among patients with delayed EUS possibly reflects disease severity confounding rather than benefit.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of chronic liver disease, yet extra-metabolic contributors such as oral health remain underexplored. While periodontitis has been linked to NAFLD, untreated caries and unmet dental care needs have been less examined under new MASLD criteria. We evaluated associations between examiner-assessed oral health indicators and MASLD in a nationally representative sample of U.S. adults.

Methods: We analyzed 2,528 adults aged ≥18 years from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) with valid liver transient elastography. MASLD was defined as steatosis (controlled attenuation parameter ≥285 dB/m) plus ≥1 metabolic risk factor. Examined oral health indicators included examiner-assessed need for dental care, decayed teeth, gum disease, and a composite of decayed teeth or gum disease. Survey-weighted logistic regression estimated odds ratios (ORs) adjusted for sociodemographic and behavioral factors.

Results: MASLD prevalence was 38.9%. In fully adjusted models, needing dental care (OR=1.42, 95% CI:1.02-1.95) and having decayed teeth (OR=1.52, 95% CI:1.05-2.20) were associated with higher MASLD odds. After false discovery rate correction, only dental care need remained significant (q=0.043). Sex-stratified analyses revealed pronounced associations in women, who had 91% higher MASLD odds if dental care was needed (OR=1.91, 95% CI:1.18-3.10) and 156% higher odds with decayed teeth (OR=2.56, 95% CI:1.35-4.84). Significant associations were also observed in adults aged 45-59 and ≥60 years.

Conclusions: Unmet dental needs and caries are associated with MASLD, with particularly strong associations observed in women. These findings highlight oral health as a potential marker for MASLD risk and underscore the value of integrated oral-systemic assessments in preventive care.

Background and aims: Calculating detection rates using data from colonoscopies for all indications, rather than screening exams (ADR-S), is simpler and can mitigate gaming by endoscopists. We hypothesized that calculating sessile serrated lesion detection rates (SSLDR-A) using all exams may also be a quality metric for predicting PCCRC risk.

Methods: The cohort included New Hampshire Colonoscopy Registry (NHCR) 115,585 patients with an index colonoscopy. The primary outcome was PCCRC, defined as CRC diagnosed ≥6 months after the index colonoscopy. The exposure variables were endoscopist-specific SSLDR-A (using all exams) and SSLDR-S (using screening exams), stratified into quintiles. Cox regression was used to model the hazard of PCCRC on SSLDR, adjusting for relevant covariates, such as patient age and sex.

Results: There were 177 PCCRCs diagnosed in 115,762 patients with index colonoscopies. Higher SSLDR-A and SSLDR-S rates were associated with lower PCCRC risks (Table 1). After adjusting for covariates, we observed that higher SSLDR-A rates were associated with lower hazard ratios (HR) as compared to the reference group (SSLDR-A:<1.5%; HR=1.0 vs. SSLDR-A:1.5-<3.0%; HR=0.53, 95%CI 0.35-0.79; SSLDR-A:3.0-<5.0%; HR=0.59, 95%CI 0.38-0.92; SSLDR:5.0-<8.0%; HR=0.44, 95%CI 0.28-0.70; and SSLDR:8.0+% HR=0.20, 95%CI 0.08-0.46). The highest quintile of SSLDR-A (8.0%+) (HR=0.20, 95%CI 0.08-0.46) and SSLDR-S (8.0%+)(HR=0.20, 95%CI 0.09-0.44) provided similar protection from PCCRC.

Discussion: These findings demonstrate that colonoscopies performed by endoscopists with higher SSLDR-A are associated with a lower risk of PCCRC, validating SSLDR-A as a quality metric. Furthermore, our data suggest that endoscopists should aim for an SSLDR-A of 6% and have an aspirational SSLDR-A of 8.0% or higher.

