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Diagnosis of cytomegalovirus (CMV) colitis in the setting of severe ulcerative colitis (UC) remains a clinical challenge. This study aimed to determine the utility of serum CMV polymerase chain reaction (PCR) as a non-invasive test for the diagnosis of CMV superinfection in patients hospitalized with UC.This retrospective study included consecutive admitted patients with UC who had serum testing for CMV completed as part of standard hospital procedure and CMV colitis diagnosed by expert pathologists.Two hundred and six patients with UC were included; 13 patients (6%) had histologically confirmed CMV colitis. Eleven of 13 patients with CMV colitis (84%) and 3 of 193 (1.5%) patients without CMV colitis had a positive serum PCR test (p 0.0001). ROC analysis showed that a CMV PCR level of 259 IU/mL had a sensitivity and specificity of 77% and 99%, respectively, for diagnosis of CMV colitis with an AUC of 0.9 (p 0.0001). Serum CMV PCR level significantly correlated to the number of inclusion bodies on biopsy specimens with data available (n = 8) (r = 0.8, p = 0.02). CMV positivity did not predict the need for salvage therapy, admission or 1-year colectomy rates.Serum CMV PCR has an excellent negative predictive value and demonstrates a strong correlation with CMV positivity on histology. This work supports a rationale for serum CMV PCR testing on admission to assess the risk of CMV colitis in patients with severe UC.

BackgroundClostridioides difficile infection (CDI) is a leading cause of health care–associated infection and may result in organ dysfunction, colectomy, and death. Published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately predict risk for complications from CDI.MethodsWe conducted a multicenter retrospective cohort study of adults diagnosed with CDI. After randomly partitioning the data into training and validation sets, we developed and compared 3 machine learning algorithms (lasso regression, random forest, stacked ensemble) with 10-fold cross-validation to predict disease-related complications (intensive care unit admission, colectomy, or death attributable to CDI) within 30 days of diagnosis. Model performance was assessed using the area under the receiver operating curve (AUC).ResultsA total of 3646 patients with CDI were included, of whom 217 (6%) had complications. All 3 models performed well (AUC, 0.88–0.89). Variables of importance were similar across models, including albumin, bicarbonate, change in creatinine, non-CDI-related intensive care unit admission, and concomitant non-CDI antibiotics. Sensitivity analyses indicated that model performance was robust even when varying derivation cohort inclusion and CDI testing approach. However, race was an important modifier, with models showing worse performance in non-White patients.ConclusionsUsing a large heterogeneous population of patients, we developed and validated a prediction model that estimates risk for complications from CDI with good accuracy. Future studies should aim to reduce the disparity in model accuracy between White and non-White patients and to improve performance overall.

BACKGROUND Drug-induced gastrointestinal injury has been increasingly reported, but its exact incidence is not known. The small and large intestines represent the most affected sites of injury, accounting for 20%-40% of all gastrointestinal side effects. AIM To provide an updated literature review detailing medications linked to the development of small bowel injury. METHODS We conducted a literature search on PubMed from its inception to May 1, 2021. We included English-language original studies, meta-analyses, systematic reviews, review articles and case reports. RESULTS Drug-induced enteropathy can range from asymptomatic histological changes resulting in a subtle, self-limited disease to a chronic inflammatory condition mimicking inflammatory bowel disease, or bowel perforation. Endoscopy can demonstrate erythema, mucosal friability, oedema, erosions, ulcers or strictures in severe cases. Histology may include mucosal erosions and ulcerations, focal active enteritis, villous atrophy, epithelial apoptosis or necrotising enteritis. A well-established association has been found with the use of nonsteroidal anti-inflammatory drugs, immunosuppressants, chemotherapeutic agents, antibiotics, immunotherapies, etanercept and olmesartan. Possible associations have been reported with other biologic agents, medications used for glycemic control, antihypertensives, cholinesterase inhibitors, potassium and iron supplements, with conflicting data regarding contraceptives/hormonal therapy and isotretinoin. CONCLUSION Physicians should be aware of the manifestations of drug-induced enteropathy as early recognition can lead to prompt discontinuation of the offending therapy and, therefore, a reduced risk of future complications.

Effective colon cancer screening requires adequate bowel preparation. Anecdotal evidence has suggested that patients with a history of bariatric surgery are more likely to have inadequate preparation. This study aims to evaluate the role of bariatric surgery as a predictive risk factor for inadequate bowel preparation.Data were collected retrospectively for consecutive colonoscopies between March 1, 2013, and November 15, 2017. Only the index colonoscopy for each patient within the review period, and those scored using the Boston Bowel Preparation Scale (BBPS) were included. Inadequate preparation was defined as any one or more colon segments with a BBPS score of less than two, and patients with a history of bariatric surgery were identified using ICD 9/10 codes. Multivariate logistic regression and propensity score matching was used to assess for independent factors predictive of inadequate bowel preparation.A total of 25,318 colonoscopies were included in the analysis. Two hundred 278 (1.1%) patients had a history of bariatric surgery, among which 171 (61.5%) had a history of bypass surgery and 107 (38.5%) had a history of restrictive surgical procedure. A history of bariatric surgery was predictive of inadequate bowel preparation in both univariate (OR: 2.87, 95% CI: 1.92-4.29, P = 0.0003) and multivariate analysis (OR: 2.16, 95% CI: 1.43-3.27, P = 0.0003) after controlling for differences in baseline characteristics. When evaluated separately, a history of bypass surgery was associated with inadequate bowel preparation (aOR: 2.96, 95% CI: 1.86-4.72, P 0.0001), whereas a history of a restrictive bariatric surgery was not associated with inadequate bowel preparation in multivariate analysis (aOR: 0.98, 95% CI: 0.4-2.45, P = 0.971).A history of bariatric surgery is an independent risk factor for inadequate bowel preparation. Furthermore, bypass bariatric surgeries had higher rates of inadequate preparation when compared to restrictive bariatric surgeries. Further quality improvement initiatives should be directed at identifying the appropriate bowel preparation regimen in this population.

