The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD)-related advanced fibrosis and cirrhosis in the United States population utilizing AGILE 3 + and AGILE 4 scores: analysis of the NHANES 2017-2018 cycle.

BACKGROUND: Studies attempted to estimate MASLD-related advanced fibrosis (AF) and cirrhosis (MC) prevalence utilized tests with low positive predictive value (PPV) which overestimates prevalence. AGILE3 + and 4 scores were developed to increase the PPV of both; respectively. In this study, we used these scores to assess the prevalence of AF and MC. METHODS: Participants aged ≥ 18 years with VCTE exam in the NHANES 2017-2018 cycle were included. We excluded pregnant women, patients with excessive alcohol intake, hepatitis B/C, and ALT or AST > 500 IU/L. MASLD was defined with CAP score > 248 dB/m. MASLD subjects with AGILE 3 + score of ≥ 0.68 and AGILE 4 score of ≥ 0.57 were considered to have advanced fibrosis and cirrhosis; respectively. AGILE 3 + of 0.45-0.67 and AGILE 4 of 0.25-0.57 were grey zone, whereas AGILE 3 + < 0.45 and AGILE 4 < 0.25 were considered a rule-out. RESULTS: 1244 subjects were included in the final analysis. The Median age was 53 (51.4-54.6) years, 55.6% were male, median BMI was 33.8 kg/m2 and 41.1% had T2DM. Based on AGILE 3+, 80.3% of the MASLD population were at low risk for AF and 11.5% were in grey zone. The prevalence of AF due to MASLD was 8.1% corresponding to 4.5 million Americans. Based on AGILE 4 score, 96.5% of the MASLD population were at low risk for cirrhosis and 2.4% were in the grey zone. The prevalence of MASLD-cirrhosis was 1.1% corresponding to 610,000 Americans. CONCLUSION: Our results suggest that approximately 4.5 million people in the U.S. have AF and 0.6 million have cirrhosis due to MASLD.

ANTIDEPRESSANT MEDICATIONS ARE ASSOCIATED WITH INCREASED RISK OF HOSPITAL-ACQUIRED CLOSTRIDIOIDES DIFFICILE INFECTION: A POPULATION-BASED STUDY.

WHAT IS ALREADY KNOWN: •The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. •Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: •The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. •The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

Medicamentos antidepressivos estão associados a um risco aumentado de infecção hospitalar por Clostridioides difficile: um estudo populacional / Antidepressant medications are associated with increased risk of hospital-acquired clostridioides difficile infection: a population-based study

ABSTRACT Background: During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications. Methods: Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results: The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion: In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

RESUMO Contexto: Na última década, a infecção por Clostridioides difficile (ICD) tornou-se a causa mais comum de diarreia associada a antibióticos. Vários fatores de risco foram implicados. Existem evidências dispersas na literatura sobre a associação da ICD com o uso de medicamentos antidepressivos. Portanto, pretendemos investigar se o risco de desenvolver infecção adquirida na comunidade por Clostridioides difficile aumenta em pacientes que usam medicamentos antidepressivos. Métodos: Pacientes que foram hospitalizados foram incluídos em nossa coorte. Indivíduos com menos de 18 anos foram excluídos. Uma análise de regressão multivariada foi realizada para calcular o risco de ICD, considerando possíveis confusões. Resultados: O risco de ICD em pacientes hospitalizados foi maior em indivíduos diagnosticados com doença inflamatória intestinal (OR: 4,44; IC95%: 4,35-4,52) e em pacientes que usavam clindamicina (OR: 1,55; IC95%: 1,53-1,57), antibióticos beta-lactâmicos (OR: 1,62; IC95%: 1,60-1,64), PPI (OR: 3,27; IC95%: 3,23-3,30), trazodona (OR: 1,31; IC95%: 1,29-1,33), nortriptilina (OR: 1,25; IC95%: 1,21-1,28) e mirtazapina (OR: 2,50; IC95%: 2,46-2,54). Depois de controlar as covariáveis, o risco de ICD não aumentou em pacientes que estavam tomando fluoxetina (OR: 0,94; IC95%: 0,92-0,96). Conclusão: Em contrário à fluoxetina; mirtazapina, nortriptilina e trazodona foram associados a um risco aumentado de ICD em pacientes hospitalizados.