Introduction: Reliable biomarkers for the diagnosis of chronic pancreatitis (CP) and pancreatic fibrosis severity are lacking, hindering effective treatment and management. Histologic fibrosis is a hallmark of late-stage CP, but non-invasive methods to evaluate fibrosis progression are limited. We utilized urine proteomics to discover biomarkers that identify patients with CP and predict fibrosis severity.

Methods: We performed a cross-sectional study of 130 total subjects (CP n=50) selected based on clinical criteria in a tertiary care setting. Urine proteomics samples were quantified using data-independent acquisition mass spectrometry. Differential biomarker candidates were identified with false discovery rate (FDR) corrected pairwise comparisons. These proteins were validated with an independent paired urine and plasma sample cohort (n=36). Machine learning was used to develop a protein panel that predicted Ammann scores for patients with histologic fibrosis.

Results: We found 34 proteins consistently differentially expressed between CP and controls in pairwise FDR-controlled tests. Of these, 25 urine proteins outperformed 19 previously suggested CP blood-based biomarkers in an independent validation cohort. Isocitrate dehydrogenase (1DH1), Calcyphosin (CAPS), Synuclein Gamma (SNCG), and Protein S100-P (S100P) all produced receiver operator curve area under the curve (ROC-AUC) values >0.95, while the best plasma marker was Interleukin 2 Receptor Subunit Alpha (IL2RA, ROC-AUC=0.80). A twelve-protein panel of identified markers predicted fibrosis severity with a linear correlation R2 value of 0.61.

Discussion: We identified a panel of proteins that may diagnose CP in children and developed a model to predict pancreatic fibrosis severity, offering promising tools for improving diagnostics and patient care.

Introduction: Limited data exist regarding the portal hypertension progression in cirrhotic patients with variceal bleeding as the initial decompensation event. This study evaluated the impact of sequential endoscopic therapy on long-term clinical outcomes.

Methods: 196 hospitalized cases were included and divided into EV, GOV1, GOV2, and GOV3 groups. Fine-Gray test was used to analyze the cumulative incidence of outcome events. Survival was calculated using the Kaplan-Meier method, and the Cox proportional risk regression model was used for multivariate analysis of factors affecting outcomes.

Results: During a median follow-up period of 104.9 months, distinct cumulative outcomes were observed across esophageal and gastric variceal subtypes. The 1-, 3-, and 5-year cumulative rebleeding rates progressively increased across subtypes: EV (16.2%, 29.7%, 41.9%), GOV1 (18.8%, 39.6%, 45.8%), GOV2 (19.1%, 34.0%, 46.8%), and GOV3 (44.4%, 63.0%, 66.7%) (Gray's test, p=0.009). Corresponding survival rates demonstrated an inverse pattern, declining with longer follow-up: EV (91.9%, 82.4%, 58.1%), GOV1 (91.7%, 79.2%, 60.4%), GOV2 (91.5%, 76.6%, 55.3%), and GOV3 (74.1%, 55.6%, 48.1%) (log-rank test, p=0.016). Rebleeding was an independent risk factor associated with survival (HR: 3.518, p < 0.001). Multivariate analysis showed that CTP score, varices shape, varices type, and the number of endoscopic treatments (whether > 3) were significant risk factors for rebleeding (p < 0.05).

Discussion: In this study, rebleeding dominated the clinical course of different subtypes and was the only independent predictor of death. More aggressive treatments, such as salvage TIPS, should be considered in patients who were at higher risk of rebleeding.

Introduction: Early detection of pancreatic ductal adenocarcinoma (PDAC) improves survival. However, screening recommendations are limited to individuals with hereditary risk, accounting for only 10% of PDAC. We explore the feasibility of developing and validating an electronic health record-based model to identify high-risk individuals for PDAC screening within the asymptomatic general population.

Methods: Using multivariable Cox regression, we developed a diagnostic model to predict time to PDAC within 3 years in the Veterans Health Administration. We evaluated the final model using internal and temporally separate datasets using Akaike Information Criterion, Harrell's c statistic, calibration curves, and sensitivity/specificity corresponding to a 3-year risk screening threshold of 1%.

