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Background: Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA. Methods: Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data. Results: The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs. Conclusion: This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA. [ABSTRACT FROM AUTHOR]

Introduction: Non-responsive coeliac disease (NRCD), where symptoms and enteropathy persist despite a prolonged gluten-free diet (GFD), is common. Refractory coeliac disease (RCD), characterised by malabsorption and extensive enteropathy, is rare but serious. In both, treatment options are limited. Topical budesonide may help and an open capsule format promoting proximal small intestinal delivery may be advantageous. Aim: To describe the effect of budesonide and its presentation on mucosal healing, symptoms, and tolerability in NRCD and RCD. Methods: A retrospective cohort study of NRCD and RCD patients who received budesonide for enteropathy despite a strict GFD for over 12 months. Primary outcome was improvement in histology. Symptoms and adverse treatment effects were recorded. Results: 50 patients with NRCD (n = 14; 86% F), RCD type 1 (n = 30; 60% F), and RCD type 2 (n = 6 based on aberrant duodenal T cells; 33% F) were identified. Common RCD symptoms were diarrhoea (68%), fatigue (40%), and weight loss (34%). 16 received closed capsule budesonide (CCB) 9 mg OD and 35 open capsule budesonide (OCB) 3 mg 3 times a day. Complete and partial mucosal healing was significantly higher after OCB compared to CCB (p < 0.001, Mann–Whitney U test). Symptom improvement was also significantly higher after OCB compared to CCB (p = 0.002, Mann–Whitney U test). Side effects were mild and self-limiting and were reported in 25% of both cohorts. Conclusion: OCB was well tolerated and associated with improvements in enteropathy (83%) and symptoms (90%) in NRCD and RCD. Our findings support OCB as the preferred 1st-line therapy for NRCD and RCD type 1. [ABSTRACT FROM AUTHOR]

Background: In the pragmatic open-label randomised controlled non-inferiority LADI trial we showed that increasing adalimumab (ADA) dose intervals was non-inferior to conventional dosing for persistent flares in patients with Crohn's disease (CD) in clinical and biochemical remission. Aims: To develop a prediction model to identify patients who can successfully increase their ADA dose interval based on secondary analysis of trial data. Methods: Patients in the intervention group of the LADI trial increased ADA intervals to 3 and then to 4 weeks. The dose interval increase was defined as successful when patients had no persistent flare (> 8 weeks), no intervention-related severe adverse events, no rescue medication use during the study, and were on an increased dose interval while in clinical and biochemical remission at week 48. Prediction models were based on logistic regression with relaxed LASSO. Models were internally validated using bootstrap optimism correction. Results: We included 109 patients, of which 60.6% successfully increased their dose interval. Patients that were active smokers (odds ratio [OR] 0.90), had previous CD-related intra-abdominal surgeries (OR 0.85), proximal small bowel disease (OR 0.92), an increased Harvey-Bradshaw Index (OR 0.99) or increased faecal calprotectin (OR 0.997) were less likely to successfully increase their dose interval. The model had fair discriminative ability (AUC = 0.63) and net benefit analysis showed that the model could be used to select patients who could increase their dose interval. Conclusion: The final prediction model seems promising to select patients who could successfully increase their ADA dose interval. The model should be validated externally before it may be applied in clinical practice. Clinical Trial Registration Number: ClinicalTrials.gov, number NCT03172377. [ABSTRACT FROM AUTHOR]

Background: The real-world application of STRIDE-II treatment targets to identify whether disease control is optimal in Crohn's disease (CD) and ulcerative colitis (UC) is not well known. Aims: This study aimed to estimate proportions of patients with suboptimally controlled CD and UC in real-world Canadian healthcare settings and the impact on quality of life (QoL). Methods: The noninterventional, multicenter, observational IBD-PODCAST Canada study comprised a single study visit involving routine assessments, patient- and clinician-completed questionnaires, and a retrospective chart review. Primary outcomes were proportions of patients with STRIDE-II-based red flags indicative of suboptimal disease control and mean ± standard deviation Short Inflammatory Bowel Disease Questionnaire (SIBDQ) scores. Secondary outcomes included proportions of patients and clinicians subjectively reporting suboptimal control. Results: Among 163 enrolled patients from 10 sites, 45/87 patients with CD (51.7%; 95% CI: 40.8%, 62.6%) and 33/76 patients with UC (43.3%; 95% CI: 32.1%, 55.3%) had suboptimal disease control based on STRIDE-II criteria. Suboptimal control was subjectively reported at lower proportions (patients: CD, 15.0%; UC, 18.6%; clinicians: CD, 19.5%; UC, 25.0%). Numerically lower SIBDQ scores were observed with suboptimal control (CD, 43.0 ± 10.8; UC, 42.5 ± 12.0) than with optimal control (CD, 58.2 ± 7.2; UC, 57.8 ± 6.6). Conclusions: Approximately 50% (CD) and 40% (UC) of patients from real-world Canadian practices had suboptimal disease control based on STRIDE-II criteria. Suboptimal control was underestimated by patients and clinicians and accompanied by reduced QoL, suggesting further efforts to implement STRIDE-II treat-to-target strategies are needed. [ABSTRACT FROM AUTHOR]

A 30-year-old woman with past medical history of primary intestinal lymphangiectasia (PIL), hypothyroidism, and well-controlled asthma was evaluated in our Emergency Department with recurrent dyspnea. PLE of PIL can be confirmed by high 24-h stool 1-antitrypsin clearance and by the presence of intestinal lymphangiectasia on endoscopic biopsies, including the presence of lacteal juice and dilated lymphatic vessels. In this patient, we considered pulmonary lymphangiectasia, malignancy, large lymphatic duct injury during pregnancy, and post-partum cardiomyopathy. 4Chylothorax drainage of thick milky pleural fluid It was felt that her chylothorax likely developed secondary to either pre-existing pulmonary lymphangiectasia concurrent with her intestinal lymphangiectasia, or chylous ascites migrating through a new diaphragmatic peritoneal-pleural fistula that had formed during pregnancy. [Extracted from the article]

The Solanaceae family of plants, commonly known as Nightshade vegetables or Nightshades, contains a diverse range of crops of over 2000 members with significant culinary, economic, and cultural importance. Familiar edible Nightshades include tomatoes, peppers, eggplants, and white potatoes. Many pharmacologically active compounds used in traditional medicine, including atropine and hyoscyamine, are derived from Nightshades. In addition to these beneficial pharmacologic agents, Nightshade-derived glycoalkaloid compounds, a key defense mechanism against predation, have been shown to disrupt intestinal epithelium and to potentially activate mast cells in the gut mucosa, leading to adverse symptoms in humans. There is a new appreciation that mast cell activation is an allergic inflammatory mechanism contributing both to pain in irritable bowel syndrome (IBS) and to gut inflammation in inflammatory bowel disease (IBD). Given their ubiquity in Western diets and their shared glycoalkaloid active compounds, edible Nightshades are attracting new interest as a potential trigger for worsening gut symptoms in functional and inflammatory gastrointestinal disorders. Here, we review the limited existing literature on the adverse effects of Nightshade consumption, including the effects of Nightshade-derived glycoalkaloids on IBD gut inflammation, and the under-recognized contribution of Nightshades to food allergies and allergic cross-reactivity. We then highlight new evidence on the contributions of mast cell activation to GI disorder pathogenesis, including potential linkages between Nightshade antigens, intestinal mast cells, and GI dysfunction in IBS and IBD. [ABSTRACT FROM AUTHOR]