Prevalence of autoimmune, cholestatic and nonalcoholic fatty liver disease in celiac disease.

BACKGROUND: While there is higher prevalence of autoimmune, cholestatic and fatty liver disease in celiac disease (CeD), most data is from small-scale studies. We evaluated the prevalence and risk factors of the same using large cohort data. METHODS: A population-based cross-sectional study was conducted using Explorys, a multi-institutional database. Prevalence and risk factors of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC) and nonalcoholic fatty liver disease (NAFLD) in CeD were assessed. RESULTS: Out of 70 352 325 subjects, 136 735 had CeD (0.19%). The prevalence of AIH (0.32%), PBC (0.15%), PSC (0.004%) and NAFLD (0.7%) were high in CeD. After adjusting for age, gender, Caucasian race and anti-tissue transglutaminase antibody (anti-TTG), CeD subjects had higher odds of AIH [adjusted odds ratio (aOR) 7.06, 95% confidence interval (CI) 6.32-7.89] and PBC (aOR 4.16, 95% CI 3.46-5.0). Even after adjusting for CeD, anti-TTG positivity concurred with higher odds of AIH (aOR 4.79, 95% CI 3.88-5.92) and PBC (aOR 9.22, 95% CI 7.03-12.1). After adjusting for age, gender, Caucasian race, diabetes mellitus (DM), obesity, hypothyroidism and metabolic syndrome, there was higher prevalence of NAFLD in CeD, with the aOR in the presence of DM type 1 being 2.1 (95% CI 1.96-2.25), and in the presence of DM type 2 being 2.92 (95% CI 2.72-3.14). CONCLUSION: Subjects with CeD are more likely to have AIH, PBC, PSC and NAFLD. AIH and PBC have higher odds in the presence of anti-TTG. The odds of NAFLD in CeD are high regardless of type of DM.

Cirrhotic patients on proton pump inhibitors are at a twofold risk of spontaneous bacterial peritonitis independently of gastrointestinal bleeding: a population-based retrospective study.

Background: Recent findings suggest that cirrhotic patients on proton pump inhibitors (PPIs) are at a higher risk for developing spontaneous bacterial peritonitis (SBP) than non-PPI users. We aimed to identify whether PPI use is an independent risk factor for the development of SBP among cirrhotic patients in the United States (US). Methods: We enrolled a retrospective cohort using a validated multicenter database. Patients with a SNOMED-CT diagnosis of "cirrhosis" between 1999 and 2022 were identified. All patients below 18 years of age were excluded. We calculated the prevalence of individuals using PPIs in the total US population and in cirrhotic patients from 1999 to date, and the incidence of SBP in the past year. Finally, we constructed a multivariate regression model, controlling for multiple covariates. Results: The final analysis included 377,420 patients. The 20-year-period prevalence of SBP in patients with cirrhosis was 3.54% and the prevalence of patients using PPIs in the US population was 12,000 per 100,000 people (12.00%). The 1-year incidence of SBP in cirrhotic patients using PPIs was 2500 per 100,000 people. After accounting for confounders, the risk of SBP was higher among males, patients with a diagnosis of gastrointestinal bleeding, and those using ß-blockers and PPIs. Conclusions: To date, this is the largest cohort used to examine the prevalence of SBP among cirrhotic patients in the US. PPI use and hepatic encephalopathy offered the highest risk for the development of SBP, independently of gastrointestinal bleeding. Focusing on judicious PPI use should be encouraged among cirrhotic patients.

Epidemiology and risk of colorectal cancer in patients with a history of Helicobacter pylori infection: a population-based study.

