Vitamin C Deficiency Masquerading as Vasculitis in a Patient With Crohn's Disease.

This case study features a 40-year-old male with Crohn's disease (CD) who was initially misdiagnosed with vasculitis but was later shown to have scurvy owing to vitamin C deficiency. The patient's diet was nearly exclusively made up of highly processed fast food, with no fresh fruits or vegetables. A mildly sensitive, violaceous rash on his lower legs, mild gingival hemorrhage and enlargement, and muscle soreness were among his symptoms. Anemia and undetectable vitamin C levels were discovered in laboratory studies. A skin sample revealed follicular hyperkeratosis, coiled hairs, and perifollicular bleeding, eliminating the possibility of vasculitis. Scurvy was confirmed by undetectable vitamin C levels and intramuscular bleeding discovered during a muscle biopsy. After one month of vitamin C administration, the patient's skin was entirely clear. This instance emphasizes the significance of taking vitamin C insufficiency into account in patients with CD and other disorders that can cause malabsorption. Misdiagnosis might result in unneeded treatments and medical expenses. Scurvy must be diagnosed as soon as possible because it might cause gastrointestinal/intracerebral hemorrhage and death.

Optimal Management of Refractory Crohn's Disease: Current Landscape and Future Direction.

Refractory Crohn's disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn's disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn's disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.

Perirectal Mucinous Adenocarcinoma After Subtotal-Colectomy for Crohn's Disease: A Case Report.

Colorectal carcinoma (CRC) represents the third most common cancer and the second highest cause of cancer-related death in the United States. CRC is particularly prevalent in patients with underlying inflammatory bowel disease. Adenocarcinoma represents more than 90% of new CRC diagnoses. The mucinous subtype of colorectal adenocarcinoma is found in approximately 10-20% of all colorectal cancer patients and is most frequently located in the proximal colon. We report a case of mucinous adenocarcinoma arising from the rectal stump of a patient who had previously undergone subtotal-colectomy with end ileostomy for Crohn's disease. She initially presented with gradually worsening chronic abdominal pain and gelatinous rectal discharge. She was found to have a complex cystic lesion communicating with her Hartman's pouch. She ultimately underwent a completion proctectomy, radical hysterectomy, and bilateral salpingo-oophorectomy in conjunction with gynecology oncology. To the best of our knowledge, this case represents the first description of a perirectal mucinous adenocarcinoma arising in a patient after subtotal-colectomy for Crohn's disease.

Massive Small Bowel Enterolith in Post Cystoprostatectomy Ileal Cul-de-sac : A Unique Presentation of a Rare Clinical Condition.

Enterolithiasis or formation of gastrointestinal concretions is an unusual medical entity that typically occurs in patients suffering from persistent intestinal stasis. We present a rare case of non-obstructive enterolith wedged in the blind end of bowel reconstruction following cystoprostatectomy and ileal conduit formation due to muscle-invasive bladder cancer. Although we watched it grow over the years, radiological characterisation was made possible when it grew to a significant size. We, herein, will discuss the aetiology and complexities associated with the diagnosis and management of such orphan cases given their non-specific clinical presentations in an already hostile abdomen due to multiple laparotomies.

Symptom management experiences of Chinese individuals with Crohn's disease: A longitudinal descriptive qualitative study.

Individuals diagnosed with Crohn's disease, a chronic lifelong condition, experience a dynamic or fluctuating process of developing symptom management behavior. However, less clear is how these individuals respond to and manage their symptoms over time. The aim of this study was to longitudinally explore the symptom management experiences of individuals with Crohn's disease in China. A longitudinal qualitative design was used. Eighteen individuals with newly diagnosed Crohn's disease were purposely selected. Semi-structured interviews were conducted on four occasions over a 12-month period. Interviews at each time point were transcribed and coded using conventional content analysis. Afterward, data analyses of each time point were compared longitudinally to form a holistic understanding. Three themes and eight subthemes emerged from the analysis: (1) disclosing symptoms strategically: voluntary disclosure, reluctance to disclose, no need to disclose; (2) decreasing vigilance in symptom prevention: preventing symptoms stringently, preventing symptoms discriminatively, preventing symptoms with decreased diligence; and (3) increasing autonomy in symptom treatment: actively seeking medical advice, self-treatment and self-observation. The participants were inclined to keep symptoms hidden from relatives and friends and showed a downward trend in actively disclosing physical discomfort to medical staff within the course of 1 year. The participants' attention to symptom prevention declined, but the enthusiasm and independence to eliminate symptoms on their own increased over time. Nurses could implement targeted interventions according to the characteristics of different periods to assist individuals with Crohn's disease in managing symptoms effectively, reducing symptom burden and improving their quality of life.