Video capsule endoscopy (VCE) has become the accepted evaluation of choice for patients with suspected small bowel bleeding. Our aim was to evaluate the impact of early as compared to delayed inpatient VCE on post-index hospitalization readmission rates. We performed a retrospective study using medical claims from the IBM® Marketscan® Commercial Database from January 1, 2004, through September 30, 2018, including adult patients that underwent an inpatient VCE. Early VCE was defined as occurring on days 0, 1, or 2 of the index hospitalizations, whereas delayed VCE was performed on days 3–7. Propensity matching was performed to create an analytic cohort, and outcomes were assessed using logistic regression. Following propensity score matching, 607 patients undergoing early VCE were matched 1:1 with 607 patients undergoing delayed VCE. The median patient age was 65 (IQR: 56–78) years, and 560 (37.9%) of the included patients were female. The mean time to VCE was 1.6 (± 0.6) days for the early VCE group and 4.0 (± 1.2) days from admission for delayed VCE. In unadjusted comparisons, we found no significant difference between early VCE and delayed VCE with respect to 90-day all-cause readmission (18.6% vs. 17.0%, P = 0.5) or 90-day rebleeding risk (10.5% vs. 8.7%, P = 0.331). Patients undergoing an early VCE had a shorter hospital LOS and less total hospitalization charges. Early as compared to delayed inpatient VCE was associated with a reduction in index hospitalization resource utilization. No differences were found with respect to reductions in readmissions or rebleeding events.

Drug-induced colitis encompasses a wide spectrum of colon disorders that can manifest microscopically or macroscopically. Patients present with new-onset colitis or exacerbations of inflammatory bowel diseases; in some cases, colitis resolves with discontinuation of medication. Mucosal injury can be focal or extensive, involving the entire colonic mucosa, and sometimes involves other parts of the gastrointestinal tract. It has been a challenge to determine the proportion of new-onset colitis caused by medication and there are few data on the overall prevalence. We review the drugs that have been linked with development of drug-induced colitis and strategies for physicians who believe their patients have this disorder-usually discontinuation of the drug believed to cause colitis and treatment with steroids or immune-modulating therapies. Physicians must be aware of medications that can cause colitis.

Background Many models have been developed to predict severe outcomes from Clostridioides difficile infection (CDI). These models are usually developed at a single institution and largely are not externally validated. Our aim in this study was to validate previously published risk scores in a multicenter cohort of patients with CDI. Methods This was a retrospective study on 4 inpatient cohorts with CDI from 3 distinct sites: the universities of Michigan (2010–2012 and 2016), Chicago (2012), and Wisconsin (2012). The primary composite outcome was admission to an intensive care unit, colectomy, and/or death attributed to CDI within 30 days of positive testing. Both within each cohort and combined across all cohorts, published CDI severity scores were assessed and compared to each other and the Infectious Diseases Society of America (IDSA) guideline definitions of severe and fulminant CDI. Results A total of 3646 patients were included for analysis. Including the 2 IDSA guideline definitions, 14 scores were assessed. Performance of scores varied within each cohort and in the combined set (mean area under the receiver operator characteristic curve [AuROC], 0.61; range, 0.53–0.66). Only half of the scores had performance at or better than IDSA severe and fulminant definitions (AuROCs of 0.64 and 0.63, respectively). Most of the scoring systems had more false than true positives in the combined set (mean, 81.5%; range, 0%–91.5%). Conclusions No published CDI severity score showed stable, good predictive ability for adverse outcomes across multiple cohorts/institutions or in a combined multicenter cohort.

The goal of colorectal cancer (CRC) screening is to detect precancerous polyps before cancer development or identification of cancer at an early stage. Guidelines have recommended screening colonoscopy to start at age 45. Our aim was to determine the impact of delays in performing the first screening colonoscopy on the risk of adenoma or CRC detection.We analyzed colonoscopy and histopathology data of average CRC risk patients who had their first screening colonoscopy between 2010 and 2017. Univariate and multivariable logistic regression was performed to determine the association between demographic variables and the risk of adenomas or CRC.A total of 1155 average risk patients underwent their initial screening colonoscopy during the study period. Median age was 54 years (range of 45-87) and 58.2% were females. In multivariable analysis, older age at first screening colonoscopy was significantly associated with the detection of adenomatous polyps (odds ratio 1.05, 95% confidence interval 1.04-1.07, P0.001) and CRC (odds ratio 1.11, 95% confidence interval 1.06-1.16, P0.001). The association between age and risk of adenomatous polyps (F-test 35.43, P=0.0019) and CRC (F-test 36.94, P=0.0017) fit an exponential growth model. It was estimated that the detection rate doubled every 14.20 years and 4.75 years for adenomas and CRC, respectively.We found that older age at the initial performance of a screening colonoscopy was associated with increased detection of adenomatous polyps and CRC. This work highlights the need for guideline adherence for the prevention of CRC development.

