Risk of Small Intestine Cancer in Inflammatory Bowel Disease: A Propensity-Matched Study from a Large Multi-Center Database in the United States.

INTRODUCTION: The risk of small bowel cancer (SBC) in inflammatory bowel disease (IBD) is unclear. We compared the recent trends of SBC in patients with IBD and stratified them based on disease type. METHODS: We used TriNetX database to access the electronic health records for patients with IBD, ulcerative colitis (UC) and Crohn's disease (CD) from 2005-2024. We used propensity score matching to compare the rate of SBC in patients with IBD, UC, and CD compared to the general population. We adjusted for all known confounders. RESULTS: From 2010-2024, there was an increasing trend of diagnosed SBC in patients with IBD, with an Average Annual Percentage Change (AAPC) of 3.2% (P<0.001). Patients with CD (aHR = 4.83; 95% CI: 3.58 - 6.53; P < .0001) had an increased risk of SBC compared to the general population without IBD, as well as patients with UC (aHR = 2.28; 95% CI: 1.65 - 3.14; P < .0001). The ileum was the most common location across all subgroups. CONCLUSION: Both patients with CD and, interestingly, UC had an elevated risk for developing SBC compared to the general population.

Sphingosine 1-phosphate (S1P) receptor modulators as an induction and maintenance therapy for ulcerative colitis: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND OBJECTIVE: One sphingosine-1-phosphate (S1P) receptor modulator is approved (ozanimod) and another (etrasimod) is under investigation for the induction and maintenance of remission of ulcerative colitis (UC). We aim to evaluate the efficacy and safety of S1P modulators in patients with active UC. METHODS: We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through May 13th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) with a 95% confidence interval (CI). RESULTS: Five RCTs with a total of 1990 patients were included. S1P receptor modulators were significantly associated with increased clinical response during both the induction (RR 1.71 with 95% CI [1.50, 1.94], P = 0.00001) and maintenance phases (RR 1.89 with 95% CI [1.33, 2.69], P = 0.0004); clinical remission rates during both induction (RR 2.76 with 95% CI [1.88, 4.05], P = 0.00001) and maintenance phases (RR 3.34 with 95% CI [1.41, 7.94], P = 0.006); endoscopic improvement during both induction (RR 2.15 with 95% CI [1.71, 2.70], P = 0.00001) and maintenance phases (RR 2.41 with 95% CI [1.15, 5.05], P = 0.02); and histologic remission during both induction (RR 2.60 with 95% CI [1.89, 3.57] [1.17, 2.10], P = 0.00001) and maintenance phases (RR 2.52 with 95% CI [1.89, 3.37], P = 0.00001). Finally, there was no difference regarding safety outcomes as compared to placebo in both the induction and maintenance phases. CONCLUSION: S1P receptor modulators are effective in inducing and maintaining remission in patients with moderate to severe UC.

Applicability of Child-Turcotte-Pugh Score in Anticipating Post-ERCP Adverse Events in Patients With Cirrhosis: A Systematic Review and Meta-analysis.

Limited objective data exist on the comparison of post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with cirrhosis based on the severity of the disease. We evaluated the effectiveness of the Child-Turcotte-Pugh (CTP) score system in anticipating the risk of post-ERCP complications in patients with cirrhosis. The PubMed, Scopus, Embase, and Cochrane databases were searched from inception through September 2022 to identify studies comparing post-ERCP complications in patients with cirrhosis based on CTP score. Odds ratios (ORs) and their associated 95% CIs were pooled using a random-effect model to calculate effect size. The reference group for analysis was the CTP class C patient group. Seven studies comprising 821 patients who underwent 1068 ERCP procedures were included. The CTP class C patient population exhibited a higher risk of overall post-ERCP adverse events compared with those with class A or B (OR: 2.87, 95% CI: 1.77-4.65, P = 0.00 and OR: 2.02, 95% CI: 1.17-3.51, P = 0.01, respectively). Moreover, CTP class B patients had a significantly higher complication rate than CTP class A patients (OR: 1.62, 95% CI: 1.04-2.53, P = 0.03). However, no statistically significant differences were found in the occurrence of specific types of complications, including bleeding, pancreatitis, cholangitis, perforation, or mortality across the three CTP groups. We demonstrated that the CTP classification system is a reliable predictor of ERCP complications in patients with cirrhosis. Consequently, caution should be exercised when performing ERCP in patients classified as CTP class C.

