Strategies for Screening and Managing Inflammatory Bowel Disease During Pregnancy

Noninvasive activity markers are extremely important in conditions, such as pregnancy, when endoscopy is not recommended. The aim of this prospective study was to determine fecal calprotectin (FC) concentrations in healthy non-pregnant and pregnant women and in patients with inflammatory bowel disease (IBD). Healthy pregnant and non-pregnant women and patients with active and inactive IBD were prospectively enrolled in this study. Demographic and clinical parameters and clinical disease activity scores in patients with IBD were recorded. Blood and stool samples of every patient were obtained to determine C-reactive protein and FC levels. FC levels were measured with a quantitative lateral flow assay. One hundred and thirty-five subjects were enrolled in the study (24 non-pregnant and 48 pregnant healthy women, 40 non-pregnant patients with active IBD and 23 non-pregnant patients with inactive IBD). FC was significantly higher in active IBD patients than in pregnant (p<0.001) and non-pregnant healthy women (p<0.001). No difference could be detected in FC concentrations between pregnant and non-pregnant healthy women. Since FC levels remained unchanged during pregnancy, it may be a useful noninvasive diagnostic tool in pregnancy for monitoring mucosal inflammation.

Background: Among children and adolescents, the diagnosis of inflammatory bowel disease (IBD) is often missed or delayed because of the nonspecific nature of the clinical symptoms. In such instances noninvasive and accurate diagnostic tests that would accurately distinguish IBD from functional disorders would be most valuable to clinicians. Several serological markers have been used as non-invasive diagnostic tools in IBD pediatric patients. The aim of our study was to determine the prevalence and diagnostic accuracy of perinuclear antineutrophil cytoplasmic antibodies (p-ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), anti-exocrine pancreatic antibodies (PAB) and anti-goblet cells antibodies (GAB) alone and in combination in children and adolescents with IBD. Patients and methods: Serum specimens were analyzed for p-ANCA, ASCA IgG, ASCA IgA, PAB and GAB antibodies in 49 children and adolescents with confirmed IBD and 53 non-IBD controls. P-ANCA, PAB and GAB antibodies were determined by indirect immunofluorescent test and ASCA by enzyme-linked immunosorbent assay. All patients with Crohn’s disease (CD) had genotyping performed using a sequence specific PCR directed against the wild type and the three principal mutations of NOD2/CARD15 gene. Disease location, body mass index (BMI) and disease activity by pediatric Crohn’s disease activity index (PCDAI) at the time of diagnosis were determined in CD patients. Results: The prevalence of p-ANCA in patients with UC and ASCA in CD patients was high (82.3 % and 67.9 %, respectively). Positivity for PAB antibodies in CD and GAB in UC was lower (35.7 % and 23.5 %, respectively). Accuracy data (sensitivity, specificity, PPV, NPV, respectively) for differentiating IBD from non-IBD controls were as follows: p-ANCA: 82 %, 100 %, 100 %, 94 %; ASCA IgG: 68 %, 94 %, 86 %, 84 %; ASCA IgA: 54 %, 100 %, 100 %, 80 %; PAB: 36 %, 98 %, 91 %, 74 %; GAB: 23 %, 100 %, 100 %, 80 %. In distinguishing CD from UC we found out the following accuracy data (sensitivity, specificity, PPV, NPV, respectively): p-ANCA: 82 %, 82 %, 74 %, 88 %; ASCA IgG: 68 %, 100 %, 100 %, 65 %; ASCA IgA: 54 %, 100 %, 100 %, 57 %; PAB: 36 %, 100 %, 100 %, 49 %; GAB: 23 %, 100 %, 100 %, 68 %. There were no significant association between ASCA positivity and the three major mutations of NOD2/CARD15 gene, disesase location and family history in CD patients, however an association between BMI and disease activity at the time of diagnosis was found out. Conclusions: Specificity and positive predictive value of serological markers p-ANCA, ASCA IgG, ASCA IgA, PAB and GAB for IBD alone and in combination are high and which make them useful in diagnosis of inflammatory bowel disease in day-to-day clinical practice, particulary in making decision about performing invasive diagnostic procedures. Because of low sensitivity they are less useful as screening tests for inflammatory bowel disease in pediatric population.

Chicken or Egg, Mental Health Disorders in Inflammatory Bowel Disease: Does It Matter?