ERAS protocols may reduce length of stay and return to full functional recovery after cytoreductive surgery and HIPEC. Prehabilitation programs and post-operative goal directed pathways, along with other essential components of ERAS are discussed with supporting evidence.

Background Patients with peritoneal carcinomatosis (PC) can develop malignant bowel obstructions (MBOs) requiring inpatient admission and nasogastric tube decompression. Palliative decompressive gastrostomy tubes (G-tubes) may affect patient disposition, allowing for self-management and reduction in inpatient services. Therefore, we sought to assess disposition and inpatient readmission rates in patients admitted with PC and MBO following G-tube placement. Methods The Vizient® Clinical Data Base was queried for inpatient admissions from October 2018 to May 2022 utilizing ICD-10 codes to identify patients admitted with PC and bowel obstruction, with or without G-tube placement. Demographics and hospital outcomes were recorded. Descriptive statistics and multivariate logistic regression analysis were performed. Results From 750 patients, 59 (7.9%) had a G-tube placed. Compared to patients without G-tubes, those with G-tubes had lower rates of disposition to home (32.2% vs 70.0%, P < .001) and higher rates of disposition to hospice (home: 30.5% vs 7.8%, P < .001, facility: 10.2% vs 3.9%, P = .02). There was no significant difference in the rate (17.3% vs 22.3%, P = .40) or risk (OR = 1.44, 95% CI .69-3.01) of 30-day readmissions with G-tubes. However, palliative care consultation (OR 33.77, 95% CI 19.16-59.52) and G-tube placement (OR 5.82, 95% CI 2.56-13.25) were independent predictors for hospice. Discussion Placement of G-tubes in patients with PC and MBO was associated with higher rates of disposition to hospice but there is no difference in 30-day readmission rates compared to those without G-tubes. Further prospective studies are needed to understand the role of G-tube placement in patients with MBO in relation to outcomes and disposition.

Background Respiratory tract infections (RTIs) and interstitial lung disease (ILD) secondary to interleukin (IL)-12/23 or IL-23 antagonists have been reported in autoimmune diseases. Objective To assess the risk of RTIs and non-infectious ILD with these drugs. Methods We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs). Risk of RTIs and non-infectious ILD was compared to placebo by Mantel-Haenszel (MH) risk difference (RD). We divided RTIs into upper RTIs (URTI), viral URTIs, and lower RTIs (LRTIs) including infectious pneumonia. Non-infectious ILD included ILD, eosinophilic pneumonia, and pneumonitis. Results We identified 54 RCTs including 10,907 patients with six IL-12/23 or IL-23 antagonists and 5,175 patients with placebo. These drugs significantly increased the risk of RTIs (MH RD 0.019, 95% confidence interval 0.005-0.033, P = 0.007) which was attributed to URTIs, but not viral URTIs or LRTIs. There was no significant difference in infectious pneumonia and non-infectious ILD between two groups. Limitations Due to the rarity of infectious pneumonia and ILD, sensitivity analysis was required. Conclusion The use of IL-12/23 or IL-23 antagonists for autoimmune diseases increased the risk of URTIs, but not viral URTIs, LRTIs, and non-infectious ILD.

Background and Aims: Vitamin D deficiency has been associated with disease activity in Crohn’s disease (CD). We assessed whether there is a correlation between vitamin D levels and the risk of postoperative recurrence in CD. Methods: CD patients who underwent surgery were identified from a prospectively maintained database at the University of Chicago. The primary endpoint was the correlation of serum 25-hydroxy vitamin D levels measured at 6–12 months after surgery and the proportion of patients in endoscopic remission, defined as a simple endoscopic score for CD of 0. Clinical, biological (C-reactive protein), and histologic recurrences were also studied. Results: Among a total of 89 patients, 17, 46, and 26 patients had vitamin D levels of 30 ng/mL, respectively. Patients with higher vitamin D levels were significantly more likely to be in endoscopic remission compared to those with lower levels (23, 42, and 67% in ascending tertile order; p = 0.028). On multivariate analysis, vitamin D >30 ng/mL (odds ratio [OR] 0.22, 95% confidence interval [CI] 0.07–0.66, p = 0.006) and anti-tumor necrosis factor agent treatment (OR 0.25, 95% CI 0.08–0.83, p = 0.01) were associated with reduced risk of endoscopic recurrence. Rates of clinical, biological, and histologic remission trended to be higher in patients with higher vitamin D levels (p = 0.17, 0.55, 0.062, respectively). Conclusion: In the present study, higher vitamin D level was associated with lower risk of postoperative endoscopic CD recurrence. Further, studies are warranted to assess the role of vitamin D in postoperative CD recurrence.

