Intestinal Host Response to SARS-CoV-2 Infection and COVID-19 Outcomes in Patients With Gastrointestinal Symptoms.

BACKGROUND & AIMS: Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of COVID-19, we investigated intestinal infection with SARS-CoV-2, its effect on pathogenesis, and clinical significance. METHODS: Human intestinal biopsy tissues were obtained from patients with COVID-19 (n = 19) and uninfected control individuals (n = 10) for microscopic examination, cytometry by time of flight analyses, and RNA sequencing. Additionally, disease severity and mortality were examined in patients with and without GI symptoms in 2 large, independent cohorts of hospitalized patients in the United States (N = 634) and Europe (N = 287) using multivariate logistic regressions. RESULTS: COVID-19 case patients and control individuals in the biopsy cohort were comparable for age, sex, rates of hospitalization, and relevant comorbid conditions. SARS-CoV-2 was detected in small intestinal epithelial cells by immunofluorescence staining or electron microscopy in 15 of 17 patients studied. High-dimensional analyses of GI tissues showed low levels of inflammation, including down-regulation of key inflammatory genes including IFNG, CXCL8, CXCL2, and IL1B and reduced frequencies of proinflammatory dendritic cells compared with control individuals. Consistent with these findings, we found a significant reduction in disease severity and mortality in patients presenting with GI symptoms that was independent of sex, age, and comorbid illnesses and despite similar nasopharyngeal SARS-CoV-2 viral loads. Furthermore, there was reduced levels of key inflammatory proteins in circulation in patients with GI symptoms. CONCLUSIONS: These data highlight the absence of a proinflammatory response in the GI tract despite detection of SARS-CoV-2. In parallel, reduced mortality in patients with COVID-19 presenting with GI symptoms was observed. A potential role of the GI tract in attenuating SARS-CoV-2-associated inflammation needs to be further examined.

The Natural History, Treatments, and Outcomes of Portal Vein Thrombosis in Patients With Inflammatory Bowel Disease.

BACKGROUND: Portal vein thrombosis (PVT) is a poorly described complication of inflammatory bowel disease (IBD). We sought to better characterize presentations, compare treatments, and assess outcomes in IBD-related PVT. METHODS: We conducted a retrospective investigation of IBD-related PVT at our institution. Multivariable Cox proportional hazards modeling was used to estimate adjusted hazard ratios across treatments. RESULTS: Sixty-three patients with IBD-related PVT (26 with Crohn disease, 37 with ulcerative colitis) were followed for a median 21 months (interquartile ratio [IQR] = 9-52). Major risk factors included intra-abdominal surgery (60%), IBD flare (33%), and intra-abdominal infection (13%). Primary hematologic thrombophilias were rare and did not impact management. Presentations were generally nonspecific, and diagnosis was incidental. Ninety-two percent of patients (58/63) received anticoagulation (AC), including 23 who received direct oral anticoagulants (DOACs), 22 who received warfarin, and 13 who received enoxaparin. All anticoagulated patients started AC within 3 days of diagnosis. Complete radiographic resolution (CRR) of PVT occurred in 71% of patients. We found that DOACs were associated with higher CRR rates (22/23; 96%) relative to warfarin (12/22; 55%): the hazard ratio of DOACs to warfarin was 4.04 (1.83-8.93; P = 0.0006)). Patients receiving DOACs required shorter courses of AC (median 3.9 months; IQR = 2.7-6.1) than those receiving warfarin (median 8.5 months; IQR = 3.9-NA; P = 0.0190). Incidence of gut ischemia (n = 3), symptomatic portal hypertension (n = 3), major bleeding (n = 4), and death (n = 2) were rare, and no patients receiving DOACs experienced these adverse outcomes. CONCLUSIONS: We show that early and aggressive use of AC can lead to excellent outcomes in IBD-associated PVT and that DOACs are associated with particularly favorable outcomes in this setting.

Gastrointestinal involvement attenuates COVID-19 severity and mortality.

