Diagnosis Of Inflammatory Bowel Disease Research Articles

OP18 Multi-analytical Approaches Reveal Robust Gut Microbial Biomarkers for Inflammatory Bowel Disease Diagnosis: A Large-scale Cohort Study

Abstract Background Inflammatory bowel disease (IBD), encompassing Crohn's disease (CD) and ulcerative colitis (UC), is strongly associated with gut microbiota dysbiosis. While numerous association studies have identified potential diagnostic gut microbial markers, their clinical utility remains limited due to substantial variability across studies and lack of robust validation. Furthermore, despite the availability of multiple analytical approaches for identifying microbial biomarkers, their relative effectiveness remains unclear, and definitive biomarkers for IBD diagnosis are still lacking. This study aims to identify robust gut microbial biomarkers for IBD diagnosis through multiple analytical approaches. Methods We analysed 3,762 participants, including healthy controls (HC, n = 2,467) and patients with IBD (n = 1,293), stratified into CD (n = 879) and UC (n = 414). Gut microbiota profiles were analysed from stool samples using 16S rRNA gene sequencing. Four analytical approaches were employed: (1) differential abundance analyses (DA: LEfSe, ANCOM-BC, and MaAsLin2), (2) supervised random forest machine learning (ML), (3) unsupervised network analysis (NW), and (4) literature-based curation (LC). Biomarker candidates generated by these methods were compared for diagnostic performance using an ensemble ML model. Results Diversity analysis revealed distinct gut microbial community structures among HC, UC, and CD groups (unweighted UniFrac distance, PERMANOVA, p < 0.001, Fig. 1A). Dysbiosis scores, calculated based on these structural differences, were significantly higher in IBD groups compared to HC (Fig. 1B). Each analytical approach identified distinct microbial biomarkers associated with IBD and its subtypes. Supervised ML produced the most effective biomarker sets, achieving the highest diagnostic performance for distinguishing IBD from HC (AUC = 0.971), surpassing LC (AUC = 0.938), DA (AUC = 0.928), and NW (AUC = 0.912), Fig. 2. ML biomarker sets also demonstrated superior accuracy in distinguishing CD from HC (AUC = 0.933) and UC from CD (AUC = 0.892). These results highlight the superiority of ML in selecting robust biomarkers for IBD diagnostics across multiple classification tasks. Conclusion This study identifies robust gut microbial biomarkers for IBD diagnosis through multiple analytical approaches. The biomarker panel demonstrates high diagnostic accuracy in distinguishing both IBD from healthy controls and CD from UC. External validation of these findings is currently ongoing in an independent cohort. These findings provide a foundation for developing reliable microbiome-based diagnostic tools for IBD, potentially enabling more precise disease diagnosis and improved patient care.

P1026 Rectal stump surveillance in the IBD population

Abstract Background Patients with inflammatory bowel disease (IBD) may require surgical resection, including subtotal colectomy, to manage symptoms and improve quality of life. However, there remains a risk of colorectal cancer (CRC) within the retained rectal stump. Although robust national and international guidelines exist for CRC surveillance in IBD patients with an intact colon, there is a significant gap in guidance for those with a retained rectal stump. We examined the current surveillance practices for the rectal stump in IBD patients, aiming to clarify current practice and optimise long-term surveillance strategies. Methods We performed a single centre, retrospective observational study. Patients with IBD undergoing surgical resection were identified using the local surgical IBD database, between January 2012 and September 2023. Cases without a rectal stump were excluded. Data was collected regarding age, sex, date of IBD diagnosis, date of surgery, frequency of surveillance, endoscopic appearance at surveillance, histology at surveillance and histological appearance at resection – this was used to assess initial risk. The British Society of Gastroenterology (BSG) guidelines for surveillance frequency of IBD were used as a comparator. Results Of the 53 patients (median age = 52 (IQR = 32), 34% female, 66% male) included, 30.2% underwent surveillance following the BSG guidelines, according to their risk at formation of the rectal stump, determined by BSG guidelines. 39.6% of patients underwent surveillance but not in accordance with the BSG guidelines and 30.2% had no surveillance documented. 51.4% of patients had their risk reclassified at first surveillance, 48.6% had no change to their risk. No patients developed colorectal cancer on surveillance. 85% of patients underwent subtotal colectomy within 10 years of diagnosis. Conclusion Conclusion IBD patients with a retained rectal stump are susceptible to adjustment of their risk based on histological and endoscopic appearance at surveillance, when using risk at initial resection as a baseline. This implies close monitoring is required, to ensure any dysplasia or CRC is adequately identified. Surveillance was inconsistent, and many patients had no surveillance documented. This study highlights the need for surveillance guidelines for patients with IBD with a retained rectal stump. The BSG guidelines suggest a screening colonoscopy 10 years post-diagnosis, yet most patients underwent initial resection before this could take place. This raises the question whether patients should undergo surveillance 10-years post-resection, or if this would be required earlier, dependant on risk following resection. The answer to this requires further research, to ensure uniformity in practice.