Background: Numerous modifiable risk factors have been associated with colon cancer. Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide and the strongest known risk factor for gastric cancer. We aim to assess whether the risk of colorectal cancer (CRC) is higher in patients with a history of H. pylori infection. Methods: A validated multicenter and research platform database of more than 360 hospitals was queried. Patients aged 18-65 years were included in our cohort. We excluded all patients who had previously had a diagnosis of inflammatory bowel disease or celiac disease. Univariate and multivariate regression analyses were used to calculate CRC risk. Results: A total of 47,714,750 patients were selected after application of the inclusion and exclusion criteria. The 20-year-period prevalence rate of CRC in the United States population from 1999 to September 2022 was 370 of 100,000 individuals (0.37%). According to multivariate analysis, the risk of CRC was higher in smokers (odds ratio [OR] 2.52, 95% confidence interval [CI] 2.47-2.57), obese patients (OR 2.26, 95%CI 2.22-2.30), those with irritable bowel syndrome (OR 2.02, 95%CI 1.94-2.09), or type 2 diabetes mellitus (OR 2.89, 95%CI 2.84-2.95), and patients who had a diagnosis of H. pylori infection (OR 1.89, 95%CI 1.69-2.10). Conclusion: We provide the first evidence from a large population-based study demonstrating an independent association between a history of H. pylori infection and CRC risk.

Non-alcoholic steatohepatitis is independently associated with a history of gestational diabetes mellitus.

BACKGROUND AND AIM: A recent study has demonstrated that women with gestational diabetes mellitus (GDM) are more likely to develop non-alcoholic fatty liver disease than those without GDM. In contrary to non-alcoholic fatty liver, the association of GDM with non-alcoholic steatohepatitis (NASH) has still not been well established in the current literature. Therefore, we aim to evaluate the association of a history of GDM and the development of NASH throughout their lives independently of type 2 diabetes mellitus (T2DM). METHODS: A validated research database of more than 360 hospitals was utilized to construct this study. Adult females included were divided into two groups: those with NASH (case) and individuals without NASH (control). Regression analysis was performed to account for potential cofounders. RESULTS: There were 70 632 640 individuals above the age of 18 years screened in the database. In patients with a history of GDM, NASH was most prevalent in middle age people compared with NASH alone, which was more prevalent in people aged 65 years and above. Compared with those without, patients with NASH tend to be Caucasian (odds ratio [OR]: 2.13), obese (OR: 4.83), have a history of GDM (OR: 1.23), diagnosed with hyperlipidemia (OR: 2.59), T2DM (OR: 4.52), metabolic syndrome (OR: 3.07), polycystic ovaries disease (OR: 1.72), and hypothyroidism (OR: 1.59). CONCLUSION: We demonstrated for the first time an increased odd of developing NASH in women who have had a diagnosis of gestational diabetes mellitus throughout their lives independently of any other factors that could interfere with the results.

Prevalence of non-alcoholic fatty liver disease in patients with nephrotic syndrome: A population-based study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a global health concern with a prevalence of about 25% amongst United States adults. Its increased prevalence is attributed to increase in patients with obesity and metabolic syndrome, partly due to similar mechanisms of injury. Nephrotic syndrome (NS) is a clinical entity resulting from extensive proteinuria leading to hypoalbuminemia, hyperlipidemia, edema, and other complications. Given its association with hyperlipidemia, there is concern that patients with NS may be at increased risk of NAFLD. AIM: To perform a cross-sectional population-based study to investigate the prevalence and risk factors of NAFLD in patients with NS. METHODS: A large multicenter database (Explorys Inc., Cleveland, OH, United States) was utilized for this retrospective cohort study. A cohort of 49700 patients with a diagnosis of "Non-Alcoholic fatty liver disease" using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) between 1999-2022 was identified. Inclusion criteria were age ≥ 18 years, presence of NAFLD, presence of NS. There were no specific exclusion criteria. Univariate and multivariate analysis were performed to adjust for multiple risk factors including age, gender, Caucasian race, NS, type II diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease. Statistical analysis was conducted using R, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. RESULTS: Among the 78734750 individuals screened in this database, there were a total of 49700 subjects with NAFLD. In univariate analysis, the odds of having NAFLD in patients with NS, type 2 diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease were 14.84 [95% confidence interval (95%CI) 13.67-16.10], 17.05 (95%CI 16.78-17.32), 6.99 (95%CI 6.87-7.11), 13.61 (95%CI 13.38-13.84), 19.19 (95%CI 18.89-19.50), 29.09 (95%CI 28.26--29.95), and 9.05 (95%CI 8.88-9.22), respectively. In multivariate analysis, the odds of having NAFLD amongst patients with NS were increased to 1.85 (95%Cl 1.70-2.02), while the odds were also remained high in patients that have type 2 diabetes mellitus [odds ratio (OR) 3.84], hypothyroidism (OR 1.57), obesity (OR 5.10), hyperlipidemia (OR 3.09), metabolic syndrome (OR 3.42) and chronic kidney disease (OR 1.33). CONCLUSION: Patients with NS are frequently found to have NAFLD, even when adjusting for common risk factors. Hence, clinicians should maintain a high index of suspicion regarding presence of NAFLD in patients with NS.