Given that gastrointestinal (GI) symptoms are a prominent extrapulmonary manifestation of coronavirus disease 2019 (COVID-19), we investigated intestinal infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and its effect on disease pathogenesis. SARS-CoV-2 was detected in small intestinal enterocytes by immunofluorescence staining or electron microscopy, in 13 of 15 patients studied. High dimensional analyses of GI tissues revealed low levels of inflammation in general, including active downregulation of key inflammatory genes such as IFNG, CXCL8, CXCL2 and IL1B and reduced frequencies of proinflammatory dendritic cell subsets. To evaluate the clinical significance of these findings, examination of two large, independent cohorts of hospitalized patients in the United States and Europe revealed a significant reduction in disease severity and mortality that was independent of gender, age, and examined co-morbid illnesses. The observed mortality reduction in COVID-19 patients with GI symptoms was associated with reduced levels of key inflammatory proteins including IL-6, CXCL8, IL-17A and CCL28 in circulation but was not associated with significant differences in nasopharyngeal viral loads. These data draw attention to organ-level heterogeneity in disease pathogenesis and highlight the role of the GI tract in attenuating SARS-CoV-2-associated inflammation with related mortality benefit. ONE SENTENCE SUMMARY: Intestinal infection with SARS-CoV-2 is associated with a mild inflammatory response and improved clinical outcomes.

Accelerated Infliximab Dosing Increases 30-Day Colectomy in Hospitalized Ulcerative Colitis Patients: A Propensity Score Analysis.

Background: Standard outpatient induction dosing of infliximab (IFX) may not be effective in hospitalized ulcerative colitis (UC) patients with higher inflammatory burden and colectomy risk. Our aim was to determine whether initial IFX induction dose affects 30-day colectomy rate and other disease-related outcomes. Methods: IFX-naive hospitalized UC patients receiving at least 1 inpatient 5 mg/kg (SD) or 10 mg/kg (HD) IFX induction dose were included. Baseline demographics and admission-related characteristics were documented. Propensity score based matching was used to control for provider bias introduced due to nonprotocolized choice of IFX dose. The primary outcome was 30-day colectomy; secondary outcomes included the need for an accelerated induction IFX (AD), length of stay (LOS), 90-day and 1-year colectomy, and complications. Results: Of 146 (120 SD/26 HD) patients included, 25 (17.1%) underwent colectomy by 30 days, 33 (22.6%) by 90 days, and 41 (28.1%) by 1 year. In 21 propensity score matched dyads (n = 42) treated with SD or HD, colectomy rates and LOS were similar. SD patients more often needed AD (23.8% vs. 0%, P = 0.048) and AD patients progressed to colectomy more rapidly within 30 days compared to non-AD (P = 0.001). Female sex and hypoalbuminemia were associated with significantly increased odds of needing AD on both univariate and multivariate analyses. Conclusions: In our propensity score based analysis, receiving accelerated IFX dosing after an initial SD infusion was associated with significantly higher 30-day colectomy rates in hospitalized acute UC patients. The most effective dosing strategy in this population remains unclear and prospective randomized studies are needed.

There is Significant Practice Pattern Variability in the Management of the Hospitalized Ulcerative Colitis Patient at a Tertiary Care and IBD Referral Center.

BACKGROUND AND GOALS: Despite published clinical guidelines, substantive data underlying the approach to the management of hospitalized ulcerative colitis (UC) patients failing outpatient therapy are lacking. Variability in practice is therefore not uncommon and may impact clinical outcomes. The degree of variability, however, is not well-studied. Our aim was to evaluate variability in management of the hospitalized UC patient to inform future efforts targeting care optimization for this high-risk population. STUDY: An internet survey was distributed among inflammatory bowel disease providers, which included: (1) nonvignette-based questions assessing provider demographics, experience, and practice setting; (2) diagnostic and therapeutic practice patterns based on a vignette of a hospitalized UC patient. Descriptive and univariate analyses were performed. RESULTS: Ninety-one percent of eligible individuals were included. Nearly 97% endorsed confidence in management of hospitalized UC patients. In general, 83% initiate intravenous corticosteroids (IVCS) as initial therapy, whereas 17% initiate infliximab (IFX) (+/-IVCS). At IVCS failure in the vignette, 74% initiated IFX, 15% increased IVCS dose, 7% initiated cyclosporine, and 4% chose colectomy. Of those choosing IFX, 65% chose 5 mg/kg as the initial dose, whereas the remainder chose 10 mg/kg. Twenty-eight percent gave an additional IFX 5 mg/kg and 7% gave an additional 10 mg/kg dose to the patient in the vignette not responding to 5 mg/kg. CONCLUSIONS: Even among experienced inflammatory bowel disease providers, there is significant practice pattern variability in the management of hospitalized UC patients. Future efforts should target this variability. Adjunctively, prospective trials are needed to guide appropriate therapeutic algorithms, especially with respect to positioning and optimally dosing IFX in this population.