Prior Appendectomy Is Associated With a Milder Clinical Course in Crohn's Disease: A Nationwide Population-based Cohort Study.

BACKGROUND: Appendectomy may affect the clinical course of Crohn's disease (CD), but rigorous evidence is sparse and contradicting. The aim of this study was to examine the association between appendectomy and the clinical course of CD. METHODS: All patients diagnosed with CD in Denmark in the period from 1977 to 2017 were identified from the Danish National Patient Registry. Patients with appendectomy were matched with up to 10 comparators with CD and no appendectomy; and rates of CD-related hospital admissions were compared between CD patients with and without appendectomy using incidence rate ratios (IRRs). We used stratified Cox regression analysis to calculate adjusted hazard ratios (aHRs) of initiating treatment with biologics or undergoing intestinal resections. RESULTS: In all, 21 189 CD patients (1936 with appendectomy and 19 253 without) were identified and followed for a median of 13.6 years. Crohn's disease patients who had undergone appendectomy experienced a lower rate of CD-related hospital admissions (appendectomy before CD: IRR = 0.83; 95% confidence interval [CI], 0.81-0.85; appendectomy after CD: IRR = 0.85; 95% CI, 0.81-0.88) compared with CD patients without appendectomy. For patients with appendectomy before CD diagnosis, the rate of initiating biologics was lower compared with CD patients with no appendectomy (aHR1-<5 years = 0.61; 95% CI, 0.46-0.81; aHR5-<10 years 0.47; 95% CI, 0.33-0.66; aHR10-20 years = 0.61; 95% CI, 0.47-0.79), as was the risk of undergoing colorectal resections (aHR1-<5 years = 0.94; 95% CI, 0.77-1.15; aHR5-<10 years 0.63; 95% CI, 0.47-0.85; aHR10-20 years = 0.75; 95% CI, 0.54-1.04). Rates of small bowel resections were comparable for CD patients with or without appendectomy prior to CD. Appendectomy performed after CD did not influence the rate of initiating treatment with biologics or undergoing intestinal resections. CONCLUSION: The clinical course of CD is milder for those who have previously undergone appendectomy.

In a large nationwide cohort study, patients with Crohn's disease who underwent appendectomy had a milder clinical course than those without appendectomy.

Increased Risk of Inflammatory Bowel Disease Among Patients With Nontyphoidal Salmonella Infections: A Population-Based Cohort Study.

BACKGROUND: Despite the known association between microorganisms and development of inflammatory bowel disease (IBD), the role of nontyphoidal Salmonella (NTS) in IBD is not adequately addressed. We aimed at elucidating the relationship between NTS infection and the risk of IBD. METHODS: Based on the National Health Insurance Research Database in Taiwan, this retrospective cohort study enrolled patients with NTS infection (exposure group; n = 4651) and those without NTS infection (comparator group; n = 4651) who were propensity score matched (1:1) by demographic data, medications, comorbidities, and index date. All patients were followed until IBD onset, individual mortality, or December 31, 2018. Cox proportional hazards regression analysis was performed to determine the hazard ratios and 95% confidence intervals (CIs). Sensitivity analyses were used for cross-validation. RESULTS: The NTS group demonstrated an increased risk of IBD compared with the non-NTS groups (adjusted hazard ratio [aHR], 2.12; 95% CI, 1.62-2.78) with a higher risk of developing ulcerative colitis in the former (aHR, 2.27; 95% CI, 1.69-3.04). Nevertheless, the small sample size may contribute to lack of significant difference in Crohn's disease. Consistent findings were noted after excluding IBD diagnosed within 6 months of NTS infection (aHR, 2.28; 95% CI, 1.71-3.03), excluding those with enteritis/colitis before index date (aHR, 1.85; 95% CI, 1.28-2.68), excluding those using antibiotics for 1 month in the year before IBD onset (aHR, 1.81; 95% CI, 1.34-2.45), inverse probability of treatment weighting (aHR, 1.64; 95% CI, 1.31-2.04), and inclusion of individuals regardless of age (n = 10 431; aHR, 1.83; 95% CI, 1.53-2.19). CONCLUSIONS: Patients with NTS were associated with an increased risk of developing IBD, especially ulcerative colitis.

