OBJECTIVE:To evaluate the associations between commonly used antidiabetic regimens and incidence of mild cognitive disorder, Alzheimer disease, and vascular dementia in adults with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS:This retrospective cohort study used the TriNetX US Collaborative Network of electronic health records from 2010 to 2024. Adults aged 40-69 years with type 2 diabetes and at least 1 year of follow-up were included. Propensity score matching was applied to balance covariates. EXPOSURE:Patients were classified into 5 treatment groups: metformin only (reference), metformin plus DPP-4 inhibitors, metformin plus GLP-1 receptor agonists, metformin plus SGLT-2 inhibitors, and insulin monotherapy. Exposure was defined by first recorded prescription and continued use during follow-up. MAIN OUTCOMES AND MEASURES:Primary outcomes were incident mild cognitive disorder, Alzheimer disease, and vascular dementia, identified using ICD-10 codes. Hazard ratios with 95% confidence intervals were estimated from Cox proportional hazards models, with landmark analyses for follow-up shorter and longer than 5 years. RESULTS:Among 1,528,885 adults with type 2 diabetes (mean age, 58 years; 49.2% women), GLP-1 receptor agonists plus metformin were associated with lower incidence of vascular dementia (HR, 0.46; 95% CI, 0.37-0.57), mild cognitive disorder (HR, 0.79; 95% CI, 0.66-0.95), and Alzheimer disease (HR, 0.46; 95% CI, 0.31-0.70). SGLT-2 inhibitors plus metformin reduced vascular dementia risk (HR, 0.68; 95% CI, 0.54-0.87) but not other outcomes. Insulin monotherapy was associated with higher incidence of vascular dementia (HR, 3.27; 95% CI, 3.03-3.52), mild cognitive disorder (HR, 1.71; 95% CI, 1.56-1.87), and Alzheimer disease (HR, 1.56; 95% CI, 1.32-1.84). CONCLUSIONS AND RELEVANCE:GLP-1 receptor agonists and SGLT-2 inhibitors combined with metformin were associated with reduced risk of cognitive decline. Insulin monotherapy was associated with higher incidence of all three outcomes; however, this association is likely influenced by confounding by indication, unmeasured markers of diabetes severity (including diabetes duration, cardiovascular and renal disease severity, and microvascular and macrovascular complications), and shorter follow-up among insulin users, and should not be interpreted as a direct drug effect. Because standard Cox models do not account for death as a competing event, reported hazard ratios reflect cause-specific hazards and may not directly correspond to cumulative incidence, particularly for the insulin group, in which mortality and censoring were substantially higher. Antidiabetic medication choice may influence long-term cognitive outcomes and should be considered in diabetes management.

Background Cyclical Vomiting Syndrome (CVS) poses a significant financial burden on the healthcare system due to frequent emergency department (ED) visits and hospitalizations. Data on the impact of cannabis use in CVS is conflicting.Aims This study evaluates the impact of cannabis use on outcomes in individuals with CVS using real-world data.Methods A retrospective cohort study was conducted using the TriNetX research network to identify adults (>= 18 years) with CVS. Patients were categorized into two groups: CVS with cannabis use and CVS without cannabis use (controls). Using propensity score matching on demographics, body mass index, comorbidities and treatments (e.g., abortive and prophylactic therapy) cohorts were matched 1:1. Outcomes included all-cause ED visits and hospitalizations.Results A total of 18,588 individuals with CVS and cannabis use were matched with 18,588 individuals with CVS who did not use cannabis (controls). Cannabis users were younger (mean age [SD]: 31.9 [12.5] vs. 39.0 [19.9] years) and had higher rates of mood/anxiety disorders, gastroparesis, and substance use. They were more likely to receive abortive therapy and less likely to receive prophylactic therapy. CVS patients who used cannabis had increased rates of ED visits (hazard ratio (HR) = 1.35, 95% confidence interval (CI): 1.31-1.39) and hospitalizations (HR = 1.11, 95% CI: 1.06-1.16) in comparison to those that did not.Conclusions This study is the first using real-world evidence to demonstrate increased risks of ED visits and hospitalizations among individuals with CVS who use cannabis. Cannabis use in this population should be approached with caution due to the increased risk of adverse outcomes and associated financial burden.

