Colitis Infection Research Articles

Low prevalence of SARS-CoV-2 infection in inflammatory bowel disease.

Treatments used in Inflammatory Bowel Disease (IBD) have been associated with enhanced risk of viral infections and viral reactivation, however, it remains unclear whether IBD patients have increased risk of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. The aim of the study was to examine the prevalence of SARS-CoV-2 IgG positivity in IBD patients followed at our referral center. The role of treatments for IBD and risk factors for infection were also evaluated. In a prospective study, all IBD patients followed at our referral centre between May 27th and July 21st, 2020 and fulfilling the inclusion criteria were tested for SARS-CoV-2 IgG. Specific IgG antibodies were evaluated by a commercial ELISA kit and SARS-CoV-2 nasopharyngeal swab was performed in seropositive patients. Two-hundred and eighteen patients, 128 Crohn's disease (CD) and 90 Ulcerative colitis (UC) [age 44, (19-77) years; ongoing biologics in 115 (52.7%)] were enrolled. No patient had major SARS-CoV-2-related symptoms. SARS-CoV-2 IgG were detected in 3 out of 218 (1.37%) patients with IBD (2 CD and 1 UC), all on biologics (2.6%). In all of the 3 seropositive patients, the nasopharyngeal swab was negative. There was no relationship between SARS-CoV-2 seroprevalence and the demographic/clinical characteristics of IBD patients. In contrast, history of recent travel was more frequent in the SARS-CoV-2 seropositive patients (2/3; 66.6%) than in SARS-CoV-2 seronegative patients [7/215 (3.25%); p<0.0001]. The prevalence of SARS-CoV-2 IgG seropositivity in IBD patients appears to be comparable to the non-IBD population and not influenced by ongoing treatments. Risk factors for infection common to the general non-IBD population should be considered when managing patients with IBD.

Integrated intra‐ and intercellular signaling knowledge for multicellular omics analysis

Molecular knowledge of biological processes is a cornerstone in omics data analysis. Applied to single‐cell data, such analyses provide mechanistic insights into individual cells and their interactions. However, knowledge of intercellular communication is scarce, scattered across resources, and not linked to intracellular processes. To address this gap, we combined over 100 resources covering interactions and roles of proteins in inter‐ and intracellular signaling, as well as transcriptional and post‐transcriptional regulation. We added protein complex information and annotations on function, localization, and role in diseases for each protein. The resource is available for human, and via homology translation for mouse and rat. The data are accessible via OmniPath’s web service (https://omnipathdb.org/), a Cytoscape plug‐in, and packages in R/Bioconductor and Python, providing access options for computational and experimental scientists. We created workflows with tutorials to facilitate the analysis of cell–cell interactions and affected downstream intracellular signaling processes. OmniPath provides a single access point to knowledge spanning intra‐ and intercellular processes for data analysis, as we demonstrate in applications studying SARS‐CoV‐2 infection and ulcerative colitis.

Treatment-based risk stratification of infections in inflammatory bowel disease: A comparison between anti-tumor necrosis factor-α and nonbiological exposure in real-world setting.