Acute graft-versus-host disease of the gut: considerations for the gastroenterologist.

Haematopoietic stem cell transplantation (HSCT) is central to the management of many haematological disorders. A frequent complication of HSCT is acute graft-versus-host disease (GVHD), a condition in which immune cells from the donor attack healthy recipient tissues. The gastrointestinal system is among the most common sites affected by acute GVHD, and severe manifestations of acute GVHD of the gut portends a poor prognosis in patients after HSCT. Acute GVHD of the gastrointestinal tract presents both diagnostic and therapeutic challenges. Although the clinical manifestations are nonspecific and overlap with those of infection and drug toxicity, diagnosis is ultimately based on clinical criteria. As reliable serum biomarkers have not yet been validated outside of clinical trials, endoscopic and histopathological evaluation continue to be utilized in diagnosis. Once a diagnosis of gastrointestinal acute GVHD is established, therapy with systemic corticosteroids is typically initiated, and non-responders can be treated with a wide range of second-line therapies. In addition to treating the underlying disease, the management of complications including profuse diarrhoea, severe malnutrition and gastrointestinal bleeding is paramount. In this Review, we discuss strategies for the diagnosis and management of acute GVHD of the gastrointestinal tract as they pertain to the practising gastroenterologist.

Early readmission in patients hospitalized for ulcerative colitis: incidence and risk factors.

OBJECTIVE: Early readmission rates are becoming an integral measure of the quality of care for hospitalized patients with chronic diseases. The incidence and predictors of early readmission in patients with inflammatory bowel disease (IBD) are uncertain. Risk factors for readmission over the first few weeks may differ from those that influence re-hospitalization at later time points. We examined the incidence and predictors of both 30-day and 90-day readmissions among ulcerative colitis (UC) patients. MATERIALS AND METHODS: A retrospective, cohort study was performed including all severe UC patients admitted to a tertiary-care hospital between January 2007 and December 2011. All-cause readmissions to the medical or surgical service within 30 and 90 days were recorded to allow the calculation of early readmission rates. We used multiple logistic regression to analyze demographic, hospital-related, general medical and IBD-specific factors as potential risk factors for readmission. RESULTS: There were a total of 229 patients discharged following hospitalization for severe UC. The 30- and 90-day readmission rates were 11.7% and 20.5%, respectively. Forty-seven percent of early readmissions were for colectomy. In the 30-day analysis, only the presence of extensive colitis (odds ratio 3.59; 95% confidence interval [CI] 1.41-9.13) compared with left-sided disease was independently associated with readmission. Extensive colitis (3.09, 95% CI 1.33-7.08), albumin on admission (0.56, 0.31-0.99) and being admitted to a housestaff service (2.87, 95% CI 1.14-6.54), were independent predictors of readmission at 90 days. CONCLUSIONS: Early readmission is common in IBD. Independent risk factors for early readmission included extensive colitis, admission albumin, and being admitted to a housestaff service.

Chromoendoscopy and Dysplasia Surveillance in Inflammatory Bowel Disease: Past, Present, and Future.

The evidence supporting the practice of dysplasia surveillance in inflammatory bowel disease (IBD) has remained sparse, and optimal detection strategies are still lacking. These issues, added to the declining incidence of dysplasia in IBD, have led to much debate over the diagnosis and management of dysplasia. White-light endoscopy with targeted and random biopsies remains the technique of choice for most practicing gastroenterologists. However, during the past decade, a surge of literature has questioned the efficacy of this strategy. Simultaneously, chromoendoscopy has emerged as an alternative, and perhaps superior, technique that has been included in some society guidelines. Nevertheless, many issues remain unclear, such as the best way to implement chromoendoscopy into everyday practice, whether there are any outcome benefits that can be attributed to the use of chromoendoscopy, and, perhaps most importantly, how to manage dysplasia uncovered by this and other advanced techniques. In this article, we discuss the various techniques currently available for dysplasia surveillance in IBD, with a focus on chromoendoscopy. Additionally, we highlight the overarching issues of setting appropriate endpoints and individualizing the care of patients with long-standing colitis.

Crohn's-like clinical and pathological manifestations of giant inflammatory polyposis in IBD: a potential diagnostic pitfall.

BACKGROUND & AIMS: Giant inflammatory polyposis (GIP), characterized by mass-like agglomerations of inflammatory polyps, is a rare complication of inflammatory bowel disease (IBD). We reviewed a series of cases of GIP to determine its diagnostic impact on the clinical and pathologic distinction between ulcerative colitis (UC) and colonic Crohn's disease (CD). METHODS: All colons with GIP resected over a 13-year period were identified prospectively and the corresponding clinical and pathologic records were reviewed. RESULTS: Twelve cases of GIP were identified, accounting for 0.8% of colectomies for IBD during the same time interval. Preoperatively, 6 (50%) patients were diagnosed with UC, 2 (17%) with CD and 4 (33%) with indeterminate colitis (IC). Postoperatively, 6 of the diagnoses (50%) were revised based on strict histopathologic criteria: all 4 diagnoses of IC to UC, one diagnosis of CD to UC, and one diagnosis of UC to CD, for a total of 10 diagnoses of UC (83%) and two of CD (17%). Significantly, 7 of 10 cases with postoperative diagnoses of UC (70%) had Crohn's-like transmural inflammation exclusively within the polyposis segments attributed to fecal entrapment and stasis and accounting for the Crohn's-like clinical complications in these cases. CONCLUSIONS: This case series of GIP, the largest reported from a single center, highlights the high rate of Crohn's-like clinical and pathological manifestations of GIP and their potential to confound the accurate classification of patients with IBD. A diagnosis of UC should not be amended to CD based on the findings of the polyposis segment alone.

Surveillance in inflammatory bowel disease: chromoendoscopy and digital mucosal enhancement.

Patients with long-standing inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer. Performing periodic dysplasia screening and surveillance may diminish this risk. To date, chromoendoscopy is the only technique that has consistently yielded positive results in large, well-designed dysplasia-detection trials. Most major society guidelines endorse chromoendoscopy as an adjunct, accepted, or preferred dysplasia-detection tool. This review outlines the available endoscopic technologies for the detection of dysplasia in IBD, considers the evidence supporting their use, and assesses which modalities are ready for use in clinical practice.

Rates of pharmacologic venous thromboembolism prophylaxis in hospitalized patients with active ulcerative colitis: results from a tertiary care center.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk for venous thromboembolism (VTE) compared to the general population. Practice guidelines recommend pharmacologic prophylaxis for IBD inpatients. AIM: Our aim was to determine the rates of pharmacologic VTE prophylaxis in ulcerative colitis (UC) inpatients at a tertiary referral center. We also assessed potential predictors of pharmacologic prophylaxis. METHODS: We conducted a retrospective cohort study of 377 UC patients between January 1st, 2007 and December 31st, 2011. The medical record of each patient was examined to determine whether pharmacologic VTE prophylaxis was ordered and administered. We conducted multiple logistic regression to determine predictors of pharmacologic prophylaxis. RESULTS: The overall VTE pharmacologic prophylaxis rate was 67.6%. The rate of patients admitted to the medical service was 57.4% compared to 93.5% for those admitted to surgery. In medical patients who received pharmacologic VTE prophylaxis, 34.0% of ordered doses were not given compared to 17.4% of doses in surgical patients (P<0.001). In the multiple logistic regression analysis, having an additional VTE risk factor (OR 2.46, 95% CI 1.41-4.30), extensive colitis (OR 2.26, 95% CI 1.32-3.87) or being admitted to a surgical service (OR 12.03, 95% CI 5.29-27.38) was associated with VTE pharmacologic prophylaxis. CONCLUSIONS: A substantial proportion of medical patients admitted with UC were not ordered for VTE pharmacologic prophylaxis despite current guidelines. Even in patients who were ordered for pharmacologic prophylaxis, one third of doses were not given. Inappropriate prophylaxis may lead to unnecessary morbidity and mortality.

A survey of current practice of venous thromboembolism prophylaxis in hospitalized inflammatory bowel disease patients in the United States.

BACKGROUND: Inflammatory bowel disease (IBD) patients are at an increased risk of thrombosis, particularly when hospitalized. Several clinical practice guidelines now recommend pharmacologic prophylaxis for hospitalized ulcerative colitis and Crohn's disease patients. It is unclear to what extent gastroenterologists are aware of these recommendations and whether they are administering pharmacologic venous thromboembolism (VTE) prophylaxis appropriately. Our aim was to explore current practice of VTE prophylaxis in hospitalized IBD patients in the United States. METHODS: A survey was mailed electronically to gastroenterologists whose electronic mail address was listed in the American College of Gastroenterology (ACG) database. This survey included clinical vignettes outlining scenarios for consideration of VTE prophylaxis. RESULTS: A total of 6227 surveys were sent to gastroenterologists nationwide, and 591 physicians chose to participate (response rate 9.5%). Respondents (80.6%) believed that hospitalized IBD patients have a higher risk of VTE than other inpatients. A total of 29.1% were unaware of any recommendations addressing pharmacologic prophylaxis included in ACG IBD guidelines and 34.6% would give pharmacologic VTE prophylaxis to a hospitalized patient with severe ulcerative colitis. Heparin VTE prophylaxis use was associated with gastroenterologists who indicated that their practices comprised more than 50% of patients with IBD (P=0.0001), being a physician at an academic hospital (P=0.0001) and providers having less than 5 years practice experience (P=0.003). CONCLUSIONS: Despite reasonable awareness of the increased risk of thrombosis in hospitalized IBD patients, many US gastroenterologists may not follow clinical practice guidelines and use pharmacologic VTE prophylaxis.

Gastroduodenal ulceration associated with radioembolization for the treatment of hepatic tumors: an institutional experience and review of the literature.

BACKGROUND: Microsphere radioembolization is a method of delivering radiation therapy directly to tumors, thereby minimizing toxicity to adjacent structures. Despite the relatively high precision of this modality, numerous adverse effects have been recognized. One particularly untoward complication is the development of severe gastroduodenal ulceration. METHODS: In order to further characterize gastroduodenal ulceration associated with radioembolization, our institutional experience as well as the reported literature were reviewed. RESULTS: The current evidence suggests that radioembolization-associated gastroduodenal ulceration results from inadvertent delivery of microspheres to the microvasculature of the gastrointestinal tract, leading to direct radiation toxicity. The reported incidence of this entity ranges between 2.9% and 4.8%. Most patients with this complication present with abdominal pain, often associated with nausea, vomiting, and anorexia. Symptoms can arise from hours to months after radioembolization treatment; diagnosis is made by endoscopic biopsy and histopathologic evaluation of the ulcer specimen. Radiation-induced ulcers have proven to be extremely difficult to treat. Current therapy based on acid suppression has had limited success, and the evidence for the addition of antioxidants and anti-inflammatory agents is still sparse. CONCLUSIONS: The increasing utilization of radioembolization will lead to adverse events including gastroduodenal ulceration. This entity must be considered in any patient treated with radioactive microspheres presenting with symptoms of dyspepsia. Accurate diagnosis and aggressive treatment are necessary to improve patient outcomes.