Factors That Influence the Speed and Completion of Double Balloon Enteroscopy in Patients with Arteriovenous Malformations.

BACKGROUND: Double balloon enteroscopy remains a resource and time-intensive procedure that is not available in many endoscopy units. AIMS: We aimed to identify variables impacting the speed and completion of double balloon enteroscopy. METHODS: We retrospectively reviewed 550 patients. Using a mean time and distance for both the antegrade and retrograde approach, we determined the procedure speed and assessed factors that influenced it. In addition, we assessed the factors that contributed to a complete double balloon enteroscopy. RESULTS: A total of 386 antegrade and 164 retrograde double balloon enteroscopies were performed. Greater than 10 AVMs requiring treatment was a negative predictor (AOR 0.25, CI 0.11-0.51, p < 0.001), whereas age greater than 60 years (AOR 2.66, CI 1.18-6.65, p = 0.025) was a positive predictor of a fast antegrade enteroscopy. For retrograde, prior abdominal surgery was the only factor that trended to significance (AOR 0.38, CI 0.14-0.99, p = 0.052). A total of 120 combined procedures were performed. Female gender (AOR 2.62, CI 1.16-6.24, p = 0.02), history of prior abdominal surgery (AOR 0.31, CI 0.13-0.70, p = 0.006) and Boston bowel pre-preparation score of greater than 6 (AOR 4.50, CI 1.59-14.30, p = 0.006) were the only significant predictors of a complete procedure. CONCLUSION: By applying double balloon enteroscopy speed, a novel method of measuring procedure efficiency, we were able to more reliably identify the factors that will negatively impact the speed and success of the procedure.

Abnormal findings on abdominopelvic cross-sectional imaging in patients with microscopic colitis: a retrospective, multicenter study.

OBJECTIVES: Patients with microscopic colitis may have subtle macroscopic findings on colonoscopy such as erythema, edema, or altered vascular pattern; however, radiographic abnormalities on cross-sectional imaging have not been investigated. We aimed at identifying the abdominopelvic radiographic abnormalities in patients with microscopic colitis, as well as possible correlation with endoscopic findings and the need for extended duration of treatment. MATERIALS AND METHODS: This was a retrospective study of patients with biopsy-proven microscopic colitis at two tertiary centers between 1 January 2010 and 30 April 2020. Patients underwent computed tomography scan or magnetic resonance imaging within 30 days of a diagnostic flexible sigmoidoscopy or colonoscopy. Patients with colon ischemia and other causes of colitis were excluded. Radiographic abnormalities from imaging reports included bowel wall thickening, mucosal hyperenhancement and mesenteric fat stranding. Univariate and multivariable logistic regression models were used to identify predictors of radiographic abnormalities. RESULTS: 498 patients with microscopic colitis underwent abdominopelvic cross-sectional imaging within 30 days of flexible sigmoidoscopy/colonoscopy. Lymphocytic colitis was diagnosed in 54.6% of patients, and collagenous colitis in 45.4%. Endoscopic and radiographic abnormalities were identified in 16.1% and 12.4% of patients, respectively. Radiographic abnormalities were associated with the need for budesonide therapy (p = .029) and budesonide therapy long-term (p = .0028). Budesonide therapy long-term (p = .047) was associated with radiographic abnormalities in multivariate analysis. CONCLUSIONS: Radiographic abnormalities may be present on abdominopelvic cross-sectional imaging in a minority of patients with biopsy-proven microscopic colitis, suggesting cross-sectional imaging has low clinical value in the evaluation and treatment of this disease.

Incidentalomas are associated with an increase in liver transplantation in patients with cirrhosis: a single-center retrospective study.

BACKGROUND: Incidentalomas, defined as incidental findings on imaging, are a growing concern. Our aim was to determine the impact and outcomes of extrahepatic incidentalomas on liver transplantation. METHODS: Patients at a large liver transplant center, who had an initial MRI for hepatocellular carcinoma screening between January 2004 and March 2020 were identified. Clinical data were collected retrospectively. Survival analysis, utilizing Kaplan Meier estimates and Cox proportional hazards regression analysis, was utilized to determine factors associated with liver transplantation. RESULTS: 720 patients were included. NASH (24.9%), HCV (22.1%) and alcohol (20.6%) were the most common causes of cirrhosis. 79.7% of patients had an extrahepatic incidentaloma. Older age and having received a liver transplant by the end of the study were associated with an incidentaloma. MELD was not associated with the presence of an incidentaloma. On univariate Cox proportional hazards regression, male sex, history of moderate alcohol use, smoking history, MELD, and incidentalomas were predictors of liver transplantation. On multivariate analysis, only MELD and the presence of an incidentaloma were found to be significant. Discovery of an incidentaloma was associated with a 30% increase in the risk of liver transplantation. Median time to transplantation did not differ based on the presence on an incidentaloma. Patients with cirrhosis from alcohol or HCV had a significantly shorter median time to transplantation than those with NASH. Renal and pancreatic lesions comprised 91% of all incidentalomas. CONCLUSIONS: In this single-center retrospective study, extrahepatic incidentalomas were common in patients with cirrhosis. The finding of an incidentaloma was associated with a higher risk of liver transplantation despite a similar median time to transplantation if no incidentaloma was discovered.

Endoscopic Management of Luminal Strictures: Beyond Dilation.

Luminal strictures can occur as part of many different gastrointestinal (GI) disorders anywhere along the GI tract and affect all age groups. The end goal of managing any stricture is to re-establish an adequate and durable luminal patency that is sufficient to resolve the presenting clinical symptoms. Treatment options can be generally categorized into medical, endoscopic, and surgical. However, within each of these categories, multiple different options are available. Therefore, choosing the best treatment modality is often challenging and depends on multiple factors including the type, location, and complexity of the stricture, as well as the preference of the treating physician. In this article, we will review the most current literature regarding foregut strictures, particularly esophageal and gastric, beyond dilation.

Colchicine as an Alternative First-Line Treatment of Sclerosing Mesenteritis: A Retrospective Study.

BACKGROUND: Sclerosing mesenteritis is a rare condition characterized by chronic inflammation and fibrotic changes of the mesentery. AIMS: To determine the long-term management and outcomes of patients with sclerosing mesenteritis. METHODS: Patients with biopsy-proven sclerosing mesenteritis at the Mayo Clinic between January 2006 and December 2016 were identified. Clinical data were collected retrospectively. RESULTS: One hundred and three patients were identified, median age 68.0 years (range 35.0-85.3). Most patients were symptomatic (87.4%) at presentation. Patients received no treatment (52.4%), medical therapy (42.7%) or surgery (4.9%) on initial diagnosis. The most common initial regimens were prednisone plus tamoxifen (41.9%), prednisone alone (23.3%), and prednisone plus colchicine (11.6%) with 55.6%, 57.2%, and 60% of patients improving, respectively, p = 0.85 for a difference in response rates. At least half of the patients responded to prednisone plus tamoxifen, prednisone plus colchicine, or prednisone alone at 6.0, 7.2, and 8.4 months, respectively. At a median follow-up of 45.6 months (95% CI 24.1-69.7), 65.4% of patients were receiving medical therapy. Of those receiving tamoxifen-based, steroid-based, or steroid-sparing regimens, 100%, 87.5%, and 77.8% had improved by their last follow-up appointment respectively, p = 0.15. CONCLUSION: Prednisone plus colchicine has a similar efficacy to prednisone plus tamoxifen for the initial and long-term treatment of sclerosing mesenteritis. The majority of patients were initiated on medical therapy over the long term with most reporting symptomatic improvement within a year. Death from SM was rare.

