Alzheimer Disease Occurs More Frequently In Patients With Inflammatory Bowel Disease: Insight From a Nationwide Study.

Alzheimer disease (AD) affects 5 million Americans and early recognition improves cognitive function. Chronic inflammation and gut microbiome alteration are linked to cognitive decline which are common in inflammatory bowel disease (IBD). We investigated the association of IBD with development of AD. A commercial database (Explorys Inc., Cleveland, OH), an aggregate of electronic health records from 26 major US health care systems, was surveyed. Cohorts of patients with Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnoses of Crohn's disease (CD), ulcerative colitis (UC), and AD were identified. IBD patients with new diagnosis of AD were characterized based on demographic and traditional AD risk factors and IBD-related features. Among 342,740 IBD patients in the database, AD developed in 5750 IBD patients (1.55%). After adjusting for traditional AD risk factors, IBD was identified as an independent risk factor for development of AD [odds ratio (OR)=2.30, 95% confidence interval (CI)=2.10-2.51]. IBD patients with AD were younger in comparison to AD patients without IBD. On sub-group analysis, patients with CD had higher odds of developing AD (adjusted OR=3.34, 95% CI=3.25-3.42) than UC (adjusted OR=1.09, 95% CI=1.06-1.14). Use of tumor necrosis factor (TNF-α) inhibitors in IBD was associated with significantly lower odds of developing AD in both CD and UC. In this population based study, IBD was independently associated with development of AD. Among IBD; the association was stronger in patients with CD in comparison with UC. Use of TNF-α inhibitors was associated with lower odds of developing AD.

Gastrointestinal Hemorrhage With Gastritis and Pancolitis as the Sole Presentation for Granulomatosis With Polyangiitis Flare.

Granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis, is a rare small vessel vasculitis affecting mainly Whites. The prevalence of GPA in the United States is estimated to be 3 of 100,000 individuals. Classically, GPA affects upper airways, lungs, and kidneys, with the upper airways being the most common site. Occasionally, other organs affected by GPA include eyes, skin, joints, and the nervous system. The gastrointestinal system is rarely affected; however, some cases have been reported. In this case report, we present a patient with hemorrhagic gastritis and pancolitis consistent with GPA and discuss features from the literature of gastrointestinal manifestations in patients with GPA.

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.

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 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.

Pancreatic manifestations in rheumatoid arthritis: a national population-based study.

OBJECTIVES: RA is a systemic autoimmune disease characterized by persistent joint inflammation. Extra-articular manifestations of RA can involve different organs including the gastrointestinal (GI) system. Using a large database, we sought to describe the epidemiology of pancreas involvement in RA. METHODS: We queried a multicentre database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 major integrated US healthcare systems in the US from 1999 to 2019. After excluding patients younger than 18, a cohort of individuals with Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) diagnosis of RA was identified. Within this cohort, patients who developed a SNOMED-CT diagnosis of acute pancreatitis (AP), chronic pancreatitis (CP) and primary pancreatic cancer (PaCa) after at least 30 days of RA diagnosis were identified. Statistical analysis for multivariate model was performed using Statistical Package for Social Sciences (SPSS version 25, IBM Corp) to adjust for several factors. RESULTS: Of the 56 183 720 individuals in the database, 518 280 patients had a diagnosis of RA (0.92%). Using a multivariate regression model, patients with RA were more likely to develop AP [odds ratio (OR): 2.51; 95% CI: 2.41, 2.60], CP (OR: 2.97; 95% CI: 2.70, 3.26) and PaC (OR: 1.79; 95% CI: 1.52, 2.10). CONCLUSION: In this large database, we found a modest increased risk of AP and CP among patients with RA after adjusting for the common causes of pancreatitis. Further studies are required to better understand this association and the effect of medications used for RA.

Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy.