Beyond diagnosis: investigating hospital referral impact on biological treatment initiation, hospital admission, and surgery patterns in inflammatory bowel disease - a Danish population based study.

OBJECTIVES: Early biological treatment in patients with inflammatory bowel disease (IBD) is important in disease control. Previous studies have suggested that patients with IBD from Non-Academic Hospitals were less likely to receive biologics. The aims of this study were (1) to use the granular data in the clinical database, GASTROBIO, to study detailed differences in time from IBD diagnosis to first administration of biologics, hospital admission, and surgery in patients referred to Academic Hospitals versus to Non-Academic Hospitals, and (2) to explore differences in disease extent, behavior, and indication for biological treatment. MATERIAL AND METHODS: This was a retrospective cross-sectional descriptive population-based quality study of patients with IBD initiating biologics in the North Denmark Region between 2016 and 2018. Data from GASTROBIO were extracted, namely demographic data, time of diagnosis, biological treatments with indications, hospital admission, and surgery. RESULTS: Of the 146 patients included, 84 were from the Academic and 62 from the Non-Academic Hospitals. No significant differences in median time from diagnosis to (1) treatment, (2) hospital admission or (3) IBD surgery between the groups were observed. A higher percentage of patients with luminal Crohn's disease were treated with biologics at the Academic Hospital (78% and 66%). CONCLUSIONS: Based on the findings of this population-based study, we found no evidence that the referral area had a significant impact on the duration from diagnosis to the initiation of biological treatment, hospital admissions, or surgery. However, the data suggested that fewer patients with luminal Crohn's disease were referred to biologics from Non-Academic Hospitals.

Ozanimod Differentially Impacts Circulating Lymphocyte Subsets in Patients with Moderately to Severely Active Crohn's Disease.

BACKGROUND: Ozanimod showed efficacy and safety in the phase 2 STEPSTONE study conducted in patients with moderately to severely active Crohn's disease. AIMS: This analysis assessed the effects of ozanimod on circulating lymphocytes in Crohn's disease. METHODS: Patients received ozanimod 0.92 mg for 12 weeks. Lymphocyte subtypes were evaluated using multicolor flow analysis on blood samples collected before treatment and on Week 12. Absolute lymphocyte count changes were analyzed by Wilcoxon signed rank tests. Disease activity changes and efficacy outcomes were evaluated at Week 12, and associations with lymphocyte subtype levels were assessed using Spearman's correlation and logistic regression. RESULTS: Reductions in median total T, Th, and cytotoxic T cells occurred at Week 12 (45.4%-76.8%), with reductions in most subtypes of 47.5% to 91.3% (P < 0.001). CD8+ terminally differentiated effector memory cells were largely unaffected (median change, - 19%; P = 0.44). Reductions in median total B cells occurred at Week 12 (76.7%), with reductions in subtypes of 71.4% to 81.7% (P < 0.001). Natural killer and monocyte cell counts were unchanged. Greater baseline levels and changes in nonswitched memory B cells were significantly associated with clinical, endoscopic, and histologic efficacy (P < 0.05, all comparisons). CONCLUSIONS: Ozanimod reduced circulating levels of all B-cell and most T-cell subsets but not monocytes or natural killer cells. Key subsets relevant to immune surveillance were not reduced, supporting the low risk of infection and malignancy with ozanimod in chronic inflammatory diseases. Levels of nonswitched memory B cells were associated with efficacy, providing a potential marker for ozanimod response. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02531113, EudraCT: 2015-002025-19.