BackgroundClostridioides difficile infection (CDI) is a leading cause of healthcare-associated infections and may result in organ dysfunction, colectomy, and death. We recently showed that published risk scores to predict severe complications from CDI demonstrate poor performance upon external validation. We hypothesized that building and validating a model using geographically and temporally distinct cohorts would more accurately identify patients at risk for complicated CDI.MethodsWe conducted a multi-center retrospective cohort study of adult subjects diagnosed with CDI in the US. After randomly partitioning the data into training/validation set, we developed and compared three machine learning algorithms (Lasso regression, random forest, stacked ensemble models) with 10-fold cross-validation that used structured EHR data collected within 48 hours of CDI diagnosis to predict disease-related complications from CDI (intensive care unit admission, colectomy, or death attributable to CDI within 30 days of diagnosis). Model performance was assessed using area under the receiver operating curve (AUC).ResultsA total of 3,762 patients with CDI were included of which 218 (5.8%) had complications. Lasso regression, random forest, and stacked ensemble models all performed well with AUC ranging between 0.89-0.9. Variables of importance were similar across models, including albumin, bicarbonate, change in creatinine, systolic blood pressure, non-CDI-related ICU admission, and concomitant non-CDI antibiotics. Sensitivity analyses indicated that model performance was robust even when varying derivation cohort inclusion and CDI testing approach.ConclusionUsing a large heterogeneous population of patients, we have developed and validated a prediction model based on structured EHR data that accurately estimates risk for complications from CDI.Key PointsMachine learning models using structured electronic health records can be leveraged to accurately predict risk of severe complications related to Clostridiodes difficile infection, including intensive care unit admission, colectomy, and/or death.

Introduction Clostridioides difficile infection (CDI) rates and outcomes can vary based on differences in testing strategy. Our aim was to assess the prevalence of toxin detection in inflammatory bowel disease (IBD) when compared to those without IBD. Secondly, the clinical outcomes of CDI in IBD were assessed using two-step testing strategies. Methods We included patients undergoing CDI testing from four academic centers in the United States between January 1, 2018 and June 30, 2020. First the prevalence of toxin detection was compared between individuals with IBD and those without IBD. Secondly, among patients with IBD a primary composite outcome of abdominal colectomy, admission to an intensive care unit (ICU) or death within 30 days of C. difficile testing was assessed across the three categorical groups (screen positive/toxin positive, screen positive/toxin negative and screen negative assay) resulting from the two-step testing strategy. Results When comparing individuals with a positive screening assay, patients with IBD were less likely to have toxin detected by enzyme immunoassay (EIA) as compared to the non-IBD population (22/145 (15.2%) vs. 413/1144 (36.1%), p Conclusion When compared to those without IBD, patients with IBD have a reduced proportion of cases of C. difficile with toxin positivity. Differences in clinical outcomes among patients with IBD were not detected and limited by the infrequent detection of expressed toxin.

ObjectivesThe prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases who are frequently treated with disease modifying therapies remains poorly understood. This meta-analysis aims to assess the prevalence and clinical outcomes of COVID-19 in autoimmune diseases.MethodsElectronic databases were searched for observational and case–controlled studies. We sorted medications into glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and biologic or targeted synthetic DMARDs (b/tsDMARDs), which was also divided into monotherapy and b/tsDMARDs–csDMARDs combination therapy.ResultsWe analysed 62 observational studies with a total of 319 025 patients with autoimmune diseases. The prevalence of COVID-19 was 0.011 (95% CI: 0.005 to 0.025). Meta-analysis of seven case–controlled studies demonstrated that the risk of COVID-19 in autoimmune diseases was significantly higher than in control patients (OR: 2.19, 95% CI: 1.05 to 4.58, p=0.038). Meta-regression analysis showed glucocorticoids were significantly associated with the risk of COVID-19. For clinical outcomes, we assessed 65 studies with 2766 patients with autoimmune diseases diagnosed with COVID-19. The rates of hospitalisation and mortality were 0.35 (95% CI: 0.23 to 0.50) and 0.066 (95% CI: 0.036 to 0.12), respectively. Glucocorticoids, csDMARDs and b/tsDMARDs–csDMARDs combination therapy increased the risk of these outcomes, whereas b/tsDMARDs monotherapy, particularly antitumour necrosis factor agents, were associated with a lower risk of hospitalisation and death.ConclusionsOur meta-analysis demonstrated that patients with autoimmune diseases had an increased risk of COVID-19, primarily attributed to glucocorticoid use. b/tsDMARDs monotherapy was associated with a lower risk of severe COVID-19 suggesting its safety in the COVID-19 pandemic.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is an important prognostic factor for outcomes in patients with cirrhosis. Antibiotic prophylaxis is recommended in patients at high risk for developing SBP, but the choice of antibiotics remains unclear. AIM: To evaluate the efficacy of various antibiotics for prophylaxis of SBP based on randomized control trials (RCTs). METHODS: Electronic databases were searched through November 2018 for RCTs evaluating the efficacy of therapies for primary or secondary prophylaxis of SBP. The primary outcome was the development of SBP. Sensitivity analyses limited to studies of primary or secondary prophylaxis and studies reported after 2010 were performed. The secondary outcome was the risk of all-cause mortality or transplant. The outcomes were assessed by rank of therapies based on network meta-analyses. Individual meta-analyses were also performed. RESULTS: Thirteen RCTs (1742 patients) including norfloxacin, ciprofloxacin, rifaximin, trimethoprim-sulfamethoxazole (TMP-SMX), or placebo/no comparator were identified. Individual meta-analyses showed superiority of rifaximin over norfloxacin as well as norfloxacin and TMP-SMX over placebo. Network meta-analysis demonstrated the rank of efficacy in reducing the risk of SBP as: Rifaximin, ciprofloxacin, TMP-SMX, norfloxacin, and placebo/no comparator. Rifaximin ranked highest in sensitivity analyses limited to studies of primary or secondary prophylaxis and studies reported after 2010. Similarly, rifaximin ranked highest in reducing the risk of death/transplant. CONCLUSION: The present comprehensive network meta-analysis provides RCT based evidence for superior efficacy of rifaximin compared to other antibiotics for the prophylaxis of SBP and reducing risk of death/transplant. Further RCTs are warranted to confirm our findings.