Infective issues about anti-tumor necrosis factor (TNF)-α agents in inflammatory bowel disease (IBD) remain controversial, especially when compared with nonbiological treatments. This study aimed to evaluate the incidence and prevalence of several infections in anti-TNF-α-exposed patients compared with nonbiological treatments. All naïve IBD subjects treated with anti-TNF-α and matched nonbiologic-exposed patients were included. Among 3453 patients in the database, 288 anti-TNF-α-exposed subjects and 288 nonbiologic-exposed IBD controls met inclusion criteria. Fifty-eight infections (20.1%) occurred during anti-TNF-α treatment versus 23 (8%) in the matched group (odds ratio [OR] 2.9, P<0.001) (incidence 5.72 vs 0.96/100 patient-years, incidence ratio [IR] 6, P<0.001). IR was higher for anti-TNF-α versus mesalamine/sulfasalazine (IR 40.8, P<0.001), similar to azathioprine/6-mercaptopurine/methotrexate (IR 0.78, P=0.32) and lower than corticosteroids (IR 0.05, P<0.001). The incidence rate of serious infections was 1.3 in the anti-TNF-α-exposed versus 0.38/100 patient-years in nonexposed subjects (IR 3.44, P=0.002), without significant difference between anti-TNF-α and azathioprine/6-mercaptopurine/methotrexate (1.3 vs 3.03/100 patient-years, IR 0.43, P=0.1). Predictors of infections in anti-TNF-α-exposed patients were concomitant use of systemic steroids (OR 1.9, P=0.02) or azathioprine (OR 2.6, P=0.01) and a body mass index<18.5 at time of infection (OR 2.2, P=0.01). The risk of developing infections during anti-TNF-α therapy remains high, although not dissimilar to that found for other immunosuppressants, while concomitant immunosuppression and malnutrition appear the most important causes of infection.

Acute lower gastrointestinal bleeding from a polyp: An unusual etiology

An 81-year-old woman, without relevant pathologies or usual medication, presented with 3-day history of hematochezia. She denied diarrhea, fever, abdominal pain, similar prior episodes, and previous colonoscopy. No consumption of nonsteroidal anti-inflammatory drugs, antiplatelet agents, or anticoagulants. No family history of colorectal cancer or polyposis syndrome. She was hemodynamically stable. The laboratory examination revealed normal blood urea nitrogen (7 mg/dL), normal creatinine (0.55 mg/dL) and coagulation factors, and an anemia of 10.2 g/dL, normocytic and normochromic. A colonoscopy was performed identifying a 30-mm pedunculated polyp with active bleeding in the proximal descending colon (Figure 1A). An endoloop-assisted polypectomy technique was performed (Figure 1B). Since the stalk had more than 1 cm, hemostasis was reinforced with two hemoclips (Figure 1C) and the polyp recovered for histological evaluation (Figure 2). The patient was hospitalized for a short period of time and there was no hemorrhagic recurrence. Anatomopathological evaluation was compatible with an inflammatory pseudopolyp (Figure 2). Polyps usually induce chronic blood loss being the source of acute lower gastrointestinal bleeding in only a small percentage of patients.1 However, the exact frequency of this event is not known. In literature, only two cases of acute lower gastrointestinal bleeding due to polyps in adults were found and both patients were under anticoagulants.2,3 Risk factors for polyp's bleeding are size greater than 10 mm, presence of a stalk and a cherry-red color.4 The usual histopathological findings include marked vascular congestion and intramucosal blood lakes and these features can be seen in inflammatory pseudopolyps.4 This non-neoplastic polyps usually are found in regenerative and healing phases of inflammation so any form of severe colitis as inflammatory bowel disease, ischemic colitis, or infection colitis can originate them. However, inflammatory pseudopolyps may develop sporadically in up to one third of the cases as happened in this situation.5 We present this case due to the rarity of its etiology in a patient with no coagulation changes or antithrombotic medication. The authors declare no conflict of interest. The patient authorized the publication of the data and the patient's anonymity is preserved in the article. Cláudia Macedo was responsible for the data acquisition and editing, manuscript writing, and reviewed the literature. Nuno Almeida was responsible for the data acquisition and reviewed the manuscript. Pedro Figueiredo reviewed the manuscript.

