Faculty Bibliography

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: 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

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

Prior international studies have shown mixed results regarding the association of hepatitis B and hepatitis C with adverse pregnancy outcomes. We performed an updated evaluation of the prevalence of associated adverse pregnancy outcomes and evaluated trends over time of diagnosis of chronic hepatitis B (HBV) and chronic hepatitis C (HCV) in pregnant women in a national database. All pregnant women with HBV and HCV were identified from the National Inpatient Sample database 2012 to 2018. Multivariate logistic regression analyses were performed to compare pregnancy-related complications, including rates of preeclampsia/eclampsia, gestational diabetes, intrauterine growth restriction, antepartum/intrapartum hemorrhage, preterm labor, and Cesarean section. We evaluated all-cause in-hospital mortality, length of stay, and total cost of hospitalizations. A total of 28.7 million pregnancy-related hospitalizations that met our eligibility criteria were identified, including 51,200 with HBV and 131,695 with HCV. In comparison with the uninfected controls, the HBV group was significantly more likely to develop gestational diabetes (12.94% vs. 6.94%, p < 0.001). The HCV group was more likely to have preterm labor (9.63% vs. 6.27%, p < 0.001), intrauterine growth restriction (6.04% vs. 2.89%, p < 0.001), longer length of stay (3.4 days vs. 2.7 days, p < 0.001), and higher hospitalization cost (15,052 dollars vs. 14,258 dollars, p < 0.001). These findings should inform counseling of women who are found to have HBV or HCV during pregnancy regarding the risk of adverse pregnancy outcomes and support the need for an interdisciplinary approach to optimize maternal and neonatal outcomes.

BACKGROUND:The relationship between body weight and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) is unclear. OBJECTIVES:This study aimed to investigate the impact of obesity and morbid obesity on mortality and ERCP-related complications in patients who underwent ERCP. METHODS:We conducted a US population-based retrospective cohort study using the Nationwide Readmissions Databases (2013-2014). A total of 159,264 eligible patients who underwent ERCP were identified, of which 137,158 (86.12%) were normal weight, 12,522 (7.86%) were obese, and 9584 (6.02%) were morbidly obese. The primary outcome was in-hospital mortality. The secondary outcomes were the length of stay, total cost, and ERCP-related complications. Multivariate analysis and propensity score (PS) matching analysis were performed. The analysis was repeated in a restricted cohort to eliminate confounders. RESULTS:Patients with morbid obesity, as compared to normal-weight patients, were associated with a significantly higher in-hospital mortality (hazard ratio [HR]: 5.54; 95% confidence interval [CI]: 1.23-25.04). Obese patients were not associated with significantly different mortality comparing to normal weight (HR: 1.00; 95% CI: 0.14-7.12). Patients with morbid obesity were also found to have an increased length of hospital stay and total cost. The rate of ERCP-related complications was comparable among the three groups except for a higher cholecystitis rate after ERCP in obese patients. CONCLUSIONS:Morbid obesity but not obesity was associated with increased mortality, length of stay, and total cost in patients undergoing ERCP.