Background The aim of this study was to quantify the long-term clinical outcomes for individuals receiving teduglutide for short-bowel syndrome (SBS). Methods A single-center, retrospective study was performed for individuals commencing use of teduglutide between March 2013 and May 2019. Results Eighteen patients were included in the final analysis, among which the median duration of teduglutide administration was 3.2 (range, 0.6-6.2) years. Twelve of 16 (75%) patients at 12 months, 10 of 13 (76.9%) at 24 months, 7 of 10 (70%) at 36 months, and 3 of 3 (100%) at 60 months had a response to teduglutide therapy, defined as a >20% reduction in parenteral support (PS) requirement. Among responders at 12, 24, and 36 months, the presence of a colon-in-continuity, an ileocecal valve, a response at 3 months, the length of small bowel, nor the baseline volume affected response to therapy (P > .05 for all comparisons). Five (28%) patients were able to achieve freedom from PS, among which all had a history of Crohn's disease with loss of the ileocecal valve and among which 3 had a colon-in-continuity. Four of the 5 patients discontinued PS by 6 months of teduglutide therapy. Conclusions In a real-world experience, teduglutide therapy results in rapid and sustained reductions in PS. Larger postmarketing studies will be required to reliably predict response to treatment and the factors associated with enteral autonomy.

The Chicago Consensus Working Group provides multidisciplinary recommendations for palliative care specifically related to peritoneal surface malignancies. These guidelines are developed with input from leading experts including surgical oncologists, medical oncologists, gynecologic oncologists, pathologists, radiologists, palliative care physicians, and pharmacists. These guidelines recognize and address the emerging need for increased awareness in the appropriate management of peritoneal surface disease. They are not intended to replace the quest for higher levels of evidence.

Bile acid receptors regulate the metabolic and immune functions of circulating enterohepatic bile acids. This process is disrupted by administration of parenteral nutrition (PN), which may induce progressive hepatic injury for unclear reasons, especially in the newborn, leading to PN-associated liver disease. To explore the role of bile acid signaling on neonatal hepatic function, we initially observed that Takeda G protein receptor 5 (TGR5)-specific bile acids were negatively correlated with worsening clinical disease markers in the plasma of human newborns with prolonged PN exposure. To test our resulting hypothesis that TGR5 regulates critical liver functions to PN exposure, we used TGR5 receptor deficient mice (TGR5−/−). We observed PN significantly increased liver weight, cholestasis, and serum hepatic stress enzymes in TGR5−/− mice compared with controls. Mechanistically, PN reduced bile acid synthesis genes in TGR5−/−. Serum bile acid composition revealed that PN increased unconjugated primary bile acids and secondary bile acids in TGR5−/− mice, while increasing conjugated primary bile acid levels in TGR5-competent mice. Simultaneously, PN elevated hepatic IL-6 expression and infiltrating macrophages in TGR5−/− mice. However, the gut microbiota of TGR5−/− mice compared with WT mice following PN administration displayed highly elevated levels of Bacteroides and Parabacteroides, and possibly responsible for the elevated levels of secondary bile acids in TGR5−/− animals. Intestinal bile acid transporters expression was unchanged. Collectively, this suggests TGR5 signaling specifically regulates fundamental aspects of liver bile acid homeostasis during exposure to PN. Loss of TGR5 is associated with biochemical evidence of cholestasis in both humans and mice on PN. NEW & NOTEWORTHY Parenteral nutrition is associated with deleterious metabolic outcomes in patients with prolonged exposure. Here, we demonstrate that accelerated cholestasis and parental nutrition-associated liver disease (PNALD) may be associated with deficiency of Takeda G protein receptor 5 (TGR5) signaling. The microbiome is responsible for production of secondary bile acids that signal through TGR5. Therefore, collectively, these data support the hypothesis that a lack of established microbiome in early life or under prolonged parenteral nutrition may underpin disease development and PNALD.