OBJECTIVE:To determine whether metabolic risk factors (MRFs), metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are associated with incident mild cognitive impairment (MCI), vascular dementia (VD), and Alzheimer disease (AD). DESIGN:Retrospective cohort study using TriNetX (2003-2023) with Propensity score matching. SETTING:Multicenter, population-based sample from 69 U.S. healthcare organizations in the TriNetX electronic health record. PARTICIPANTS:Adults aged ≥50 years with ≥1 outpatient visit and sufficient clinical/laboratory data. Individuals with prior diagnoses of cognitive impairment, cerebrovascular disease, advanced liver disease, malignancy, schizophrenia, or substance use disorders were excluded. Two matched cohorts were constructed: one with 3,546,833 individuals with MRFs and 3,546,833 healthy controls, and another with 525,844 individuals with MASLD/MASH and 525,844 with MRFs only. Matching was based on age, sex, race, and ethnicity. PRIMARY AND SECONDARY OUTCOME MEASURES:Incident MCI, VD, and AD, identified using ICD-10 codes, assessed at 5-20-year intervals. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using logistic regression. Outcomes were prespecified. RESULTS:Among 7,818,146 participants (mean [SD] age, 64.9 [8.8] years; 52.0% female), individuals with MRFs had higher odds of VD (OR, 1.65; 95% CI, 1.63-1.67), MCI (OR, 1.45; 95% CI, 1.42-1.48), and AD (OR, 1.21; 95% CI, 1.19-1.24) vs healthy controls. Compared to the MRF group, individuals with MASLD/MASH had lower odds of VD (OR, 0.86; 95% CI, 0.83-0.89) and AD (OR, 0.83; 95% CI, 0.78-0.88), but higher odds of MCI (OR, 1.37; 95% CI, 1.30-1.44); all p < .001. CONCLUSIONS:In this large, propensity-matched retrospective cohort study, MRFs were independently associated with significantly increased long-term odds of MCI, VD, and AD. MASLD/MASH demonstrated a divergent cognitive risk profile relative to MRFs alone-characterized by higher odds of MCI but paradoxically lower odds of VD and AD, a pattern that warrants cautious interpretation given potential competing mortality risk, survivor bias, and residual confounding. These findings suggest that MASLD/MASH is associated with a distinct cognitive trajectory, highlighting the importance of early cognitive surveillance in this population.

Background:Although traditionally associated with White European ancestry, inflammatory bowel disease (IBD) has increased among different races and ethnicities. Large studies conducted in the United States and Canada have identified more complex disease phenotypes among Black patients. Our study aimed to investigate disparities in IBD treatments and outcomes between Black and White patients in the United States. Methods:Using the TriNetX database, adult IBD patients were divided into 2 groups based on race: Black and White patients with IBD, Crohn's disease (CD), or ulcerative colitis (UC). Medical therapy and disease outcomes were evaluated in both groups with 1:1 propensity-score matching. Methodologic limitations include the potential for missing data, lack of information on socioeconomic strata, and patient-level medication coverage plans. Results:In comparison to White patients, Black patients with CD were less likely to receive advanced therapies; Adalimumab (adjusted odds ratio- aOR 0.89), Certolizumab (0.81), Vedolizumab (0.66), Ustekinumab (0.82), or Tofacitinib (0.58). Black patients with UC were less likely to receive advanced therapies; Adalimumab (0.83), Golimumab (0.62), Vedolizumab (0.69), Ustekinumab (0.73), or Tofacitinib (0.55). Black patients with IBD were at higher odds of utilizing corticosteroids (CD 1.18 and UC 1.20) and opioids (CD 1.26 and UC 1.09). Black patients with CD had higher rates of hospitalization (1.35) and perianal abscess (1.56), perianal fistula (1.28), and intestinal fistula (1.38). Black patients with UC had higher rates of hospitalization (1.29), Clostridioides difficile infection (1.11), and toxic megacolon (1.34). Conclusions:There were racial disparities in IBD medical therapy and disease outcomes. Black IBD patients had lower treatment with advanced therapies, higher opioid and corticosteroid use, and higher IBD-related complications.