S1793 Aeromonas Spp. Enteritis in the Course of Recurrent Immune Checkpoint Inhibitor Colitis

INTRODUCTION: The role of Aeromonas spp. as a gastrointestinal pathogen is debated.1 Here we present an Aeromonas infection in a patient with recurrent immune checkpoint inhibitor (ICI) colitis. CASE DESCRIPTION/METHODS: A 61-year-old Caucasian female with Stage IV Melanoma and history of recurrent ICI colitis presented with 6 days of watery diarrhea, nausea and vomiting. The patient had recently completed 2nd induction of Ipilimumab, an anti-CTLA-4 immunotherapy agent, while being on vedolizumab concurrently with oral budesonide for previous episodes of nausea and vomiting. She endorsed intermittent abdominal cramping and decreased PO tolerance but denied fevers, bloody diarrhea, hematemesis. On exam, abdomen was benign and non-tender. Serology labs were unremarkable. Stool studies were significant for positive lactoferrin and elevated calprotectin to 432 μg/g. Patient was started on solumedrol 40 mg IV BID empirically. GI multiplex PCR panel was negative including C. Difficile. Stool culture was positive for pan-susceptible Aeromonas spp. Patient was started on a 7-day course of Ciprofloxacin 500 mg BID and prednisone taper resulting in improved PO tolerance, resolution of diarrhea and decreased nausea and vomiting on discharge. DISCUSSION: Aeromonas spp. infections, although rare, most typically present with gastrointestinal symptoms. It has been implicated as an opportunistic pathogen in inflammatory bowel disease; however, its role in patients with ICI colitis remains unclear.2 Our patient had presented with similar symptoms and negative stool cultures several months prior and was treated for ICI colitis. This diagnosis was confirmed by colonoscopy showing active cryptitis and apoptotic bodies. In the current presentation, it is unclear what the primary cause of her symptoms was. Concurrent administration of both antibiotics and steroids improved her symptoms possibly suggesting a combination of Aeromonas spp. infection and ICI colitis which has never been reported previously in literature. Further studies with larger cohorts of patients with ICI colitis are warranted to investigate the pathogenicity and role of Aeromonas infection.

AML-226: Dasatinib Plus Chemotherapy in Core Binding Factor Leukemia: A Case Study

Core binding factor (CBF) acute myeloid leukemia (AML) patients have t (8:21) and inv(16) or t (16;16). They respond to dose-intensive cytarabine regimens with a complete remission (CR) rate of over 90%. Five-year event-free survival is 44% with a median of 91 weeks. We report a case of a relapsing inv(16) CBF leukemia salvaged by adding a tyrosine kinase inhibitor (TKI) to the chemotherapeutic regimen. Case presentation Ms. J.R is a 21-year-old patient with quadriplegia and inv16 with mutated KIT exon 8 gene diagnosed December 2017. She received induction with FLAG-IDA and six consolidation courses. Four months later, she relapsed with 56,000 WBC/dL and 82% bone marrow blasts. The inv(16) FISH was 87% positive and CBFB MYH11/total ratio was 26.585. Salvage therapy was initiated with decitabine-venetoclax-gentuzumab ozogamicin (GO). There was a marrow CR with a 21% positive inv(16) FISH test and a CBFB-MYH11/total ratio of 32.191. Due to the persistence of the KIT mutation, the TKI dasatinib was added to decitabine-venetoclax-gentuzumab ozogamicin (GO). After the TKI addition, she remained in CR. The CBFB-MYH11/total ratio decreased to 9.046, and the inv(16) FISH test remained positive at 2%. A second similar course given was complicated by a pulmonary fungal infection, acute appendicitis, and CMV colitis. All resolved with antifungals, laparoscopic surgery, and anti-CMV therapy, respectively. Upon recovery, she was in CR with undetectable CBFB-MYH11 transcripts and a negative FISH test. Because a bone marrow transplant is not possible, she has started a modified maintenance regimen with dasatinib, decitabine, and venetoclax. Discussion CBF leukemia chimeric proteins disrupt normal hematopoiesis by recruiting histone deacetylases and DNA methyltransferase 1 to CBF target genes, resulting in increased chromatin deacetylation and promoter hypermethylation. KIT exon 8 and 17 mutations occur in 20–25% of t (8;21) and approximately 30% of inv(16) leukemias. KIT mutations result in constitutively activated promotion of leukemic cells survival. Screening for KIT mutations and adding TKIs during induction or salvage therapy could be important for the treatment of CBF leukemias with an analogous impact, like adding TKIs in Ph-positive diseases.

