Faculty Bibliography

Colorectal signet ring cell carcinoma is a rare type of colon cancer. Early diagnosis remains challenging because of nonspecific colonoscopy findings, such as diffuse circumferential thickening, stricture, and ulcerations, and the potential absence of typical pathological features in the initial biopsy sample. In this article, we report a 41-year-old man with ulcerating rectosigmoid stricture in the rectosigmoid colon with inconclusive histology. Subsequently, the patient developed small bowel obstruction and was diagnosed with stage 4 colorectal signet ring cell carcinoma with peritoneal carcinomatosis.

Celiac disease (CD) is a chronic autoimmune disorder that affects the small intestine in genetically predisposed individuals. Previous studies have investigated the potential link between CD and cardiovascular disease (CVD); however, the findings have been inconsistent. We aimed to provide an updated review of the literature on the association between CD and CVD. PubMed was searched from inception to January 2023 using keywords including CD, cardiovascular disease, coronary artery disease, cardiac arrhythmia, heart failure, cardiomyopathy, and myocarditis. We summarized the results of the studies, including meta-analyses and original investigations, and presented them according to the different forms of CVD. Meta-analyses published in 2015 provided mixed results regarding the relationship between CD and CVD. However, subsequent original investigations have shed new light on this association. Recent studies indicate that individuals with CD are at a higher risk of developing overall CVD, including an increased risk of myocardial infarction and atrial fibrillation. However, the link between CD and stroke is less established. Further research is needed to determine the link between CD and other cardiac arrhythmias, such as ventricular arrhythmia. Moreover, the relationship between CD and cardiomyopathy or heart failure, as well as myopericarditis, remains ambiguous. CD patients have a lower prevalence of traditional cardiac risk factors, such as smoking, hypertension, hyperlipidemia, and obesity. Therefore, it is important to discover strategies to identify patients at risk and reduce the risk of CVD in CD populations. Lastly, it is unclear whether adherence to a gluten-free diet can diminish or increase the risk of CVD among individuals with CD, necessitating further research in this area. To fully comprehend the correlation between CD and CVD and to determine the optimal prevention strategies for CVD in individuals with CD, additional research is necessary.

BACKGROUND & AIMS/OBJECTIVE:Understanding the epidemiology of bleeding and thromboembolism (clotting) in liver cirrhosis provides important data for future studies and policymaking; however, head-to-head comparisons of bleeding and clotting remain limited. METHODS:This is a populational retrospective cohort study using the US National Readmission Database of 2018 to compare the incidence and outcomes of bleeding and clotting events in patients with liver cirrhosis. The primary outcomes were the 11-month incidence proportion of bleeding and clotting events. RESULTS:Of 1 304 815 participants, 26 569 had liver cirrhosis (45.0% women, mean age 57.2 [SD, 12.7] years). During the 11-month follow-up, in patients with cirrhosis, for bleeding and clotting events, the incidence proportions was 15.3% and 6.6%; the risk-standardized all-cause mortality rates were 2.4% and 1.0%; the rates of intensive care intervention were 4.1% and 1.9%; the rates of rehabilitation transfer were .2% and .2%; the cumulative length of stays were 45 100 and 23 566 days; total hospital costs were 147 and 84 million US dollars; total hospital charges were 620 and 365 million US dollars. Compared to non-cirrhosis, liver cirrhosis was associated with higher rates of bleeding (adjusted hazard ratio, 3.02 [95% CI, 2.85-3.20]) and portal vein thrombosis (PVT) (18.46 [14.86-22.92]), and slightly lower risks of other non-PVT venous thromboembolic events (.82 [.75-.89]). CONCLUSIONS:Bleeding is more common than thromboembolism in patients with liver cirrhosis, causes higher morbidity, mortality and resource utilization. Liver cirrhosis is an independent risk factor for bleeding and PVT, but not non-PVT thromboembolism including venous thromboembolism, acute myocardial infarction and ischemic stroke.

BACKGROUND:Current guidelines suggest antibiotics prophylaxis is not necessary for patients with orthopedic prosthetics undergoing gastrointestinal endoscopy. Clinical evidence to support this recommendation is lacking. AIMS/OBJECTIVE:To analyze the association between inpatient gastrointestinal endoscopy and prosthetic joint infection (PJI) in patients with a recent arthroplasty. METHODS:We included patients admitted from July to October of each calendar year (index admissions) who had an arthroplasty in the same calendar year prior to the index admission. We followed the occurrence of PJI for 60 days after the index admission. Only admissions from July to October were chosen as index admissions, and the follow-up period was limited to 60 days because the database structure prohibits the analysis of events in different calendar years. We compared the rate of 60-day PJI between those who had gastrointestinal endoscopy on index admissions to those who had not. We excluded patients aged less than 18 years, who died on index admission, or had any infection in the same calendar year before or during the index admission. RESULTS:Of 1,831,218 patients with arthroplasty, 88,345 met the inclusion criteria, out of which 5,855 had gastrointestinal endoscopy. The rate of 60-day PJI in those who had endoscopy was 0.23%, and in those who had not was 0.52% (P < 0.001). EGD without excision (adjusted odds ratio [95% confidence interval]: 0.20 [0.03-1.42], P = 0.107), EGD with excision (0.58 [0.21-1.60], P = 0.295), colonoscopy without excision (0.43 [0.11-1.72], P = 0.233), colonoscopy with excision (0.31 [0.04-2.21], P = 0.241), and PEG/PEJ (0.38 [0.05-2.71], P = 0.337) were not associated with risk of 60-day PJI. We found no PJI cases in patients underwent esophageal dilation, ERCP, and EUS with FNA. CONCLUSIONS:Gastrointestinal endoscopy in hospitalized patients with a recent previous arthroplasty is not associated with an increased risk of 60-day prosthetic joint infection.