Background: Visceral adipose tissue (VAT) is related to SAP prognosis. As a depot of VAT, mesenteric adipose tissue (MAT) resides between pancreas and gut, which might affect SAP and the secondary intestinal injury. Aims: To investigate the changes of MAT in SAP. Methods: 24 SD rats were randomly divided into four groups. 18 rats in SAP group were euthanized in time gradients (6 h, 24 h, and 48 h after modeling) and the others in control group. Blood samples and tissues of pancreas, gut, and MAT were taken for analysis. Results: Compared to the control group, SAP rats appeared MAT inflammation, presenting higher mRNA expression of TNF-α and IL-6 and lower IL-10, and histological changes after 6 h of modeling, which became worse over time. Flow cytometry showed that B lymphocytes increased in MAT after 24 h of SAP modeling and lasted up to 48 h, earlier than the changes of T lymphocytes and macrophages. The intestinal barrier integrity was damaged after 6 h of modeling, presenting lower mRNA and protein expression of ZO-1 and occludin, higher serum levels of LPS and DAO, with pathological changes, which gradually aggravated after 24 h and 48 h. SAP rats had higher serum levels of inflammatory indicators and revealed histological inflammation of pancreas, the severity of which increased with the passage of modeling time. Conclusion: MAT appeared inflammation in early-stage SAP, and became worse over time, with the same trend as the intestinal barrier injury and the severity of pancreatitis. B lymphocytes infiltrated early in MAT, which might promote the MAT inflammation. [ABSTRACT FROM AUTHOR]

Background: Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, the mechanism of which is involved in oxidative stress, can be lethal due to hemorrhage. Thus, we aimed to investigate the effect of hydrogen-rich water (HRW), in terms of oxidative stress, on intestinal mucosal damage as well as changes in the gut microbiome and the short-chain fatty acids (SCFAs) content in feces. Methods: Hydrogen-rich water was orally administered for 5 days to investigate the effectiveness of indomethacin-induced enteropathy in mice. Small intestinal damage and luminal reactive oxygen species (ROS) were evaluated to investigate the ameliorating effects of hydrogen. Then, components of the gut microbiome were analyzed; fecal microbiota transplantation (FMT) was performed using the cecal contents obtained from mice drinking HRW. The cecal contents were analyzed for the SCFAs content. Finally, cells from the macrophage cell line RAW264 were co-cultured with the supernatants of cecal contents. Results: Hydrogen-rich water significantly ameliorated IND-induced enteropathy histologically and reduced the expression of IND-induced inflammatory cytokines. Microscopic evaluation revealed that luminal ROS was significantly reduced and that HRW did not change the gut microbiota; however, FMT from HRW-treated animals ameliorated IND-induced enteropathy. The SCFA content in the cecal contents of HRW-treated animals was significantly higher than that in control animals. The supernatant had significantly increased interleukin-10 expression in RAW264 cells in vitro. Conclusion: Hydrogen-rich water ameliorated NSAID-induced enteropathy, not only via direct antioxidant effects but also via anti-inflammatory effects by increasing luminal SCFAs. These results suggest that hydrogen may have therapeutic potential in small intestinal inflammatory diseases. [ABSTRACT FROM AUTHOR]

Introduction: Growing evidence supports the role of the intestinal microbiome in the development of different intestinal and extraintestinal diseases. Diverticular disease (DD) is one of the most common disorders in western countries. In the last years, different articles have suggested a possible role of the intestinal microbiome in DD pathogenesis and in the development of acute diverticulitis (AD). This systematic review aimed to clarify the current knowledge on the role of the intestinal microbiome in colonic diverticulitis in different stages according to the 2009 PRISMA guidelines. Materials and Methods: Two independent reviewers searched the literature in a systematic manner through online databases, including Medline, Scopus, Embase, Cochrane Oral Health Group Specialized Register, ProQuest Dissertations and Theses Database, and Google Scholar. Patients with any stage of disease were included. The Newcastle-Ottawa scale for case-control and cohort studies was used for the quality assessment of the selected articles. Results: Overall, nine studies were included in the review. Only one article was focused on patients with AD, while all other articles only considered patients with DD without acute inflammation signs. Enterobacteriaceae seems to be the microbiota most associated with the disease, followed by Bifidobacteria. Conclusions: All the included studies showed great heterogeneity in population characteristics and sampling methods. Therefore, given the high prevalence of colonic diverticulitis in the general population, further studies are needed to clarify the role of the intestinal microbiome, paving the way to new target therapies with important social implications. [ABSTRACT FROM AUTHOR]

The article discusses the use of non-invasive biomarkers for measuring gut inflammation in patients with inflammatory bowel disease (IBD). It highlights concerns about the sensitivity and specificity of current biomarkers, such as faecal calprotectin (fCal) and C-reactive protein (CRP), and the preference of patients for blood-based testing. The article introduces the endoscopic mucosal healing index (EHI), a panel of 13 blood-based biomarkers, which has shown promise in predicting endoscopic remission in patients with Crohn's disease (CD). However, the article also presents findings from a study that suggest limitations in the real-world utility of the EHI, particularly in patients with prior exposure to biological treatments. The article concludes by emphasizing the need for a combination of modalities and tests to accurately assess disease activity in IBD patients. [Extracted from the article]

Background: Few data describing pre-diagnosis changes in patients with inflammatory bowel disease (IBD) exist. We aimed to determine if there is a pattern of change in use of health resources, medications and laboratory results in the years preceding diagnosis. Methods: This retrospective study used electronic medical records of Maccabi Health Services (MHS). Patients with IBD ≥ 16 years of age and minimum of 5-years follow-up were identified by entry into the MHS IBD registry and included in the analysis. Demographic, clinical, medication and laboratory data were collected. Generalized estimating equation model was applied to study trends and compare between years. Results: This study included 5643 patients with IBD. Of these, 3039 (53.8%) had Crohn's disease (CD), 2322 (41.1%) had ulcerative colitis (UC) and 282 (5%) had indeterminate colitis (IC). Laboratory parameters including white blood cells, platelets and C-reactive protein showed significant increases while haemoglobin and mean cell volume showed significant decreases in mean values in the 2 years prior to diagnosis with stable values prior to that (p < 0.0001). Parameters such as creatinine, total protein and albumin showed significant, progressive decreases in mean values starting 5 years prior to diagnosis (p < 0.0001). Patients with CD had distinct laboratory trends when compared with patients with UC. Conclusions: Changes in laboratory parameters, healthcare service and medication use occur during the 5-year period before IBD diagnosis. These data can have future clinical applicability by developing a composite score and referral algorithm introducing red flags into primary care visits and appropriate referral for specialist care. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBD) frequently manifest in pediatric age, but may have atypical clinical, histological and laboratory features. Their underlying immune pathophysiology is incompletely understood, rendering quick diagnosis followed by tailored therapy difficult. The tumor necrosis factor superfamily receptor CD30 has been proposed as a potential marker of ulcerative colitis (UC) and has also been associated with elevated Th2 helper T cells. Methods: A cohort of pediatric patients with UC and Crohn's disease (CD) was evaluated for serum soluble CD30 (sCD30) using ELISA and expression of CD30 and subpopulations of Th1/Th2/Th17 lymphocytes in the gastrointestinal mucosa using flow cytometry (FCM). The dataset is supported by endoscopic and microscopic activity of the disease and basic laboratory markers of inflammation. Results: The cohort consisted of 102 observations from 94 patients. sCD30 levels did not differ between patients with CD or UC. However, sCD30 levels correlated with levels of CRP, ESR, fecal calprotectin and albumin and also with clinical activity of the disease in patients with both UC and CD. FCM was not helpful in evaluation of mucosal CD30, which was lowly expressed and not associated with the diagnosis or disease activity. We show augmented Th2 and Th1/17 response in terminal ileum and right-sided colon and decreased Th1/17 response in left-sided colon of UC patients. T lymphocyte subsets were also affected by anti-TNF treatment and patients' age. Conclusions: Neither sCD30 nor mucosal CD30 expression was helpful in differentiating between UC and CD. sCD30 seems to reflect a degree of systemic inflammation and clinical activity in IBD. [ABSTRACT FROM AUTHOR]

Introduction: Traditional cigarette use adversely impacts disease outcomes in Crohn's disease (CD). There has been a worldwide increase in the use of e-cigarettes over the past decade. The impact of use of nicotine containing e-cigarettes on disease outcomes in CD or ulcerative colitis (UC) has not been well defined. Methods: This was a retrospective case-control study of patients with CD or UC who were current users of nicotine containing e-cigarettes (cases). Each case was matched to two non-vaping controls. Our primary study outcome was a composite of new biologic initiation, switch of existing biologic therapy, or IBD-related hospitalization or surgery over 2 years. Multivariable models adjusting for relevant covariates were construction. Results: The study consisted of 127 patients with IBD who were current e-cigarette users compared to 251 controls. Current e-cigarette users were younger than non-users and were more likely to have had an IBD-related surgery previously. On multivariable analysis among those with CD, current e-cigarette use was not associated with higher risk of study outcome (OR 0.82, 95% CI 0.36–1.87). No difference was observed separately among those who were current or former smokers. Similarly, in those with UC, current e-cigarette use was not associated with the primary outcome (OR 1.05, 95% CI 0.33–3.39). Conclusion: Current e-cigarette use was not associated with worse outcomes among patients with IBD. However, larger studies particularly of patients de novo initiating vaping are needed to draw robust conclusions. Patients should be discouraged from initiating vaping recognizing overall adverse health effects. [ABSTRACT FROM AUTHOR]