Naringin Alleviates Intestinal Fibrosis by Inhibiting ER Stress-Induced PAR2 Activation.

Fibrosis characterized by intestinal strictures is a common complication of Crohn's disease (CD), without specific antifibrotic drugs, which usually relies on surgical intervention. The transcription factor XBP1, a key component of endoplasmic reticulum (ER) stress, is required for degranulation of mast cells and linked to PAR2 activation and fibrosis. Many studies have confirmed that naringin (NAR) can inhibit ER stress and reduce organ fibrosis. We hypothesized that ER stress activated the PAR2-induced epithelial-mesenchymal transition process by stimulating mast cell degranulation to release tryptase and led to intestinal fibrosis in CD patients; NAR might play an antifibrotic role by inhibiting ER stress-induced PAR2 activation. We report that the expression levels of XBP1, mast cell tryptase, and PAR2 are upregulated in fibrotic strictures of CD patients. Molecular docking simulates the interaction of NAR and spliced XBP1. ER stress stimulates degranulation of mast cells to secrete tryptase, activates PAR2-induced epithelial-mesenchymal transition process, and promotes intestinal fibrosis in vitro and vivo experiments, which is inhibited by NAR. Moreover, F2rl1 (the coding gene of PAR2) deletion in intestinal epithelial cells decreases the antifibrotic effect of NAR. Hence, the ER stress-mast cell tryptase-PAR2 axis can promote intestinal fibrosis, and NAR administration can alleviate intestinal fibrosis by inhibiting ER stress-induced PAR2 activation.

Fibrosis characterized by intestinal strictures is a common complication of Crohn's disease. The endoplasmic reticulum stress­mast cell tryptase­PAR2 axis promotes intestinal fibrosis, and naringin administration alleviates intestinal fibrosis by inhibiting endoplasmic reticulum stress­induced PAR2 activation.

The Time to Inflammatory Bowel Disease Diagnosis for Patients Presenting with Abdominal Symptoms in Primary Care and its Association with Emergency Hospital Admissions and Surgery: A Retrospective Cohort Study.

BACKGROUND: Patients with inflammatory bowel disease (IBD) presenting to primary care may experience diagnostic delays. We aimed to evaluate this and assess whether time to diagnosis is associated with clinical outcomes. METHODS: A retrospective cohort study using English primary care data from January 1, 2010, to December 31, 2019, linked to hospital admission data was undertaken. Patients were followed from the first IBD-related presentation in primary care to IBD diagnosis. Associations of time to diagnosis exceeding a year were assessed using a Robust Poisson regression model. Associations between time to diagnosis and IBD-related emergency hospital admissions and surgery were assessed using Poisson and Cox proportional hazards models, respectively. RESULTS: Of 28 092 IBD patients, 60% had ulcerative colitis (UC) and 40% had Crohn's disease (CD). The median age was 43 (interquartile range, 30-58) years and 51.9% were female. Median time to diagnosis was 15.6 (interquartile range, 4.3-28.1) months. Factors associated with more than a year to diagnosis included female sex (adjusted risk ratio [aRR], 1.23; 95% CI, 1.21-1.26), older age (aRR, 1.05; 95% CI, 1.01-1.10; comparing >70 years of age with 18-30 years of age), obesity (aRR, 1.03; 95% CI, 1.00-1.06), smoking (aRR, 1.05; 95% CI, 1.02-1.08), CD compared with UC (aRR, 1.13; 95% CI, 1.11-1.16), and a fecal calprotectin over 500 µg/g (aRR, 0.89; 95% CI, 0.82-0.95). The highest quartile of time to diagnosis compared with the lowest was associated with IBD-related emergency admissions (incidence rate ratio, 1.06; 95% CI, 1.01-1.11). CONCLUSION: Longer times to IBD diagnoses were associated with being female, advanced age, obesity, smoking, and Crohn's disease. More IBD-related emergency admissions were observed in patients with a prolonged time to diagnosis.