Objective: We aimed to assess the hospital frailty risk score on the inpatient mortality, morbidity, and health care resource utilization among endoscopic retrograde cholangiopancreatography (ERCP)-related hospitalizations. Background: Data regarding the inpatient mortality, morbidity, and health care resource utilization of ERCP among frail individuals remain limited. Materials and Methods: Using the Nationwide Inpatient Sample, we compared the odds of inpatient mortality and morbidity of ERCP-related hospitalizations among individuals with low frailty scores, intermediate frailty scores (IFSs), and high frailty scores (HFSs). Results: Overall, 776,025 ERCP-related hospitalizations were recorded from 2016 to 2020. 552,045 had a low frailty score, whereas 217,875 had an IFS, and 6105 had an HFS. Frail individuals had a 5-fold increase in mortality [IFS: adjusted odds ratio (aOR) = 4.81, 95% CI: 3.77-6.14; HFS: aOR = 4.62, 95% CI: 2.48-8.63]. An IFS was associated with a 24% increase in post-ERCP pancreatitis (aOR = 1.25, 95% CI: 1.11-1.41), a 3-fold increase in post-ERCP bleeding (aOR = 2.59, 95% CI: 1.82-3.67), and a 2-fold increase in post-ERCP duct perforation (aOR = 1.91, 95% CI: 1.38-2.64). Frail individuals experienced higher odds of in-hospital morbidity, including secondary sepsis, respiratory failure, acute kidney injury, cerebrovascular accidents, deep vein thrombosis, and pulmonary embolism. Conclusions: In summary, our study presents strong evidence in support of using the hospital frailty risk score as an index to predict mortality and morbidity during ERCP-related hospitalizations. Additional caution is warranted in the management of frail individuals undergoing ERCP.

Branched-Chain Amino Acid (BCAA) supplementation has shown benefits in reducing liver cirrhosis complications, improving survival, and potentially lowering hepatocellular carcinoma risk, but evidence on long-term outcomes remains limited. This real-world study evaluates clinical outcomes of liver cirrhosis patients receiving BCAA supplementation. This retrospective cohort study used the TriNetX US Collaborative Network to identify liver cirrhosis patients aged ≥ 18 years, stratified by BCAA supplementation after diagnosis. Propensity score matching (PSM) balanced cohorts by demographics, body mass index, Model for End-Stage Liver Disease (MELD) score components, and baseline history of cirrhosis complications, including hepatic encephalopathy (HE), sarcopenia, spontaneous bacterial peritonitis (SBP), acute kidney injury (AKI), and falls. Composite and individual outcomes within 5 years were assessed using odds ratios (OR) with 95

INTRODUCTION:Cannabinoids are being explored as potential treatments for gastroparesis due to their anti-emetic, gastric motility modulation, appetite stimulation, and analgesic properties coupled with their increasing use due to legalization in many states. Although these theoretical benefits are promising, clinical evidence remains limited. This study aimed to evaluate the effects of cannabis use on clinical outcomes and healthcare utilization in patients with gastroparesis using large-scale real-world data. METHODS:We conducted a cohort study using the TriNetX research network to identify US adults (≥18 years) with gastroparesis. From an initial cohort of 119 million individuals patients were stratified into cannabis users and non-users (controls). Propensity score matching (1:1) accounted for demographics, body mass index, comorbidities, laboratory parameters, and treatments. Primary outcomes included emergency department visits, hospitalizations, and esophagogastroduodenoscopy rates. RESULTS:Among 41,374 patients with gastroparesis, cannabis users (n = 20,687) and non-users (n = 20,687) were propensity-matched. Cannabis users were younger with higher rates of diabetes, mood/anxiety disorders, elevated hemoglobin A1c, and opioid use ( P < 0.001). Cannabis use was associated with increased emergency department visits (adjusted odds ratio [aOR] = 1.73, 95% confidence interval [CI]: 1.66-1.80) and hospitalizations (aOR = 1.44, 95% CI: 1.39-1.50) but reduced esophagogastroduodenoscopy utilization (aOR = 0.93, 95% CI: 0.88-0.98). DISCUSSION:Cannabis use in patients with gastroparesis seems to increase healthcare utilization. These findings underscore the need to carefully assess the risks and benefits of cannabis in gastroparesis management. Prospective studies are essential to evaluate cannabinoids' efficacy and safety in this context.

