Faculty Bibliography

Remdesivir has been the mainstay of coronavirus disease 2019 treatment since the start of the severe acute respiratory syndrome coronavirus 2 pandemic. Despite its growing use, safety data are limited. We present the case of an elderly man with obesity and coronavirus disease 2019 who developed acute liver failure after initiation of remdesivir. This report broadens our knowledge of the side effect profile of remdesivir and discusses potential risk factors and an approach to remdesivir-induced liver failure. Our case also highlights the importance of monitoring hepatic function after initiation of therapy with remdesivir.

Rhythm control strategies in patients with esophageal varices and atrial arrhythmias pose a unique challenge. The left atrium should be imaged for a thrombus prior to attempting cardioversion or ablation, but the presence of varices is a relative contraindication for transesophageal echocardiography. We present a safe, novel technique of evaluating for left atrial thrombus with simultaneous transesophageal echocardiography and esophagogastroduodenoscopy using slim probes in a patient with large, high-risk esophageal varices, and symptomatic atrial flutter with rapid ventricular rates despite medical therapy.

BACKGROUND & AIMS/OBJECTIVE:The incidence of colorectal cancer (CRC) is increasing in individuals younger than 50 years, who do not usually undergo screening if they are of average risk. We sought to identify risk factors for CRC in this population. METHODS:We compared sociodemographic and medical characteristics of patients who received a diagnosis of CRC at an age of 18-49 years (early-onset) with patients who received a diagnosis of CRC at an age of 50 years or older (late-onset) and with age-matched, cancer-free individuals (controls) at a tertiary academic hospital. We collected data from all adult patients with a diagnosis of CRC from January 1, 2011 through April 3, 2017 from electronic health records. Associations with risk factors were assessed using univariable and multivariable logistic regression models. RESULTS:We identified 269 patients with early-onset CRC, 2802 with late-onset CRC, and 1122 controls. Compared with controls, patients with early-onset CRC were more likely to be male (odds ratio [OR], 1.87; 95% CI, 1.39-2.51), have inflammatory bowel disease (IBD) (3% vs 0.4% for controls; univariable P<.01), and have a family history of CRC (OR, 8.61; CI, 4.83-15.75). Prevalence values of well-established modifiable CRC risk factors, including obesity, smoking, and diabetes, were similar. Compared to patients with late-onset CRC, patients with early-onset CRC were more likely to be male (OR, 1.44; 95% CI, 1.11-1.87), black (OR, 1.73; 95% CI, 1.08-2.65) or Asian (OR, 2.60; 95% CI, 1.57-4.15), and have IBD (OR, 2.97; 95% CI, 1.16-6.63) or a family history of CRC (OR, 2.87; 95% CI, 1.89-4.25). Sensitivity analyses excluding IBD and family history of CRC showed comparable results. Early-onset CRC was more likely than late-onset disease to be detected in the left colon or rectum (75% vs 59%, P=.02) and at a late stage of tumor development (77% vs 62%, P=.01). CONCLUSIONS:In a retrospective study of patients with early-onset CRC vs late-onset CRC or no cancer, we identified non-modifiable risk factors, including sex, race, IBD, and family history of CRC, to be associated with early-onset CRC.

INTRODUCTION: Gastrointestinal symptoms of SARS-CoV-2 infection common, but usually mild in severity. We describe a case of severe gastrointestinal bleeding (GIB) in a patient with a COVID-19 associated hyperinflammatory response. CASE DESCRIPTION/METHODS: A 25-year-old man with no significant medical history presented with 2 weeks of fevers, cough, dyspnea, and diarrhea. He tested positive for COVID-19 on nasopharyngeal PCR and imaging showed multifocal pneumonia. Initial labs were notable for markedly elevated CRP and ferritin, pancytopenia and acute kidney injury. He was treated for suspected COVID-19 associated hyperinflammatory syndrome with anakinra (5 mg/kg twice daily) and hydroxychloroquine. He became anuric requiring hemodialysis and renal biopsy complicated by retroperitoneal bleeding and emergent embolization of the left renal artery. He was intubated for worsening acute respiratory distress syndrome (ARDS) and developed hematemesis and melena leading to hemorrhagic shock. EGD showed diffuse inflammation, erosions and oozing from the esophagus to the proximal duodenum, non-bleeding gastric ulcers and petechiae (Figure 1A, B). Given clinical suspicion for COVID-19 associated macrophage activation syndrome (MAS)/ secondary hemophagocytic lymphohistiocytosis (sHLH), anakinra was restarted and intravenous immunoglobulin (IVIG, 1mg/kg) was given with clinical improvement. The patient continued to have melena. Repeat EGD showed severe esophagitis with large clots and sloughing mucosa, a focal 3-4 cm area of necrosis in the fundus, unresolved non-bleeding stomach ulcers and improved duodenitis from prior (Figure 1C, D). DISCUSSION: We describe a case of a young adult who developed catastrophic GIB as a complication of COVID-19. The pathogenesis of SARS-CoV2 infection is incompletely understood, but there is mounting evidence that it can induce a MAS/sHLH-like hyperinflammatory response. Several laboratory hallmarks of COVID-19 infection are also seen in MAS/sHLH including elevated CRP, ferritin, IL-1, and IL-6. This hyperinflammatory response can manifest in a variety of ways, including a Kawasaki-like presentation in pediatric patients responsive to IVIG and IL-1 antagonism. GIB is rare in COVID-19, occurring in 4% of cases, but can occur in up to 20% of MAS/sHLH cases. Clinicians should recognize that COVID-19 can provoke a MAS/sHLH-like hyperinflammatory syndrome with gastrointestinal involvement