COVID-19 and inflammatory bowel disease: Questions arising from patient care and follow-up during the initial phase of the pandemic (February–April 2020)

COVID-19 is a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was described in China in late 2019. There are currently more than three million diagnosed cases, constituting a pandemic which has caused a worldwide crisis. The devastating effects of this infection are due to its highly contagious nature and although mild forms predominate, in absolute values, the rates for severe forms and mortality are very high. The information on the characteristics of the infection in inflammatory bowel disease is of special interest, as these patients have higher attendance at health centres, which may increase their risk of infection. Furthermore, the treatments used to control the inflammatory activity may modify the disease course of COVID-19. The Spanish Working Group on Crohn’s Disease and Ulcerative Colitis and the Spanish Nurses Working Group on Inflammatory Bowel Disease have prepared this document as a practical response to some common questions about the treatment of these patients.

Leishmania infantum asymptomatic infection in inflammatory bowel disease patients under anti-TNF therapy

BackgroundIn recent years anti-TNF therapy has been associated with leishmaniasis in immunocompromised patients from endemic areas. Nevertheless, data on asymptomatic Leishmania infection in such patients is scarce. The aim of this study was to determine the prevalence of asymptomatic infection in inflammatory bowel disease (IBD) patients treated with TNF inhibitors living in an endemic area (Catalonia) and to follow up them to study how the infection evolved. Methods192 IBD patients (143 Crohn's disease; 49 ulcerative colitis) from Catalonia (Spain), an area endemic for L. infantum, were recruited. Peripheral blood samples were collected and tested for anti-Leishmania antibodies by Western blotting (WB). Leishmania kinetoplast DNA was detected in peripheral blood mononuclear cells (PBMC) by a quantitative PCR. ResultsSerology was positive in 3.1% and Leishmania DNA was found in 8.8%, with a low parasitic load and humoral response. The prevalence was 10.9%, patients being considered infected if they tested positive by at least one of the techniques. Eight out of the 21 patients with asymptomatic leishmaniasis were monitored for 3–8 months after the first test. None of them showed an increased parasitemia or humoral response, or developed leishmaniasis during the follow-up period. ConclusionThe prevalence of Leishmania asymptomatic infection detected in our IBD cohort is similar to that found in healthy population in close endemic areas. Due to the short monitoring period, it is not possible to reach a conclusion about the risk of Leishmania reactivation from this study.

Ulcerative Colitis and Cytomegalovirus Infection: From A to Z

Despite multiple studies, the role of cytomegalovirus [CMV] infection in exacerbating the severity of inflammation in ulcerative colitis [UC], and its response to treatment, remain debatable. Additionally, the optimal diagnostic tests for CMV infection in the setting of UC relapse, and timing of antiviral treatment initiation, remain unclear. The challenge faced by gastroenterologists is to differentiate between an acute UC flare and true CMV colitis. It seems that the presence of CMV colitis, as defined by the presence of intranuclear or intracellular inclusion bodies on haematoxylin and eosin [H&E] staining and/or positive immunohistochemistry [IHC] assay on histology, is associated with more severe colitis. Patients with CMV infection and acute severe colitis are more resistant to treatment with corticosteroids than non-infected patients. This refractoriness to steroids is related to colonic tissue CMV viral load and number of inclusion bodies [high-grade CMV infection] which may have a pronounced effect on clinical outcomes and colectomy rates. Whereas many studies showed no effect for antiviral treatment on colectomy rates in CMV-infected UC patients, there was a significant difference in colectomy rates of patients with high-grade infection who received anti-viral therapy compared with those who did not receive treatment. It was therefore proposed that high-grade CMV disease indicates that the virus is acting as a pathogen, whereas in those with low-grade CMV disease, the severity of IBD itself is more likely to influence outcome. The different algorithms that have been put forward for the management of patients with UC and concomitant CMV infection are discussed.