OBJECTIVE:We aimed to assess the hospital frailty risk score on the inpatient mortality, morbidity, and health care resource utilization among endoscopic retrograde cholangiopancreatography (ERCP)-related hospitalizations. BACKGROUND:Data regarding the inpatient mortality, morbidity, and health care resource utilization of ERCP among frail individuals remain limited. MATERIALS AND METHODS:Using the Nationwide Inpatient Sample, we compared the odds of inpatient mortality and morbidity of ERCP-related hospitalizations among individuals with low frailty scores, intermediate frailty scores (IFSs), and high frailty scores (HFSs). RESULTS:Overall, 776,025 ERCP-related hospitalizations were recorded from 2016 to 2020. 552,045 had a low frailty score, whereas 217,875 had an IFS, and 6105 had an HFS. Frail individuals had a 5-fold increase in mortality [IFS: adjusted odds ratio (aOR) = 4.81, 95% CI: 3.77-6.14; HFS: aOR = 4.62, 95% CI: 2.48-8.63]. An IFS was associated with a 24% increase in post-ERCP pancreatitis (aOR = 1.25, 95% CI: 1.11-1.41), a 3-fold increase in post-ERCP bleeding (aOR = 2.59, 95% CI: 1.82-3.67), and a 2-fold increase in post-ERCP duct perforation (aOR = 1.91, 95% CI: 1.38-2.64). Frail individuals experienced higher odds of in-hospital morbidity, including secondary sepsis, respiratory failure, acute kidney injury, cerebrovascular accidents, deep vein thrombosis, and pulmonary embolism. CONCLUSIONS:In summary, our study presents strong evidence in support of using the hospital frailty risk score as an index to predict mortality and morbidity during ERCP-related hospitalizations. Additional caution is warranted in the management of frail individuals undergoing ERCP.

INTRODUCTION:Despite the growing recognition of autoimmune hepatitis (AIH)-metabolic dysfunction-associated steatotic liver disease (MASLD) overlap, studies today are limited by small sample sizes. The aim of this study was to investigate the impact of MASLD on the outcomes of patients with AIH using large-scale real world data. METHODS:This cohort study used the TriNetX research network to identify US adults (≥18 years) with AIH. Patients were stratified into those with MASLD (AIH-MASLD cohort) and controls (AIH without MASLD). Propensity score matching (1:1) between AIH-MASLD and controls accounted for demographics, comorbidities, and treatments. Outcomes were classified as short-term (within 1 year after diagnosis) or long-term (within 10 years) outcomes. RESULTS:Among 4,798 records with AIH, 1,440 AIH-MASLD patients were propensity matched with 1,440 controls. AIH-MASLD patients demonstrated reduced 1-year risks of all-cause mortality (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.44-0.98) and immunosuppressive medication use (HR 0.69, 95% CI 0.63-0.76), along with increased 10-year risks of cirrhosis (HR 1.22, 95% CI 1.06-1.40) and hepatocellular carcinoma (HR 2.03, 95% CI 1.09-3.78) compared with controls. DISCUSSION:In summary, our study using real-world evidence showed a significant association between MASLD and worse clinical outcomes in patients with AIH. Future efforts should be targeted toward facilitating early detection and management of MASLD in patients with AIH.