Lymphocytic Esophagitis: Assessing Risk Factors and Clinical Outcomes.

BACKGROUND: Lymphocytic esophagitis is a rare esophageal condition. Our knowledge of potential risk factors and treatment outcomes of lymphocytic esophagitis is limited. AIM: To investigate potential risk factors associated with the development of lymphocytic esophagitis and compare clinical characteristics and treatment outcomes of patients diagnosed with lymphocytic esophagitis to patients diagnosed with eosinophilic esophagitis. METHODS: This is a multicenter retrospective study. Lymphocytic esophagitis patients were identified based on pathology results between 1997 and 2019. Control groups consisted of patients with normal esophageal biopsies and patients diagnosed with eosinophilic esophagitis. Thirteen potential risk factors for lymphocytic esophagitis were analyzed using univariate and multivariate models including IBD, achalasia, hyperlipidemia, hypothyroidism, celiac sprue, CVID, H. pylori, thymoma, aspirin, opioids, ACE-I, metformin, and statin use. Comparative statistics were performed. RESULTS: Ninety-four adult patients with lymphocytic esophagitis, 344 with eosinophilic esophagitis, and 5202 control patients with normal esophageal biopsies were analyzed. Age older than 60 [adjusted odd ratio (AOR) 1.03, 95% CI 1.02-1.05, p = 0.001], aspirin use (2.7, 95% CI 1.4-4.9, p = 0.001), statin use (2.2, 95% CI 1.2-4.2, p = 0.01), or a diagnosis of achalasia (2.4, 95% 1.08-5.67, p = 0.03) were associated with lymphocytic esophagitis. Compared to eosinophilic esophagitis, lymphocytic esophagitis patients were more likely to respond to medical treatment (95% CI 2.54-12.8, p = 0.0001). CONCLUSIONS: Our data suggests that lymphocytic esophagitis is more likely to be found in older female patients and is significantly associated with achalasia, statin, and aspirin use. Compared to eosinophilic esophagitis, lymphocytic esophagitis is more likely to respond to treatment with medical therapy.

Hepatocellular Carcinoma Detection by Plasma Methylated DNA: Discovery, Phase I Pilot, and Phase II Clinical Validation.

Early detection improves hepatocellular carcinoma (HCC) outcomes, but better noninvasive surveillance tools are needed. We aimed to identify and validate methylated DNA markers (MDMs) for HCC detection. Reduced representation bisulfite sequencing was performed on DNA extracted from 18 HCC and 35 control tissues. Candidate MDMs were confirmed by quantitative methylation-specific PCR in DNA from independent tissues (74 HCC, 29 controls). A phase I plasma pilot incorporated quantitative allele-specific real-time target and signal amplification assays on independent plasma-extracted DNA from 21 HCC cases and 30 controls with cirrhosis. A phase II plasma study was then performed in 95 HCC cases, 51 controls with cirrhosis, and 98 healthy controls using target enrichment long-probe quantitative amplified signal (TELQAS) assays. Recursive partitioning identified best MDM combinations. The entire MDM panel was statistically cross-validated by randomly splitting the data 2:1 for training and testing. Random forest (rForest) regression models performed on the training set predicted disease status in the testing set; median areas under the receiver operating characteristics curve (AUCs; and 95% confidence interval [CI]) were reported after 500 iterations. In phase II, a six-marker MDM panel (homeobox A1 [HOXA1], empty spiracles homeobox 1 [EMX1], AK055957, endothelin-converting enzyme 1 [ECE1], phosphofructokinase [PFKP], and C-type lectin domain containing 11A [CLEC11A]) normalized by beta-1,3-galactosyltransferase 6 (B3GALT6) level yielded a best-fit AUC of 0.96 (95% CI, 0.93-0.99) with HCC sensitivity of 95% (88%-98%) at specificity of 92% (86%-96%). The panel detected 3 of 4 (75%) stage 0, 39 of 42 (93%) stage A, 13 of 14 (93%) stage B, 28 of 28 (100%) stage C, and 7 of 7 (100%) stage D HCCs. The AUC value for alpha-fetoprotein (AFP) was 0.80 (0.74-0.87) compared to 0.94 (0.9-0.97) for the cross-validated MDM panel (P < 0.0001). Conclusion: MDMs identified in this study proved to accurately detect HCC by plasma testing. Further optimization and clinical testing of this promising approach are indicated.

Aspirin use and the risk of cholangiocarcinoma.

UNLABELLED: Whether aspirin use is protective against cholangiocarcinoma (CCA) remains unclear. We determined the association between aspirin use and other risk factors for each CCA subtype individually. In a hospital-based case-control study, 2395 CCA cases (1169 intrahepatic, 995 perihilar, and 231 distal) seen at the Mayo Clinic, Rochester, MN, from 2000 through 2014 were enrolled. Controls selected from the Mayo Clinic Biobank were matched two to one with cases by age, sex, race, and residence (n = 4769). Associations between aspirin use, other risk factors, and CCA risk were determined. Aspirin was used by 591 (24.7%) CCA cases and 2129 (44.6%) controls. There was a significant inverse association of aspirin use with all CCA subtypes, with adjusted odds ratios (AORs) of 0.35 (95% confidence interval [CI], 0.29-0.42), 0.34 (95% CI 0.27-0.42), and 0.29 (95% CI 0.19-0.44) for intrahepatic, perihilar, and distal CCA, respectively (P < 0.001 for all). Primary sclerosing cholangitis was more strongly associated with perihilar (AOR = 453, 95% CI 104-999) than intrahepatic (AOR = 93.4, 95% CI 27.1-322) or distal (AOR = 34.0, 95% CI 3.6-323) CCA, whereas diabetes was more associated with distal (AOR = 4.2, 95% CI 2.5-7.0) than perihilar (AOR = 2.9, 95% CI 2.2-3.8) or intrahepatic (AOR = 2.5, 95% CI 2.0-3.2) CCA. Cirrhosis not related to primary sclerosing cholangitis was associated with both intrahepatic and perihilar CCA, with similar AORs of 14. Isolated inflammatory bowel disease without primary sclerosing cholangitis was not associated with any CCA subtype. CONCLUSIONS: Aspirin use was significantly associated with a 2.7-fold to 3.6-fold decreased risk for the three CCA subtypes; our study demonstrates that individual risk factors confer risk of different CCA subtypes to different extents. (Hepatology 2016;64:785-796).

The national burden of inflammatory bowel disease in the United States from 1990-2019: results from the Global Burden of Disease study database.

Background: Inflammatory bowel disease (IBD) epidemiology has changed rapidly in recent years. We aimed to provide a systematic report of the burden of IBD at a state level in the United States (US), and to study the age- and sex-specific trends of incidence, prevalence and mortality rates for the past 3 decades. Methods: Using the Global Burden of Disease (GBD) 2019 Study Database, we examined the incidence, prevalence and mortality rate, and the disability-adjusted life-years from GBD 2019 at national and state level from 1990-2019. Results: There was an overall decrease in incidence and prevalence rates of IBD in the US from 1990-2019, while a simultaneous increase in the overall mortality rates was identified. However, a distinct trend of increasing incidence and prevalence rates emerged starting in 2000, with incidence rates rising from 21 cases per 100,000 persons in 2000 to 23 cases per 100,000 persons in 2019. From 1990-2019, incidence and prevalence decreased in males at a higher rate than in females. However, mortality rates increased more in females than males. Incidence rates were highest in Midwestern and Eastern states, and were lowest across the northern Great Plains and Western states, with the highest incidence noted in Michigan (31 cases per 100,000 persons). California had the greatest decrease in incidence rates from 1990-2019 (-63.3%). Conclusion: Our results concerning recent trends and geographic variations in IBD offer policymakers crucial insights for informed decision-making in policy, research, and investment, facilitating more effective strategies and allocation of resources.