Efficacy of Fecal Microbiota Transplantation for Recurrent C. Difficile Infection in Inflammatory Bowel Disease.

Clostridioides difficile infection (CDI) is associated with poor outcomes in inflammatory bowel disease (IBD) patients. Data are scarce on efficacy of fecal microbiota transplant (FMT) for recurrent CDI in IBD patients. We reviewed health records of IBD patients (18 years of age or older) with recurrent CDI who underwent FMT. Outcomes of FMT for CDI were assessed on the basis of symptoms and stool test results. We included 145 patients (75 women [51.7%]; median age, 46 years). Median IBD duration was 8 (range, 0-47) years, 36.6% had Crohn disease, 61.4% had ulcerative colitis, and 2.1% had indeterminate colitis. Median number of prior CDI episodes was 3 (range, 3-20), and 61.4% had received vancomycin taper. Diarrhea resolved after FMT in 48 patients (33.1%) without further testing. Ninety-five patients (65.5%) underwent CDI testing owing to post-FMT recurrent diarrhea; 29 (20.0%) had positive results. After FMT, 2 patients received empiric treatment of recurrent CDI without symptom resolution, suggesting IBD was the cause of symptoms. The overall cure rate of CDI after FMT was 80.0%, without CDI recurrence at median follow-up of 9.3 (range, 0.1-51) months. Forty-three patients (29.7%) had planned IBD therapy escalation after CDI resolution; none de-escalated or discontinued IBD therapy. Overall, 7.6% had worsening IBD symptoms after FMT that were treated as new IBD flares. No clinical predictors of FMT failure were identified. Few patients had new IBD flare after FMT. Fecal microbiota transplantation effectively treats recurrent CDI in IBD patients but has no apparent beneficial effect on the IBD course.

P076 Active Tuberculosis Infection in Patients With Inflammatory Bowel Disease Followed in a Referral Center

BACKGROUND: Despite the decline in the incidence of Tuberculosis (TB) worldwide, this disease still causes high rates of morbimortality. It is estimated that TB caused 1.3 million deaths worldwide in 2017. Brazil is an endemic country and it counts nearly 70,000 new cases of TB per year (1). Whether the risk of TB infection in Inflammatory Bowel Disease (IBD) patients is related to immunosuppressants or to the disease itself is controversial. This study aimed to evaluate the incidence of active TB in patients with IBD, and its relationship with immunosuppressive treatment in a tertiary referral center. METHODS: Patients with active TB were identified among 1040 IBD patients in a regular follow up at Hospital das Clínicas, São Paulo, Brazil, from 2010 to 2017. Data regarding disease phenotype, IBD treatment at the time of TB diagnosis and the previous status of TB screening was retrospectively collected from electronic medical records. The diagnosis of active TB was based on symptoms, tuberculin skin test (TST), sample cultures, images, and endoscopic exams. RESULTS: Twenty-three patients with active TB were identified (mean age at TB diagnosis 49 [28–69]; 13/23 [56.5%] female). The person-time incidence rate of active TB was 2.21 cases/100 inhabitants/year in our IBD population. The relative risk of active TB was increased (RR 6.6) compared to general Brazilian population. Fifteen patients (65.2%) had Crohn’s Disease (7 perianal; 4 stricturing; 4 non-penetrating non-stricturing) and eight (34.7%) had Ulcerative Colitis (7 extensive disease). Regarding IBD treatment, 13/23 (56.5%) patients were under anti-TNF drugs (9 Infliximab; 4 Adalimumab), six of them (46.1%) in monotherapy and seven (53.8%) under combotherapy with thiopurines. Five patients (21.7%), were under AZA monotherapy and one was under steroids. Regarding the interval between anti-TNF use and TB diagnosis, just one case was diagnosed in the first 6 months of treatment. Most patients (14/19; 73.6%) developed active TB after 24 months of exposition to immunosuppressant medications; two (2/19; 10.5%) between 12–24 months of exposure and three (3/19; 15.7%) between 6–12 months. All four of the patients (4/23; 17.4%) that were not under immunosuppressant drugs were smokers, one of them was also an alcoholic and another one treated active TB seven years before the reinfection. The most common TB site was pulmonary (16/23, 69.5%) and no deaths resulted from active TB. One case of TB occurred three years after isoniazid chemoprophylaxis for latent TB in a patient under combotherapy (anti-TNF and AZA). CONCLUSION(S): Our patients presented an incidence of TB higher than the general population in Brazil. Immunosuppressive drugs seem to be a major causal factor, especially anti-TNF. Most cases occurred after the first six months of treatment suggesting a new infection. This study reinforced the importance of an accurate screening for TB at IBD diagnosis and prior to initiation of immunosuppressive therapy. Appropriate follow-up is required in immunosuppressed patients living in endemic areas for TB.