Introduction: Delays in diagnosing pediatric inflammatory bowel disease (IBD) are common, but the extent of this delay remains unclear due to variations in reported time-periods between studies. The objectives of this systematic review were to examine the extent of diagnostic delay in pediatric IBD and examine any association between specific characteristics and length of diagnostic delay. Methods: We identified studies from several medical bibliographical databases (EMBASE, Medline and CINAHL) from their inception to April 2021. Studies examining pediatric cohorts (< 18 years old) defined as having a diagnosis of Crohn's Disease (CD), ulcerative colitis (UC), or by the more general definition of IBD, and reporting a median time-period between the onset of symptoms and a final diagnosis (diagnostic delay) were included. Two reviewers selected each study, extracted data, and assessed their quality using the Newcastle–Ottawa scale. Narrative synthesis was then used to examine the extent of overall diagnostic delay and delay associated with specific sample characteristics. Results: Of the 10,119 studies initially identified, 24 were included in the review. The overall median diagnostic delay range was 2–10.4 months for IBD, 2.0–18.0 months for UC and 4.0–24.0 months for CD. However, for approximately two thirds of UC (68.8%) and CD (66.7%) studies, delay ranged from 2.0–3.0 and 4.0–6.3 months, respectively. A longer delay was significantly associated with several sample characteristics; however, these were too infrequently examined to draw robust conclusion on their role. Conclusion: Children continue to wait several months for a final diagnosis of IBD, and those with CD experience longer delay than those with UC. The role of specific characteristics on delay needs further exploration. [ABSTRACT FROM AUTHOR]

Objectives and Study: Endoscopic assessments of disease activity are important to diagnose and evaluate treatment responses in patients with Crohn's disease (CD). However, the invasiveness of endoscopy limits the application of this technique in routine examination. Thus, interest has been increasing in identifying noninvasive surrogate markers to predict endoscopic CD activity. Methods: We retrospectively analyzed pediatric patients with new-onset CD from January 2013 to December 2018 at Zhejiang University Affiliated Children's Hospital. The disease severity was scored according to the Crohn's Disease Endoscopic Index of Severity (CDEIS). Routine blood tests were determined individually. Clinical activity was assessed based on the Pediatric Crohn's Disease Activity Index (PCDAI). Results: A total of 91 patients with CD had undergone one or more ileocolonoscopies (n = 146), the mean CDEIS for all the pediatric patients with CD was 7.0 (95% CI 5.7–8.2), and the mean PCDAI was 20.9 (95% CI 18.3–23.5). Pearson's linear analysis of the CDEIS and PCDAI in pediatric patients with CD showed a moderate correlation (r = 0.508, P < 0.001). Weak correlations were found between the PCDAI and CDEIS at the first diagnosis (r = 0.408, P < 0.001) and after completing induction therapy (r = 0.286, P < 0.05). Routine blood tests also did not correlate well with the CDEIS. Conclusions: This study identified weak correlations between the PCDAI and CDEIS in assessing pediatric patients with CD severity both at first diagnosis and after induction therapy. A comprehensive assessment of PCDAI, CDEIS and multiple laboratory factors should be performed at diagnosis and during the follow-up of patients with CD. [ABSTRACT FROM AUTHOR]

Background: Uric acid (UA) has anti- and pro-inflammatory properties. We previously revealed that elevated serum UA levels provide protection against murine small intestinal injury probably via luminal UA secreted in the small intestine. Luminal UA may act as an antioxidant, preventing microbiota vulnerability to oxidative stress. However, whether luminal UA is increased under hyperuricemia and plays a protective role in a dose-dependent manner as well as the mechanism by which luminal UA exerts its protective effects on enteropathy remains unknown. Methods: Inosinic acid (IMP) (1000 mg/kg, i.p.) was administered to obtain high serum UA (HUA) and moderate serum UA (500 mg/kg IMP, i.p.) mice. UA concentrations and levels of oxidative stress markers in the serum and intestine were measured. Mice received indomethacin (20 mg/kg, i.p.) to evaluate the effects of UA on indomethacin-induced enteropathy. Reactive oxygen species (ROS) on the ileal mucosa were analyzed. The fecal microbiota of HUA mice was transplanted to investigate its effect on indomethacin-induced enteropathy. Results: IMP increased luminal UA dose-dependently, with higher levels of luminal antioxidant markers. Indomethacin-induced enteropathy was significantly ameliorated in both UA-elevated groups, with decreased indomethacin-induced luminal ROS. The microbiota of HUA mice showed a significant increase in α-diversity and a significant difference in β-diversity from the control. Fecal microbiota transplantation from HUA mice ameliorated indomethacin-induced enteropathy. Conclusions: The protective role of luminal UA in intestinal injury is likely exerted via oxidative stress elimination and microbiota composition modulation, preferably for gut immunity. Therefore, enhancing anaerobic conditions using antioxidants is a potential therapeutic target. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a group of chronic intestinal inflammatory disorders with a prolonged duration characterized by recurrent relapse and remission. The exact etiology of IBD remains poorly understood despite the identification of relevant risk factors, including individual genetic susceptibility, environmental triggers, and disruption of immune homeostasis. Dysbiosis of the gut microbiota is believed to exacerbate the progression of IBD. Recently, increasing evidence has also linked oral microbiota dysbiosis with the development of IBD. On the one hand, IBD patients show significantly unbalanced composition and function of the oral microbiota known as dysbiosis. On the other, overabundances of oral commensal bacteria with opportunistic pathogenicity have been found in the gut microbiota of IBD patients. Herein, we review the current information on the causative factors of IBD, especially recent evidence of IBD-associated oral microbiota dysbiosis, which has seldom been covered in the previous literature review, highlighting the pathogenic mechanisms of specific oral bacteria in the development of IBD. Ectopic colonization of several oral bacteria, including a subset of Porphyromonas gingivalis, Streptococcus mutans, Fusobacterium nucleatum, Campylobacter concisus, and Klebsiella pneumoniae, may lead to destruction of the intestinal epithelial barrier, excessive secretion of inflammatory cytokines, disruption of the host immune system, and dysbiosis of gut microbiota, consequently aggravating chronic intestinal inflammation. Studying oral microbiota dysbiosis may open future horizons for understanding IBD pathogenesis and provide novel biomarkers for IBD. This review also presents the current treatment and new perspectives for IBD treatment. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic and nonspecific intestinal inflammatory condition with high relapse rate. Its pathogenesis has been linked to dysbacteriosis, genetic and environmental factors. In recent years, a new type of lymphocytes, termed innate lymphoid cells, has been described and classified into three subtypes of innate lymphoid cells—group 1, group 2 and group 3. An imbalance among these subsets' interaction with gut microbiome, and other immune cells affects intestinal mucosal homeostasis. Understanding the role of innate lymphoid cells may provide ideas for developing novel and targeted approaches for treatment of IBD. [ABSTRACT FROM AUTHOR]