Background Intestinal failure-associated liver disease (IFALD) is one of the leading complications in type III intestinal failure (IF). Early recognition of liver-fibrosis development in IFALD is crucial to the development of strategies aimed at reducing the risk of complications secondary to IFALD. Our aim was to identify patients with advanced fibrosis using a noninvasive index and to study the risk factors for fibrosis development in the Sustain registry. Methods Using the Sustain registry, patients requiring >3 months of parenteral nutrition (PN) support were identified. The presence or absence of advanced fibrosis was identified using the Fibrosis-4 (FIB-4) index. Risk factors for the presence of a high FIB-4 score were identified using univariable logistic regression. Results Two hundred seventy-one adult patients were included. Sixty-three patients (23.2%) were at risk for advanced fibrosis based on the FIB4-index. Risk factors for advanced fibrosis included short-bowel syndrome (odds ratios [ORs]: 1.84; 95% confidence interval [CI], 1.03-3.28), receipt of PN for >1 year (OR: 2.6; 95% CI, 1.46-4.64), receipt of PN for >5 years (OR: 3.05; 95% CI, 1.67-5.59), and days of lipid emulsion use (OR: 1.11; 95% CI, 1-1.24). Small-intestine-remnant length was inversely associated with advanced fibrosis (OR: 0.97, 95% CI, 0.95-0.99). Conclusion Advanced fibrosis, as guided by FIB-4 index, is associated with known risk factors for IFALD. Therefore, the FIB-4 index is potentially a useful noninvasive tool for identification of individuals at risk for fibrosis in IFALD. Further studies utilizing a gold-standard fibrosis assessment will be required to validate these results.

Background Anti-TNF therapy remains the cornerstone of moderate to severe inflammatory bowel disease (IBD) treatment. There are few data regarding switching from subcutaneous (SubQ) to intravenous (IV) agents. We evaluated the clinical utility of cycling adalimumab (ADA) for infliximab (IFX) in IBD patients (pts) treated at a tertiary center. Methods This is a retrospective observational study where we evaluated pts with IBD who cycled from ADA to IFX from 2010 to 2018. Pts were followed for 1 year following IFX initiation. We reviewed baseline demographic and clinical data. Primary outcomes included changes in CRP and clinical disease activity indices which were statistically analyzed using Wilcoxon Signed Rank Test. Results 24 pts with Crohn’s disease (CD) and 11 with ulcerative colitis (UC) were included. Median age at time of IFX initiation in the overall cohort was 33 years with median disease duration of 10 years. Most pts in the UC cohort had pancolitis (63.6%), while the CD cohort mostly had ileocolonic disease (79.2%). Prior to IFX initiation, median baseline CRP was 8 (IQR 15), with median HBI of 3.5 (IQR 5), and SCCAI of 3.5 (IQR 4) in the CD and UC cohorts, respectively. Additional baseline demographics are in Table 1. Following median 12 months on ADA therapy in the overall cohort, 16 pts (45.7%) discontinued ADA due to primary or secondary loss of response, 8 pts (22.8%) due to anti-drug antibody formation, and 11 pts (31.4%) due to adverse events or unclear causes. At the time of starting IFX therapy, 17 pts (48.6%) were using steroids, while 24 pts (68.6%) were on immunomodulatory therapy. In the overall cohort, after cycling to IFX, median CRP was lower at 8 weeks (4; IQR 9), 26 weeks (3; IQR 11), and 52 weeks (5; IQR 10) as compared to baseline; only the 8 week CRP reached statistical significance (P=0.0447, 0.0662, and 0.0876, respectively). In the CD cohort, median CRP was significantly lower at 8 weeks (7; IQR 6; P=0.0314) and 52 weeks (5; IQR 7; P=.0410) as compared to baseline (12.5; IQR 14). Although signals of median HBI and SCCAI scores trended lower after 8 weeks, 26 weeks, and 52 weeks of IFX therapy, these did not reach statistical significance. A total of 15 pts (43.0%) stopped IFX prior to one year. Subgroup analysis of 5 pts who developed anti-ADA antibodies demonstrated statistically significant reduction of median CRP (10; IQR 22.5; P=.043) after 52 weeks of IFX therapy. Additional results are detailed in Table 2. Conclusion Cycling anti-TNF therapy from ADA to IFX offers clinical utility in preserving mechanistic benefit of TNF-α blockade in IBD pts leading to improvement of CRP, particularly in CD pts and those who developed immunogenicity to ADA.

Background Models to predict colectomy in ulcerative colitis (UC) are valuable for identification, clinical management, and follow-up of high-risk patients. Our aim was to develop a clinical predictive model based on admission data for one-year colectomy in adults hospitalized for severe UC. Methods We performed a retrospective analysis of patients hospitalized at a tertiary academic center for management of severe UC from 1/2013 to 4/2018. Multivariate regression was performed to identify individual predictors of one-year colectomy. Outcome probabilities of colectomy based on the prognostic score were estimated using a bootstrapping technique. Results Two hundred twenty-nine individuals were included in the final analytic cohort. Four independent variables were associated with one-year colectomy which were incorporated into a point scoring system: (+) 1 for single class biologic exposure prior to admission; (+) 2 for multiple classes of biologic exposure; (+) 1 for inpatient salvage therapy with cyclosporine or a TNF-alpha inhibitor; (+) 1 for age Conclusion Risk factors most associated with one-year colectomy for severe UC included: prior biologic exposure, need for inpatient salvage therapy, and younger age. We developed a simple scoring system using these variables to identify and stratify patients during their index hospitalization.