Effects of preoperative anti‐tumour necrosis factor alpha infusion timing on postoperative surgical site infection in inflammatory bowel disease: A systematic review and meta‐analysis

Anti-tumour necrosis factor alpha agents (anti-TNF-α) have been widely used in patients with inflammatory bowel disease (IBD). However, few published meta-analyses have focused on timing of the last infusion before surgery. We evaluated the relationship between preoperative anti-TNF-α timing and postoperative surgical site infection to provide additional evidence for surgeons to choose appropriate dates for surgery. We searched from inception until January 2019 for studies that documented postoperative complications of adults with IBD who underwent preoperative anti-TNF-α treatment. Primary outcomes of included studies were the odds ratios of preoperative anti-TNF-α time frames (4, 8 and 12 weeks). In addition, surgical site infection and its subtypes (anastomotic leakage, abscesses and wound infection) were analysed. Twenty-seven publications were included. No significant difference between anti-TNF-α and control cohorts was observed for most postoperative surgical site infections (or its subtypes) when the preoperative anti-TNF-α infusion time window was within 4, 8 or 12 weeks. Additionally, no significant difference in postoperative complications was observed between preoperative anti-TNF-α windows of within four weeks and more than four weeks. In terms of surgical site infection and its subtypes, anti-TNF-α may be safe for ulcerative colitis and Crohn's disease patients who receive their last infusion of anti-TNF-α more than four weeks before surgery. We also found no evidence that anti-TNF-α was a risk factor when administered within four weeks, with the exception of subgroup results from a single study. Stratified by time window, use of anti-TNF-α until surgery has the potential to become a more considered strategy in clinical practice.

767 Inflammatory Bowel Disease Patients Prior to Starting on Anti-TNF Are Over 5 Times More Likely to Be Screened for Hepatitis B Infection Compared to Those Starting High Dose Corticosteroids

INTRODUCTION: Screening for hepatitis B virus (HBV) infection in inflammatory bowel disease (IBD) patients prior to initiating anti-tumor necrosis factor alpha (anti-TNF) therapy has significantly improved over the past decade. HBV screening prior to initiating high dose corticosteroids (HDC) is largely unknown despite potentially greater risks of HBV reactivation compared to anti-TNF. This study aims to determine the factors associated with HBV screening and whether the type of immunosuppression affects screening practices. METHODS: This retrospective chart review included Veterans with diagnostic codes for Crohn's Disease (CD: ICD-9-CM 555.x and ICD-10-CM K50.x) and ulcerative colitis (UC: ICD-9-CM 556.x and ICD-10-CM K51.x) first recorded between 01/2013 to 08/2016 at the Cleveland Veterans Affairs Medical Center. IBD patients who were started on anti-TNF or HDC were assessed whether HBV screening was conducted within 12 months of initiating therapy. HDC was defined as ≥10 mg for ≥4 consecutive weeks. Patient factors including gender, age, race, service connectivity (SC), and type of immunosuppression were assessed as independent predictors for screening. RESULTS: Among 571 Veterans, 56 started immunosuppression with 17 on anti-TNF and 39 on HDC. A total of 31/56 (56%) were screened: 90% male, mean age 49, 32% mean SC, 45% on anti-TNF and 55% on HDC. A total of 25/56 (44%) were not screened: 96% male, mean age 58,17% mean SC, 12% on anti-TNF and 88% on HDC. In those on anti-TNF, 88% were screened compared to 44% on HDC (P = 0.007). In multivariate analysis, immunosuppression type was significantly associated with screening where patients initiated on anti-TNF were 5.5 times more likely to be screened compared to those on HDC (OR 0.18, P = 0.025). Age, gender, race, and service connectivity did not have any impact on screening. CONCLUSION: Overall, 56% of IBD patients receiving immunosuppression were screened for HBV. 88% were screened prior to anti-TNF compared to 44% prior to HDC. Patients initiated on anti-TNF were over 5 times more likely to be screened compared to those on HDC. Importance of HBV screening prior to high dose corticosteroids in IBD patients should be emphasized in societal guidelines and clinical practice, given that HDC poses a potentially greater risk of HBV reactivation compared to a biologic.