GOALS/BACKGROUND/OBJECTIVE:Patients who "no-show" for colonoscopy or present with poor bowel preparation waste endoscopic resources and do not receive adequate examinations for colorectal cancer (CRC) screening. Using the Health Belief Model, we modified an existing patient education pamphlet and evaluated its effect on nonattendance rates and bowel preparation quality. STUDY/METHODS:We implemented a color patient education pamphlet to target individual perceptions about CRC and changed bowel preparation instructions to include a low-residue diet instead of the previous clear liquid diet. We compared the nonattendance rate over a 2-month period before and after the introduction of the pamphlet, allowing for a washout period during which pamphlet use was inconsistent. We compared the Boston Bowel Preparation Scale (BBPS) in 100 consecutive patients who underwent colonoscopy during each of the 2 periods. RESULTS:Baseline characteristics between the 2 groups were similar, although patients who received the pamphlet were younger (P=0.03). The nonattendance rate was significantly lower in patients who received the pamphlet (13% vs. 21%, P=0.01). The percentage of patients with adequate bowel preparation increased from 82% to 86% after introduction of the pamphlet, although this was not statistically significant (P=0.44). The proportion of patients with a BBPS score of 9 was significantly higher in the pamphlet group (41% vs. 27%, P=0.03). There was no difference in adenoma and sessile serrated adenoma detection rates before and after pamphlet implementation. CONCLUSIONS:After implementing a theory-based patient education intervention with a low-residue diet, our absolute rate for colonoscopy nonattendance decreased by 8% and the proportion of patients with a BBPS score of 9 increased by 14%. The Health Belief Model appears to be a useful construct for CRC screening interventions.

BACKGROUND:Because most pancreatic intraductal papillary mucinous neoplasms (IPMNs) will never become malignant, currently advocated long-term surveillance is low-yield for most individuals. AIM:To develop a score chart identifying IPMNs at lowest risk of developing worrisome features or high-risk stigmata. METHODS:We combined prospectively maintained pancreatic cyst surveillance databases of three academic institutions. Patients were included if they had a presumed side-branch IPMN, without worrisome features or high-risk stigmata at baseline (as defined by the 2012 international Fukuoka guidelines), and were followed ≥ 12 months. The endpoint was development of one or more worrisome features or high-risk stigmata during follow-up. We created a multivariable prediction model using Cox-proportional logistic regression analysis and performed an internal-external validation. RESULTS:875 patients were included. After a mean follow-up of 50 months (range 12-157), 116 (13%) patients developed worrisome features or high-risk stigmata. The final model included cyst size (HR 1.12, 95% CI 1.09-1.15), cyst multifocality (HR 1.49, 95% CI 1.01-2.18), ever having smoked (HR 1.40, 95% CI 0.95-2.04), history of acute pancreatitis (HR 2.07, 95% CI 1.21-3.55), and history of extrapancreatic malignancy (HR 1.34, 95% CI 0.91-1.97). After validation, the model had good discriminative ability (C-statistic 0.72 in the Mayo cohort, 0.71 in the Columbia cohort, 0.64 in the Erasmus cohort). CONCLUSION:In presumed side branch IPMNs without worrisome features or high-risk stigmata at baseline, the Dutch-American Risk stratification Tool (DART-1) successfully identifies pancreatic lesions at low risk of developing worrisome features or high-risk stigmata.

Objectives To develop a score chart to identify IPMN with low risk to progress and fulfill resection criteria. Methods We retrospectively reviewed the prospectively-maintained databases of three international academic institutions, containing patients with a pancreatic cystic lesion identified in the period 2003-2015. Patients were included if they had a presumed IPMN on imaging, no worrisome features or high-risk stigmata at baseline, as defined by the 2012 international Fukuoka guidelines, and were followed at least 12 months. Fulfilling resection criteria was defined as any of the following: jaundice, an enhancing solid component, main pancreatic duct 5 mm, cyst size 3 cm, non-enhancing mural nodule, abrupt change in caliber of pancreatic duct with distal pancreatic atrophy, and cytology suspect or positive for malignancy. A multivariable prediction model was developed with cox proportional hazard regression analysis using stepwise backward selection. The prediction model was internally validated with bootstrap resampling. The Dutch American Risk stratification Tool (DART-I) was developed to identify patients with low risk to progress and fulfill the resection criteria. Results 559 patients with presumed IPMN were included (mean age 65 years, 38% male, 72% Caucasian). After a mean follow-up of 48 months (range 12-157) and a total follow-up of 2,254 person-years, 71 patients progressed to fulfill resection criteria. Age, history of diabetes, BMI, smoking, cyst size, and cyst multifocality were analyzed as predictors. The final model included cyst size (HR 1.11, 95% CI 1.08-1.16), cyst multifocality (HR 2.26, 95% CI 1.39-3.65), and smoking (1.53, 95% CI 0.94-2.50) and had a moderate discriminative ability (C-statistic 0.705, corrected for optimism). When using the DART-I (figure 1), a patient with unifocal IPMN <10 mm and without a history of smoking has a predicted 3-year risk of 1-2% and 5-year risk of 2-5% to progress and fulfill resection criteria. The Dutch American Risk stratification Tool (DART-I) to identify IPMN with low risk to progress and fulfill resection criteria. Conclusion In presumed IPMNs without worrisome features or highrisk stigmata, the DART-I score chart successfully identifies lesions with low risk to progress and fulfill resection criteria. When validated, this model may be used to explore strategies that will reduce unnecessary surveillance (Figure presented)