Background New onset IBD has been reported with the use of anti-IL-17 agents, but it remains unclear to what extent this is attributed to treatment or to underlying disease. Aim To evaluate the risk of new onset IBD with the use of anti-IL-17 agents METHODS: Electronic databases were searched for randomised controlled trials (RCT) of anti-IL-17 agents (brodalumab, ixekizumab and secukinumab). Risk of new onset IBD was compared to placebo by Mantel-Haenszel (MH) risk difference (RD). Sensitivity analyses including meta-analysis using fixed-effect model, MH and Peto odds ratio and MH risk ratio were performed due to incidence of rare adverse events. The risk of diarrhoea was also assessed due to the possibility of underdiagnosis of IBD. Results Thirty-eight RCTs including 16 690 patients treated with anti-IL-17 agents were included. Twelve cases of new onset IBD were reported with anti-IL-17 agents in five studies, whereas no cases were reported with placebo. There was no difference in the risk of developing new onset IBD with anti-IL-17 agents compared to placebo (MH RD 0.00062, 95% CI -0.00072-0.0021, P = 0.35). Sensitivity analyses demonstrated no consistent risk with any method. There was no difference in the risk of diarrhoea (MH RD 0.0013, 95% CI -0.0014-0.0041, P = 0.34). Conclusions New onset IBD with the use of anti-IL-17 agents was rare. Interpretation of the results needs caution due to the presence of many zero-event studies.

The 2010 Affordable Care Act introduced the Hospital Readmissions Reduction Program to reduce health care utilization. Diverticular disease and its complications remain a leading cause of hospitalization among gastrointestinal disease. We sought to determine risk factors for 30-day hospital readmissions after hospitalization for diverticular bleeding.We utilized the 2013 National Readmission Database sponsored by the Agency for Healthcare Research and Quality focusing on hospitalizations with the primary or secondary discharge diagnosis of diverticular hemorrhage or diverticulitis with hemorrhage. We excluded repeat readmissions, index hospitalizations during December and those resulting in death. Our primary outcome was readmission within 30 days of index hospital discharge. Secondary outcomes of interest included medical and procedural comorbid risk factors. The data were analyzed using logistic regression analysis.In total, 29,090 index hospitalizations for diverticular hemorrhage were included. There were 3484 (12%) 30-day readmissions with recurrent diverticular hemorrhage diagnosed in 896 (3%).Index admissions with renal failure [odds ratio (OR), 1.31; 95% confidence interval (CI), 1.19-1.43], congestive heart failure (OR, 1.30; 95% CI, 1.17-1.43), chronic pulmonary disease (OR, 1.19; 95% CI, 1.09-1.29), coronary artery disease (OR, 1.12; 95% CI, 1.03-1.21), atrial fibrillation (OR, 1.12; 95% CI, 1.02-1.22) cirrhosis (OR, 1.95; 95% CI, 1.29-2.93, performance of blood transfusion (OR, 1.23; 95% CI, 1.15-1.33), and abdominal surgery (OR, 1.24; 95% CI, 1.03-1.49) had increased risk of 30-day readmission.The 30-day readmission rate for diverticular hemorrhage was 12% with multiple identified comorbidities increasing readmission risk.

Background Patients with immune-mediated disorders such as ankylosing spondylitis, inflammatory bowel disease, psoriasis and rheumatoid arthritis are increasingly treated with tumor necrosis factor (TNF) inhibitors. The safety of anti-TNF therapy in patients with a history of cancer requires further evaluation. We conducted a systematic review and a meta-analysis of observational studies including patients with a history of cancer exposed to anti-TNF therapy assessing for a risk of new cancer or cancer recurrence. Materials and methods A computerized literature search of MEDLINE, Google scholar, and Cochrane Database of Systematic Reviews was performed through September 1, 2015. Study characteristics, quality, and risk of bias were assessed. Random-effects model meta-analyses were used to estimate the risk of new cancer development or cancer recurrence. Results Nine English-language observational studies including patients with a history of cancer and exposed to anti-TNF therapy were idenitifed. The pooled incidence rate ratio of new or recurrent cancer among individuals with a history of cancer exposed to anti-TNF therapy was not significantly different compared with control therapies (incidence rate ratio, 0.90; 95% confidence interval, 0.59-1.37). Subgroup analyses were performed according to disease type, underlying cancer diagnosis, time to initiation of anti-TNF therapy and study quality. Heterogeneity of study populations, heterogeneity of the included cancer subtypes and utilization of observational studies limits the study quality. Conclusions The risk of new cancer or cancer recurrence among patients with a history of cancer and use of anti-TNF therapy is similar to the risk with nonbiological disease modifying therapies. These results support the use of anti-TNF medications in select populations despite prior diagnosis of cancer.