Prevalence and Risk Factors Associated With Inflammatory Bowel Disease in Patients Using Proton-Pump Inhibitors: A Population-Based Study.

Background and aim Proton pump inhibitor (PPI) is a heavily prescribed medication in the United States that is used to treat several gastrointestinal disorders. Although it has been considered to be safe compared to other medications, multiple gastrointestinal side effects have been reported. These effects of PPIs might stem from the progressive alteration of the intestinal microbiome. Patients with inflammatory bowel disease (IBD) using PPI are also seen to be less likely to achieve remission. However, in the current literature, there is very little evidence of the risk of developing IBD in patients who have been using PPIs. Therefore, our aim was to perform a cross-sectional population-based study with in-depth analysis to assess the prevalence and risk factors of IBD amongst PPI users in the United States. Methodology  A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. A cohort of patients with a diagnosis of ulcerative colitis (UC) and Crohn's disease (CD) between 1999-2022 was identified using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). Patients aged 18 to 65 years were included. We excluded any individual who had a diagnosis of chronic liver disease, autoimmune disease (excluding IBD), or cancer. The risk of IBD was calculated using a multivariate regression analysis to account for potential confounders including non-steroidal anti-inflammatory drugs (NSAIDs) use, smoking, patients who have had a diagnosis of alcoholism, gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and metabolic syndrome. A two-sided P-value <0.05 was considered statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). Results  A total of 79,984,328 individuals were screened in the database and 45,586,150 patients were selected in the final analysis after accounting for inclusion and exclusion criteria. Using multivariate regression analysis, the risk of developing UC and CD was calculated. The odds of having UC amongst patients on PPI was 2.02 (95%CI 1.98-2.06), P-value <0.001. Similarly, the odds of having CD were high amongst PPI users (OR 2.79, 95%CI 2.75-2.84), P- value <0.001 Conclusion  Our study demonstrates that patients on PPIs are frequently found to have UC and CD even when adjusting for common risk factors. Hence, we urge clinicians to be aware of this association in order to limit unnecessary prescriptions of PPIs, especially for patients who are at risk for autoimmune diseases.

Epidemiology and prevalence of lean nonalcoholic fatty liver disease and associated cirrhosis, hepatocellular carcinoma, and cardiovascular outcomes in the United States: a population-based study and review of literature.