BackgroundMalaria burden remains high in some Peruvian regions, especially in the Northeast Amazon rainforest state of Loreto and the tropical coastal state of Tumbes. Novel non-invasive diagnostic tools for malaria are being developed, and formative research in malaria-endemic areas with community members and health professionals who would potentially use these devices is vital for this process. This study aimed to examine the acceptability and feasibility of four new non-invasive malaria diagnostic tools in development in two regions of Peru with significant malaria burden.MethodsThe research team conducted focus group discussions and key informant interviews in Spanish to assess acceptability and ascertain questions and concerns regarding the non-invasive diagnostic tools. Focus group discussions included a range of community members (pregnant women, parents), professionals (health, education), and community leaders in Loreto. Vector control authorities and health professionals from Loreto, Tumbes, and Lima participated as key informants.ResultsParticipants were initially enthusiastic about all non-invasive diagnostic tools. However, as discussions proceeded, high enthusiasm remained for two devices that were easy to use, acceptable for the communities they were intended for, feasible to carry in remote areas, and did not require new supplies nor generate waste: the skin scan and the skin odour test. The breath and saliva tests were considered less hygienic. They were less acceptable to community members and health professionals due to concerns of disease transmission and other environmental and cultural concerns. Health professionals felt the finger scan test and the skin odour test would help triage community members in endemic sites and would be valuable in remote regions with difficult access to health facilities or laboratories.ConclusionsNovel non-invasive malaria diagnostic tools can be valuable in malaria-endemic settings. As manufacturers evaluate the efficacy and effectiveness of these non-invasive diagnostic tools, international recommendations should be created to ensure their agile integration into national malaria programmes.

Objective To explore the value of plasma cell-free DNA (cfDNA) in the assessment of inflammatory bowel disease (IBD) activity. Methods From July 2014 to June 2017, 145 IBD patients from the First Affiliated Hospital of Fujian Medical University were selected. The plasma content of cfDNA was detected by picogreen-based fluorescent quantitative method. At the same period, 37 healthy individuals were enrolled as control group. The correlation between cfDNA content and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and IBD activity was analyzed. The diagnostic capability of cfDNA in IBD activity was assessed by the receiver operating characteristic (ROC) curve. T-test was performed for comparison between two independent samples, and Pearson correlation coefficient test was used for correlation analysis between two variants. Results The content of plasma cfDNA of patients with Crohn′s disease (CD) and patients with ulcerative colitis (UC) were (29.17±2.07) μg/L and (26.86±1.97) μg/L, respectively; which were both higher than those of healthy control group (21.10±1.02) μg/L, and the differences were statistically significant (t=2.609 and 2.082, both P<0.05). Moreover, the content of cfDNA of patients with active CD or UC were (35.72±3.26) μg/L and (32.37±3.42) μg/L, respectively, which were both higher than those of patients with CD or UC in remission ((21.12±1.43) μg/L and (20.82±1.02) μg/L), and the differences were statistically significant (t=3.806 and 3.116, both P<0.01). The cfDNA content of CD patients was positively correlated with CRP, ESR and disease activity (r=0.555, 0.393 and 0.400, all P<0.01). The cfDNA content of UC patients was also positively correlated with CRP, ESR and disease activity (r=0.640, 0.421 and 0.360, all P<0.01). The diagnostic capability of the combination of CRP and ESR was the highest in CD diagnosis, with the area under curve (AUC) value being 0.841, and the sensitivity and specificity being 81.4% and 74.3%, respectively. The diagnostic capability of the combination of cfDNA, CRP and ESR was the highest in UC diagnosis, with the AUC value being 0.851, and the sensitivity and specificity being 74.3% and 96.9%, respectively. Conclusions Increased cfDNA levels in IBD patients are correlated with IBD activity. Detection of cfDNA is helpful in the identification of active IBD, and the combination of ESR and CRP can improve the diagnostic efficiency of UC. Key words: Inflammatory bowel diseases; Crohn disease; Colitis, ulcerative; Cell-free DNA; Disease activity

Precision Medicine in Inflammatory Bowel Diseases: Challenges and Considerations for the Path Forward

SARS-CoV-2 Testing, Prevalence, and Predictors of COVID-19 in Patients with Inflammatory Bowel Disease in Northern California