BACKGROUND AND AIM/OBJECTIVE:Emerging data showed patients with chronic inflammatory disorders, including inflammatory bowel disease, are more likely to develop atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. This article aims to review the evidence of those associations. METHODS:PubMed was searched from inception to January 2022 using the keywords, including inflammatory bowel diseases, Crohn's disease, ulcerative colitis, atherosclerotic cardiovascular disease, coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, and premature coronary artery disease. Relevant literature, including retrospective/prospective cohort studies, clinical trials, meta-analyses, and guidelines were reviewed and summarized. RESULTS:Both ulcerative colitis and Crohn's disease are associated with an increased risk of atherosclerotic cardiovascular diseases, cerebrovascular accidents, premature coronary artery disease, and atrial fibrillation. Ulcerative colitis is associated with an increased risk of heart failure. The increased atrial fibrillation occurred during inflammatory bowel disease flares and persistent activity, but not during periods of remission. Hypotheses for the mechanism underlying the association of inflammatory bowel disease and atherosclerotic cardiovascular diseases include shared risk factors (i.e., obesity, diabetes, smoking, diet) and pathophysiology (gut microbiome dysfunction), or adverse effects from inflammatory bowel disease itself or its treatment (i.e., chronic inflammation, dyslipidemia, thrombocytosis, steroids). CONCLUSION/CONCLUSIONS:Inflammatory bowel disease is associated with an increased risk of atherosclerotic cardiovascular diseases, heart failure, and atrial fibrillation. A multidisciplinary team with gastroenterologists and cardiologists is needed to optimize the care for patients with inflammatory bowel disease and associated cardiac diseases.

Nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases are both highly prevalent conditions around the world, and emerging data have shown an association between them. This review found several longitudinal and cross-sectional studies showing that NAFLD was associated with coronary artery disease, cardiac remodeling, aortic valve remodeling, mitral annulus valve calcifications, diabetic cardiomyopathy, diastolic cardiac dysfunction, arrhythmias, and stroke. Although the specific underlying mechanisms are not clear, many hypotheses have been suggested, including that metabolic syndrome might act as an upstream metabolic defect, leading to end-organ manifestations in both the heart and liver. Management of NAFLD includes weight loss through lifestyle interventions or bariatric surgery, and pharmacological interventions, often targeting comorbidities. Although there are no Food and Drug Administration-approved nonalcoholic steatohepatitis-specific therapies, several drug candidates have demonstrated effect in the improvement in fibrosis or nonalcoholic steatohepatitis resolution. Further studies are needed to assess the effect of those interventions on cardiovascular outcomes, the major cause of mortality in patients with NAFLD. In conclusion, a more comprehensive, multidisciplinary approach to diagnosis and management of patients with NAFLD and cardiovascular diseases is needed to optimize clinical outcomes.

Introduction: Inborn errors of immunity are a group of primary immunodeficiency disorders caused by over 400 genetic defects. Enteropathy has been common in PID patients, which presents with chronic diarrhea, malabsorption, growth delay, iron deficiency, and failure to thrive. This article systemically reviewed the clinical presentations, treatments, and genetic defects of enteropathy observed in PIDD.
Method(s): We have reviewed published cases with the clinical diagnosis of both enteropathy and PIDD using 3 databases (Pubmed, Scopus, EMBASE). A total of 346 cases met our inclusion criteria.
Result(s): The most common enteropathy-associated PIDD is common variable immunodeficiency (32.4%), IPEX (21%), selective IgA deficiency (18.1%), and hypogammaglobulinemia (7.9%; Figure). Celiac disease (26.2%) is the most common enteropathy presentation in PIDD, followed by IPEX (20.7%), autoimmune enteropathy (6.4%), and CVID enteropathy (5.8%). Selective IgA deficiency and CD/Celiac like disease were also frequently reported. More than half of documented PIDD-related CD showed positive serology test results and histopathological findings. Eighty-eight percent of PIDD-related CD cases are responsive to a gluten-free diet. FOXP3 mutation (70) was the most common gene mutation in PIDD, followed by CTLA-4 (17), CD55 (8), NFKB1 (8), GoF-STAT1 (5), GoF-STAT3 (5), and C1-INH (4; Table)). CTLA-4 mutation was found related to CVID, hypogammaglobulinemia, and autoimmune enteropathy. NFKB1was found mainly linked to CVID. We observed frequent giardiasis (21), norovirus (3), CMV (4), Candidiasis (2), and histoplasmosis (2) infections causing enteropathy in PIDD. No significant difference in treatments of the enteropathy between PIDD and non-PIDD was noticed.
Conclusion(s): Enteropathy can be common clinical presentations in IEIs. With early recognition of clinical manifestations and enteropathy-associated gene mutation, PIDD can be diagnosed and treated timely, preventing complications and mortalities