P1269 Assessing the prevalence and incidence of recorded fatigue codes amongst IBD patients: A nationwide study from the epi-IIRN

Abstract Background Fatigue is a common and burdensome symptom experienced by patients with Inflammatory Bowel Diseases (IBD), yet it remains under-recognised and understudied. This study aimed to assess the prevalence and incidence of recorded fatigue in the first nationwide cohort investigation of this topic. Methods We utilised the epi-IIRN cohort, encompassing all IBD patients in Israel across the four Health Maintenance Organisations (HMOs), covering 98% of the population. These patients were matched to non-IBD controls (by birth year, sex, district, HMO). We included patients with IBD diagnosed from 2005 onwards and followed until June 2021. Fatigue was identified using ICD-9 codes for "Malaise and Fatigue" or "Chronic Fatigue". Patients with fatigue codes >2 years prior to IBD diagnosis were excluded. Prevalence of fatigue codes was compared with matched non-IBD controls, and incidence rates were analysed using Kaplan-Meier survival curves. Associations with disease activity, reflected in blood tests, and other recorded comorbidities known to contribute to fatigue were explored. Predictors of fatigue in IBD patients were assessed using a multivariate Cox model. Results The study comprised of 32,908 IBD patients (18,555 with Crohn’s disease [56%]; 47% female; mean age at diagnosis 35.4±18.5 years) were matched to 74,688 controls. Fatigue was recorded in 6,210 (18.9%) IBD patients compared to 9,593 (12.8%) controls (OR=1.58, 95%CI 1.52–1.63; p<0.001). Among IBD patients, fatigue was more frequent in females (OR=1.52, 95%CI 1.44–1.60). Time to fatigue onset was shorter in both male and female IBD patients compared to matched controls (p<0.001; figure). Fatigue rates were similar between Crohn’s disease (3,548 [19.1%]) and ulcerative colitis (2,662 [18.5%]; OR=1.04, 95%CI 0.98–1.10; p=0.2). IBD patients with fatigue had higher rates of anaemia, iron deficiency, anxiety, depression, and sleep disorders compared to those without (Table). In a multivariate Cox model, female sex, frequent physician visits, anaemia, sleep disorders, and steroid use were associated with fatigue. In contrast, the use of 5-ASA, immunomodulators, anti-TNFs, and vedolizumab was protective (figure). Disease severity, reflected by cluster analysis of blood tests (moderate vs mild and severe vs mild), was not independently associated with fatigue (HR=1.08 95%CI 1.01-1.15 and 0.94 95%CI 0.84-1.05 respectively). Conclusion In this nationwide, unselected cohort, fatigue was more frequently reported in IBD patients compared to controls and was associated with several disease-related and comorbid factors. The burden of fatigue is underscored by its strong association with anxiety, sleep disorders, and depression.

P0984 Treatment with allopurinol and low-dose azathioprine during pregnancy in patients with Inflammatory Bowel Disease. A Danish single center experience

Abstract Background Low-dose azathioprine in combination with allopurinol (LD-AZA/ALLO) is a widely used treatment option in inflammatory bowel disease (IBD). Data on pregnancy and birth outcomes from exposure to combination therapy are sparse. The aim of this study was to provide data on safety and risk for adverse pregnancy and birth outcomes in women with IBD treated with LD-AZA/ALLO at the Gastrounit, Hvidovre Hospital, Copenhagen. Methods The study was a retrospective single center study. Inclusion criteria were established IBD diagnosis and treatment with LD-AZA/ALLO (AZA 50-75 mg/ ALLO 100 mg) during conception and pregnancy between 2013-2023. Data was collected from electronic medical charts and by questionnaire to all included women. Data registered was; demographics, diagnosis, disease characteristics, disease activity, IBD medications and number of pregnancies. Pregnancy outcomes were neonatal characteristics, obstetric complications, lactation and congenital malformations, disease, infections and admission to the hospital during the first year of life. Results In all, 44 women with 62 pregnancies (one twin pregnancy) and 59 live births were included. There were 1 spontaneous and 3 provoked abortions due to genetic disorders (1 trisomy 21 and 2 spinocerebellar ataxia). Obstetric complications were present in 8 (13%) pregnancies, (1 pre-eclampsia, 1 HELLP syndrome, 6 hypertension and/or gestational diabetes mellitus). 7 (11%) women had an IBD flare during pregnancy, none resulting in obstetrical complications. 5 (9 %) children were born prematurely, 4 (7 %) had low birth weight. No congenital malformations were reported. One child was born with facial nerve paralysis and later diagnosed with hyper-IgD syndrome. 8 (14 %) were admitted to neonatal ward (hours to days), mainly due to immature lungs. During the first year of life, one child was admitted to the hospital due to COVID. One child was suspected to have an immune defect, but all symptoms and biochemical abnormalities resolved and interpreted as side effect to LD-AZA/ALLO. 5 children (9%) were treated with antibiotics due to minor infections. In total 84 % of the children were breastfed during LD-AZA/ALLO treatment. Conclusion In this large single center experience with 62 pregnancies in women treated with LD- AZA/ALLO, no malformations or indications of increased risk of complications of pregnancy and birth were observed. The majority of children were breastfed and no serious signals or complications were reported first year of life. Treatment with LD-AZA/ALLO during pregnancy and breastfeeding seems safe.

