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Gastro Hep Advances 2024The dual sugar absorption test as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay...
BACKGROUND AND AIMS
The dual sugar absorption test as a classic measure of human intestinal permeability has limited clinical utility due to lengthy and cumbersome urine collection, assay variability, and long turnaround. We aimed to determine if the orally administered fluorophore MB-102 (relmapirazin) (molecular weight [MW] = 372) compares to lactulose (L) (MW = 342) and rhamnose (R) (MW = 164)-based dual sugar absorption test as a measure of gut permeability in people with a spectrum of permeability including those with Crohn's disease (CD).
METHODS
We performed a single-center, randomized, open-label, crossover study comparing orally administered MB-102 (1.5 or 3.0 mg/kg) to L (1000 mg) and R (200 mg). Adults with active small bowel CD on magnetic resonance enterography (cases) and healthy adults (controls) were randomized to receive either MB-102 or L and R on study day 1, and the other tracer 3 to 7 days later. Urine was collected at baseline and 1, 2, 4, 6, 8, 10, and 12 hours after tracer ingestion to calculate the cumulative urinary percent excretion of MB-102 and L and R.
RESULTS
Nine cases and 10 controls completed the study without serious adverse events. Urinary recovery of administered MB-102 correlated with recovery of lactulose (r-squared = 0.83) for all participants. MB-102 urine recovery was also tracked with the L:R ratio urine recovery (r-squared = 0.57). In controls, the percentages of L and MB-102 recovered were similar within a narrow range, unlike in CD patients.
CONCLUSION
This first-in-human study of an orally administered fluorophore to quantify gastrointestinal permeability in adults with CD demonstrates that MB-102 is well tolerated, and its recovery in urine mirrors that of percent L and the L:R ratio.
PubMed: 38813093
DOI: 10.1016/j.gastha.2024.02.003 -
Frontiers in Genetics 2024Circulating metabolites act as biomarkers of dysregulated metabolism and may inform disease pathophysiology. A portion of the inter-individual variability in...
Circulating metabolites act as biomarkers of dysregulated metabolism and may inform disease pathophysiology. A portion of the inter-individual variability in circulating metabolites is influenced by common genetic variation. We evaluated whether a genetics-based "virtual" metabolomics approach can identify novel metabolite-disease associations. We examined the association between polygenic scores for 724 metabolites with 1,247 clinical phenotypes in the BioVU DNA biobank, comprising 57,735 European ancestry and 15,754 African ancestry participants. We applied Mendelian randomization (MR) to probe significant relationships and validated significant MR associations using independent GWAS of candidate phenotypes. We found significant associations between 336 metabolites and 168 phenotypes in European ancestry and 107 metabolites and 56 phenotypes in African ancestry. Of these metabolite-disease pairs, MR analyses confirmed associations between 73 metabolites and 53 phenotypes in European ancestry. Of 22 metabolitephenotype pairs evaluated for replication in independent GWAS, 16 were significant (false discovery rate p < 0.05). These included associations between bilirubin and X-21796 with cholelithiasis, phosphatidylcholine (16:0/22:5n3,18:1/20:4) and arachidonate with inflammatory bowel disease and Crohn's disease, and campesterol with coronary artery disease and myocardial infarction. These associations may represent biomarkers or potentially targetable mediators of disease risk.
PubMed: 38812968
DOI: 10.3389/fgene.2024.1392622 -
Therapeutic Advances in Gastroenterology 2024Capsule endoscopy (CE) is a valuable tool for assessing inflammation in patients with Crohn's disease (CD). The current standard for evaluating inflammation are...
Deep learning and minimally invasive inflammatory activity assessment: a proof-of-concept study for development and score correlation of a panendoscopy convolutional network.