Clostridium difficile infection in inflammatory bowel disease: epidemiology over two decades.

The incidence of Clostridium difficile infection (CDI) has been rising in the overall population as well as in patients with inflammatory bowel disease (IBD). However, the incidence of CDI in IBD may be changing owing to alterations in medical therapies. The aim of this study was to establish the incidence of CDI in IBD over the past two decades and compare risk factors, disease characteristics and outcomes between IBD and non-IBD patients. In this retrospective case-control study, the incidence of CDI in IBD was followed for 18 years. The electronic database of our centre was reviewed for all stool samples received from patients admitted to gastroenterology wards or visiting the outpatient clinic. Diagnosis of CDI was based on diagnostic criteria that evolved throughout the years. IBD patients (n=44) with CDI were found to be younger (P=0.0001), have less cardiovascular comorbidity (P=0.023), fewer prior hospitalizations (P=0.009) and fewer prior antibiotic use (P=0.005). More IBD patients were on biologic therapy (P=0.0001) or steroids (P=0.001) but less likely taking proton pump inhibitors (P=0.001). The number of stool testing per year increased as well as the median number of positive stool samples for CDI (2% in 2000-2008 to 3% in 2009-2017, P=0.032). Pseudomembranes were only seen in non-IBD patients (28%, P=0.048). There was no difference in the choice of antibiotics between IBD and non-IBD patients [metronidazole (36 vs. 51%) and vancomycin (36 vs. 26%), P=0.090 and 0.190]. The 1-year mortality rate was lower in IBD patients compared with non-IBD patients (0 vs. 32%, P=0.0001). In the past two decades, the incidence of CDI in IBD and non-IBD patients has increased. However, the overall outcome of CDI in IBD patients was favourable compared with non-IBD patients.

Nutrition Pathway for Clostridium Difficle Infection (CDI) Colitis in Long-Term Care

Nutrition Pathway for Clostridium Difficle Infection (CDI) Colitis in Long-Term Care

Relevant Infections in Inflammatory Bowel Disease, and Their Relationship With Immunosuppressive Therapy and Their Effects on Disease Mortality.

There is controversy as to whether the risk of relevant infection in IBD is related to immunosuppressants or the disease itself. The aims of this study were to evaluate: [1] the life-long prevalence and types of relevant infections in patients with IBD related to immunosuppressive treatment, and [2] the relationship of both infection and patient comorbidity to mortality. Observational multicentre retrospective study of IBD patients that presented a relevant infection. For each case, four periods of infection exposure were analysed: P1: pre-IBD diagnosis, P2: from IBD diagnosis to immunosuppressant initiation, P3: during immunosuppressant therapy, and P4: after treatment withdrawal. The life-long prevalence of relevant infection in the total cohort of patients [6914] was 3%, and 5% in immunosuppressed patients [4202]. 366 relevant infections were found in 212 patients [P1: 9, P2: 17, P3: 334, and P4: 6]. Differences between periods were significant [p < 0.0001]. The most frequent types of infection were respiratory, intestinal and urinary. The most frequent opportunistic infections were tuberculosis [prevalence: 2.6/1000] and herpes zoster [prevalence: 3.9/1000]. Herpes zoster infection was associated with thiopurines alone or in combination with anti-TNF in 75% of the cases, whereas tuberculosis was associated with anti-TNF in 94% of patients. The overall mortality was 4.2%. Infection-related mortality was 2.8% and it was not influenced by comorbidity. Relevant infections in IBD patients are rare and appear to be related to immunosuppression. Relevant infection is a major cause of death in IBD.