BACKGROUND: Chronic inflammation is a key factor for the development of colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD). Despite the increased use of biologic agents in patients with IBD, their impact on colorectal carcinogenesis remains unclear. With the use of a large database, we sought to describe the effect of biologics on CRC among patients with IBD. METHODS: We evaluated a multicenter database (Explorys) consisting of electronic medical records from several U.S. hospitals between 1999 and 2020. A cohort of patients with a diagnosis of IBD was identified. We performed a multivariate analysis to adjust for multiple factors including medical and surgical therapies. RESULTS: There were a total of 62,007,510 patients in the database between 1999 and 2020. Amongst those, 225,090 (0.36%) individuals had Crohn's disease and 188,420 (0.30%) had ulcerative colitis. After adjusting for confounding factors using multivariate analysis, patients with IBD were more likely to develop CRC. Among the IBD cohort, patients treated with anti-TNF agents were less likely to develop CRC; patients with Crohn's disease: odds ratio, 0.69; 95% confidence interval, 0.66-0.73; P < 0.0001 vs patients with ulcerative colitis: odds ratio, 0.78; 95% confidence interval, 0.73-0.83; P < 0.0001. CONCLUSIONS: Patients with IBD who were treated with anti-tumor necrosis factor agents were less likely to develop CRC. Prospective studies are needed to evaluate whether anti-tumor necrosis factor drugs provide a chemoprotective effect in patients with IBD by inflammation control and mucosal healing.

Epidemiology of Diverticulitis and Prevalence of First-Ever Colorectal Cancer Postdiverticulitis in Adults in the United States: A Population-Based National Study.

BACKGROUND: The incidence of acute diverticulitis is increasing, and previous studies showed a wide range of prevalence of colorectal cancer after diverticulitis. There is a lack of high-quality evidence to support performing colonoscopy after diverticulitis. OBJECTIVE: We aimed to describe the incidence of first-ever diverticulitis and prevalence of first-ever colorectal cancer postdiverticulitis in the United States. DESIGN: This is a retrospective cohort study. SETTINGS: We queried a national database that contains data from 26 major integrated healthcare systems in the United States. PATIENTS: We identified an aggregated patient cohort aged ≥18 years with a diagnosis of first-ever diverticulitis from February 2015 to February 2020, followed by first-ever colorectal cancer diagnosis, at least 1 day after and within 1 year of diverticulitis. MAIN OUTCOME MEASURES: The incidence of first-ever diverticulitis was calculated. The prevalence and OR of first-ever colorectal cancer after diverticulitis were analyzed. RESULTS: Among 31,778,290 individuals, we found the incidence of first-ever acute diverticulitis to be 2.9%. The prevalence of colorectal cancer within 1 year of first-ever acute diverticulitis was 0.57%, whereas the prevalence of colorectal cancer without a history of diverticulitis was 0.31% (OR = 1.8 (95% CI, 1.76-1.86)). The majority (92.3%) of the postdiverticulitis colorectal cancer were diagnosed within the first 6 months. The risk of colorectal cancer postdiverticulitis was higher in women (OR = 1.9), African Americans (OR = 2.0), and adults aged 18 to 65 years (OR = 2.3). LIMITATIONS: We are unable to validate the diagnostic code because patient information in our database is deidentified. CONCLUSIONS: Individuals are twice as likely to be diagnosed with colorectal cancer within 1 year of their first episode of acute diverticulitis compared with individuals without diverticulitis. We advocate for colonoscopy after the first occurrence of acute diverticulitis to screen for colorectal cancer, particularly for patients without a recent colonoscopy. See Video Abstract at http://links.lww.com/DCR/B412.