BACKGROUND
Capsule endoscopy (CE) is a valuable tool for assessing inflammation in patients with Crohn's disease (CD). The current standard for evaluating inflammation are validated scores (and clinical laboratory values) like Lewis score (LS), Capsule Endoscopy Crohn's Disease Activity Index (CECDAI), and ELIAKIM. Recent advances in artificial intelligence (AI) have made it possible to automatically select the most relevant frames in CE.
OBJECTIVES
In this proof-of-concept study, our objective was to develop an automated scoring system using CE images to objectively grade inflammation.
DESIGN
Pan-enteric CE videos (PillCam Crohn's) performed in CD patients between 09/2020 and 01/2023 were retrospectively reviewed and LS, CECDAI, and ELIAKIM scores were calculated.
METHODS
We developed a convolutional neural network-based automated score consisting of the percentage of positive frames selected by the algorithm (for small bowel and colon separately). We correlated clinical data and the validated scores with the artificial intelligence-generated score (AIS).
RESULTS
A total of 61 patients were included. The median LS was 225 (0-6006), CECDAI was 6 (0-33), ELIAKIM was 4 (0-38), and SB_AIS was 0.5659 (0-29.45). We found a strong correlation between SB_AIS and LS, CECDAI, and ELIAKIM scores (Spearman's = 0.751, = 0.707, = 0.655, = 0.001). We found a strong correlation between LS and ELIAKIM ( = 0.768, = 0.001) and a very strong correlation between CECDAI and LS ( = 0.854, = 0.001) and CECDAI and ELIAKIM scores ( = 0.827, = 0.001).
CONCLUSION
Our study showed that the AI-generated score had a strong correlation with validated scores indicating that it could serve as an objective and efficient method for evaluating inflammation in CD patients. As a preliminary study, our findings provide a promising basis for future refining of a CE score that may accurately correlate with prognostic factors and aid in the management and treatment of CD patients.
PubMed: 38812708
DOI: 10.1177/17562848241251569 -
PloS One 2024[This corrects the article DOI: 10.1371/journal.pone.0246393.].
Correction: Linking bacterial enterotoxins and alpha defensin 5 expansion in the Crohn's colitis: A new insight into the etiopathogenetic and differentiation triggers driving colonic inflammatory bowel disease.
[This corrects the article DOI: 10.1371/journal.pone.0246393.].
PubMed: 38809824
DOI: 10.1371/journal.pone.0304732 -
World Journal of Psychiatry May 2024Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising...
BACKGROUND
Psychological distress, especially depression, associated with perianal fistulizing Crohn's disease (PFCD) is widespread and refractory. However, there is a surprising paucity of studies to date that have sought to identify the prevalence and risk factors of depression associated with PFCD.
AIM
To estimate the prevalence of depressive symptoms and investigate the depression-related risk factors in patients with PFCD.
METHODS
The study was conducted in the form of survey and clinical data collection questionnaire and specialized medical staff. Depressive symptoms, life quality, and fatigue severity of patients with PFCD were assessed by Patient Health Questionnaire-9, Inflammatory Bowel Disease Patient Quality of Life Questionnaire (IBDQ), and Inflammatory Bowel Disease (IBD) Fatigue Patient Self-assessment Scale. The basic demographic information, overall disease features, perianal clinical information, and laboratory inflammation indicators were also gathered. Multivariate regression analysis was ultimately used to ascertain the risk factors of depression associated with PFCD.
RESULTS
A total of 123 patients with PFCD were involved, and 56.91% were suffering from depression. According to multivariate logistic regression analysis, Perianal Disease Activity Index (PDAI) score [odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.50 to 0.95], IBDQ score (OR = 0.93, 95%CI: 0.88 to 0.97), modified Van Assche index (OR = 1.24, 95%CI: 1.01 to 1.53), and IBD Fatigue score (OR = 1.72, 95%CI: 1.23 to 2.42) were independent risk factors of depression-related prevalence among patients with PFCD ( < 0.05). Multiple linear regression analysis revealed that the increasing perianal modified Van Assche index ( value = 0.166, 95%CI: 0.02 to 0.31) and decreasing IBDQ score ( value = -0.116, 95%CI: -0.14 to -0.09) were independently associated with the severity of depression ( < 0.05).