Collagenous colitis (CC) is associated with non-bloody, watery diarrhea, which is pathophysiologically reasonable because normal colonic absorption (or excretion) of water and electrolytes can be blocked by the abnormally thick collagen layer in CC. However, CC has also been associated with six previous cases of protein-losing enteropathy (PLE), with no pathophysiologic explanation. The colon does not normally absorb (or excrete) amino acids/proteins, which is primarily the function of the small bowel. Collagenous duodenitis (CD) has not been associated with PLE. This work reports a novel case of CD (and CC) associated with PLE; a pathophysiologically reasonable mechanism for CD causing PLE (by the thick collagen layer of CD blocking normal intestinal amino acid absorption); and a novel association of PLE with severe COVID-19 infection (attributed to relative immunosuppression from hypoproteinemia, hypoalbuminemia, hypogammaglobulinemia, and malnutrition from PLE). [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) causes inter-related symptoms of fatigue, pain and urgency which can persist in remission. Aim: To understand how people with IBD experience and self-manage these symptoms and to inform the future development of an online self-management programme. Methods: Using exploratory qualitative methods, we recruited participants from clinic and community settings. Focus groups, conducted across the UK, were audio-recorded and professionally transcribed. Transcripts were analysed over four rounds using framework analysis. Eight patients were consulted to agree the final structure of data and themes. Results: Seven focus groups were held; five gave useable data. Twenty-six participants (15 female; ages 21–60 years; disease duration 2–40 years) with Crohn's disease (n = 10), ulcerative colitis (n = 14) and IBD-unclassified (n = 2) attended one of these five focus groups. Three core themes emerged: The Negative Impact of Symptoms, Positively Taking Control and Seeking and Receiving Support. The persistent, often stark impact of multiple co-existing symptoms on physical and emotional wellbeing can force unwanted adjustments and limitations in working, social and intimate arenas of life. Unpredictable symptoms are challenging and impact each other in negative vicious cycles. Managing diet, pacing, accepting background levels of fatigue, pain and urgency, seeking support, exercising and attending to mental wellbeing, are all perceived as helpful in self-managing symptoms. Conclusion: Fatigue, pain and urgency are troublesome for patients, especially in combination, suggesting that these should be addressed simultaneously by clinicians. Participants reported several strategies for self-management, providing patient-focused evidence to inform future development of a self-management intervention programme. [ABSTRACT FROM AUTHOR]

Background and Aims: DNA damage-regulated autophagy modulator 1 (DRAM1) is required for induction of autophagy and apoptosis. However, the influence of DRAM1 on the pathogenesis of inflammatory bowel disease (IBD) has not been explored. Methods: DRAM1 expression was examined in the intestinal mucosa of patients with IBD and colons of colitis mice. We used a recombinant adeno-associated virus carrying small hairpain DRAM1 to knock down the DRAM1 gene to treat colitis in the mice. The effect of DRAM1 on autophagy and apoptosis of intestinal epithelial cells was explored. DRAM1-mediated interaction with the c-Jun N-terminal kinase (JNK) pathway was also examined. Results: DRAM1 expression in the intestinal mucosa of the IBD patients was higher than that in the control participates. DRAM1 expression in the inflammatory cells in patients with Crohn's disease (CD) was lower than that in patients with ulcerative colitis (UC). Additionally, DRAM1 expression was correlated with the Simple Endoscopic Score for CD and the Mayo endoscopic score for UC. Serum levels of DRAM1 in the IBD group were substantially higher than those in the normal group. The knockdown of DRAM1 could alleviate colitis symptoms in mice. In in vitro experiments, knocking down DRAM1 could reduce autophagy and apoptosis levels. Mechanistically, DRAM1 may participate in the regulation of these two processes by positively regulating JNK activation. Conclusions: During intestinal inflammation, the upregulation of DRAM1 may promote the activation of JNK and further aggravate intestinal epithelium damage. [ABSTRACT FROM AUTHOR]

Background and Aims: Limited means exist to assess gastrointestinal activity in a noninvasive, objective way that is highly predictive of underlying motility disorders. The aim of this paper is to demonstrate the feasibility of recording myoelectric gastrointestinal activity by cutaneous patches and to correlate myoelectric signals with gastrointestinal function in various clinical settings. Methods: A novel wireless patch system (WPS) (G-Tech Medical) that acquires gastrointestinal myoelectrical signals was placed on the patients' anterior abdomens. Data were transmitted wirelessly to a mobile device with a user interface and forwarded to a cloud server where processing algorithms identified episodes of motor activity, quantified their parameters, and nominally assigned them to specific gastrointestinal organs based on their frequencies. Results: The inherent reproducibility of the WPS measurement technique itself and from the underlying gut activity, coupled with source validation and sensitivity to changes in gut activity in several physiologic and pathologic states, demonstrates its feasibility, safety, and performance in clinical settings. Conclusions: The novel WPS technology, measuring myoelectric intestinal activity noninvasively and continuously over multiple days, is feasible in a wide range of clinical settings, highlighting its promise in the diagnosis and management of motility disorders. Further research is required for more extensive validation and to determine how best to employ this information to optimize patient care. [ABSTRACT FROM AUTHOR]

Anemia is the most common extraintestinal systemic complication of inflammatory bowel disease. Iron deficiency anemia and anemia of chronic disease are among the most frequent types. Intestinal iron absorption is controlled by the activity of ferroportin. Cells with high expression of ferroportin include enterocytes, and also macrophages and hepatocytes. Iron homeostasis is controlled by the hepcidin-ferroportin axis. Hepcidin is a central regulator of iron metabolism and can also serve as a marker of systemic inflammation. During systemic inflammatory response, the synthesis of hepcidin increases, and hepcidin binds to ferroportin and inhibits its activity. Thus, iron is not absorbed from the bowel into the circulation and also remains sequestered in macrophages. Conversely, hepcidin synthesis is suppressed during conditions requiring increased iron intake for enhanced erythropoiesis, such as iron deficiency anemia or hypoxia. Here, ferroportin is not blocked, and iron is actively absorbed into the bloodstream and also released from the stores. Production of hepcidin is influenced by the status of total body iron stores, systemic inflammatory activity and erythropoietic activity. Oral iron therapy is limited in inflammatory bowel diseases due to ongoing gastrointestinal inflammation. It is less effective and may worsen the underlying disease. Therefore, the choice between oral and parenteral iron therapy must be made with caution. Oral iron would be ineffective at high hepcidin levels due to concurrent ferroportin blockage. Contrarily, low levels of hepcidin indicate that oral iron therapy should be successful. An understanding of hepcidin can help in understanding the body's reaction to iron depletion during the inflammatory process. [ABSTRACT FROM AUTHOR]

Background: Chronic enteropathy associated with the SLCO2A1 gene (CEAS) is an enteropathy characterized by multiple small intestinal ulcers of nonspecific histology, also known as chronic nonspecific multiple ulcers of the small intestine. The SLCO2A1 gene encodes a prostaglandin transporter (PGT). Aims: The aim of this study was to investigate the clinical characteristics of ten Chinese patients with intestinal ulcers of unknown origin, screen them for variants of SLCO2A1, and to investigate the expression of PGT in the small intestinal mucosa of patients with CEAS. Methods: Ten Chinese patients with intestinal ulcers of unknown origin were included in this study. Blood samples were collected for whole-exome sequencing and Sanger sequencing of candidate gene variants. Immunohistochemical staining was used to investigate the expression of PGT. Results: These ten patients were clinically diagnosed with intestinal ulcers of unknown origin based on criteria established according to earlier publications. Three of them were genetically diagnosed as having CEAS and four candidate variants of the SLCO2A1 gene were identified, among which c.941-1G>A, c.178G>A and c.1681C>T were detected in patients with CEAS for the first time. The terminal ileum was involved in all three patients with CEAS in our study, which was different from the results of Japanese patients. The expression of PGT in the vascular endothelial cells of the intestinal mucosa tissues of patients with CEAS was negative or intermediate. Conclusion: We summarized the clinical data of ten Chinese patients with intestinal ulcers of unknown origin and identified three novel SLCO2A1 variants from three patients with CEAS. This study improves our understanding of CEAS and broadens the spectrum of SLCO2A1 variants known to cause CEAS. [ABSTRACT FROM AUTHOR]