BACKGROUNDS: Nonalcoholic fatty liver disease (NAFLD) is linked to obesity and metabolic syndrome conditions. However, a subset of NAFLD patients express a normal or low body mass index (lean NAFLD [L-NAFLD]). Our aim is to compare the prevalence of L-NAFLD to the obesity-associated NAFLD in the United States by assessing prevalence, potential risk factors, liver-related complications, and coronary artery disease outcomes. METHODOLOGY: A multicenter database (Explorys Inc.) of >70 million patients across the United States was screened. A cohort of patients with "nonalcoholic fatty liver" between 1999 and 2021 was identified. Two sub-cohorts of NAFLD patients were identified: those with a body mass index (BMI) < 25 kg/m2 (L-NAFLD) and those with a BMI > 30 kg/m2 (obesity-associated NAFLD). We excluded patients with age <18 and those who have viral hepatitis, hemochromatosis, Wilson's disease, biliary cirrhosis, alcoholic liver disease, cystic fibrosis, alpha-1-antitrypsin deficiency, and autoimmune hepatitis. Multivariate analysis was performed to adjust for confounders. RESULTS: 68 892 260 individuals were screened. NAFLD prevalence was four per 100 000, and L-NAFLD prevalence was 0.6 per 100 000. Compared with those without, patients with L-NAFLD tended to be older (OR 2.16), females (OR 1.28), and smokers (OR 4.67) and of Asian race (OR 2.12). L-NAFLD patients were more likely to have acute coronary syndromes (OR 30.00) and metabolic syndrome (OR 2.31) despite the normal/low BMI. Esophageal varices and hepatocellular carcinoma risks were high in both cirrhosis patients. CONCLUSION: This is the largest study to assess L-NAFLD prevalence in the United States. L-NAFLD are at a significantly higher risk for acute coronary syndromes, esophageal varices, and hepatocellular carcinoma.

The Natural Course of Pancreatic Cysts in Inflammatory Bowel Disease: Results of a Long-term Follow-up.

OBJECTIVES: The natural course of pancreatic cysts in inflammatory bowel disease (IBD) is unknown. We aim to describe the natural course of pancreatic cysts in IBD and evaluate long-term outcomes. METHODS: A database of patients with abdominal imaging diagnosis of pancreatic cysts (2008-2019) was reviewed. Patients with IBD and pancreatic cysts (study group) and pancreatic cysts without IBD (controls) were selected. Outcomes were measured at 1, 3, 5, and 10 years. Several logistic regression models were used for analysis. RESULTS: Of the 1789 patients evaluated, 1690 had pancreatic cysts without IBD, and 78 had IBD and pancreatic cysts. Majority of cysts were intraductal papillary mucinous neoplasms. Patients with IBD and pancreatic cysts were more likely to be diagnosed with pancreatic cysts at a younger age (P < 0.001) and were more likely to undergo surgical intervention at a younger age (P < 0.001). CONCLUSIONS: This is the first study to evaluate the natural course of pancreatic cysts in IBD patients. Patients with IBD were more likely to have pancreatic cysts detected at a younger age. Despite the early presentation, there were no differences in long-term outcomes. Patients with IBD with pancreatic cysts should be managed similarly to those without IBD.

The prevalence of alcoholic and nonalcoholic fatty liver disease in adolescents and young adults in the United States: analysis of the NHANES database.