CONCLUSION
Depressive symptoms in PFCD patients have significantly high prevalence. PDAI score, modified Van Assche index, quality of life, and fatigue severity were the main independent risk factors.
PubMed: 38808090
DOI: 10.5498/wjp.v14.i5.715 -
Sisli Etfal Hastanesi Tip Bulteni 2024Granulomatous appendicitis (GA) is granulomatous inflammation of the appendix wall. It is generally idiopathic; however, it may also be associated with many diseases...
Granulomatous appendicitis (GA) is granulomatous inflammation of the appendix wall. It is generally idiopathic; however, it may also be associated with many diseases such as Crohn's disease, parasitic infections, tuberculosis, or foreign bodies. An 11-year-old male patient, with a 3-month history of abdominal pain and bilious vomiting, had right lower quadrant abdominal tenderness. His white blood cell count was 8.6 x10/µL. An abdomen ultrasound was considered to show plastron appendicitis and an appendectomy was performed. Microscopically, thickening of the appendix wall with edema, fibrosis and lymphoid infiltration was observed. The patient was evaluated as idiopathic GA since no disease was detected that caused GA. When the appendix has a firm consistency and is difficult to separate from the surrounding tissues, GA should be considered before malignancy, particularly in the pediatric age group. An appendectomy should be performed before deciding on radical surgery.
PubMed: 38808059
DOI: 10.14744/SEMB.2023.03780 -
Rheumatology Advances in Practice 2024Assuming SpA manifestations may vary among patients with different inflammatory bowel disease (IBD) subtypes, we explored the clinical characteristics associated with...
OBJECTIVES
Assuming SpA manifestations may vary among patients with different inflammatory bowel disease (IBD) subtypes, we explored the clinical characteristics associated with the presence of Crohn's disease (CD) or ulcerative colitis (UC) in patients with spondyloarthritis (SpA).
METHODS
We included 3152 patients of ASAS-PerSpA study diagnosed with either axial SpA or peripheral SpA, according to their treating rheumatologist. Of these, 146 (4.6%) had confirmed IBD by endoscopy and were categorized into CD or UC groups. Demographics, clinical characteristics, treatments and patient-reported outcomes were compared between the two subgroups.
RESULTS
From 146 patients included in the current analysis, 87 (59.6%) had CD [75 (86.2%) axial SpA and 12 (13.8%) peripheral SpA], and 39 (26.7%) had UC [34 (87.2%) axial SpA and 5 (12.8%) peripheral SpA]. CD and UC groups had similar age with average of 44.9 (13.5) 44.0 (13.0) years, respectively, and a slight male predominance in CD (63.2%) compared with UC (51.3%). Diagnostic delay for SpA was 7.0 (6.9) years for CD and 8.8 (8.1) years for UC. Chronic back pain was the most reported symptom present in 95.4% of CD patients and 89.7% of UC patients. Both groups had similar musculoskeletal phenotyping, with higher frequency of psoriasis (15.4%) and uveitis 28.2% in UC; and higher tendency to be HLA-B27 positive in CD (51.9% in CD .s 39.4% in UC).
CONCLUSION
In our analysis patients with SpA and concurrent CD or UC had mainly similar musculoskeletal phenotypes. However, they differ slightly in extra-musculoskeletal manifestations and HLA-B27 prevalence.