Key Themes in the Care of Inflammatory Bowel Diseases Among Immigrant Populations: A Systematic Review.

The care of inflammatory bowel disease (IBD) requires special attention among immigrants due to different disease incidence, phenotype, and risk profiles. We aimed to highlight key themes among existing literature to inform equitable care in all immigrants living with IBD. A systematic literature search was conducted in MEDLINE, EMBASE, the Cochrane library, Scopus, and ProQuest from inception to February 2023 to identify studies capturing the care of IBD among immigrants who moved from one country to another, irrespective of the timing of IBD diagnosis. Studies on immigrant children and children of immigrants were also included. We reported qualitative and quantitative data as reported in each individual study, and where applicable, we noted comparisons between immigrants and non-immigrants, defined as natives of the adopted country. This review included 50 eligible studies. 12/19 (63.1%) studies reported lower incidence of IBD among immigrants, although rates increased from first- to second-generation immigrants in five studies. Most immigrants had significant changes in their diet after immigration, and their gut microbiota was different compared to non-immigrants. Immigrants had different environmental exposures and in certain populations, more severe IBD phenotypes and extra-intestinal manifestations (EIMs). Medical and surgical treatments were lower among immigrants in certain regions, although they had appropriate healthcare utilization and similar hospitalization rates compared to non-immigrants. IBD care among immigrants is unique due to their different risk profiles and disease phenotypes, and the potential barriers with healthcare access. Understanding IBD among immigrants is key to ensure equitable care in this unique population.

N31 Stress after an Ulcerative Colitis diagnosis: examining factors causing or alleviating stress in Ulcerative Colitis using Interpretative Phenomenological Analysis

Abstract Background Stress significantly affects disease flares and quality of life in people with ulcerative colitis (UC), with over 25% of individuals experiencing symptoms of anxiety or depression irrespective of disease activity.1–3 However, there is limited research on the specific stressors introduced by a UC diagnosis. This study aims to explore how stress is experienced following diagnosis and identify factors affecting it. Methods Ten UC patients participated in online semi-structured interviews about their experience of stress and coping during their first year post-diagnosis. The group included 7 females and 3 males, aged 16-76, with 9 being treated in England and 1 in Scotland. Nine participants were white. All had high scores on Cohen’s Perceived Stress Scale before interview and were diagnosed with UC within the last 6 years, with 7 diagnosed in the past year. The interviews were audio-recorded and analysed using Interpretative Phenomenological Analysis to capture individuals’ unique perspective on this period and synthesise these insights into Group Experiential Themes.4 Results Initial analysis reveals a complex relationship between stress, resilience and UC, encompassing emerging themes including: 1. UC interrupts life 2. Disconnect between personal experience and clinical characterisation of UC 3. Emotion intrinsic to UC experience 4. Information is a double-edged sword 5. Healthcare’s mixed effect on stress 6. Attitude is important 7. Communication is integral to managing stress 8. Reliance on others Conclusion These preliminary findings provide a foundation for exploring further the stressors that UC and its treatment place on individuals. While those affected developed various strategies to cope, the support provided by others (including healthcare professionals) plays a significant role in both alleviating and exacerbating stress levels. There is a pressing need to expand and improve resources for individuals newly diagnosed with UC and those who support them to help understand and navigate the challenges the stress of the condition presents.