Pre- and Post-Implant Endoscopy in Left Ventricular Assist Device Recipients: A Single-Center Experience.

Background: Gastrointestinal bleeding (GIB) is common in left ventricular assist devices (LVADs) patients, but the optimal screening approach before LVAD implantation is still unclear. The aim of the study was to describe our experience with pre- and post-LVAD implantation endoscopic screening and subsequent GI bleeding in this cohort. Methods: A retrospective review was conducted among all patients who underwent LVAD implantation at Saint Luke's Hospital, between 2010 and 2020. The data were reviewed to determine the yield and safety of endoscopic procedures performed within 1 month before LVAD placement and the incidence of GIB within 1 year after implantation. Results: A total of 167 LVAD patients met the inclusion criteria, and 23 underwent pre-implantation endoscopic evaluation. Angiodysplasia had a significantly higher odds ratio (OR) of 9.41 (95% confidence interval (CI): 2.01 - 44.09) in post-LVAD endoscopy, while there was no significant difference in bleeding from other sources such as peptic ulcer disease or diverticular bleeding. There was no difference in the incidence of GIB in patients who underwent endoscopic evaluation pre-LVAD compared to post-LVAD GIB (32.6% vs. 39.1%, P = 0.64). Endoscopy was well-tolerated in this cohort, and argon plasma coagulation was the most commonly used intervention to achieve hemostasis. Conclusions: According to our results, we recommend against routine pre-LVAD endoscopic screening. Instead, we suggest an individualized approach, where decisions are made on a case-by-case basis.

Inpatient outcomes of inflammatory bowel disease in hospitalized patients with COVID-19: analysis of a nationally representative sample.

Purpose: To compare the risks of adverse outcomes, including mortality, gastrointestinal bleeding, and venous thromboembolism, between COVID-19 patients with inflammatory bowel disease (IBD) and those without IBD. Methods: We analyzed data from the National Inpatient Sample between January and December 2020. The study included adult patients with Crohn's disease (CD) and ulcerative colitis (UC) who contracted COVID-19. Inpatient outcomes were compared between the IBD and non-IBD COVID-19 cohorts. Results: Out of 1,050,045 COVID-19 hospitalizations, 0.28% had CD (2954 patients) and 0.26% had UC (2794 patients). After adjusting for confounding factors, UC patients had a significantly higher risk of deep vein thrombosis compared to non-IBD patients, with an adjusted odds ratio (aOR) of 2.55 (P < 0.001). However, CD patients did not show a significant association with deep vein thrombosis (aOR 1.29, P = 0.329). There were no significant associations between IBD patients (both UC and CD) and pulmonary embolism, nonvariceal gastrointestinal bleeding, or in-hospital mortality. UC patients had a longer average hospital stay (8.25 days) compared to non-IBD patients (adjusted mean difference 0.89, P = 0.007). Healthcare resource utilization was similar among the three groups. Conclusion: Our national study on COVID-19 hospitalizations indicates that patients with IBD have comparable rates of gastrointestinal bleeding, pulmonary embolism, and mortality as those without IBD. However, patients with UC hospitalized with COVID-19 have a higher risk of deep vein thrombosis than COVID-19 patients hospitalized without UC. Further research is needed to better understand the relationship between COVID-19 and IBD.

Endoscopic Ultrasound-Guided Fine-Needle Biopsy Versus Aspiration for Tissue Sampling Adequacy for Molecular Testing in Pancreatic Ductal Adenocarcinoma.