Backgrounds: Behçet's disease (BD) and Crohn's disease (CD) cannot be easily differentiated in young adults presenting with nonspecific gastrointestinal (GI) manifestations due to similar extraintestinal manifestations. We recently showed that increased common femoral vein (CFV) thickness is a distinctive feature of BD, rarely present in other inflammatory or vascular diseases with a specificity higher than 80% for the cutoff value of ≥ 0.5 mm. We suggest that CFV thickness measurement with ultrasonography (US) can be a diagnostic tool for BD. Aims: To assess the diagnostic performance of CFV thickness measurement in the differential diagnosis of BD and CD. Methods: Patients with BD (n = 69), CD (n = 38), and healthy controls (HC) (n = 38) were included in the study. Bilateral CFV thickness was measured with Doppler US. Results: Both right and left CFV thicknesses were significantly higher in BD compared to HC and CD (for right: 0.76 mm vs 0.33 mm, for left: 0.78 mm vs 0.35 mm, p < 0.001 for both). CFV thicknesses in CD were similar to HC (p > 0.05 for both). CFV thickness was also similar between BD patients with and without GI involvement (p = 0.367). The diagnostic cutoff values of ≥ 0.5 mm for CFV thickness performed well against to both CD and HCs for discrimination of BD. The sensitivity and specificity rates were > 85% for both HC and CD. Positive and negative predictive values in our tertiary clinical setting were > 90%. Conclusion: We found significantly lower CFV thickness in CD compared to BD. Our results suggest that CFV wall thickness measurement is a distinctive diagnostic tool for the differentiation of BD and CD and can be helpful in daily practice for the differentiation of two diseases. [ABSTRACT FROM AUTHOR]

Background and Aims: In rare cases, the diagnosis of Crohn's disease (CD) can only be achieved using small bowel capsule endoscopy (SBCE). We investigate the characteristics of patients with CD only visible on SBCE and assess their disease course. Methods: Data of all adult patients with confirmed CD diagnosis based on SBCE with normal endoscopic and cross-sectional imaging findings were retrospectively collected in three tertiary-level hospitals from January 2014 to March 2020. Results: Thirteen patients were included. Ten patients were females, and the mean age at diagnosis was 36 years. Ileum was mostly involved (85%), while duodenum and jejunum were affected in 23% and 38% of the cases, respectively. Nine patients had one segment involved, while four subjects had two or three segments affected. All patients had inflammatory behavior. First treatment consisted of steroids in all cases, and six patients were later treated with immunosuppressant or biologics. After a mean follow-up of 27.5 months, no change in disease behavior, hospitalization, or CD-related surgery was observed. Conclusions: CD only visible at SBCE is a rare condition with a more favorable disease course compared to general CD with a lower rate of complicated behavior, hospitalization, and surgery, despite a similar use of immunosuppressant or biologics. [ABSTRACT FROM AUTHOR]

Background: Currently, because the population is aging, use of medications has been increasing, including use of nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents. Aims: This study aims to investigate whether NSAIDs can cause damage to the small bowel (SB) mucosa. Methods: Endoscopic videos of subjects who had undergone capsule endoscopy (CE) were evaluated by three experts in order to identify SB injury. All medications taken within 2 weeks from the time of CE were investigated. Cases with a final diagnosis of intestinal tuberculosis, inflammatory bowel disease, Behcet's disease, Peutz–Jeghers syndrome, small bowel lymphoma, or Henoch–Schönlein purpura were excluded from the analysis. Results: Among the 273 subjects, 125 (45.8%) had SB erosions or ulcers (erosion group) and the remaining 148 (54.2%) did not (no erosion group). SB erosions or ulcers were more common in females, patients aged > 60 years, and subjects taking NSAIDs (p = 0.048, 0.032, and < 0.001, respectively). No statistically significant differences were found between the two groups in the following variables: history of cancer and GI surgery, reasons for the test, comorbidities, and use of anticoagulants and antiplatelet agents. Multivariate analysis showed that use of NSAIDs [OR 4.191 (95% CI 1.858–9.458), p < 0.001] was an independent risk factor for SB erosions or ulcers. Conclusions: Use of NSAIDs is the only independent risk factor for SB injury identified in this study. Antithrombotic agents do not cause or exacerbate damage to the SB, according to our results. Clinical trial registration: KCT0004795. [ABSTRACT FROM AUTHOR]

Background: Data regarding hospitalization outcomes in patients with inflammatory bowel disease (IBD) with respect to hospital teaching status are largely unknown. Aims: We aimed to investigate the impact of hospital teaching status on IBD hospitalization outcomes. Methods: In this retrospective analysis, we queried the 2016 and 2017 National Inpatient Sample (NIS) databases using the International Classification of Diseases 10th revision (ICD-10) coding system. All adult patients with a principal diagnosis of IBD were included. We stratified the IBD group into ulcerative colitis (UC), Crohn's disease (CD), and complicated IBD. Our primary outcome was mortality. Statistical analysis was performed using STATA, version 16.0. Results: Of the 189,950 adult patients with IBD, the majority were admitted to teaching hospitals (70.9%). There was no significant difference in mortality based upon hospital teaching status (aOR 1.18, p = 0.48); however, these patients had an increased mean length of stay (adjusted coefficient: 0.82, p < 0.01), charges (adjusted coefficient: $8732, p < 0.01), and costs ($2871, p < 0.01). On subgroup analysis, patients with UC admitted to teaching hospitals had a significantly increased in-hospital mortality (aOR 2.11, p < 0.05), while those admitted with CD did not (aOR 0.80, p = 0.4). Among patients with complicated IBD, 73.17% were admitted to teaching hospitals, and no significant difference in in-hospital mortality was seen (aOR 1.06, p = 0.8). Conclusion: While outcome differences are likely related to multiple unaccounted factors, greater efforts should be placed to cost-effectively manage patients with IBD at teaching institutions. Future studies are warranted to fully comprehend these variations. [ABSTRACT FROM AUTHOR]

Objectives: To test two methods for reporting of fecal incontinence (FI) in people with inflammatory bowel disease. Methods: Consecutive patients from IBD clinics in six UK hospitals completed a short three-item case-finding survey about FI; they either completed the survey themselves or were asked the same questions face to face by a clinician. Results: Of 1336 eligible patients with complete data (48% male; mean 43 years; 55% Crohn's disease, 41% ulcerative colitis), 772 were asked about FI face to face, and 564 self-completed the survey: FI was reported in 63% and 56%, respectively (p = 0.012). In regression analyses, those aged 51–60, having Crohn's disease and higher disease activity, were more likely to report FI. Of all respondents, 38.7% were interested in receiving help for their incontinence. Conclusions: Fecal incontinence affects the majority of people with IBD. Although more patients reported fecal incontinence when asked face to face than self-reported, routine screening by either method in clinical practice is recommended. Over one-third of patients with IBD want help for bowel control problems. [ABSTRACT FROM AUTHOR]

Background: Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others.Aims: Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date.Methods: Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018.Results: The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease, p < 0.001), gender (female, p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs.Conclusions: One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear. [ABSTRACT FROM AUTHOR]

Background: Ileocecal thickening (ICT) on imaging could result from diverse etiologies but may also be clinically insignificant.Aim: Evaluation of role of combined 2-deoxy-2-fluorine-18-fluoro-D-glucose(18F-FDG)-positron emission tomography and computed tomographic enterography (PET-CTE) for determination of clinical significance of suspected ICT.Methods: This prospective study enrolled consecutive patients with suspected ICT on ultrasound. Patients were evaluated with PET-CTE and colonoscopy. The patients were divided into: Group A (clinically significant diagnosis) or Group B (clinically insignificant diagnosis) and compared for various clinical and radiological findings. The two groups were compared for maximum standardized uptake values of terminal ileum, ileo-cecal valve, cecum and overall.Results: Of 34 patients included (23 males, mean age: 40.44 ± 15.40 years), 12 (35.3%) had intestinal tuberculosis, 11 (32.4%) Crohn's disease, 3 (8.8%) other infections, 1 (2.9%) malignancy, 4 (11.8%) non-specific terminal ileitis while 3 (8.8%) had normal colonoscopy and histology. The maximum standardized uptake value of the ileocecal area overall (SUVmax-ICT-overall) was significantly higher in Group A (7.16 ± 4.38) when compared to Group B (3.62 ± 9.50, P = 0.003). A cut-off of 4.50 for SUVmax-ICT-overall had a sensitivity of 70.37% and a specificity of 100% for prediction of clinically significant diagnosis. Using decision tree model, the SUVmax-ICT with a cut-off of 4.75 was considered appropriate for initial decision followed by the presence of mural thickening in the next node.Conclusion: PET-CTE can help in discrimination of clinically significant and insignificant diagnosis. It may help guide the need for colonoscopy in patients suspected to have ICT on CT. [ABSTRACT FROM AUTHOR]

Given that CD activity and MH do not always correlate with clinical and biochemical remission, evaluation of the mucosal response to therapy might be a new indication for SBCE for patients with small bowel CD [[3]]. Crohn's disease (CD) is a chronic relapsing immune-mediated disease affecting the gastrointestinal tract. [Extracted from the article]

10.1053/j.gastro.2015.08.055 11 Louis E, Mary JY, Vernier-Massouille G. Maintenance of remission among patients with Crohn's disease on antimetabolite therapy after infliximab therapy is stopped. Anti-tumor necrosis factor (TNF) therapy helps to achieve disease remission and improve long-term outcomes in patients with inflammatory bowel disease (IBD) [1]. Among patients who experience secondary loss of response to anti-TNF therapy, dose intensification recaptures response in a proportion of patients [4]. [Extracted from the article]

Autoimmune enteropathy is an extremely rare condition characterized by an abnormal intestinal immune response which typically manifests within the first 6 months of life as severe, intractable diarrhea that does not respond to dietary modification. Affected individuals frequently present with other signs of autoimmunity. The diagnosis is made based on a characteristic combination of clinical symptoms, laboratory studies, and histological features on small bowel biopsy. Autoimmune enteropathy is associated with a number of other conditions and syndromes, most notably immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome and autoimmune polyglandular syndrome type 1 (APS-1). Diagnosis and treatment is challenging, and further research is needed to better understand the pathogenesis, disease progression, and long-term outcomes of these conditions. [ABSTRACT FROM AUTHOR]

Background: Predictors besides symptoms of obstruction indicating small bowel stenosis are little known.Aims: To detect predictors of small bowel stenosis in balloon-assisted enteroscopy.Methods: Over a 6-year period, 461 patients had enteroscopy for suspected small intestinal disease. Details of clinical manifestations, medical history, demographic characteristics, findings of examinations, information on enteroscopy, and treatment were retrospectively collected based on medical records. Small bowel stenosis was defined as stricture that over-tube cannot go through in enteroscopy. Univariate and multivariate analyses were performed to identify predictors for small bowel stenosis.Results: A total of 314 patients had definite diagnosis after enteroscopy, imaging modalities, and/or even surgical exploration. They were included in this study for analyses. Mean age for them was 48.2 years old (range 15-81 years). Small bowel stenosis was present in 59 patients (18.8%). Analyses showed that CT/MRI indicating stenosis was significantly associated with severe stenosis (p = 0.014) but insignificant related to general stenosis (p = 0.097). Predictive factors that accompanied stenosis were age ≥ 60 years (OR = 2.1, 95% CI 1.1-4.0), underweight (BMI ≤ 18.5) (OR = 3.4, 95% CI 1.4-8.4), symptoms of obstruction (OR = 3.6, 95% CI 1.8-7.4), and overt small bowel bleeding (OR = 0.5, 95% CI 0.2-0.9).Conclusions: Small bowel stenosis more tended to occur to patients with symptoms of obstruction, no overt small bowel bleeding, age ≥ 60 years, or underweight. [ABSTRACT FROM AUTHOR]

Background: The differentiation between untypical intestinal tuberculosis (UITB) and untypical Crohn's disease (UCD) is a challenge.Aims: To analyze phenotypic variables and propose a novel prediction model for differential diagnosis of two conditions.Methods: A total of 192 patients were prospectively enrolled. The clinical, laboratory, endoscopic, and radiological features were investigated and subjected to univariable and multivariable analyses. The final prediction model for differentiation between UCD and UITB was developed by logistic regression analysis and Fisher discriminant analysis on the training set. The same discriminant function was tested on the validation set.Results: Twenty-five candidates were selected from 52 phenotypic variables of typical Crohn's disease (TCD), UCD, and UITB patients. UCD's variables overlapped with both TCD and UITB. The percentages of tuberculosis history, positive PPD, and positive T-SPOT result in UCD were all significantly higher than that in TCD (11.6% vs. 0.0%, 27.9% vs. 0.0%, 25.6% vs. 4.5%, respectively, P < 0.05). The regression equations and Fisher discriminant function for discrimination between UCD and UITB were developed. In the training data, the area under the receiver operating characteristic of equations was 0.834, 0.69, and 0.648 in the clinical-laboratory, endoscopic, and radiological model, respectively. The accuracy of Fisher discriminant function for discrimination was 86% in UCD and 73% in UITB in the validation data.Conclusions: Phenotypes of UCD patients in TB-endemic countries may be associated with TB infection history. Fisher discriminant analysis is a good choice to differentiate UCD from UITB, which is worthy of verification in clinical practice. [ABSTRACT FROM AUTHOR]

Autoimmune enteropathy (AIE) is a complex disease affecting both children and adults. Although associated with significant morbidity and mortality, the pathophysiology of the disease and its treatment have not been well characterized. This study aims to review the medical literature available on this rare but clinically significant ailment, to help establish a better understanding of its pathophysiology and enumerate the available diagnostic and treatment modalities. A literature search was conducted on PubMed using key terms related to autoimmune enteropathy and intractable diarrhea, with no restrictions on the date of publication or language. We found a total of 98 reports of AIE published in the form of case reports and case series. The evidence reviewed suggests that AIE is a multifaceted disorder that requires a high index of suspicion in the appropriate clinical setting to be able to make an early diagnosis. Current evidence supports the use of supportive care to correct nutritional and metabolic deficiencies, and immunosuppressives and immunomodulators as directed therapies. Hematopoietic stem cell transplant is an aggressive, but successful curative modality for patients with AIE as part of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Cumulative clinical experience with management of AIE has allowed improved outcomes in transplanted and non-transplanted AIE patients even though morbidity and mortality with are still high in patients with this condition. More research is needed to further define the role of new therapies for AIE, and a central registry with participation of multiple institutions might help share and standardize care of patients with this rare but serious condition. [ABSTRACT FROM AUTHOR]

Background: There is considerable individual variability in nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy.Aim: To identify the SNP that is most significantly involved with NSAID-induced enteropathy.Methods: One hundred fifty human subjects who were known to have a certain degree of loxoprofen- or celecoxib-induced small-intestinal damage from a previous study were enrolled. The subjects were divided into groups based on treatments and also on the increased number of small intestinal mucosal breaks. The candidate SNP was selected by an initial analysis of GWAS among the groups in various combinations. After the initial analysis, the gene including the specified SNP was analyzed in detail using GWAS and genotype imputation.Results: After analysis, 70 subjects receiving the loxoprofen treatment and 69 subjects receiving celecoxib treatment were determined to be eligible for the analysis. The minimum p value in GWAS was detected in the analysis of 16 cases with an increase of five or more mucosal breaks and 123 controls with zero to four mucosal breaks. In the GWAS, five SNPs in the bactericidal/permeability-increasing fold-containing family B member 4 (BPIFB4) gene showed the lowest p value (p = 2.69 × 10-7 with an odds ratio of 40.9). Of the five SNPs, four were nonsynonymous SNPs (rs2070325: V268I, rs2889732: T320N, rs11699009: F527L, rs11696307: T533I, and rs11696310: intronic). Furthermore, 23 SNPs in BPIFB4 detected by genotype imputation based on the GWAS data also showed suggestive associations (p < 1 × 10-6).Conclusion: The results indicate that SNPs in BPIFB4 were associated with NSAID-induced small intestinal mucosal injury (UMIN: 000007936). [ABSTRACT FROM AUTHOR]

Background: Microscopic colitis (MC), a subtype of inflammatory bowel disease, is a chronic condition of unknown etiology. Recent evidence has linked MC with intriguing changes in the stool microbiota, which may be linked to disease pathogenesis. The composition of the mucosal microbiome in patients with MC remains unclear.Methods: We performed a cross-sectional study comparing colonic tissue samples from patients with MC to those of healthy controls at the Michael E. DeBakey VA Medical Center. We included adults older than 18 who underwent a colonoscopy with biopsies to evaluate chronic diarrhea. Cases were defined by histology consistent with MC and controls by the absence of histologic disease. We conducted structured chart review to exclude other gastrointestinal diseases and obtain demographic (age, sex, race) and clinical (duration of symptoms and concurrent medications) information for cases and controls. We extracted bacterial DNA from formalin-fixed paraffin-embedded tissue samples and sequenced the v4 region of the 16S rRNA gene. Operational taxonomic unit (OTU) clustering was performed using UPARSE, and OTUs were assigned using the SILVA database. Statistical analysis was performed in QIIME and LEfSe. Comparisons with FDR-adjusted p values of less than 0.05 were considered statistically significant.Results: We included 20 MC patients and 20 controls with mean ages of 62 and 54, respectively. Most cases were White (95%), 60% had symptoms for greater than 12 months, and 50% were taking PPIs and NSAIDs at the time of their diagnosis. Compared to controls, MC patients had a significant increase in the proinflammatory sulfur-reducing bacterial family Desulfovibrionales. The Coriobacteriaceae family, abundant in the healthy gut, was significantly decreased in MC cases. There was also an increase in the genus Actinomyces in MC patients on PPI and an increase in the class Bacilli among those taking NSAIDs.Discussion: Patients with MC have an increase in the proinflammatory family Desulfovibrionales. Actinomyces and Bacilli were associated with medications (PPI and NSAID) known to increase the risk of MC. Our findings may have important implications for understanding the pathogenesis of MC. [ABSTRACT FROM AUTHOR]

Background and Aims: Gastrointestinal pathogen panels (GPPs) are increasingly being used for evaluation of diarrhea. The impact of these tests on patients with inflammatory bowel diseases (IBD) is unknown. We performed a time-interrupted cohort study comparing GPPs and conventional stool evaluation in patients with IBD with diarrhea.Methods: We included 268 consecutive patients with IBD who underwent GPP (BioFire Diagnostics®) (n = 134) or conventional stool culture and Clostridium difficile polymerase chain reaction testing (n = 134) during suspected IBD flare between 2012 and 2016. Primary outcome was composite of 30-day IBD-related hospitalization, surgery, or emergency department visit; secondary outcome was IBD treatment modification.Results: Overall, 41/134 (30.6%) patients tested positive on GPP (18 C. difficile, 17 other bacterial infections, and 6 viral pathogens) versus 14/134 patients (10.4%, all C. difficile) testing positive on conventional testing. Rate of IBD treatment modification in response to stool testing was lower in GPP group as compared conventional stool testing group (35.1 vs. 64.2%, p < 0.01). On multivariate analysis, diagnostic evaluation with GPP was associated with three times higher odds of IBD-related hospitalization/surgery/ED visit (95% CI, 1.27-7.14), as compared to conventional stool testing. This negative impact was partly mediated by differences in ordering provider specialty, with non-gastroenterologists more likely to order GPP as compared to gastroenterologists.Conclusions: In patients with suspected flare of IBD, GPPs have higher pathogen detection rate and lead to lower rate of IBD treatment modification. A diagnostic testing strategy based on GPPs is associated with higher hospital-related healthcare utilization as compared to conventional stool testing, particularly when utilized by non-gastroenterologists. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBD) are multifactorial disorders affecting millions of people worldwide with alarmingly increasing incidences every year. Dysfunction of the intestinal epithelial barrier is associated with IBD pathogenesis, and therapies include anti-inflammatory drugs that enhance intestinal barrier function. However, these drugs often have adverse side effects thus warranting the search for alternatives. Compatible solutes such as bacterial ectoines stabilize cell membranes and proteins.Aim: To unravel whether ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidinecarboxylic acid) and homoectoine (4,5,6,7-tetrahydro-2-methyl-1H-(1,3)-diazepine-4-carboxylic acid), a synthetic derivative of ectoine, have beneficial effects during dextran sulfate sodium (DSS)-induced colitis in mice.Methods/results: We found that the disease activity index was significantly reduced by both ectoines. DSS-induced edema formation, epithelial permeability, leukocyte recruitment and tissue damage were reduced by ectoine and homoectoine, with the latter having stronger effects. Interestingly, the claudin switch usually observed during colitis (decreased expression of claudin-1 and increased expression of the leaky claudin-2) was completely prevented by homoectoine, whereas ectoine only reduced claudin-2 expression. Concomitantly, only homoectoine ameliorated the drop in transepithelial electrical resistance induced by IFN-γ and TNF-α in Caco-2 cells. Both ectoines inhibited loss of ZO-1 and occludin and prevented IFN-γ/TNF-α-induced increased paracellular flux of 4 kDa FITC-dextran in vitro. Moreover, both ectoines reduced expression of pro-inflammatory cytokines and oxidative stress during colitis.Conclusion: While both ectoine and homoectoine have protective effects on the epithelial barrier during inflammation, only homoectoine completely prevented the inflammatory claudin switch in tight junctions. Thus, homoectoine may serve as diet supplement in IBD patients to reach or extend remission. [ABSTRACT FROM AUTHOR]

Background: The Advisory Committee on Immunization Practices (ACIP) recommends using the immunization record and not serologic testing to determine immunity against measles and rubella in the general population, due to potential false negatives. However, it is unknown whether the immune response is less durable among patients who are immunosuppressed.Aims: The primary aim of this study was to evaluate sustained vaccine-induced measles, mumps, and rubella (MMR) antibody concentrations in immunosuppressed patients with inflammatory bowel disease (IBD).Methods: We performed a cross-sectional study to compare antibody concentrations following the two-dose (MMR) vaccine among 46 patients with IBD and 20 healthy controls (HC). Three IBD groups stratified by the immunosuppressive regimen that preceded study entry for at least 3 months: (1) thiopurine monotherapy, (2) anti-TNF monotherapy, or (3) combination therapy (anti-TNF agent combined with an immunomodulator) were enrolled.Results: All subjects had measurable antibody concentrations to the three vaccine viruses. Age and time since receipt of MMR series were similar in both groups. There were no difference in the antibody concentration of measles (IBD 667 mIU/ml vs HC 744 mIU/ml; p = 0.45), mumps (IBD 339 EU/ml vs HC 402 EU/ml; p = 0.62), or rubella (IBD 25 mIU/ml vs HC 62 mIU/ml; p = 0.11) among the groups. No differences in antibody concentrations were found among the IBD treatment groups.Conclusion: Immunosuppressed patients with IBD have sustained antibody concentrations comparable to healthy controls. Thus, gastroenterologist should follow the ACIP recommendations and use the immunization record when available to determine immunity to measles and rubella in patients with IBD. Clinical Trials Registry # NCT02434133. [ABSTRACT FROM AUTHOR]

Introduction: The impact of antithrombotic treatment on the findings of small-bowel capsule endoscopy for patients with obscure gastrointestinal bleeding remains contentious. We aimed to determine the effect of these agents on small-bowel video capsule endoscopy positive findings.Methods: MEDLINE, Cochrane Library, and Google Scholar were searched for studies reporting on patients receiving concurrent antithrombotic treatment, while undergoing capsule endoscopy for obscure gastrointestinal bleeding (OGIB). Outcomes were the effect of antithrombotic therapy-overall and per type of antithrombotic agent-on the examination's positive findings and re-bleeding risk. The effect size of study outcomes is presented as odds ratio (OR) with 95% confidence interval (CI).Results: Fourteen studies with 1023 patients were included. We detected significant heterogeneity with no evidence of publication bias. Compared to antithrombotic drug nonusers, antithrombotic treatment was associated with an increased prevalence of positive findings [OR 1.98 (95% CI 1.34-2.93); P = 0.0006]. This effect did not differ between antiplatelet and anticoagulant treatments [OR 2.22 (95% CI 1.28-3.84); P = 0.005 and 2.53 (95% CI 1.66-3.87); P < 0.0001, respectively]. Antithrombotic use over no use was not associated either with overt [OR 1.17 (95% CI 0.51-2.66); P = 0.71] or with occult [OR 0.86 (95% CI 0.38-1.95); P = 0.71] bleeding pattern. However, concurrent antithrombotic treatment was associated with higher odds for re-bleeding compared to no treatment [OR 2.53 (95% CI 1.46-4.37); P = 0.0009].Conclusions: Antithrombotic treatment is associated with more positive findings in small-bowel video capsule endoscopy in OGIB as well as higher odds of re-bleeding. [ABSTRACT FROM AUTHOR]