PubMed: 38807853
DOI: 10.1093/rap/rkae064 -
Cureus Apr 2024Entering and acclimatizing to a university is crucial for achieving academic goals and graduation. Chronic illnesses can reduce a person's capacity to perform tasks,... (Review)
Review
Entering and acclimatizing to a university is crucial for achieving academic goals and graduation. Chronic illnesses can reduce a person's capacity to perform tasks, whether physically, cognitively, or emotionally, about inflammatory bowel disease (IBD), there is a lack of research about the impact of IBD on the daily lives of students. IBD can be seen as having an adverse effect on the life of college students. The objective of this review was to examine the psychological ramifications, particularly in relation to stress levels, that IBD elicits in the daily lives of students. The elementary search utilized specific databases, including PubMed, Web of Science, and Google Scholar. The search terms employed were "IBD," "University," "Students," and "Stress." We reviewed 80 papers and selected 25 for their applicability and relevance. The current review includes at least a total of 12 articles. The following issues arose: 1) adaption to university, 2) managing IBD individually and from the university setting, 3) social impact, and 4) methods of controlling and coping with the IBD. Students with IBD have a tough time adapting to new situations. Their emotional and social status plays a significant role in this. The proper management and treatment of IBD throughout studies can have a significant impact on student's academic achievement as well as their later lives.
PubMed: 38807823
DOI: 10.7759/cureus.59176 -
Caspian Journal of Internal Medicine 2024According to the significance of extraintestinal symptoms in inflammatory bowel disease (IBD) patients and their connection with obesity, we aimed to investigate the...
BACKGROUND
According to the significance of extraintestinal symptoms in inflammatory bowel disease (IBD) patients and their connection with obesity, we aimed to investigate the prevalence of fatty liver in IBD patients of Sayyad Shirazi Hospital in Gorgan, Iran, in relation to obesity, anthropometric indicators and body image in these patients.
METHODS
Forty patients with IBD were recruited from all registered patients at the Golestan Research Center of Gastroenterology and Hepatology, following the specified inclusion and exclusion criteria. After obtaining written informed consent and filling in the questionnaire, the demographic and anthropometric indicators, and variables related to the disease were measured. The liver sonography was performed on all patients and graded by an expert radiologist. Data were analyzed using SPSS Version 16.0 statistical software at the significance level of 0.05.
RESULTS
We showed no significant difference between the distribution of demographic and anthropometric indicators in different groups of IBD patients. However, we demonstrated that the inappropriate values of HDL (0.004) and high values of LDL (0.015) were associated with fatty liver in IBD patients. Our findings also showed that NAFLD was significantly associated with overweight and obesity among IBD patients (P = 0.003).
CONCLUSION
Our findings showed the epidemiological burden of NAFLD in IBD patients. Since fatty liver was associated with obesity, it is recommended that IBD patients be screened for risk factors associated with NAFLD to prevent liver disease.
PubMed: 38807729
DOI: 10.22088/cjim.15.2.299 -
Nature Communications May 2024Despite major advances in linking single genetic variants to single causal genes, the significance of genetic variation on transcript-level regulation of expression,...
Despite major advances in linking single genetic variants to single causal genes, the significance of genetic variation on transcript-level regulation of expression, transcript-specific functions, and relevance to human disease has been poorly investigated. Strawberry notch homolog 2 (SBNO2) is a candidate gene in a susceptibility locus with different variants associated with Crohn's disease and bone mineral density. The SBNO2 locus is also differentially methylated in Crohn's disease but the functional mechanisms are unknown. Here we show that the isoforms of SBNO2 are differentially regulated by lipopolysaccharide and IL-10. We identify Crohn's disease associated isoform quantitative trait loci that negatively regulate the expression of the noncanonical isoform 2 corresponding with the methylation signals at the isoform 2 promoter in IBD and CD. The two isoforms of SBNO2 drive differential gene networks with isoform 2 dominantly impacting antimicrobial activity in macrophages. Our data highlight the role of isoform quantitative trait loci to understand disease susceptibility and resolve underlying mechanisms of disease.
Topics: Quantitative Trait Loci; Crohn Disease; Humans; Genetic Predisposition to Disease; Protein Isoforms; Lipopolysaccharides; Interleukin-10; Promoter Regions, Genetic; DNA Methylation; Macrophages; Gene Expression Regulation
PubMed: 38806456
DOI: 10.1038/s41467-024-47218-3