AGA Medical Position Statement on the Diagnosis and Management of Colorectal Neoplasia in Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) characterizes chronic gastrointestinal inflammation manifested by abdominal pain, diarrhea, malabsorbtion and bleeding, of which two phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC) have been described [1-3]. It affects about 1.4 million people in the USA and 2.2 million people in Europe [4, 5]. The nuclear receptor farnesoid X receptor senses intracellular bile acid levels. In response to elevated levels of intracellular bile acids, activated FXR induces gene expression of bile acid efflux transporters whereas the expression of bile acid uptake transporters are down regulated, thus protecting against bile acid toxicity in the liver and intestine. FXR regulates several genes that can protect against intestinal inflammation and bacterial overgrowth. FXR-deficient mice have increased ileal concentrations of gut bacteria and exhibit defects in the integrity of the intestinal epithelial barrier. Furthermore, in rodent models of colitis and in CD patients, it has been reported that reduced expression of FXR is associated with colon inflammation [6]. The fact that FXR thus appears to play a role in the protection of the integrity of the intestinal epithelial barrier and its inverse correlation with the level of intestinal inflammation suggest a potential connection between FXR and the molecular pathogenesis of IBD. In the first chapter of this thesis, we have investigated five FXR single nucleotide polymorphisms - two common SNPs and three rare variants - which have been previously studied in the context of human disease, in a well sized IBD vs non-IBD cohort, and report that two of these genetic variants are associated with IBD. NF-κB activity is upregulated in patients with IBD, characterized by high circulatory levels of cytokines especially tumor necrosis factor (TNF). Low plasma concentration of high density lipoprotein (HDL) cholesterol is a marker and considered as a risk factor for coronary heart disease, diabetes mellitus, and several cancers including colorectal cancers [7-9]. The intestine plays a crucial role in HDL metabolism. In addition, the classical anti-atherogenic function of HDL, the mediation of reverse transport of excess cholesterol from macrophages of the arterial wall to the liver is completed by biliary excretion of cholesterol into the intestine. Intestinal dysfunction and inflammation leads to decrease in serum levels of HDL cholesterol and ApoA1 [10-13]. Consistent with this, clinical studies show significantly lower HDL-cholesterol levels in patients with active IBD [14]. Traditionally, the low HDL cholesterol in IBD patients is interpreted as the consequence of IBD. The association of low HDL-cholesterol with IBD together with the many anti-inflammatory properties of HDL however raises the question of whether HDL and its protein and lipid components have any causal impact on intestinal inflammation in IBD patients. In the second chapter of the thesis, we approached this question and investigated the effect of HDL and ApoA1 on intestinal inflammation both in vitro and in vivo. Autophagy, a catabolic process involving intracellular degradation of organelles and proteins, has been shown to be compromised in many human diseases including IBD. Autophagy malfunction has been attributed to defective clearance of pathogens and dysfunction of paneth and goblet cells, which are relevant for pathogenesis of IBD. In the third chapter of the thesis, we put forward autophagy as a mechanism by which HDL suppress intestinal inflammation.

Background Inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) share overlapping symptoms, making differentiation challenging. IBD, which includes ulcerative colitis (UC) and Crohn's disease (CD), involves chronic inflammation requiring long-term management, whereas IBS is a functional gastrointestinal disorder without organic pathology. Fecal lactoferrin, a biomarker of intestinal inflammation, has emerged as a potential noninvasive diagnostic tool for distinguishing IBD from IBS. Objective This study aimed to measure and compare fecal lactoferrin levels in patients with IBD, IBS, and healthy controls to evaluate its diagnostic accuracy in differentiating IBD from IBS in a resource-limited setting. Methods A cross-sectional comparative study was conducted at the Department of Gastroenterology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, from January 2016 to June 2017. The study included 50 diagnosed IBD patients, 25 IBS patients (based on Rome III criteria), and 25 healthy controls. Fecal lactoferrin levels were measured using enzyme-linked immunosorbent assay (ELISA), with a cutoff value of 7.75 µg/g considered indicative of intestinal inflammation. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Data were analyzed using IBM SPSS Statistics for Windows, Version 25 (Released 2017; IBM Corp., Armonk, New York, United States), with statistical significance set at p < 0.05. Results The mean fecal lactoferrin levels were significantly higher in IBD patients (83.01 ± 48.54 µg/g) compared to IBS patients (6.39 ± 2.69 µg/g) and healthy controls (6.80 ± 2.30 µg/g) (p < 0.001). At a cutoff of 7.75 µg/g, fecal lactoferrin demonstrated 88% sensitivity, 84% specificity, 92% PPV, and 78% NPV in distinguishing IBD from IBS. The area under the receiver operating characteristic (ROC) curve was 0.908, indicating excellent diagnostic performance. Conclusion Fecal lactoferrin is a highly sensitive and specific biomarker for differentiating IBD from IBS. Its use as a noninvasive diagnostic tool could reduce unnecessary endoscopic procedures and aid in early and accurate diagnosis, particularly in resource-limited settings like Bangladesh. Further large-scale studies are recommended to validate these findings.