Background: Studies have shown that prophylactic biologic therapy can reduce post-surgical Crohn's disease recurrence.Aims: We aimed to identify the frequency of delay and risk factors associated with a delay in the initiation of prophylactic post-surgical biologic therapy in high-risk patients.Methods: We performed a cohort study of Crohn's disease patients who underwent a bowel resection. We identified those at risk of recurrence and explored multiple characteristics for those with and without a delay post-operatively.Results: A total of 84 patients were included in our analysis of which 69.0% had a greater than 4-week delay and 56.0% a greater than 8-week delay in post-surgical biologic prophylaxis. Publicly insured patients had a 100% delay in post-surgical prophylaxis initiation (p = 0.039, p = 0.003 at 4 and 8 weeks, respectively). Patients on a biologic pre-surgery were less likely to have a delay (p < 0.001) in post-operative prophylaxis. Care at an inflammatory bowel disease (IBD) center was associated with timely therapy when considering a post-operative immunomodulator or biologic strategy.Conclusions: There are a substantial number of delays in initiating post-operative prophylactic biologic therapy in high-risk patients. Identifying susceptible patients by insurance type or absence of pre-operative therapy can focus future improvement efforts. Additionally, consultation with IBD-specialized providers should be considered in peri-surgical IBD care. [ABSTRACT FROM AUTHOR]

Background: Whipple disease (WD) is an infection caused by the bacterium Tropheryma whipplei (TW). Few cases have been reported in the USA.Aims: To report on the demographics, clinical manifestations, diagnostic findings, treatment, and outcomes of TW infection.Methods: Cases of TW infection diagnosed from 1995 to 2010 were identified in three US referral centers and from 1995 to 2015 in one. Definite classic WD was defined by positive periodic acid-Schiff (PAS) staining and probable WD by specific positive TW polymerase chain reaction (PCR) of intestinal specimens. Localized infections were defined by a positive TW PCR result from samples of other tissues/body fluids.Results: Among the 33 cases of TW infections, 27 (82%) were male. Median age at diagnosis was 53 years (range 11-75). Diagnosis was supported by a positive TW PCR in 29 (88%) and/or a positive PAS in 16 (48%) patients. Classic WD was the most frequent presentation (n = 18, 55%), with 14 definite and 4 probable cases. Localized infections (n = 15, 45%) affected the central nervous system (n = 7), joints (n = 4), heart (n = 2), eye (n = 1), and skeletal muscle (n = 1). Blood PCR was negative in 9 of 17 (53%) cases at diagnosis. Ceftriaxone intravenously followed by trimethoprim and sulfamethoxazole orally was the most common regimen (n = 23, 70%). Antibiotic therapy resulted in clinical response in 24 (73%).Conclusions: TW infection can present as intestinal or localized disease. Negative small bowel PAS and PCR do not exclude the diagnosis of TW infection, and blood PCR is insensitive for active infection. [ABSTRACT FROM AUTHOR]

The gut microbiome is increasingly being described as one of the underlying mechanisms for development of immune checkpoint inhibitor (ICI)-induced colitis. Similarities in gut microbiome profiles have been found among various diseases associated with intestinal inflammation, including inflammatory bowel disease. Certain bacterial species have been reported to be preventive for colitis, as well as beneficial for cancer outcome, in patients receiving ICI therapy. Alternatively, other bacterial classes have been shown to be associated with immunologic alterations causing intestinal inflammation with subsequent increase in the risk of ICI-related colitis. Gut microbiome manipulation by fecal transplantation has been proposed as one of the modalities to ameliorate inflammation in patients with ICI-related colitis refractory to immunosuppressive therapy. Additional investigations are needed to clarify the role of gut microbiome in the pathogenesis of ICI-related colitis. [ABSTRACT FROM AUTHOR]

Background and Aims: Melena is a symptom of upper gastrointestinal bleeding and usually indicates bleeding proximal to the ligament of Treitz. However, whether melena predicts bleeding in the proximal small intestine in patients with obscure gastrointestinal bleeding (OGIB) is unknown and the objective of this study.Methods: A retrospective cohort study of consecutive patients undergoing capsule endoscopy for OGIB between July 2009 and May 2016 was conducted. Subjects were categorized based on the presence of melena, and the primary outcome was identification of a bleeding source within the proximal 2/3 of the small intestine. Multi-variable regression was performed to control for confounders.Results: During the study, 288 patients met the eligibility criteria. Subjects with melena accounted for 37.1% of the cohort and were more likely to be older (mean age 66.9 vs. 63.9, p = 0.0457), take warfarin (15.1 vs. 9.4%, p = 0.0122), and have a lower 12-month hemoglobin nadir (7.3 vs. 8.3 g/dL, p = 0.0002). On crude analysis, 56.1% of patients with melena had a bleeding source within the proximal small intestine compared to 34.8% for those without (RR 1.61, 95% CI 1.24-2.09, p = 0.0004). On multi-variable analysis, the presence of melena doubled the odds of finding a bleeding site within the proximal small intestine (OR 1.97, 95% CI 1.17-3.33, p = 0.010).Conclusions: The presence of melena doubles the odds of finding a bleeding site within the proximal small intestine among patients with OGIB, and deep enteroscopy, if performed before a capsule study, should begin with an antegrade approach in these patients. [ABSTRACT FROM AUTHOR]

Background and Aims: Proton pump inhibitors (PPIs) are among the most frequently prescribed medications. Side effects including an increased risk of intestinal infections have been reported. It is assumed that PPIs can increase susceptibility to enteropathogens; however, the underlying mechanisms are unknown. Here in this study, we explored whether Lansoprazole (Laz), one of the PPIs, increases the susceptibility to enteropathogens, and further investigated the mechanism of it.Methods: Mice were administered Laz intraperitoneally once daily and orally infected with Citrobacter rodentium (C. rodentium). The establishment of intestinal infection was assessed by histology and inflammatory cytokine expression levels measured by quantitative PCR. To test whether Laz changes the intestinal environment to influence the susceptibility, intestinal pH, microbiota, metabolites and immune cell distributions were evaluated via pH measurement, 16S rRNA gene sequencing, metabolome, and flow cytometry analyses after Laz administration.Results: Colitis was induced with less C. rodentium in Laz-treated mice as compared with the controls. We found that increased numbers of C. rodentium could reach the cecum following Laz administration. Laz increased pH in the stomach but not in the intestines. It induced dysbiosis and changed the metabolite content of the small intestine. However, these changes did not lead to alterations of immune cell distribution.Conclusions: Laz raised susceptibility to C. rodentium as increased numbers of the pathogen reach the site of infection. Our results suggest that it was due to increased stomach pH which allowed more peroral enteropathogens to pass the stomach, but not because of changes of intestinal environment. [ABSTRACT FROM AUTHOR]

Background: Most studies have focused on evaluating the association between the presence of small bowel vascular lesions (SBVLs) and patients' comorbidities.Aims: We sought to uncover a more fundamental indicator that may predict the presence of SBVLs by considering atherosclerosis qualitatively and quantitatively.Methods: We enrolled 79 consecutive patients with obscure gastrointestinal bleeding who had undergone computed tomography (CT) and capsule endoscopy or double-balloon endoscopy from January 2015 to June 2017. The SBVL frequency, type, and location, and the relationship between the presence of SBVLs and the patients' clinical characteristics were evaluated. Arterial wall calcification was assessed on unenhanced CT images, and a modified Agatston scoring system was used to determine the abdominal aorta calcium scores.Results: Of the 27 (34%) patients with SBVLs, 15 (19%) had type 1a, 12 (15%) had type 1b, and 2 (3%) had type 2a SBVLs. Most of the lesions were located in the jejunum. Cardiovascular disease (P = .017), chronic kidney disease (P = .025), and arteriosclerosis (P = .0036) were associated with the presence of SBVLs. Subsequent multivariate analysis revealed that arteriosclerosis (odds ratio [OR] 7.29; 95% confidence interval [CI] 1.13-143.9) and superior mesenteric artery calcification (OR 16.3; 95% CI 3.64-118.6) were independent predictors of the presence of SBVLs. The modified Agatston score was significantly higher in SBVL cases than in non-SBVL cases (6384 vs. 2666, P = .0023).Conclusions: Arteriosclerosis, especially increased superior mesenteric artery calcification, is associated with an increased likelihood of SBVLs. [ABSTRACT FROM AUTHOR]