Results: Among 9,351,261 individuals, 26,119 (0.3%) developed PDAC (107.6 cases per 100,000 person-years) within 3 years. The final model included age, pancreatic cyst, pancreatitis, smoking status, history of a localized solid tumor, race/ethnicity, and BMI. Glucose and albumin values were highly important, in addition to other metabolic, inflammatory, and liver related laboratory values. The c statistic (95% CI) was 0.75 (0.75 - 0.76) in development, 0.75 (0.75 - 0.76) in internal validation, and 0.74 (0.73 - 0.75) in temporal validation. At a three-year risk threshold of 1.0%, 11% of the population would undergo screening, capturing 30% of the PDAC cases.

Discussion: We demonstrate good model discrimination in independent data. Compared to current screening practices targeting only genetically predisposed individuals, its implementation could identify three times as many PDAC cases. However, predictors beyond the EHR may be needed to further improve the feasibility of generalized screening.

Background: This study employed the novel C-reactive protein-albumin-lymphocyte (CALLY) index to explore its relationship with the risk of developing gallstones.

Methods: This study conducted a cross-sectional analysis of the NHANES data from 2017 to 2020, multivariable logistic regression examined the CALLY-gallstone association. Restricted cubic splines (RCS) tested non-linearity. Subgroup and mediation analyses explored population variations and mediating effects (Conicity, LAP, ABSI). Receiver operating characteristic (ROC) curves compared CALLY, SII, SIRI, and AISI predictive performance.

Results: After comprehensive adjustments, the highest CALLY quartile had significantly lower gallstone risk versus the lowest (OR 0.56, 95% CI 0.34-0.94). RCS revealed a linear inverse correlation. Subgroup analyses generally supported this inverse relationship. Mediation analysis identified the Conicity index as the strongest mediator (21.47%, P<0.001), followed by LAP and ABSI (10.72% each, P<0.001). ROC analysis showed CALLY (AUC=0.604) outperformed SII (0.540), SIRI (0.550), and AISI (0.546).

Conclusions: A significant inverse association exists between the CALLY index and gallstone prevalence. The CALLY index demonstrates superior predictive ability compared to other indices, suggesting its potential utility as an objective biomarker for early gallstone risk identification.

Background and aims: Factors associated with decline of hepatic function and increase in portal-systemic shunting, which herald clinical outcome in persons with compensated cirrhosis, are poorly characterized. We used cholate challenge to evaluate the associations of liver disease etiology, concomitant diabetes, and maintenance drug therapy, with the degree of hepatic dysfunction and portal-systemic shunting.

Methods: In the SHUNT-V study there were 255 subjects with compensated (Child-Pugh class A) cirrhosis who underwent cholate challenge, involving oral administration of [2,2,4,4-2H] cholate and measurement of its serum concentrations at 20 and 60 minutes. Test outputs included a disease severity index (DSI) to assess global liver function, and SHUNT% to assess portal systemic shunting.

Results: Eighty-seven percent of subjects were overweight, 65% were obese, 48% had MASLD/MASH, 51% had type II diabetes mellitus (DM), 49% were taking anti-diabetic drugs, and 45% were taking lipid-lowering drugs. Laboratory values and clinical scores of MASLD/MASH subjects were similar to subjects with other etiologies for liver disease. In univariable regression, MASLD/MASH, DM, metformin, and statins were associated with lower DSI and SHUNT%. In multiple regression, lower DSI was attributable to statins (p=0.0354) and metformin (p=0.0561). The combined use of lipid-lowering and anti-diabetic drugs, compared to no use, was associated with 19% reduction in DSI.

Conclusions: Concomitant use of statins alone or in combination with metformin was independently associated with preserved hepatic function (DSI) and reduced portal-systemic shunting (SHUNT%).