P1087 Opioid Use Before and After Ulcerative Colitis Diagnosis: A Nationwide Cohort Study in Sweden 2006-2021

Abstract Background Opioid misuse has been declared in the US since 2017 [1]. Population-based studies to describe opioid use among adults with ulcerative colitis (UC) are scarce [2]. This study aimed to evaluate patterns of opioid use two years before and up to five years after UC diagnosis date among adults with UC compared to reference individuals in Sweden. Methods We conducted a nationwide cohort study including individuals aged ≥18 years with an incident UC diagnosis between 2008 and 2019, identified through two International Classification of Disease 10 code K51 recorded in the National Patient Register. Each patient with UC was matched with up to 10 reference individuals without inflammatory bowel disease (IBD) by birth year, sex, calendar year, and place of residence. Observation started on January 1, 2006, age 18, or 24 months before the first UC diagnosis date (index date), whichever came last, and ended at emigration, death, or December 31, 2021. Data on opioid dispensations were obtained from the Prescribed Drug Register. Opioid use was defined as ≥1 dispensed opioid prescription per six-months periods. We categorized opioids as weak (codeine combinations, tramadol, dextropropoxifen) and strong (oxycodone, morphine, hydromorphone, fentanyl, buprenorphine, tapentadol, petidine). Opioid use during 24 months before the index date was classified as non-use (no dispensations), intermittent use (≥1 dispensation in 1–3 of the four preceding six-month periods), or chronic use (≥1 dispensation in all four six-months periods). Mean daily doses (MDD) of opioids were calculated using oral morphine equivalents. Opioid use prevalence and MDDs were reported with 95% confidence intervals. Results The cohort included 20,265 patients with incident UC (48.7% female) and 185,973 reference individuals. At the index date, 2.4% of UC patients and 1.4% of reference individuals chronically used opioids, while 15.0% and 11.1% used opioids intermittently. Among patients with UC, opioid use increased right after the index date to 12.0% and stabilized at approximately 10% thereafter (Figure 1). The use of stronger opioids increased after diagnosis, while the use of weak opioids remained unchanged (data not shown). The MDD of opioids among patients with UC increased from 0.75 mg (0.60 mg in the reference group) at 18-24 months before the index date to 1.45 mg (0.65 mg in the reference group) at 54-60 months post-diagnosis. Conclusion Overall prevalence of opioid use among adults with UC increased only modestly following diagnosis, with a shift toward using stronger opioids. The main limitation of this research was the inability to account for illegal opioid use, which may result in underestimating the use of opioids among the reference group.

P0995 Use of biologics before ileal pouch-anal anastomosis is not associated with inflammatory pouch disease

Abstract Background Inflammatory pouch disease (IPD) is a common complication after ileal pouch-anal anastomosis (IPAA) surgery. The risk factors contributing to the onset of IPD, particularly the role of preoperative biological treatment, remain unclear. The purpose of this study was to investigate the effects of biologic use on the occurrence of post-IPAA complications and the risk factors for IPD. Methods These was a retrospective cohort analysis of patients who underwent IPAA at Jinling hospital between November 2003 and September 2023. The patients were divided into two groups according to the presence or absence of exposure to biologics. The primary outcome was the occurrence of postoperative IPD. The postoperative complications were compared between groups, and logistic regression was used to identify IPD risk factors. Results Among the 175 patients, 47.43% had received biologics before surgery, and 38.9% developed IPD. No significant difference was observed in the incidence of postoperative IPD between groups (p = 0.484). Logistic regression revealed that biologic use was not a risk factor for IPD (OR = 0.8, 95% CI: 0.44–1.48, p = 0.485), whereas ulcerative colitis diagnosis at >35 years of age was a protective factor against IPD (OR = 0.47, 95% CI: 0.24–0.93, p = 0.029), and C-reactive protein >45 mg/L was a risk factor for IPD (OR = 2.37, 95% CI: 1.12–5.02, p = 0.025). Conclusion The use of biologics before IPAA was not associated with IPD, but might be associated with a high preoperative CRP level and younger age at UC diagnosis.

Helicobacter pylori infection is associated with significant elevations to fecal calprotectin, systemic inflammatory markers.

Fecal calprotectin (FC) is a marker commonly used in the diagnosis and follow-up of inflammatory bowel diseases (IBD). However, other gastrointestinal conditions, like H. pylori (HP) infection, can result in increased neutrophil activity as well. We set out to assess the impact of HP infection on FC and downstream gastrointestinal care via a retrospective study. In this study, we collected data from two institutions in Brooklyn, NY, in a high immigrant density community. We reviewed data from patients who underwent esophagogastroduodenoscopy (EGD) between January 2017 and October 2022. Patients aged 6-18 years old with an FC level 6 months prior to EGD and HP testing were included. Of 129 patients, 37 (28.7%) tested positive for HP infection. The mean FC level was significantly elevated in HP-positive patients (241.2, confidence interval [CI]: 161.0-321.3) as compared with HP-negative patients (88.1, CI: 59.1-117.0) (p < 0.001). Patients with higher FC levels were also more likely to undergo colonoscopies (p = 0.003). HP infection is associated with increased calprotectin, and calprotectin increases in HP patients are associated with an increased risk of colonoscopy.

Severe obesity, a susceptibility factor for developing inflammatory bowel disease. Results of a population-based study.

Inflammatory bowel disease (IBD) develops in genetically susceptible individuals exposed to certain environmental factors, of which only a few have been established. We aimed to assess whether bariatric surgery (BS) and severe obesity are associated with an increased risk of developing IBD. Adults diagnosed with obesity or severe obesity between 2005 and 2020 were identified from the Catalan Health Surveillance System; those diagnosed with IBD prior to the diagnosis of obesity or severe obesity were excluded. Individuals who had undergone BS and those with a new diagnosis of IBD were identified and their likelihood of developing IBD was analysed. A total of 93,473 individuals with severe obesity, 1,009,256 with obesity and 14,698 who underwent BS were identified. The incidence rates of IBD among individuals who had undergone BS prior to IBD diagnosis was 0.84 cases per 1000 person-years, 0.90 cases per 1000 person-years among individuals with severe obesity without BS and 0.60 cases per 1000 person-years in individuals with obesity. In the multivariable regression analysis, severe obesity (HR 1.46; 95%CI 1.31-1.62), BS (HR 1.57; 95%CI 1.25-1.97) and smoking habit (HR 1.57; 95%CI 1.46-1.69) were risk factors for developing IBD (as well as for Crohn's disease and ulcerative colitis). Conclusions: Severe obesity and BS were independent risk factors for the development of IBD. Non-invasive screening for IBD seems to be warranted in this population.

Position statement of the Spanish Society of Primary Care Physicians (SEMERGEN) and Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) on the management of inflammatory bowel disease in Primary Care

Primary Care is the first point of contact for most patients after the onset of symptoms of inflammatory bowel disease (IBD). Establishing an initial diagnostic process based on compatible symptoms and agreed criteria and referral pathways, depending on the degree of suspicion and the patient's situation, can reduce diagnostic delays. Once the patient is referred to the Digestive specialist and the diagnosis of IBD is established, a treatment and follow-up plan is structured. The management of the patient must be shared with the participation of the family practitioners in the diagnosis and treatment of concomitant or intercurrent pathologies, the recognition of flare-ups or complications (of IBD or treatments), education tasks or adherence control. With the purpose of developing a comprehensive guide on the management of IBD aimed at Primary Care doctors, we have developed this positioning document collaboratively between the Spanish Society of Primary Care Physicians (SEMERGEN) and the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU).

EXPLORING THE UTILITY OF CELLULAR INDICES IN THE DIAGNOSIS OF ULCERATIVE COLITIS.

To describe the usefulness of cellular indices in the diagnosis of ulcerative colitis (UC). Diagnostic study of patients under 15 years of age undergoing colonoscopy ± esophagogastroduodenoscopy for suspected inflammatory bowel disease between 2015-2022 in a pediatric hospital. Patients with normal biopsy and anatomopathological diagnosis of UC were included. Using the area under the ROC curve, the values of platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio (NLR) and monocyte-lymphocyte ratio (MLR), calculated by dividing the number of platelets, neutrophils, and monocytes by the number of lymphocytes, respectively, were compared to establish the sensitivity, specificity, predictive values and Odds Ratio of each parameter in the diagnosis of UC. Twenty-six patients were included: 14 with normal biopsy and 12 with UC. PLR and MLR values were significantly higher in patients with UC (p <0.05). The sensitivity, specificity, and negative predictive value of PLR, NLR and MLR for diagnosing UC were 58%, 83% and 91%; 85%, 35% and 50%; 70%, 71% and 87%, respectively. The biomarker with the highest diagnostic performance was MLR with a cutoff point of 0.235, area under the curve of 0.735 and Odds Ratio of 11 (95%CI 1.1-109.6; p= 0.041). MLR has a high sensitivity, negative predictive value, and Odds Ratio in the pre-endoscopic diagnosis of ulcerative colitis. These findings, although exploratory, suggest that MLR could be useful in clinical practice in the initial diagnostic workup of UC, and perhaps in the future in the prioritization of endoscopic studies according to MLR values.

Childhood-onset inflammatory bowel disease and chronic non-bacterial osteomyelitis: a Swedish nationwide cohort study 2002-2022.

Nationwide, population-based studies of chronic non-bacterial osteomyelitis (CNO) in patients with childhood-onset inflammatory bowel disease (IBD) are lacking. We used nationwide registers to identify all children in Sweden diagnosed with IBD during 2002-2022 and the occurrence of CNO in this IBD cohort and general population non-IBD comparators. To estimate the temporal associations between IBD and CNO we used Cox regression. We compared clinical data for IBD patients with CNO (IBD+CNO) and the IBD patients without CNO. We identified 8244 children with IBD and 82 400 non-IBD comparators. At IBD diagnosis, CNO had been diagnosed in 0.13% (11/8244) of the IBD cohort and 0.03% (26/82 400) of the non-IBD comparators. During follow-up, 13 additional CNO cases occurred in the IBD cohort and 22 in the non-IBD comparators (adjusted hazard ratio = 5.87 [95% CI 2.95-11.66]). The prevalence of CNO among all prevalent children with IBD and prevalent matched non-IBD comparators December 31, 2022 was 0.48% (9/1885) and 0.02% (4/18 567), respectively. Median age at IBD diagnosis was lower in IBD + CNO compared to IBD without CNO (11 vs 14 years [-3 years, 95% CI -5 to -1]). Extraintestinal manifestations (except CNO) were more frequent in IBD + CNO (62% vs 21%, P < .0001). Treatment with biologics was more common in the IBD + CNO group (78% vs 44%, P = .004), prescribed for IBD and/or CNO. We found a 6-fold increased risk of CNO in childhood-onset IBD compared to non-IBD comparators. Patients with IBD + CNO are characterized by younger age at IBD onset, more frequent extraintestinal manifestations, and higher usage of biologics.

A Nitrate/Nitrite Biosensor Designed with an Antiterminator for In Vivo Diagnosis of Colitis Based on Bacteroides thetaiotaomicron.

Bacteroides thetaiotaomicron is a common microorganism in the human gut that has been linked to health benefits. Furthermore, it is an emerging synthetic biology chassis with the potential to be modified into diagnostic or therapeutic engineered probiotics. However, the absence of biological components limits its further applications. In this study, we developed an antiterminator microbial whole-cell biosensor (MWCB) based on B. thetaiotaomicron. The antiterminator-based element allows the chassis to detect colitis in mice by responding to nitrate and nitrite in an inflammatory environment. In particular, the nitrate/nitrite-inducible promoter was obtained by combining the constitutive promoter with the inducible terminator. Subsequently, the promoter and RBS were replaced to optimize a sensitive and specific response to nitrate/nitrite. A preliminary in vitro assessment was conducted to ascertain the functionality of the biosensor. Its in vivo sensing ability was evaluated in a chemically induced mouse model of ulcerative colitis (UC). The results demonstrated that the MWCB exhibited a robust response to colitis, with a notable positive correlation between the intensity of the response and the level of inflammation. This novel sensing element may provide a new avenue for the development of components for unconventional chassis, like B. thetaiotaomicron. It will also facilitate the development of engineered probiotics based on B. thetaiotaomicron, thereby providing patients with a wider range of medical treatment options.

Engineering Acid-Promoted Two-Photon Ratiometric Nanoprobes for Evaluating HClO in Lysosomes and Inflammatory Bowel Disease.

HClO is considered a potential contributing factor and biomarker of inflammatory bowel disease (IBD). Accurate monitoring of lysosomal HClO is important for further developing specific diagnostic and therapeutic schedules for IBD. However, only rare types of fluorescent probes have been reported for detecting HClO in IBD so far. Herein, an acid-promoted two-photon semiconducting polymer dot (Lyso-RS Pdot) with dual emission in green and red channels and dual-sensing sites is successfully fabricated with two newly designed polymers NADE-PSMA and PFNA-10TBT as precursors. The red conjugated polymer PFNA-10TBT with pH-inert and HClO-sensitive units is employed to evaluate the HClO concentration in turn-off fluorescence. Meanwhile, the amphiphilic green fluorescent polymer NADE-PSMA sensitive to pH and HClO is employed to evaluate the pH value or HClO concentration in turn-on fluorescence. The resultant Lyso-RS Pdots not only display satisfactory performances for detecting HClO and pH but also achieve accurate two-photon imaging of HClO in lysosomes and the colon of IBD mice based on the distinguished properties such as ratiometric signal output, acid-promoted signal amplification, ultrafast response, and two-photon excitation. The results demonstrate that the HClO level in IBD mice is elevated, and the fast early diagnosis of IBD can be achieved through fluorescence imaging by the proposed Lyso-RS Pdots. This work may provide some solid perspectives for fluorescent diagnosis of H+ and HClO-related diseases.

Usefulness of Magnifying Endoscopy With Narrow‐Band Imaging for Diagnosis of Ulcerative Colitis–Associated Neoplasia

ABSTRACTBackground and AimQualitative diagnosis of ulcerative colitis–associated neoplasia (UCAN) is crucial for surveillance colonoscopy in patients with ulcerative colitis (UC). Although the utility of magnifying endoscopy with narrow‐band imaging (ME‐NBI) in sporadic neoplasia diagnosis has been reported, its efficacy in UCAN remains unclear. This study aimed to evaluate the usefulness of ME‐NBI for qualitative diagnosis of UCAN.MethodsWe generated 60 ME‐NBI images (30 UCANs and 30 nonneoplasia lesions, including 10 polypoid and 20 nonpolypoid lesions) from patients with UC who underwent colonoscopy at our hospital between 2015 and 2023. Eleven endoscopists (seven experts and four trainees) independently assessed these images. Lesions were categorized into high‐ (≥ 80%), moderate‐ (50%–79%), and low‐ (&lt; 50%) accuracy groups on the basis of the correct diagnostic rate.ResultsOverall sensitivity, specificity, and correct diagnostic rates were 66.5%, 79.0%, and 71.8%, respectively. Experts tended to exhibit higher specificity than trainees (83% vs. 70%). Polypoid lesions showed higher sensitivity (92% vs. 54%) and lower specificity (61% vs. 88%) than nonpolypoid lesions. Overall, the kappa value was 0.411. In UCAN, 37%, 37%, and 24% were classified into the high‐, moderate‐, and low‐accuracy groups, respectively. All endoscopists assessed one case of UCAN in the low‐accuracy group as a nonneoplastic vessel with a surface pattern. Only two nonneoplasias were identified as having nonneoplastic vessel and surface patterns by all endoscopists.ConclusionsThis study demonstrated the usefulness of ME‐NBI for qualitative diagnosis, along with its limitations. A unique endoscopic diagnostic algorithm for UCAN, incorporating ME‐NBI and other modalities, is necessary.

Anthropometric Trajectories in Children Prior to Development of Inflammatory Bowel Disease

Poor nutrition and growth in childhood have short-term and long-term consequences, so understanding the timing of the onset of an impaired nutritional status is crucial for diagnosing and treating inflammatory bowel disease (IBD) at its earliest stage. To assess anthropometric trajectories before a pediatric diagnosis of IBD and growth recovery after diagnosis. This population-based cohort study included children born in Denmark from January 1, 1997, through December 31, 2015, with weight and length or height measurements at birth and at least 1 length or height and weight measurement at school age based on the Danish Medical Birth Register and the Danish National Child Health Register. Within this population, all individuals diagnosed with IBD at ages 5 to 17 years, according to the Danish National Patient Register, were identified. Data were analyzed from October 13, 2023, to April 17, 2024. A pediatric diagnosis of IBD compared with the corresponding population without the disease. The outcome measures were z scores for length or height, weight, and body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) before and after pediatric IBD diagnosis compared with reference and sibling populations. The final study population included 916 133 individuals (51.2% male) with a median of 3 pairs of length or height and weight measurements collected (IQR, 2-6 pairs). Of those, 1522 (median age, 14.3 years [IQR, 11.8-16.3 years]; 763 female [50.1%]) were diagnosed with IBD (851 [55.9%] with Crohn disease [CD] and 671 [44.1%] with ulcerative colitis [UC]). Compared with children without IBD, individuals with a later diagnosis of CD had declining anthropometric measures 3 years (weight: mean, -0.12 g [95% CI, -0.20 to -0.03 g]; BMI: mean, -0.13 [95% CI, -0.21 to -0.04]) and 1 year (length or height: mean, -0.20 cm [95% CI, -0.29 to -0.10 cm]) prior to diagnosis, whereas this was observed 1 year prior to a diagnosis of UC for weight (mean, -0.12 g [95% CI, -0.22 to -0.02 g]) and BMI (mean, -0.13 [95% CI, -0.23 to -0.03]). Deviating anthropometric patterns persisted after diagnosis, with the slowest recovery observed in children with CD. The findings of this large-scale population-based cohort study of anthropometrics in children suggest impaired nutritional status as assessed by weight up to 3 years and by length or height 1 year before a diagnosis of CD and by weight up to 1 year before a diagnosis of UC. These findings emphasize that the onset of pediatric IBD may occur years prior to diagnosis, that growth recovery may first occur after diagnosis and treatment, and that frequent nutritional screenings may help ensure a healthy transition to adulthood.