BACKGROUND AND AIMS: There is limited literature on sample adequacy for molecular testing in pancreatic ductal adenocarcinoma obtained via endoscopic ultrasound (EUS) fine-needle aspiration (FNA) versus EUS fine-needle biopsy (FNB). We aimed to compare these two modalities regarding sample adequacy for molecular and genomic sequencing. METHODS: We reviewed all patients with pancreatic ductal adenocarcinoma who underwent EUS at Saint Luke's Hospital from 2018 to 2021. The patients were categorized based on the method of EUS tissue acquisition, specifically FNA or FNB. A comprehensive evaluation was conducted for all cases by cytotechnologists. RESULTS: Out of 132 patients who underwent EUS-guided biopsies, 76 opted for FNA, 48 opted for FNB, and 8 opted for a combination of both. The average number of passes required for FNB and FNA was 2.58 ± 1.06 and 2.49 ± 1.07, respectively (p = 0.704), indicating no significant difference. Interestingly, 71.4% (35) of FNB-obtained samples were deemed adequate for molecular testing, surpassing the 32.1% (26) adequacy observed with FNA (p < 0.001). Additionally, 46.4% (26) of FNB-obtained samples were considered adequate for genomic testing, a notable improvement over the 23.8% (20) adequacy observed with FNA (p = 0.005). CONCLUSION: Although the number of passes required for cytologic diagnosis did not differ significantly between EUS-FNB and EUS-FNA, the former demonstrated superiority in obtaining samples adequate for molecular testing. Tumor surface area and cellularity were crucial parameters in determining sample adequacy for molecular testing, irrespective of the chosen tissue acquisition modality.

Systemic Lupus Erythematosus in Disguise: Acute Pancreatitis as Initial Presentation.

Macrophage activation syndrome (MAS) can rarely coexist with lupus pancreatitis. We report on a 20-year-old woman with abdominal pain, nausea, and vomiting. Laboratories were notable for pancytopenia, elevated liver enzymes, elevated ferritin, lipase, and triglycerides. Chest and abdominal computerized tomography (CT) scans revealed bilateral axillary lymphadenopathy, patchy lower lobe consolidations, small pleural effusions, ascites, and splenomegaly. Peritoneal fluid cytology showed lymphocytes and histiocytes with hemophagocytic changes. Immunological workup met the criteria for systemic lupus erythematosus (SLE). Pulse-dosed steroids relieved her condition. Given the high mortality rate associated with MAS, early detection of concomitant pancreatitis and MAS in the context of underlying SLE is critical.

Pilot Study: Personalized Medicine in Endoscopy, Can Pharmacogenomics Predict Response to Conscious Sedation?

BACKGROUND: Adequate response to moderate (conscious) sedation varies significantly between individuals. Polymorphisms in genes encoding drug metabolizing enzymes can lead to inter-individual variability in drug efficacy, potentially influencing sedation requirements during endoscopic procedures. OBJECTIVES: The aim of this study was to assess the potential role of inter-individual variation in inherited polymorphisms of drug-metabolizing enzymes, cytochrome P450 (CYP450), specifically CYP3A4 and CYP3A5, in sedation requirements for outpatient endoscopic procedures. METHODS: A retrospective analysis of sedation requirements and pharmacogenomics data in 106 unique patients who received outpatient esophagogastroduodenoscopy (EGD), colonoscopy, or both between December 2011 and February 2019 was conducted. Patients were divided into two groups based on their sedation requirements during endoscopy (high vs. normal sedation). RESULTS: Patients with reduced a CYP2C19 metabolism (poor + intermediate metabolizers) (odds ratio [OR] = 0.38, 95% confidence interval [CI]: 0.16-0.91, p = 0.03), poor CYP3A5 metabolism (OR = 0.25, 95% CI: 0.095-0.65, p = 0.0046), and poor UGT1A1 (OR = 2.76, 95% CI: 1.07-7.13, p = 0.08) had higher odds of requiring normal sedation compared to those with CYP2C19 increased metabolism, CYP3A5 intermediate metabolism, and UGT1A1 intermediate metabolism. CONCLUSION: Information about inter-individual variation in (CYP450) genes may be useful for determining the sedation requirements for outpatient endoscopic procedures. We found that patients with reduced CYP2C19 metabolism, poor CYP3A5 metabolism, and poor UGT1A1 metabolism were more likely to require normal sedation requirements during outpatient endoscopic procedures.