ANTECEDENTES: La incidencia de diverticulitis aguda está aumentando y los estudios anteriores mostraron una amplia gama de prevalencia de cáncer colorrectal después de diverticulitis. Hay una falta de evidencia de alta calidad para apoyar la realización de una colonoscopia después de la diverticulitis. OBJETIVOS: Nuestro objetivo fue describir la incidencia de la primera diverticulitis y la prevalencia del cáncer colorrectal posterior a la primera diverticulitis en los Estados Unidos.DISEÑO:Este es un estudio de cohorte retrospectivo. AJUSTES: Consultamos una base de datos nacional que contiene datos de 26 sistemas de salud integrados importantes en los Estados Unidos. PACIENTES: Identificamos una cohorte agregada de pacientes mayores de 18 años con un diagnóstico de diverticulitis por primera vez entre febrero de 2015 y febrero de 2020, seguido de un diagnóstico de cáncer colorrectal por primera vez, al menos 1 día después y dentro de 1 año de diverticulitis. PRINCIPALES MEDIDAS DE RESULTADO: Se calculó la incidencia de la primer diverticulitis. Se analizaron la prevalencia y el odds ratio del primer CCR después de la diverticulitis. RESULTADOS: Entre 31,778,290 individuos, encontramos que la incidencia de la primera diverticulitis aguda fue del 2.9%. La prevalencia de cáncer colorrectal dentro de 1 año de la primera diverticulitis aguda fue del 0,57%, mientras que la prevalencia del cáncer colorrectal sin antecedentes de diverticulitis fue del 0,31% (OR 1,8; IC del 95%: 1,76-1,86). La mayoría (92,3%) de los pacientes con cáncer colorrectal posterior a diverticulitis se diagnosticaron dentro de los primeros 6 meses. El riesgo de CCR después de diverticulitis fue mayor en mujeres (OR 1,9), afroamericanos (OR 2,0) y adultos de 18 a 65 años (OR 2,3). LIMITACIONES: No podemos validar el código de diagnóstico debido a que la información del paciente en nuestra base de datos no está identificada. CONCLUSIONES: Las personas tienen el doble de probabilidades de ser diagnosticadas con cáncer colorrectal dentro del primer año de su primer episodio de diverticulitis aguda en comparación con las personas sin diverticulitis. Abogamos por la colonoscopia después de la primera aparición de diverticulitis aguda para detectar cáncer colorrectal, particularmente en pacientes sin una colonoscopia reciente.

The Epidemiology of Pancreatic Cancer and the Association With Acetylsalicylic Acid in the United States: A Population-Based Study.

OBJECTIVES: Pancreatic cancer (PaC) is the third leading cause of cancer-related death in the United States. Multiple studies have investigated the epidemiology and the association between PaC and acetylsalicylic acid (ASA) use, revealing mixed results. Using a large database, we sought to investigate the epidemiology of PaC. METHODS: Using a commercial database (Explorys Inc, Cleveland, Ohio), which includes electronic health record data from 26 major integrated US health care systems, all patients 18 years and older diagnosed with PaC for 5 years were identified based on Systematized Nomenclature Of Medicine-Clinical Terms. We determined the prevalence of PaC and the potential associated factors using univariable and multivariable analysis. RESULTS: Of the 32,970,850 individuals, we identified 30,250 individuals with PaC with an overall prevalence of 0.08%. Individuals with PaC were more likely to be males, seniors (age, >65 years), and White, compared with patients without PaC. In subgroup analysis of chronic pancreatitis, individuals on ASA, individuals >65 years, White, and White males were less likely to have PaC, and non-White females were more likely to have PaC. CONCLUSIONS: This is the largest population-based study evaluating the epidemiology of PaC. We observed a protective association of ASA on a subgroup of patients with PaC and chronic pancreatitis.

Opportunistic Infections Are More Prevalent in Crohn's Disease and Ulcerative Colitis: A Large Population-Based Study.

BACKGROUND: Opportunistic infections (OIs) are more common in patients with inflammatory bowel disease (IBD); however, there have been limited large-scale studies of OIs in IBD. We investigated the epidemiological characteristics of OI in Crohn's disease (CD) and ulcerative colitis (UC) using a large population-based database. METHODS: Data were collected from a commercial database (Explorys Inc., Cleveland, OH, USA) that provided electronic health records from 26 major integrated US health care systems from 1999 to March 2018. In this data set, we identified all CD and UC patients, based on Systemized Nomenclature of Medicine-Clinical Terms. Within these cohorts, we identified a variety of OIs and compared the prevalence rate of OI in individuals with IBD with that of controls (patients in the database between March 2013 and March 2018 without the diagnosis of IBD). RESULTS: Explorys included 153,290 patients with CD and 128,540 patients with UC between March 2013 and March 2018. The prevalence of OIs was 17.8% in CD, 19.2% in UC, and 7% in non-IBD controls. When compared with non-IBD controls, all OIs were more common in CD (prevalence ratio [PR], 2.54; 95% confidence interval [CI], 2.51-2.57) and UC (PR, 2.74; 95% CI, 2.71-2.77). Overall, viral infections were numerically more common, whereas bacterial infections had the highest PRs in CD and UC when compared with controls without IBD. CONCLUSIONS: We found significantly higher rates of OI in IBD. Our study suggests the need for close follow-up of IBD patients to diagnose and provide vaccinations where applicable for prevention of infections.