Usefulness of Fecal Calprotectin Measurement in a Pediatric Patient with Crohn’s Disease

Acute pancreatitis in children in Japan is often caused by an anatomical abnormality of the pancreatic and bile duct, resulting in fever, abdominal pain, vomiting, diarrhea, and other symptoms. Crohn's disease, however, is a chronic granulomatous inflammatory bowel disease with ulcerative lesions of the intestinal tract of unknown cause that occurs mainly in young people, with symptoms similar to those of acute pancreatitis. We report a case of acute pancreatitis diagnosed in a patient not only with incomplete fusion of the pancreatic duct but also with Crohn's disease. A 14-year-old girl, healthy by nature, presented to our hospital with complaints of abdominal pain and diarrhea. She was initially diagnosed as having acute pancreatitis due to incomplete pancreas divisum. However, a high level of fecal calprotectin led to endoscopic examination, which resulted in the diagnosis of Crohn's disease. Fecal calprotectin can be useful in the diagnosis of inflammatory bowel disease associated with acute pancreatitis in children. Although the relationship between inflammatory bowel disease and acute pancreatitis has not yet been clarified, we suggest that in the present case, acute pancreatitis may have manifested as a complication of Crohn's disease and an underlying case of incomplete pancreas divisum.

Utility of fecal calprotectin in the diagnosis of inflammatory bowel diseases

Introduction: Inflammatory bowel disease involves two main disorders: Crohn's disease and ulcerative colitis. Colonoscopy with biopsy is considered the gold standard for the diagnosis of IBD, although these are invasive and costly techniques. In recent years, fecal calprotectin has gained relevance as a non-invasive biomarker with significant clinical utility. The effectiveness of fecal calprotectin has been demonstrated in distinguishing between IBD and irritable bowel syndrome, predicting endoscopic and histological activity, as well as disease recurrence.Objective: Review the current literature on the clinical utility of fecal calprotectin in the diagnosis and management of inflammatory bowel diseases.Methods: Systematic review based on the PRISMA method, of studies obtained through searches in Scopus, PubMed, Virtual Health Library, Web of Science, Latindex, and Google Scholar. Primary and secondary studies published in the last five years in English and Spanish were included.Results: Nineteen studies were analyzed, describing high sensitivity and specificity in distinguishing IBD from IBS, helping to reduce the rate of unnecessary colonoscopies in patients with non-specific gastrointestinal symptoms. Additionally, fecal calprotectin was found to significantly correlate with endoscopic and histological activity.Conclusions: Fecal calprotectin is a reliable biomarker of mucosal inflammation, capable of identifying patients with a higher likelihood of having IBD, allowing for better management of colonoscopy resources and reducing associated costs.

Predictive Value of Albumin to Fibrinogen Ratio and CALLY Index for Diagnosis of Ulcerative Colitis and Mucosal Healing After Vedolizumab Treatment.

The albumin to fibrinogen ratio (AFR), a biomarker associated with inflammatory, nutritional, and coagulation status, and the CALLY index, a biomarker combining C-reactive protein, albumin, and lymphocyte count, have been suggested to correlate with prognosis in a variety of diseases in previous studies; however, studies of these two markers in ulcerative colitis (UC) are lacking. The aim of this study was to evaluate the clinical significance of AFR and CALLY index in UC. The study included 109 UC patients and 126healthy controls. For UC patients treated with Vedolizumab (50 patients), they were categorized into mucosal healing group (MH group) and non- mucosal healing group (non-MH group) based on Mayo endoscopic score (MES) after 14weeks of treatment. The differences in AFR and CALLY index were compared between the UC group and the healthy control group, and between the MH group and the non-MH group. Then, the correlation of the AFR and CALLY index with UC activity was assessed, and the predictive value of the AFR and CALLY index was evaluated using the receiver operating characteristic (ROC) curve. The results showed that both AFR and CALLY index were significantly decreased in the UC group compared with the healthy control group (both p<0.001); the area under the curve (AUC) of the AFR and CALLY index differentiating between the healthy control group and the UC group were 0.782 and 0.773, respectively. For Vedolizumab treatment, the non-MH group had significantly lower baseline AFR and CALLY index compared to the MH group; the AUC for baseline AFR and CALLY index discriminating the MH group from the non-MH group were 0.665 and 0.721, respectively. In addition, AFR and CALLY index were negatively correlated with the MES and inflammatory load of UC. The results of multivariate logistic regression analysis showed that the CALLY index was an independent predictor of UC diagnosis and mucosal healing after 14weeks of Vedolizumab treatment. AFR and CALLY index can be used as novel serologic markers for diagnosing UC and predicting the efficacy of Vedolizumab treatment.