Winter Is Coming! Clinical, Immunologic, and Practical Considerations for Vaccinating Patients With Inflammatory Bowel Disease During the Coronavirus Disease-2019 Pandemic

Background:Pain perception is critical for detection of noxious bodily insults. Gastrointestinal hypoalgesia in inflammatory bowel disease (IBD) is a poorly understood phenomenon previously linked to poor patient outcomes. We aimed to evaluate the risk factors associated with this condition and to discern characteristics that might differentiate these patients from pain-free quiescent counterparts.Methods:We performed a retrospective analysis using an IBD natural history registry based in a single tertiary care referral center. We compared demographic and clinical features in 3 patient cohorts defined using data from simultaneous pain surveys and ileocolonoscopy: a) active IBD without pain (hypoalgesic IBD); b) active IBD with pain; and c) inactive IBD without pain.Results:One hundred fifty-three IBD patients had active disease and 43 (28.1%) exhibited hypoalgesia. Hypoalgesic IBD patients were more likely to develop non-perianal fistulae (P=0.03). On logistic regression analysis, hypoalgesic IBD was independently associated with male sex, advancing age and mesalamine use, and inversely associated with anxious/depressed state and opiate use. Hypoalgesic IBD patients were demographically and clinically similar to the pain-free quiescent IBD cohort (n=59). Platelet count and C-reactive protein were more likely to be pathologically elevated in hypoalgesic IBD (P=0.03), though >25% did not exhibit elevated inflammatory markers.Conclusions:Hypoalgesia is common in IBD, particularly in male and older individuals, and is associated with an increased incidence of fistulae and corticosteroid use. Novel noninvasive diagnostic tools are needed to screen for this population, as inflammatory markers are not always elevated.

Su1325 Women With Inflammatory Bowel Disease Are At Higher Risk of Gestational Diabetes: A Novel Finding

Inflammatory bowel disease (IBD) is associated with significant disability and morbidity, and may require hospitalization and surgery. In recently reported data from the Dutch Nationwide cohort (1), disability was more prevalent in Crohn disease than ulcerative colitis, and was mainly driven by inflammatory activity of the disease and by disease perception of the patient. A complicated disease course was not apparently related to disability. Disability has significant societal costs and more effort is needed to prevent disability from IBD to reduce the impact of it on health care costs and productivity. It is important, therefore, to introduce the most effective therapy to control inflammatory activity in a timely manner so that patients do not suffer from prolonged active inflammation. Illness identity and emotional response to IBD are also associated with disability in IBD. Similar to other chronic disease management, specific treatment of inflammation in IBD needs to be combined with emotional support to improve coping behaviour in a multidisciplinary setting. Currently, few IBD units in Canada have a robust multidisciplinary support structure in their clinic. In a recent study from Italy (2), continuity of care and information about their disease were identified by patients as areas of concern. It will be important to explore whether improving these areas of quality of care can reduce the impact of illness identity and emotional response on disability due to IBD. The high levels of disability in patients with IBD is of concern. Physicians tend to underestimate the impact of IBD on their patients’ lives (3). In the current issue of the Journal, a survey of Canadian patients by Becker et al (4) (pages 77–84) and their family members reinforces the impact of the disease on a number of important areas of their life such as leisure activities, interpersonal relationships and emotional wellness. It is important to understand the relationship between the impact of disease on the patient’s lives and their disability. Not only does the physician need to have a patient-centred perspective to appreciate the impact of disabilities on the patient’s quality of life, but insurance companies need to consider the IBD disability index – or a modification of it – as a way of assessing the patient’s need for support such as disability insurance and disability tax credits. For such purposes, in which third-party adjudication is necessary, patient-reported measures may not be adequate. The conventional measures of disability currently applied are often inadequate. The disability from chronic diseases, such as diabetes mellitus, obesity, cardiovascular diseases, chronic obstructive pulmonary disease and cancer, are better appreciated by society and public policy makers and, hence, it is important to advocate on behalf of the patient with IBD so that public policy makers realize both the disability these patients experience, and the widespread impact of the disease on the lives of the patients and their families. Physicians themselves need to be trained to appreciate the cultural, social and psychological dimensions of the illness due to IBD to fully understand the impact of the disease on disability. The unpredictability of a relapse often prevents patients from planning their lives, and depression and anxiety resulting from the disease are common. The young age at onset of IBD affects lives at a time when it should be most productive. The societal costs of IBD, therefore, tend to be enormous. Crohn’s and Colitis Canada has recognized the need for urgent, further advocacy for and research investigating quality of life, symptom management, bathroom access and public policy. It is encouraging to note that the Crohn’s and Colitis Canada website is a preferred source of information for many patients. This gives an opportunity for the website to emphasize the emotional dimensions of disease, strategies for adherence to therapy, support for family members and prevention of disability. Many dimensions of disability and impact of disease on IBD patients are hidden (Box 1), and require a multidisciplinary team to have coherent strategies for management – these are better developed in pediatric practice compared with adult practice. The IBD disability index provides us with the means to follow patients longitudinally and assess the impact of care pathways and therapeutic strategies on disease course, disabilities and impact of disease. We need to move on from cross-sectional studies to longitudinal, population-based studies to obtain robust data that can influence public policy. BOX 1

Inflammatory bowel disease in children and adolescents: Working Group Report of the First World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition.