The Evolution of Iron-Related Comorbidities and Hospitalization in Patients with Hemochromatosis: An Analysis of the Nationwide Inpatient Sample.

Hemochromatosis, either hereditary hemochromatosis (HH) or secondary hemochromatosis, consists of the accumulation of iron in the liver, heart, and other organs. It leads to end-organ damage in a proportion of affected subjects. Although liver-related morbidity (cirrhosis and hepatocellular carcinoma [HCC]) and mortality are well established, the frequency of these complications remains controversial. The aim of this study is to examine the rate of hospitalization and the incidence of iron overload-related comorbidities in patients with hemochromatosis between the years of 2002 and 2010. We queried the Nationwide Inpatient Sample (NIS) database from the year 2002 to 2010. We included adults (age ≥18 years) and used the ICD-CM 9 code 275.0x to identify hospitalized patients with a diagnosis of hemochromatosis. Data analysis for this study was generated using SAS software version 9.4. A total of 168,614 hospitalized patients between 2002 and 2010 had a diagnosis of hemochromatosis. The majority were males (57%) with a median age of 54 years (37-68), with a predominance of white patients (63.3%) followed by black (26.8%). The rate of hospitalization among patients with hemochromatosis increased by 79% between the years 2002 and 2010 (34.5/100,000 in 2002 vs 61.4/100,000 in 2010). The main associated diagnoses were diabetes mellitus (20.2%), cardiac disease, including arrhythmias (14%) and cardiomyopathy (dilated 3.8%; peri-, endo-, myocarditis 1.3%), liver cirrhosis (8.6%), HCC (1.6%), and acute liver failure (0.81%). Of note, HCC was associated with cirrhosis in 1188 patients (43% of HCC patients) and male sex (87%). Diagnostic biopsies were performed in 6023 (3.6%) of those patients and liver transplant was performed in 881 (0.5%). In-hospital mortality occurred in 3638 (2.16%) patients. In this large database study, we found a rising trend in hospitalization for hemochromatosis, possibly due to the increased recognition of this entity and billing for the condition. The incidence of cirrhosis in hemochromatosis was found to be similar to other studies (8.6% vs 9%). However, the rate of HCC was lower than previous reports (1.6% vs 2.2%-14.9%), and only 43% of HCC was associated with cirrhosis. This raises important pathophysiologic questions regarding the impact of iron overload in HCC. There has been an increase in the rate of hospitalization for patients with a diagnosis of hemochromatosis. This may be related to an increased recognition of hemochromatosis as the underlying etiology for conditions such as diabetes, cardiomyopathy, cirrhosis, and HCC. Further prospective studies are needed to clarify the burden of liver disease in HH and secondary iron overload.

Proton Pump Inhibitors Use and Increased Risk of Spontaneous Bacterial Peritonitis in Cirrhotic Patients: A Retrospective Cohort Analysis.

Background: Since their introduction in the early 1980s, proton pump inhibitors (PPIs) have been used worldwide for a broad range of indications. Unfortunately, however, PPIs have become overly prescribed by healthcare providers, sometimes in the absence of clear indications. Although PPIs were initially presumed to have an excellent safety profile, emerging studies have shed light on the association between their long-term use and a myriad of side effects, including the possibility of an increased risk of spontaneous bacterial peritonitis (SBP). Data available to date regarding the association between PPI use and SBP development in cirrhotic patients is conflicting. While some observational studies provide no association between PPI use in cirrhotic patients and an increased risk of SBP development, many others support this association. As a result of the conflicting conclusions from case controls, cohorts, and meta-analyses, we aimed to carry out this retrospective cohort analysis of data from cirrhotic patients included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Our aim was to evaluate for a possible association between PPIs use and the risk of SBP development in cirrhotic patients and to compare the prevalence of SBP development between cirrhotic patients who were actively using PPIs and those who were not. Methods: A retrospective cohort analysis with chart review was conducted on patients with cirrhosis who were included in the electronic medical record-based commercial database, EXPLORYS (IMB-WATSON, Cleveland, Ohio). Using this database, records were reviewed between December 2017 and 2020. Included patients were adults aged 30 to 79 years with a Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) diagnosis of liver cirrhosis. Included patients with a SNOMED-CT diagnosis of liver cirrhosis were divided into two groups: the first group included all cirrhotic patients who did not use PPIs and the second group included all cirrhotic patients who were on PPIs at home. Results: In our analysis, SBP occurred in 1.7% (1,860 patients) of the included cirrhotic patients whether they were actively taking PPIs or not. Among the 40,670 cirrhotic patients who were on PPIs at home, 1,350 (3.3%) patients developed SBP. On multivariate analysis, PPI use was the strongest predictor for SBP in cirrhotic patients (odds ratio (OR) = 4.24; 95% confidence interval (CI): 3.83 - 4.7, P value < 0.0001), with cirrhotic patients taking PPIs being 4.24 more likely to develop SBP than those not on PPIs. In addition, PPI use, history of bleeding varices, age, race, and gender were found to be independent predicting factors for SBP, in descending order of importance. Conclusions: Our retrospective cohort analysis has shown that the use of PPIs in patients with liver cirrhosis is an independent predicting risk factor for SBP development. It solidified the argument that cirrhotic patients receiving this form of therapy seem to have a higher risk of developing SBP. In the setting of the emerging evidence that PPIs might impose health risks in cirrhotic patients, further studies are needed to settle the current debate between supporters and opponents of this proposition. In addition, future studies may help clarify the relationship between the occurrence of SBP in cirrhotic patients and the type, dose, and duration of PPIs used. We recommend that unless it is clearly indicated, PPI therapy should be avoided or administered with caution in patients with cirrhosis.

The Association Between Gastroesophageal Reflux Disease and Non-Small Cell Lung Cancer: A Retrospective Case-Control Study.

Background: Lung cancer is a leading cause of mortality in the USA. Non-small cell lung cancer (NSCLC) contributes to 85% of all lung cancers. It is the most prevalent subtype amongst non-smokers, and its incidence has risen in the last 20 years. In addition, gastroesophageal reflux disease (GERD) has been associated with several lung pathologies, namely idiopathic pulmonary fibrosis and asthma. We aimed to investigate the association between GERD and NSCLC by performing a retrospective, multicenter, case-control study. This is the first study of this nature to be carried out in the USA. Methods: Data were retrieved from 17 Northwell health care facilities in the New York area between the years 2010 and 2018. Inclusion criteria were patients > 18 years of age with NSCLC (large cell, adenocarcinoma, and squamous cell). They were appropriately matched with controls based on age, gender, weight, comorbidities, and medication use. Our exposure group had a diagnosis of GERD based on the International Classification of Diseases, Ninth/10th Revision (ICD 9/10) codes and endoscopic, in addition to histological evidence if present. We excluded patients with secondary lung cancers, esophageal adenocarcinoma, other primary malignancies, Barrett's esophagus, and smokers. Logistic regression was conducted to determine the adjusted odds ratio (OR) and corresponding 95% confidence interval (CI) for the association between NSCLC and GERD. Results: A total of 1,083 subjects were included in our study: 543 (50%) patients were diagnosed with NSCLC. In this population, GERD was twice as prevalent compared to controls (20.4% vs. 11.6%, P < 0.001). Multivariate analysis demonstrated that GERD was associated with a higher risk of NSCLC compared to matched controls (OR = 1.86, 95% CI = 1.26 - 2.73). In addition, GERD patients treated with either antihistamines or proton pump inhibitors did not demonstrate an overall reduced risk of NSCLC (OR = 1.01, 95% CI = 0.48 - 2.12). Conclusions: Our study demonstrates that GERD is associated with a higher risk of NSCLC, irrespective of GERD treatment. We postulate that GERD patients suffer from chronic micro-aspirations leading to a prolonged inflammatory state within the lung parenchyma, triggering specific proliferative signaling pathways that may lead to malignant transformation.

Predictors of Deep Venous Thrombosis in Hospitalized Patients With Liver Cirrhosis in the US.

Background Patients with liver cirrhosis were previously considered as anticoagulated; thus, their risk of developing venous thromboembolism (VTE) is lower. Recently, several studies showed contradicting results regarding deep venous thrombosis (DVT) occurrence in cirrhotic patients. The aim of this study is to evaluate the prevalence and risk associated with developing DVT in hospitalized cirrhotic patients in a large US population. Methods We queried the commercial database Explorys (IMB Inc., Armonk, New York), an aggregate of electronic health record data from 26 US healthcare systems. After excluding patients under 20 years old, a cohort of patients with a Systematized Nomenclature of Medicine - Clinical Terms of "cirrhosis of the liver" and "inpatient care" between 2015-2019 were identified, and prevalence of DVT was calculated in the exposure and the control groups. Statistical analysis for a multivariable model was performed. Factors adjusted for include gender, race, obesity, hypoalbuminemia, diabetes mellitus, viral hepatitis, and liver malignancy. Results Among 9,990,290 patients who were hospitalized between 2015 and 2019, 157,400 patients had a diagnosis of liver cirrhosis. The prevalence of DVT in hospitalized patients with liver cirrhosis was 3.29% compared to 3.18% in non-cirrhotic patients. Using the multivariate analysis model, DVT was inversely associated with cirrhosis in hospitalized patients [OR: 0.921; p<0.0001] compared to patients without liver cirrhosis. Predictors of developing DVT among patients with cirrhosis were non-Caucasian race, obesity (BMI>30), liver malignancy, hypoalbuminemia, and diabetes mellitus. Cirrhotic patients due to viral hepatitis were less likely to develop DVT [OR: 0.775; p<0.001] compared to non-cirrhotic patients. Conclusion In this database, although the prevalence of DVT in cirrhotic hospitalized patients was slightly higher than in non-cirrhotic patients (3.29% vs. 3.18%, respectively), cirrhosis as an independent factor was associated with less risk of DVT during hospitalization. This poses a question regarding DVT prophylaxis necessity in this group of patients. Further studies are needed to clarify the benefit and risks of DVT prophylaxis in cirrhotic patients.

Epidemiology of Depressive Disorders in Patients With Liver Cirrhosis: A Population-Based Study in the United States.

Objective: Major depressive disorder (MDD) is a chronic, debilitating mood disorder associated with poor medical outcomes. MDD has a multifactorial etiology with numerous biopsychosocial factors implicated as risk factors. Functional and psychiatric impairments have been evaluated in patients with liver cirrhosis; however, less is known about the prevalence and risk factors for the development of MDD in those patients. The objective of this study was to evaluate the risk of developing depression among adult patients with liver cirrhosis in the United States.Methods: Data were collected using a commercial database, an aggregate of electronic health record data from 26 major integrated US health care systems consisting of 360 hospitals in the US from 1999 to 2019.The study cohort was retrieved by searching the database for a Systematized Nomenclature of Medicine-Clinical Terms diagnosis of "cirrhosis of liver" during the designated period of the study.The following factors were adjusted for in the analyses: age, sex, race, smoking, alcohol, substance abuse, underlying mental disorders, and comorbidities.Results: 56,197,690 adults were identified between 1999 and 2019. Of those, 293,150 had a diagnosis of liver cirrhosis. The prevalence of depression among those cirrhotic patients was 23.93% versus 7.61% in the noncirrhotic control group (95% CI, 16.1836%-16.4770%; P < .0001). By applying a multivariate analysis model, cirrhotic patients were found to be more likely to develop depression (odds ratio = 2.172; 95% CI, 2.159-2.185; P < .0001) compared to patients with no prior history of liver cirrhosis.Conclusions: Liver cirrhosis is associated with increased risk of depression and is likely to be an independent risk factor in its development. Future efforts should focus on the identification and treatment of this debilitating condition in those with liver cirrhosis via an integrated care model.

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.

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.

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.

Clostridioides difficile infection in liver cirrhosis patients: A population-based study in United States.

BACKGROUND: Clostridioides (formerly Clostridium) difficile infection (CDI) is an increasingly frequent cause of morbidity and mortality in hospitalized patients. Multiple risk factors are documented in the literature that includes, but are not limited to, antibiotics use, advanced age, and gastric acid suppression. Several epidemiological studies have reported an increased incidence of CDI in advanced liver disease patients. Some have also demonstrated a higher prevalence of nosocomial infections in cirrhotic patients. AIM: To use a large nationwide database, we sought to determine CDI's risk among liver cirrhosis patients in the United States. METHODS: We queried a commercial database (Explorys IncTM, Cleveland, OH, United States), and obtained an aggregate of electronic health record data from 26 major integrated United States healthcare systems comprising 360 hospitals in the United States from 2018 to 2021. Diagnoses were organized into the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) hierarchy. Statistical analysis for the multivariable model was performed using Statistical Package for Social Sciences (SPSS version 25, IBM CorpTM). For all analyses, a two-sided P value of < 0.05 was considered statistically significant. RESULTS: There were a total of 19387760 patients in the database who were above 20 years of age between the years 2018-2021. Of those, 133400 were diagnosed with liver cirrhosis. The prevalence of CDI amongst the liver cirrhosis population was 134.93 per 100.000 vs 19.06 per 100.000 in non-cirrhotic patients (P < 0.0001). The multivariate analysis model uncovered that cirrhotic patients were more likely to develop CDI (OR: 1.857; 95%CI: 1.665-2.113, P < 0.0001) compared to those without any prior history of liver cirrhosis. CONCLUSION: In this large database study, we uncovered that cirrhotic patients have a significantly higher CDI prevalence than those without cirrhosis. Liver cirrhosis may be an independent risk factor for CDI. Further prospective studies are needed to clarify this possible risk association that may lead to the implementation of screening methods in this high-risk population.

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.

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.

Increasing Prevalence of Anxiety and Depression Disorders After Diagnosis of Chronic Pancreatitis: A 5-Year Population-Based Study.

OBJECTIVES: Chronic pancreatitis (CP) is often associated with poor quality of life. Only a few small associative studies have reported the prevalence of mood disorders in CP. Using a large database, we sought to describe the epidemiology and risk association of anxiety and depression in CP and evaluate their outcomes. METHODS: A multicenter database (Explorys), an aggregate of electronic health record data from 26 US healthcare systems, was surveyed. A cohort of patients with a diagnosis of CP between 2014 and 2019 was identified. Within this cohort, rates of anxiety and depression were calculated. Demographics, comorbidities, and outcomes were described. RESULTS: Of the 30,276,810 individuals in the database (2014-2019), 67,260 patients had a CP diagnosis (0.22%). When compared with patients with no history of CP, patients with CP were more likely to develop anxiety (odds ratio, 6.94; 95% confidence interval, 6.85-7.04) and depression (odds ratio, 5.09; 95% confidence interval, 5.01-5.17). Chronic pancreatitis patients with depression had an increased risk of suicidal ideation compared with controls. CONCLUSIONS: Patients with CP are at a higher risk of developing anxiety and depression compared with those without CP, with overall worse outcomes. Clinicians should screen CP patients and make appropriate referral to psychiatry when indicated.

Corticosteroid and Biologic Use Not Associated With Adverse Outcomes for Inflammatory Bowel Disease Patients Hospitalized With COVID-19.

BACKGROUND: To date, studies investigating the inflammatory bowel disease (IBD) patient experience with coronavirus disease 2019 (COVID-19) have consistently reported that the observed rate of COVID-19 within this population is similar to the general population. Limited research has suggested that corticosteroid use in the IBD population may be associated with worse COVID-19 outcomes, but it is still yet to be determined if specific IBD-related clinical factors are associated with worse outcomes. Our goal was to describe clinical COVID-19 outcomes for IBD patients and to identify the clinical factors that may be associated with worse outcomes. METHODS: In this retrospective study, we utilized the inpatient database within the largest hospital network in the New York City Metropolitan area to identify all IBD patients with confirmed COVID-19. RESULTS: Of 83 IBD/COVID-19 patients presenting to a hospital network emergency room, 56 were hospitalized. Overall, 19.6% of hospitalized IBD patients died, compared with 22.2% of all hospital system COVID-19 patients during the time period. There was no association between pre-admission corticosteroid use or biologic treatment with a severe course of COVID-19. CONCLUSIONS: In contrast to some prior reports, we did not observe an association of pre-admission corticosteroid use and adverse outcomes. While the mortality rate was high for IBD/COVID-19 patients, it was not greater than that for hospitalized COVID-19 patients generally. Though our results are encouraging, we continue to support the recommendations of the leading gastrointestinal and IBD societies to regard our patients as "at risk", and to observe caution in their care.

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.

The Risk of Acute and Chronic Pancreatitis in Celiac Disease.

BACKGROUND AND AIMS: Celiac disease (CD) is a chronic immune-mediated enteropathy that is precipitated by dietary gluten in genetically predisposed individuals. A few studies reported a higher incidence of pancreatitis in the CD population. Using a large US database, we sought to describe the epidemiology, risk, and outcomes of acute pancreatitis (AP) and chronic pancreatitis (CP) in CD patients. METHODS: We queried a multiple health system data analytics and research platform (Explorys Inc, Cleveland, OH, USA). A cohort of patients with a diagnosis of CD was identified. Subsequently, individuals who developed a new diagnosis of AP and CP after at least 30 days of being diagnosed with CD were identified. A multivariate regression model was performed to adjust for multiple confounding factors. RESULTS: Of the 72,965,940 individuals in the database, 133,400 (0.18%), 362,050 (0.50%), and 95,190 (0.13%) had CD, AP, and CP, respectively. New diagnosis of AP and CP after at least 30 days of CD diagnosis was 1.06%, 0.52%, respectively, compared to non-CD patients with 0.49% for AP and 0.13% for CP, P < .0001. In multivariate regression analysis, patients with CD were at higher risk of developing AP [OR 2.66; 95% CI 2.55-2.77] and CP [OR 2.18; 95% CI 2.04-2.34]. Idiopathic AP was the most common etiology among CD patients [OR 1.54; 95% CI 1.34-1.77]. CONCLUSIONS: In this largest US population database and after adjusting for several confounders, patients with CD were at increased risk of developing AP and CP. Celiac disease patients had worse outcomes and higher medical burden compared to non-CD patients. Recurrent abdominal pain that suggests pancreatic etiology, idiopathic pancreatitis, or elevation of pancreatic enzymes should warrant investigation for CD as a potential cause of pancreatic disease.