BACKGROUND: The prevalence of fatty liver disease is potentially increasing in adolescents and young adults (AYAs) due to the obesity and alcohol pandemics. The aim of this study was to assess the prevalence of alcohol-associated fatty liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) in a representative U.S. cohort utilizing transient elastography to directly measure hepatic steatosis and suspected fibrosis. METHODS: AYAs (age 15-39 years) with valid FibroScan® measurements in the National Health and Nutrition Examination Survey (NHANES) database (2017-2018) were included in the analyses. Those with viral hepatitis, pregnancy, or ALT/AST > 500 U/L were excluded. The population was divided into those with excessive alcohol consumption (ALQ130) and those without. Controlled attenuation parameter (CAP) score ≥ 248 dB/m was used to identify suspected ALD and NAFLD. In those with evidence of ALD, the following cutoffs of liver stiffness measurement (LSM) were used for suspected fibrosis: F ≥ F2 at LSM ≥ 7.5 kPa and F ≥ F3 at ≥ 9.5 kPa, respectively. In those with suspected NAFLD, the following LSM cutoffs were used: F ≥ F2 at 6.1 and F ≥ F3 at ≥ 7.1, respectively. Cutoffs were chosen based on published literature to maximize sensitivity. RESULTS: Comparing to those without, subjects with excessive alcohol consumption tended to be older (29.8 vs 28.5 years), have a higher BMI (29.3 vs 28.9 kg/m2), and be from a White ethnicity (65.3% vs. 55.4%). In subjects with excessive alcohol consumption, suspected ALD was present in 56.59% (95% CI 41.57-70.49). In those with suspected ALD, suspected significant fibrosis (F ≥ F2) was present in 12.3% (95% CI 4.74-28.34) and advanced fibrosis (F ≥ F3) was present in 6.31% (95% CI 0.69-39.55). Similarly, in subjects without excessive alcohol consumption, suspected NAFLD was present in 40.04% (36.64-43.54). In those with suspected NAFLD, suspected significant fibrosis (F ≥ F2) was present in 31.07% (27.25-35.16) and suspected advanced fibrosis (F ≥ F3) was present in 20.15% (16.05-24.99). CONCLUSION: A significant percentage of AYAs are at risk for ALD and NAFLD and a subset of these subjects is at risk for significant fibrosis. Efforts should focus on increasing awareness of the prevalence of ALD and NAFLD in this population and to mitigate modifiable risk factors.

Prevalence of hypothyroidism and effect of thyroid hormone replacement therapy in patients with non-alcoholic fatty liver disease: A population-based study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is currently considered as the most common cause of chronic liver disease worldwide. Risk factors for NAFLD have been well-described, including obesity, type 2 diabetes mellites (T2DM), dyslipidemia (DLP) and metabolic syndrome. Hypothyroidism has been identified as an independent risk factor for the development of NAFLD, although the literature is inconsistent. AIM: To evaluate the prevalence of hypothyroidism in patients with NAFLD, assess if it is an independent risk factor and explore the effect of thyroxine replacement therapy. METHODS: Our cohort's data was obtained using a validated, large, multicenter database (Explorys Inc, Cleveland, OH, United States) aggregated from pooled outpatient and inpatient records of 26 different healthcare systems, consisting of a total of 360 hospitals in the United States, and utilizing Systematized Nomenclature of Medicine-Clinical Terms for coding. We evaluated a cohort of patients with hypothyroidism and NAFLD. Multivariate analysis was performed to adjust for confounding risk factors including hypertension (HTN), T2DM, DLP, obesity and metabolic syndrome. SPSS version 25, IBM Corp was used for statistical analysis, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant. Exclusion criteria were limited to age < 18 years. RESULTS: Among the 37648180 included individuals in this database who are above the age of 18 years, there were a total of 2320 patients with NAFLD (6.16 per 100000) in the last five years (2015-2020), amongst which 520 patients (22.4%) had hypothyroidism. Baseline characteristics of patients in this database are described in Table 1. Patients with NAFLD were also more likely to have obesity, T2DM, DLP, HTN, and metabolic syndrome (Table 2). While males and females were equally affected, patients in the age group 18-65 years as well as Caucasians seem to be at a higher risk. There was an increased risk of NAFLD among patients with hypothyroidism (OR = 1.587). Furthermore, thyroid hormone replacement was not associated with a decreased risk for developing NAFLD (OR = 1.106, C = 0.952-1.285, P = 0.303). CONCLUSION: Hypothyroidism seems to be an independent risk factor for the development of NAFLD. Thyroid hormone replacement did not provide a statistically significant risk reduction. Further studies are needed to evaluate the effect of thyroid hormone replacement and assess if being euthyroid while on thyroid replacement therapy affects development and/or progression of NAFLD.

Patients With Inflammatory Bowel Disease on Treatment Have Lower Rates of Celiac Disease.