Introduction: Gastrointestinal bleeding from vascular malformation is hard to treat. Thalidomide has been shown with therapeutic effects in several studies. We performed a meta-analysis for its efficacy on GI bleeding due to vascular malformation.
Method(s): MEDLINE, the Cochrane Library, and EMBASE were searched up to June 5th. The following keywords were used: "Arteriovenous Malformation", "AVM", "Angioectasia", "Angiodysplasia", "Vascular Malformation", "Telangiectasia", "Thalidomide", "Contergan", "Thalomid", "a-Phthalimidoglutarimide". Observational studies and clinical trials that utilized Nivolumab for refractory esophageal cancer were included. Bleeding cessation rates were studied as primary outcomes. Data were analyzed with STATA version 16.0 (Stata Corp, College Station, TX, USA).
Result(s): A total of 405 manuscripts were identified and four observational or clinical studies with 194 patients meeting inclusion criteria. Patient median or mean ages were more than 50 in all 4 studies and 89 (45.4%) individuals were male. The dose of thalidomide ranged from 50 mg to 200 mg per day. The duration was from 3 months to 45 months. For patients with gastrointestinal bleeding from vascular malformation, thalidomide has a bleeding cessation rate of 41% (95%, 28%-60%) in 6-12 months.
Conclusion(s): Many of the studies claimed that thalidomide was able to decrease bleeding cessation rates significantly, while our meta-analysis with all available studies did not show a significant decrease in bleeding cessation rates compared to the non-thalidomide group reported by Wang's study (41% vs 46%) (Figure). Several studies showed that thalidomide was helpful in the yearly bleeding episodes, yearly red blood cell transfusion requirement, transfusion dependence, overall and bleeding-related hospitalization rate, endoscopic treatment requirement, and hemoglobin level changes, but none of the above topics had enough data to perform a meta-analysis. Therefore, further studies are needed to evaluate the efficacy of thalidomide on Gastrointestinal bleeding from vascular malformation, besides the bleeding cessation rates

Introduction: The United States Preventive Services Taskforce lowered the recommended starting age for colorectal cancer (CRC) screening in average-risk adults from 50 to 45 years due to a rapid increase in young CRC incidence and overall favorable benefit-to-burden ratio in the US. This recommendation has not been widely adopted by other countries partially because the burden of young CRC in these countries is unclear compared to the United States Methods: The incidence rates of early-onset CRC in young adults (defined as the onset of CRC in individuals aged between 20 to 49 years) from 1990 to 2019 were collected from the Global Health Data Exchange (GHDx) results tool (available at https://vizhub.healthdata.org/gbd-results). Data from 204 countries and geographic areas were available. The socio-demographic index (SDI) was used to categorize countries and geographic areas by development (low, low-middle, middle, high-middle, and high).
Result(s): The global incidence rate of young CRC increased from 4.2/100,000 to 6.7/100,000 from 1990 to 2019, with an annual percentage change (APC) of 1.6%. The increase in CRC incidence rate was faster in young adults than in individuals aged 50-74 years (APC 0.6%). In the high HDI region, the CRC incidence rate decreased in adults aged 50-74 years old while it increased in adults 20-49 years old from 1995 to 2019 (Table). The increase in young CRC incidence rate was consistently observed in all five SDI regions and 185 out of 204 countries and territories (Figure a). Middle (120.8%), high-middle (98.5%), and lowmiddle (63.7%) SDI regions experienced the most rapid increase in young CRC incidence rate, while the high SDI region had the highest incidence rate by 2019 (11.5 per 100,000). By 2019, nine countries and territories (Taiwan, Monaco, Portugal, Andorra, Japan, China, Bulgaria, Hungary, and Slovakia) had higher young CRC incidence rates than the United States (Figure b); CRC screening for average-risk adults aged 45-49 years should be studied in these countries. A concerning 142 countries had a higher annual percentage increase of young CRC than the United States, which warrants further attention and investigation. (Table) (Figure a/b)
Conclusion(s): The global incidence, mortality, and DALYs of young CRC increased from 1990 to 2019. The increase in young CRC incidence was prevalent in most countries worldwide. Several countries were found to have higher incidence rates or faster increase in young CRC, which warrants further attention