On average, patients with inflammatory bowel disease experience a 16-month diagnostic delay from symptom onset in primary care. Fecal calprotectin testing expedited diagnosis. Longer diagnostic periods were associated with an increased risk of emergency hospital admissions but not with inflammatory bowel disease­related surgery.

Role of Calprotectin, IL-6, and CRP in Distinguishing Between Inflammatory Bowel Disease and Diarrhea Predominant Irritable Bowel Syndrome.

Background: The early establishment of prophylaxis and immediate administration of anticoagulant therapy upon the diagnosis of venous thromboembolism should be the treatment objectives in these patients. Objective: The study aimed to determine the optimal cut-off point of Calprotectin, IL-6 (interleukin-6), CRP (C reactive protein) to differentiate UC, IBS-D. Methods: A cross-sectional descriptive study of 335 individuals ≥15 years old was performed, including 31 healthy controls, 215 with IBS-D, 71 diagnosed with UC, and 18 diagnosed with CD. Receiver Operating Characteristics (ROC), sensitivity, specificity, and area under curve (AUC) were computed. Results: The results showed that the median value of calprotectin (IQR) in healthy participants was 20.0 (6.0 - 34.0) µg/g; 17,7 (8,7-38,9) µg/g in IBS-D group; 1710.0 (588 - 4260,0) µg/g in UC group; and 560.5 (177.8 - 1210.0) µg/g in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of CRP (range IQR) was 1,3 (0,9 - 2,3) mg/L in IBS-D group; 7.0 (2.4 -16.6) mg/L in UC group; and 10.1 (2.2 - 42.5) mg/L in CD group. CRP concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The median value of IL-6 (range IQR) was 2.3 (1.6 - 5.7) pg/mL in IBS-D group; 16.8 (9.4 - 47.0) pg/mL in UC group; and 9.4 (7.9 - 11.0) pg/mL in CD group. Calprotectin concentration in IBD group including UC and CD was higher than IBS-D with p<0.05. The optimal cut-off point of calprotectin that differentiated IBS-D from IBD was 110.5 µg/g, with sensitivity and specificity of 93.3% and 91.4%, respectively; of IL-6 was 7.2 pg/mL with sensitivity and specificity of 92.0% and 78.0%, respectively; of CRP of 2.4 mg/L had specific sensitivities of 83.3% and 86.0%, respectively. Conclusion: The Calprotectin immunoassay has the best value in discriminating between IBD and IBS-D.

Pan-Enteric Capsule Endoscopy: Current Applications and Future Perspectives.

Background: The role of capsule endoscopy in the evaluation of the small bowel is well established, and current guidelines position it as a first-line test in a variety of clinical scenarios. The advent of double-headed capsules further enabled the endoscopic assessment of colonic mucosa and the opportunity for a one-step noninvasive examination of the entire bowel (pan-enteric capsule endoscopy [PCE]). Summary: We reviewed the technical procedure and preparation of patients for PCE, as well as its current clinical applications and future perspectives. In non-stricturing and non-penetrating Crohn's disease affecting the small bowel and colon, PCE monitors disease activity by assessing mucosal healing, a major treatment outcome, with a higher diagnostic yield than cross-sectional imaging or conventional colonoscopy. Also in ulcerative colitis, double-headed capsules have been used to monitor disease activity noninvasively. Currently, validated scoring systems have been specifically devised for these double-headed capsules and permit a standardized assessment of the inflammatory burden. In suspected mid-lower digestive bleeding, some exploratory studies have demonstrated the feasibility and high diagnostic yield of PCE, which may work as a filter indicating which patients may benefit of further invasive procedures, namely, for planned hemostatic procedures. The possibility of using PCE is also discussed in the context of polyposis syndromes with simultaneous involvement of the small intestine and colon. Key Messages: PCE is a feasible, effective, and safe diagnostic procedure to evaluate the small bowel and colon. It has been increasingly explored in the setting of inflammatory bowel diseases and, more recently, in suspected mid-lower digestive bleeding. PCE is expected to reduce the demand for invasive procedures and expand the scope of noninvasive intestinal evaluation in the coming future.

Introdução: O papel da endoscopia por cápsula na avaliação do intestino delgado encontra-se bem estabelecido, e as orientações atuais posicionam-na como um teste de primeira linha numa variedade de cenários clínicos. O advento das cápsulas de dupla câmara permitiu expandir a sua aplicação para a avaliação endoscópica da mucosa do cólon, oferecendo a oportunidade de um exame não invasivo de todo o intestino (endoscopia pan-entérica por cápsula, PCE). Sumário: Procedemos a uma revisão de vários aspectos do procedimento e preparação dos doentes para a PCE, bem como as aplicações clínicas atuais e as perspetivas futuras das cápsulas de dupla câmara. Na doença de Crohn não estenosante e não penetrante localizada ao intestino delgado e cólon, a PCE permite monitorizar a atividade da doença e avaliar a cicatrização da mucosa, um indicador importante da eficácia da terapêutica, com um rendimento de diagnóstico superior aos métodos convencionais, nomeadamente os exames imagiológicos ou a colonoscopia invasiva. Também na colite ulcerosa, as cápsulas de dupla câmara têm sido utilizadas para monitorizar a atividade da doença de forma não invasiva. Existem índices endoscópicos validados e especificamente concebidos para as cápsulas de dupla câmara, que permitem uma avaliação sistematizada e quantificação objetiva da atividade inflamatória. Na suspeita de hemorragia digestiva média ou baixa, alguns estudos exploratórios demonstraram a aplicabilidade e o elevado rendimento diagnóstico da PCE, podendo funcionar como um filtro de modo a permitir indicar quais os doentes que mais irão beneficiar de um procedimento invasivo subsequente, nomeadamente para a realização de procedimentos hemostáticos dirigidos. A possibilidade de utilização da PCE é também discutida no contexto das síndromes de polipose com envolvimento simultâneo do intestino delgado e do cólon. Mensagens-chave: A PCE é um procedimento diagnóstico eficaz e seguro para avaliar diretamente a mucosa do intestino delgado e cólon. A sua aplicação tem vindo a expandir-se no contexto das Doenças Inflamatórias Intestinais e, mais recentemente, na suspeita de hemorragia digestiva média ou baixa. Existe a expectativa de que no futuro próximo possamos assistir a uma redução substancial da demanda por procedimentos endoscópicos invasivos, face à utilização crescente da PCE enquanto método de diagnóstico pan-intestinal não invasivo.

Self-screening questionnaire for perianal fistulizing disease in patients with Crohn's disease.

Background/Aims: A poor prognostic factor for Crohn's disease (CD) includes perianal fistulizing disease, including perianal fistula and/or perianal abscess. Currently, a tool to assess perianal symptoms in patients with CD remains nonexistent. This study aimed to develop a perianal fistulizing disease self-screening questionnaire for patients with CD. Methods: This prospective pilot study was conducted at three tertiary referral centers between January 2019 and May 2020. We formulated questions on perianal symptoms, including tenesmus, anal discharge, bleeding, pain, and heat. A 4-point Likert scale was used to rate each question. Patients with CD completed a questionnaire and underwent pelvic magnetic resonance imaging (MRI). Results: Overall, 93 patients were enrolled, with 51 (54.8%) diagnosed with perianal fistulizing disease, as determined by pelvic MRI. The Spearman correlation findings demonstrated that anal pain (p = 0.450, p < 0.001) and anal discharge (p = 0.556, p < 0.001) were the symptoms that most significantly correlated with perianal disease. For anal pain and discharge, the area under the receiver operating characteristic curve of the scores was significantly higher than that of the combined score for all five symptoms (0.855 vs. 0.794, DeLong's test p = 0.04). For the two symptoms combined, the sensitivity, specificity, and positive predictive and negative predictive values were 88.2, 73.8, 80.4, and 83.8%, respectively, with 81.7% accuracy for detecting perianal fistulizing disease. Conclusions: This study indicates that simple questions regarding anal pain and discharge can help accurately identify the presence of perianal fistulizing disease in patients with CD.

Higher incidence of paediatric inflammatory bowel disease by increasing latitude in Norway, but stable incidence by age.

AIM: To examine possible geographical and temporal differences in the incidence of childhood-onset inflammatory bowel disease (IBD) in Norway, motivated by previous research indicating relevant environmental factors explaining changing epidemiology. METHODS: We analysed data from children born in Norway from 2004 to 2012 (n = 541 036) in a registry-based nationwide study. After validating registry diagnoses against medical records, we defined IBD as ≥2 entries of International Classification of Diseases, 10th revision (ICD-10) codes K50, K51 and K52.3 in the Norwegian Patient registry. We estimated hazard ratios (HR) for IBD across four geographical regions with a south-to-north gradient and the incidence by period of birth. RESULTS: By the end of follow-up on 31 December 2020, 799 IBD diagnoses were identified (Crohn's disease: n = 465; ulcerative colitis, n = 293, IBD: unclassified, n = 41). Compared to children in the southernmost region, there was almost a two-fold HR for IBD in children in the most Northern region (HR = 1.94, 95% Cl = 1.47-2.57; Mid region: HR = 1.68, 95% CI = 1.29-2.19, ptrend <0.001). These estimates remained largely unchanged after adjustment for potential confounding factors. The cohorts born in 2004-2006 and 2010-2012 had comparable cumulative incidences, with a slightly higher incidence for those born in 2007-2009. CONCLUSION: We observed an increase in the risk of IBD by increasing latitude which may suggest that environmental factors influence the development of IBD, although non-causal explanations cannot be ruled out.

New surgery and hospital-diagnosed infections in elderly patients with inflammatory bowel disease undergoing surgery - a nationwide cohort study.

BACKGROUND: Elderly patients with inflammatory bowel disease (IBD) are fragile in many aspects. Therefore, in these patients, we studied post-operative complications (new abdominal surgery and serious infections after the first IBD surgery). METHODS: This is a nationwide cohort study based on Danish health registries and included patients with IBD undergoing surgery. The study population was split into ulcerative colitis (UC) and Crohn's disease (CD). The exposed cohort (elderly) constituted those at an age of ≥ 60 years at first IBD surgery, and the unexposed (adults) those with surgery at the age of 18-59 years. We estimated adjusted Hazard Ratios (aHR) of a) new abdominal surgery within 2 years, and b) serious (hospital-diagnosed) infections within 6 and 12 months. We adjusted for several confounders including type of index surgery (laparoscopic or open). RESULTS: The aHR for a new surgery among elderly with UC and CD were 0.69 (95% CI 0.58-0.83) and 0.98 (95% CI 0.83-1.15), respectively. In elderly with UC, the aHRs of infections within 6 and 12 months after surgery were 1.07 (95% CI 0.81- 1.40) and 0.85 (95% CI 0.67-1.08), respectively. In the elderly with CD, the aHRs of infections within 6 and 12 months were 1.45 (95% CI 1.12-1.88) and 1.26 (95% CI 1.00-1.59), respectively. CONCLUSION: The elderly with IBD did not have an increased risk of new abdominal surgery within two years of the first surgery. Elderly with CD, but not UC, had an increased risk of serious infections within 6 months of surgery.

Toward Patient Centricity: Why Do Patients With Inflammatory Bowel Disease Participate in Pharmaceutical Clinical Trials? A Mixed-Methods Exploration of Study Participants.

Background: A better understanding of motivations to participate as well as recommendations to reduce barriers to enrollment may assist in design of future clinical trials. Methods: We developed a 32-item electronic questionnaire to explore motivations, experiences, and recommendations of inflammatory bowel disease patients, who had participated in pharmaceutical clinical trials in a tertiary center in Canada over the last decade. We employed a mixed-methods approach that integrates both quantitative and qualitative research methods. Results: We distributed a total of 69 e-mails with surveys and received 46 responses (66.6% response rate). Study participants were mostly male (27/46, 58.7%), non-Hispanic White (43/46, 93.5%), with a mean age of 45.5 years (SD 10.9). Most decided to participate in a clinical trial to benefit future patients (29/46, 63.0%). Half of the participants (23/46, 50.0%) reported they were worried about the possibility of receiving placebo, although the majority (29/46, 63.0%) understood they could improve on placebo. The most challenging aspect reported was the number and length of questionnaires (15/46, 32.6%), as well as the number of colonoscopies (14/46, 30.4%). Strategies recommended to increase enrollment were reduction of the chance of receiving placebo (20/46, 43.5%), facilitating inclusion of patients who have failed multiple therapies (20/46, 43.5%), allowing virtual visits (18/46, 39.1%), including subtypes of disease traditionally excluded from trials (16/46, 34.8%) and improving outreach to underrepresented populations (13/46, 28.3%). The vast majority (37/46, 80.4%) reported their experience of participation to be better than expected. Conclusions: These results should help inform the design of future clinical trials with a focus on patient-centricity.

Differential diagnosis of Crohn's disease and intestinal tuberculosis based on ATR-FTIR spectroscopy combined with machine learning.

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.

Capsule endoscopy and panendoscopy: A journey to the future of gastrointestinal endoscopy.

In 2000, the small bowel capsule revolutionized the management of patients with small bowel disorders. Currently, the technological development achieved by the new models of double-headed endoscopic capsules, as miniaturized devices to evaluate the small bowel and colon [pan-intestinal capsule endoscopy (PCE)], makes this non-invasive procedure a disruptive concept for the management of patients with digestive disorders. This technology is expected to identify which patients will require conventional invasive endoscopic procedures (colonoscopy or balloon-assisted enteroscopy), based on the lesions detected by the capsule, i.e., those with an indication for biopsies or endoscopic treatment. The use of PCE in patients with inflammatory bowel diseases, namely Crohn's disease, as well as in patients with iron deficiency anaemia and/or overt gastrointestinal (GI) bleeding, after a non-diagnostic upper endoscopy (esophagogastroduodenoscopy), enables an effective, safe and comfortable way to identify patients with relevant lesions, who should undergo subsequent invasive endoscopic procedures. The recent development of magnetically controlled capsule endoscopy to evaluate the upper GI tract, is a further step towards the possibility of an entirely non-invasive assessment of all the segments of the digestive tract, from mouth-to-anus, meeting the expectations of the early developers of capsule endoscopy.

"Decoding inflammation: glycoprotein a repetition predominant, microRNA-142-3-p, and metastasis associated lung adenocarcinoma transcript 1: as novel inflammatory biomarkers of inflammatory bowel disease".

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic gastrointestinal (GI) condition comprising Crohn's disease (CD) and ulcerative colitis (UC). The pathogenesis involves immune system dysregulation, with increased Th (T helper cell)17 cells and reduced regulatory T cell (Treg) differentiation. Transforming growth factor-ß (TGF-ß) secretion from Tregs helps control inflammation, and its production is regulated by glycoprotein-A repetition predominant (GARP) protein along with non-coding RNAs (ncRNAs) like microRNA(miR)-142-3p and metastasis associated lung adenocarcinoma transcript 1 (MALAT1) long non-coding RNAs (LncRNAs). This study analyzed their expression in IBD. METHODS: Blood samples were collected from 44 IBD patients, and 22 healthy controls (HC). RNA extraction and circular DNA (cDNA) synthesis were performed. Real-time polymerase chain reaction (RT-PCR) measured gene expression of GARP, MALAT1, and miR-142-3p. Correlations and group differences were statistically analyzed. RESULTS: Compared to controls, GARP was downregulated while MALAT1 and miR-142-3p were upregulated significantly in IBD group. GARP and MALAT1 expressions positively correlated in controls. MALAT1 and miR-142-3p expressions positively correlated in IBD group. MALAT1 was downregulated in aged HC but upregulated with smoking history across groups. No correlations occurred between gene expression and gender, diet, infections, or disease activity scores. CONCLUSIONS: Dysregulation of GARP, MALAT1, and miR-142-3p likely contributes to inflammation in IBD by reducing TGF-ß. MALAT1 is linked to smoking and age-related changes. These genes have potential as diagnostic markers or therapeutic targets for personalized IBD treatment.