BACKGROUND: The association between celiac disease and inflammatory bowel disease (IBD) has been studied; however, the impact of IBD therapy on celiac disease is not known. Using a large database, we sought to describe the association of celiac disease and IBD and the impact of IBD treatment. METHODS: We queried a large multicenter database (Explorys Inc.), an electronic health record data aggregate from 26 American health care systems. We identified a cohort of patients with celiac disease and IBD between 1999 and 2020 and conducted a statistical analysis using a multivariate model. RESULTS: Of the 72,965,940 individuals in the database, 133,400 had celiac disease (0.18%), 191,570 (0.26%) had ulcerative colitis (UC), and 230,670 (0.32%) had Crohn disease (CD). Patients with IBD were more likely to have a diagnosis of celiac disease (odds ratio [OR], 13.680), with a greater association with CD. Treated patients with UC and with CD, respectively, had a lower risk association with celiac disease compared to those not undergoing IBD treatment, specifically corticosteroids (OR, 0.407 and 0.585), 5-aminosalicylates (OR, 0.124 and 0.127), immunomodulators (OR, 0.385 and 0.425), and anti-tumor necrosis factor drugs (OR, 0.215 and 0.242). There was no lower risk association in the vedolizumab group, but there was a higher risk association among the ustekinumab group. CONCLUSIONS: In this large dataset, we showed a bidirectional association between celiac disease and IBD that was stronger with CD. Patients with IBD treated using corticosteroids, 5-aminosalicylates, immunomodulators, or anti-tumor necrosis factor drugs had a lower association with celiac disease. Additional studies are required to determine the underlying mechanisms for IBD therapy-related modification of celiac disease incidence.

The Epidemiology of Annular Pancreas in the United States: A Population-based Study.

BACKGROUND AND AIMS: Annular pancreas is a rare congenital condition where the second part of the duodenum is encircled by pancreatic tissue. There is a scarcity of data on its natural history therefore, we aimed to evaluate the epidemiology of annular pancreas and identify underlying associations using a large database. METHODS: A multi-institutional database (Explorys) was surveyed. A cohort of patients with a Systematized Nomenclature of Medicine-Clinical Terms diagnosis of "MRI, CT, EUS and/or ERCP" between April 2015 and April 2020 was identified. Subsequently a cohort of patients with history of "annular pancreas" was identified. RESULTS: There were a total of 40,075,980 individuals in the database with 6,162,600 (15.38%) who had an magnetic resonance imaging, computed tomography, endoscopic retrograde cholangiopancreatography, and/or endoscopic ultrasound. There were 210 (3.4/100,000) had a diagnosis of annular pancreas. When compared with the control group, patients with annular pancreas were more likely to have a history of alcohol use, smoking, acute pancreatitis, chronic pancreatitis, gastritis, duodenitis, jaundice, and gastrointestinal outlet obstruction. CONCLUSIONS: This is the largest study evaluating the epidemiology of annular pancreas. We found the estimated prevalence rate of annular pancreas to be 3.4/100,000 in those who had abdominal imaging. Annular pancreas was more likely to be diagnosed in patients with symptoms pertaining to acute or chronic pancreatitis, biliary, and gastric outlet obstruction.

Epidemiology of neuroendocrine tumors of the appendix in the USA: a population-based national study (2014-2019).

BACKGROUND: The appendix is the third most common place for neuroendocrine tumors (NETs) along the digestive tract and NETs are the most common neoplasms of the appendix. However, there are limited population-based data on the epidemiology of this disease. Using a large database, we sought to describe the epidemiology and risk association of NETs of the appendix. METHOD: We queried a multi-institutional database (Explorys Inc., Cleveland, OH, USA), comprising 360 hospitals in the United States (US), for patients with a diagnosis of NETs of the appendix from 2014-2019. RESULTS: Of the 30,324,050 individuals in the database, 2020 patients had an appendiceal NET diagnosis (0.007%). The most common presenting symptoms included abdominal pain, nausea, vomiting and diarrhea. Patients with appendiceal NETs were more likely to be female (odds ratio [OR] 1.36, 95% confidence interval [CI] 1.24-1.49), Caucasian (OR 2.71, 95%CI 2.40-3.07), with a history of smoking (OR 1.82, 95%CI 1.65-2.01), family history of primary gastrointestinal malignancy (OR 7.26, 95%CI 6.31-8.33), diagnosis of multiple endocrine tumor type 1 (OR 52.31, 95%CI 23.15-118.23), or neurofibromatosis type 1 (OR 16.37, 95%CI 7.24-37.01). CONCLUSIONS: In a population-based study in the US, using the Explorys database, we found the overall prevalence of NETs of the appendix to be 7 per 100,000 persons. The incidence in the year January 2019-January 2020 was 0.4 per 100,000 individuals. These rates are higher than previously reported and may be more accurate, given the more comprehensive nature of the Explorys database.

Epidemiology of gallbladder cancer in the Unites States: a population-based study.

BACKGROUND: Gallbladder cancer (GBC) is the most common neoplasm of the biliary tract with the lowest rates of survival. Most GBCs are adenocarcinomas that arise from the epithelial lining of the gallbladder. There are limited data in the literature regarding the epidemiology of GBC. Using a large database, we aim to describe the epidemiology using a US population database. METHODS: A multi-institutional database (Explorys Inc., Cleveland, OH, USA) was surveyed. A cohort of patients with a primary malignant neoplasm of gallbladder between 1999-2019 was identified. The prevalence rate was calculated and age-, race-, and sex-based distributions were described. Multivariate analysis was done to evaluate underlying associations. RESULTS: Of the 56,197,690 individuals in the database, 4,790 individuals with GBC were identified with a prevalence rate of 8.5 per 100,000. Asian race has the highest prevalence of GBC (13.6/100,000). Patients with GBC were also more likely to be smokers, have a history of alcohol abuse, obesity, diabetes, cholelithiasis, chronic cholecystitis, primary sclerosing cholangitis (PSC), and chronic viral hepatitis. CONCLUSIONS: This is one of the largest US population studies to date evaluating the epidemiology of GBC. The 20-year period prevalence rate of GBC was 8.5 per 100,000. Patients with GBC were more likely to be elderly, females, obese, diabetic, and have chronic hepatobiliary disorders.

Epidemiology and risk of psychiatric disorders among patients with celiac disease: A population-based national study.

BACKGROUND AND AIM: Celiac disease (CD) is a chronic disorder resulting from an immune reaction to gluten in genetically predisposed individuals. Although several studies have linked CD to psychiatric diseases, there are limited data on this topic. Using a large database, we sought to describe the epidemiology of several psychiatric disorders in CD. METHODS: We queried a multicenter database (Explorys Inc), an aggregate of electronic health record data from 26 major integrated healthcare systems from 2016 to 2020 consisting of 360 hospitals in the USA. A cohort of patients with a Systematized Nomenclature Of Medicine - Clinical Terms diagnosis of CD was identified. Multivariate analysis was performed using Statistical Package for Social Sciences version 25. RESULTS: Of the 37 465 810 patients in the database between 2016 and 2020, there were 112 340 (0.30%) individuals with CD. When compared with patients with no history of CD, patients with CD were more likely to have a history of anxiety (odds ratio [OR]: 1.385; 95% confidence interval [CI]: 1.364-1.407), depression (OR: 1.918; 95% CI: 1.888-1.947), bipolar (OR: 1.321; 95% CI: 1.289-1.354), attention-deficit hyperactivity disorder (OR: 1.753; 95% CI: 1.714-1.792), eating disorder (OR: 15.84; 95% CI: 15.533-16.154), and childhood autistic disorder (OR: 4.858; 95% CI: 3.626-6.508). Patients with CD and psychiatric conditions were more likely to be smokers, with history of alcohol and substance abuse as well as a history of personality disorder. CONCLUSIONS: In this large database, patients with CD are at increased risk of having multiple psychiatric diseases including anxiety, depression, bipolar, attention-deficit hyperactivity disorder, eating disorder, and childhood autism. Individual care and referral to psychiatry when appropriate are warranted while taking care of this group of patients.