Epidemiology of Whipple's Disease in the USA Between 2012 and 2017: A Population-Based National Study.

OBJECTIVE: Prior studies on the epidemiology of Whipple's disease are limited by small sample size and case series design. We sought to characterize the epidemiology of Whipple's disease in the USA utilizing a large population-based database. METHODS: We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of electronic health record data from 26 major integrated healthcare systems in the USA. We identified a cohort of patients with a diagnosis of Whipple's disease based on systemized nomenclature of medical terminology (SNOMED CT) codes. We calculated the overall and age-, race-, ethnicity, and gender-based prevalence of Whipple's disease and prevalence of associated diagnoses using univariate analysis. RESULTS: A total of 35,838,070 individuals were active in the database between November 2012 and November 2017. Of these, 350 individuals had a SNOMED CT diagnosis of Whipple's disease, with an overall prevalence of 9.8 cases per 1 million. There was no difference in prevalence based on sex. However, prevalence of Whipple's disease was higher in Caucasians, non-Hispanics, and individuals > 65 years old. Individuals with a diagnosis of Whipple's disease were more likely to have associated diagnoses/findings of arthritis, CNS disease, endocarditis, diabetes, malignancy, dementia, vitamin D deficiency, iron deficiency, chemotherapy, weight loss, abdominal pain, and lymphadenopathy. CONCLUSIONS: To our knowledge, this is the largest study to date examining the epidemiology of Whipple's disease. In this large population-based study, the overall prevalence of Whipple's disease in the USA is 9.8 cases per 1 million people. It affects men and women at similar rates and is more common in Caucasians, non-Hispanics, and people > 65 years old.

Prevalence of Small Intestine Carcinoid Tumors: A US Population-Based Study 2012-2017.

BACKGROUND AND AIMS: Most carcinoid tumors of the gastrointestinal tract are located in the small bowel (SB). Epidemiological studies of these tumors have been limited by small sample sizes. Our aim was to evaluate the epidemiology of SB carcinoids (SBCs) using a large database. METHODS: We queried a commercial database (Explorys), an aggregate of electronic health data from 26 US healthcare systems. We identified patients with SBCs between 2012 and 2017. We evaluated the epidemiology of SBC and identified possible risk factors. RESULTS: Of the 35,798,290 individuals in the database between 2012 and 2017, we identified 3280 patients with SBCs, with a prevalence of 9.2/100,000. Prevalence was higher in men [odds ratio (OR) 1.23, 95% confidence interval (CI) 1.153-1.322, p < 0.0001], whites [OR 2.031, 95% CI 1.872-2.203, p < 0.0001], and elderly (aged > 65) [OR 4.856, 95% CI 4.533-5.203, p < 0.0001]. Patients with SBCs were more likely to have a history of smoking [OR 2.749, 95% CI 2.549-2.970, p < 0.0001], alcohol use [OR 2.031, 95% CI 1.864-2.21, p < 0.0001], obesity (BMI > 30) [OR 3.476, 95% CI 3.213-3.761, p < 0.0001], diabetes mellitus [OR 4.198, 95% CI 3.900-4.519, p < 0.0001], and a family history of cancer [OR 5.902, 95% CI 5.396-6.456, p < 0.0001]. CONCLUSIONS: This is one of the largest studies done on the prevalence of SBC. The prevalence of 9.2/100,000 individuals is higher than previously reported. Further genetic and environmental studies are needed to understand the potential mechanisms for the risk factors identified in this study.