Background/Aims: Perianal fistulas are a debilitating manifestation of Crohn’s disease (CD). Despite the advent of anti-tumor necrosis factor (anti-TNF) therapy, the medical management of fistulizing CD continues to be challenged by unmet needs. We conducted a systematic review and meta-analysis of the effectiveness of vedolizumab for the management of perianal fistulizing CD.Methods: A search of PubMed, EMBASE and the Cochrane Library was performed from inception to June 2020 for studies reporting rates of perianal fistula healing in CD patients treated with vedolizumab. The primary outcome of interest was complete healing of perianal fistulas and the secondary outcome was partial healing. The pooled fistula healing rates with 95% confidence intervals (CI) were calculated utilizing a random effects model.Results: A total of 74 studies were initially identified, 4 of which met the inclusion criteria. A total of 198 patients with active perianal fistulas were included, 87% of whom had failed previous anti-TNF therapy. The pooled complete healing rate was 27.6% (95% CI, 18.9%–37.3%) with moderate heterogeneity (I2=49.4%) and the pooled partial healing rate was 34.9% (95% CI, 23.2%–47.7%) with high heterogeneity (I2=67.1%).Conclusions: In a meta-analysis of 4 studies that included 198 patients with perianal fistulizing CD, the majority of whom had failed previous anti-TNF therapy, vedolizumab treatment led to healing of perianal fistulas in nearly one-third of the patients. The lack of high-quality data and significant study heterogeneity underscores the need for future prospective studies of fistula healing in patients receiving anti-integrin therapy.

Video capsule endoscopy (VCE) has become the accepted evaluation of choice for patients with suspected small bowel bleeding. Our aim was to evaluate the impact of early as compared to delayed inpatient VCE on post-index hospitalization readmission rates.We performed a retrospective study using medical claims from the IBM® Marketscan® Commercial Database from January 1, 2004, through September 30, 2018, including adult patients that underwent an inpatient VCE. Early VCE was defined as occurring on days 0, 1, or 2 of the index hospitalizations, whereas delayed VCE was performed on days 3-7. Propensity matching was performed to create an analytic cohort, and outcomes were assessed using logistic regression.Following propensity score matching, 607 patients undergoing early VCE were matched 1:1 with 607 patients undergoing delayed VCE. The median patient age was 65 (IQR: 56-78) years, and 560 (37.9%) of the included patients were female. The mean time to VCE was 1.6 (± 0.6) days for the early VCE group and 4.0 (± 1.2) days from admission for delayed VCE. In unadjusted comparisons, we found no significant difference between early VCE and delayed VCE with respect to 90-day all-cause readmission (18.6% vs. 17.0%, P = 0.5) or 90-day rebleeding risk (10.5% vs. 8.7%, P = 0.331). Patients undergoing an early VCE had a shorter hospital LOS and less total hospitalization charges.Early as compared to delayed inpatient VCE was associated with a reduction in index hospitalization resource utilization. No differences were found with respect to reductions in readmissions or rebleeding events.

Video capsule endoscopy and device-assisted enteroscopy are complementary technologies. Capsule endoscopy is a highly acceptable technology with high diagnostic yield that can guide a subsequent enteroscopy approach. This article aims to focus on the role of video capsule endoscopy as a prelude to deep enteroscopy with a focus on the strengths and limitations of either approach.

The purpose of this article is to provide an updated review of the definition, prevalence, causes, and clinical management of malnutrition in inflammatory bowel disease (IBD). Prevalence of malnutrition in IBD is estimated to be between 6.1% and 69.7% depending on the definition used, the type of IBD, the clinical setting, and whether the IBD is active or in remission. Whereas older definitions of malnutrition have been found to be correlated with mortality and length of hospital stay, the more recent European Society for Clinical Nutrition and Metabolism (ESPEN) 2015 and the Global Leadership Initiative on Malnutrition (GLIM) definitions provide significantly different prevalence estimates of malnutrition when applied to the same patient population, and further work is needed to validate these two definitions against clinical outcomes. In patients with IBD with identified malnutrition, oral nutrition supplementation, enteral nutrition, or parenteral nutrition should be started. In malnourished patients with Crohn's disease undergoing surgery, preoperative enteral nutrition has been demonstrated to reduce the rate of postoperative complications. Overall, patients with IBD are at significant risk for malnutrition and should be screened for malnutrition by using a validated screening tool. The management of malnutrition in IBD is complex, and studies are often limited in their size or their ability to demonstrate an improvement in clinical outcomes based on specific nutrition-related interventions. Future studies particularly regarding the validation of new screening tools and perioperative management of malnutrition may provide insight into the standardization of diagnosis and management of malnutrition in IBD.

We thank Lee1 for his comments to our research article ‘Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis’.2 In our study, included patients were likely on glucocorticoids (GCs) for their underlying autoimmune diseases (ADs), not for COVID-19-associated pneumonia and cytokine release syndrome. Hence, our data suggested the possibility of harmful effects of chronic use of GCs on the risk of developing SARS-CoV-2 infection and severe COVID-19. We were unable to analyse the therapeutic effect of GCs in patients with ADs who developed COVID-19 pneumonia. As stated in the correspondence by Lee,1 a systematic review and …