18F-FDG PET/CT Findings in Cytomegalovirus Colitis.

We present a case demonstrating the diagnostic work-up of a patient undergoing azathioprine treatment for inflammatory bowel disease (IBD), diagnosed with an acute cytomegalovirus (CMV) infection and CMV colitis. An 18F-FDG positron emission tomography/computed tomography (PET/CT) performed 2 weeks after debut of symptoms revealed pathological 18F-FDG uptake in the left side of the colon mucosa, mimicked activity of IBD. However, a diagnosis of CMV colitis was based on the presence of CMV IgM antibodies, a seroconversion of CMV IgG antibodies, presence of CMV DNA in plasma and the finding af CMV DNA in biopsies from the intestinal mucosa. The patient responded to treatment with ganciclovir. This case highlights that a positive 18F-FDG PET/CT scan of the colon can be due to CMV colitis.

Reply to Letter on: 'Risk Factors Associated With Clostridium difficile Infection in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis'.

Reply to Letter on: 'Risk Factors Associated With Clostridium difficile Infection in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis'.

T-bet controls intestinal mucosa immune responses via repression of type 2 innate lymphoid cell function

Innate lymphoid cells (ILCs) play an important role in regulating immune responses at mucosal surfaces. The transcription factor T-bet is crucial for the function of ILC1s and NCR+ ILC3s and constitutive deletion of T-bet prevents the development of these subsets. Lack of T-bet in the absence of an adaptive immune system causes microbiota-dependent colitis to occur due to aberrant ILC3 responses. Thus, T-bet expression in the innate immune system has been considered to dampen pathogenic immune responses. Here, we show that T-bet plays an unexpected role in negatively regulating innate type 2 responses, in the context of an otherwise intact immune system. Selective loss of T-bet in ILCs leads to the expansion and increased activity of ILC2s, which has a functionally important impact on mucosal immunity, including enhanced protection from Trichinella spiralis infection and inflammatory colitis. Mechanistically, we show that T-bet controls the intestinal ILC pool through regulation of IL-7 receptor signalling. These data demonstrate that T-bet expression in ILCs acts as the key transcriptional checkpoint in regulating pathogenic vs. protective mucosal immune responses, which has significant implications for the understanding of the pathogenesis of inflammatory bowel diseases and intestinal infections.

Infectious Complications in Critically Ill Liver Failure Patients.

Infections remain a leading cause of morbidity and mortality among patients with liver failure. A number of factors, including relative immune dysfunction and systemic inflammation, bacterial translocation, gut dysbiosis, small intestine bacterial overgrowth, altered bile acid pools, and changes in pH due to acid suppression, contribute to the high rates of infection in this population. Though a range of infections can complicate the course of cirrhotic patients, spontaneous bacterial peritonitis (SBP), cholangitis, and cholecystitis in addition to other infections (i.e. pneumonia, urinary tract infection, bacteremia, and Clostridioides difficile colitis) are more common in this population and will be reviewed in this article. Preventative strategies are directed at minimizing the risk of SBP through the use of targeted antimicrobial prophylaxis. Lastly, the critically ill cirrhotic patient may present with an acute need for liver transplantation. Thus, careful assessment for ongoing infection should be performed and treated to optimize outcomes of transplant, if needed.