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.

Prevalence of Myocardial Infarction in Patients With Chronic Pancreatitis.

OBJECTIVE: We conducted this study to ascertain whether chronic inflammation secondary to chronic pancreatitis (CP) has any association with myocardial infarction(MI). METHODS: Data were collected from a commercial database (Explorys, Inc, IBM Watson, Ohio). Adults with the diagnosis of "chronic pancreatitis," based on Systematized Nomenclature of Medicine-Clinical Terms, were included in the CP group, and the rest of the patients were included in the non-CP group. The prevalence of MI was compared in both groups, and statistical multivariate model was performed. RESULTS: A total of 28,842,210 patients were included in the study. The overall prevalence of MI was 14.22% in the CP group as compared with 3.23% in the non-CP group (P < 0.0001). In the multivariate analysis, the odds ratio (OR) for MI in CP group was 1.453 (95% confidence interval, 1.418-1.488, P < 0.0001). Hypertension was a strong predictor for MI in the CP group with an OR of 3.2 (95% confidence interval, 3.0-3.5), followed by chronic kidney disease, older than 65 years, dyslipidemia, diabetes mellitus, obesity, alcohol abuse, smoking, White race, and male sex. CONCLUSIONS: This study showed that CP is associated with comorbidities, which can increase the prevalence and OR of MI.

Neutropenic Enterocolitis Secondary to Sulfasalazine in a Woman With Psoriatic Arthritis.

Neutropenic enterocolitis (NE) also known as typhlitis is a serious condition that has been described in immunosuppressed hosts including patients with leukemia, HIV and in patients on chemotherapy. We present the first case of female on sulfasalazine for psoriatic arthritis, otherwise healthy, who was diagnosed with NE involving the cecum and rectum. This adds up to the cases of NE diagnosed in nononcologic conditions. A 65-year-old female with a history of psoriatic arthritis on sulfasalazine, presented to the emergency department (ED) after an episode of syncope. She was complaining of a fever and mild generalized abdominal pain. Physical exam was remarkable for peri-umbilical tenderness. Severe neutropenia and acute kidney injury were found on blood work. CT scan of the abdomen showed evidence of colitis, involving the cecum, ascending colon and rectum, which in light of neutropenia was consistent with NE. Clostridium difficile colitis was ruled out. Intravenous fluids and broad-spectrum antibiotics were initiated, and sulfasalazine was discontinued. The patient was subsequently afebrile and was out of neutropenia by day 3 without the need for granulocyte-macrophage colony-stimulating factor (GM-CSF). By day 5, the patient was pain free and was discharged. Even though NE is primarily described in the setting of malignancies and chemotherapy, one should keep in mind that this entity can occur in people on any immunosuppressive therapy. Early discontinuation of sulfasalazine and conservative management were essential in the treatment of NE in this case. Whether neutropenia precipitates colitis or the latter causes agranulocytosis by bone marrow suppression through cytokines remains to be proved. The diagnosis of medication-related adverse reactions remains a big challenge for clinicians and therefore requires a high index of suspicion. Resolution of the symptoms can simply occur with the discontinuation of the offending drug and often does not require extensive workup or treatments that might cause harm to the patient's health.

Endobronchial aspergilloma-a comprehensive literature review with focus on diagnosis and treatment modalities.

Endobronchial aspergilloma (EBA) is a rare manifestation of pulmonary infection with Aspergillus spp. Comprised of hyphae, mucus, and cellular debris, the massive fungus overgrowth can lead to obstructive pneumonitis in large airways, manifesting as cough, dyspnea, hemoptysis, or weight loss. The aim of this paper is to review the literature on endobronchial aspergilloma to further elucidate this disease entity and to classify it as a non-invasive form of pulmonary aspergillosis. A descriptive analysis was performed on articles on PubMed database that contained the key word "endobronchial aspergilloma." A total of 28 cases were obtained. Four articles were excluded as they were not available in the English format. Although EBA is extremely rare, it should be considered in the differential diagnosis of endobronchial masses in immunocompromised patients. There is a potential for the disease entity to progress to tracheobronchitis and fulminant respiratory failure. As such, early detection with bronchoscopy, biopsy, and culture is required to confirm pulmonary aspergillosis. Current treatment regimens remain to be optimized, though piecemeal resection of the mycetoma with bronchoscopic techniques with the addition of systemic antifungals and their combinations has been reported as efficacious.