Ulcerative colitis (UC) is a chronic inflammatory bowel disease with rising global prevalence.Histological healing (HH) is a key treatment target associated with better long-term outcomes. Although endoscopic ultrasound (EUS) is known to be related to both clinical and endoscopic activity in UC, its role in defining HH remains unclear. Therefore, this study was aimed at investigating the association between EUS and histological activity (HA), as well as the predictive potential of EUS for HH.

In this cross-sectional analysis, 68 UC adults underwent EUS and colonoscopy with biopsies. We used the Mayo Endoscopic Score (MES) for endoscopic activity, the Nancy Index (NI) for biopsy grading, and the Endoscopic Ultrasound-Ulcerative Colitis (EUS-UC) score for EUS analysis, defining endoscopic remission as MES ≤ 1 and HH as NI ≤ 1.A receiver operating characteristic (ROC) curve was employed to evaluate the ability of the indices to predict HH.

Totally 23 patients (33.80%) achieved HH, while 45 (66.20%) showed HA. The EUS-UC scores were significantly lower in the HH group (p < 0.001) and correlated strongly with NI (ρ = 0.73). EUS-UC score was an independent risk factor for HH (adjusted OR = 1.918, 95% CI: 1.195-3.080, p = 0.007). The EUS-UC score demonstrated a strong predictive value for HH, with an AUC of 0.840, a sensitivity of 75.56%, and a specificity of 78.26%.

The EUS-UC score has a significant correlation with histological outcomes and shows strong potential as a reliable, invasive predictor of HH in UC, with implications for improved disease monitoring.

Mucosal healing (MH) has established as a long-term therapeutic goal for inflammatory bowel disease (IBD). Regenerative Islet-derived Protein 1α (reg1α) was reported to be closely related to gastrointestinal mucosal injury; however, its potential in monitoring MH remains unexplored.

Serum reg1α levels were quantified in 156 consecutive IBD patients (January 2021-December 2023) and stratified by endoscopic findings into MH (n = 136) and non-mucosal healing (NMH) groups. Diagnostic performance of reg1α was evaluated and compared to C-reactive protein (CRP) using receiver operating characteristic analysis.

A total of 136 patients (85 with CD and 51 with UC) were finally included. Serum reg1α levels were significantly correlated with endoscopic activity. Patients in NMH group demonstrating markedly higher reg1α levels than those in MH group (92.6 vs. 55.5 ng/ml, p < 0.001). In UC, reg1α outperformed CRP in sensitivity (82.4% vs. 55.9%, p = 0.012) and accuracy (80.4% vs. 70.6%, p = 0.001) for monitoring MH. This superiority persisted in UC subgroups with non-or mild clinical symptoms. Combined index (reg1α + CRP) and multivariate model (incorporating clinical indices, reg1α and CRP) also enhanced sensitivity and accuracy over CRP alone in UC (all p < 0.05). However, reg1α showed no significantly higher efficacy in monitoring NMH compared to CRP in CD. In CRP-normal patients, patients with NMH had higher reg1α levels than those with MH in UC (77.6 vs. 49.8 ng/ml, p = 0.018), but not in CD.

Reg1α represents as a novel and sensitive biomarker of endoscopic disease activity in patients with UC, even in patients with non- or mild clinical symptoms or normal CRP levels.

Inflammatory bowel disease (IBD) is a chronic autoimmune condition whose pathogenesis has not been fully elucidated, and current treatments are not definitive and often carry several side effects. The Complementary and Alternative Medicine (CAM) offers a new approach to conventional medicine. However, their clinical application and mechanisms remain limited.Objective: The aim of this review is to evaluate the anti-inflammatory, impact on microbiota and antioxidant efficacy of currently available CAM for IBD.Methods: The literature collection was obtained from Google Scholar, MEDLINE, PubMed and Web of Science (WOS). Studies in both human and animal models, published in English language between 2018 and 2024, were selected. Sixty-seven studies were included in the current review after inclusion and exclusion screening processes.Results: Mostly, studies showed significant anti-inflammatory, gut microbiota restoring, antioxidant effects of polyphenols, polysaccharides, emodin, short-chain fatty acids (SCFA; including butyrate, propionate and acetate), and probiotics although some contrasting results were noted. Current evidence shows that polyphenols exhibit the most consistent result in alleviating IBD pathophysiology, primarily due to their significant SCFA-elevating effect.Discussion: Future studies may focus on human studies, narrowing down on individual factors which may change natural product's metabolism. Further research studies are also essential to obtain therapeutic recommendations.

Insomnia has been suggested as a potential modulator of systemic inflammation. However, few studies have examined the longitudinal association between insomnia and inflammation as well as the role of sex differences, despite accumulating evidence of the vulnerability of women to immune consequences of disturbed sleep. In this study, we tested the association between self-reported insomnia symptoms and serum C-reactive protein, a marker of systemic inflammation, at 1-year follow-up, in 54 outpatients with inflammatory bowel disease (52.81 ± 16.09, 40.7% women). Insomnia symptoms were measured using the Insomnia Severity Index. After controlling for baseline inflammation and health variables, longitudinal moderated regression analysis showed that baseline insomnia symptoms predicted C-reactive protein levels at follow-up in women (β = 0.416, p = 0.014), but not in men (β = -0.179, p = 0.212). Results were not influenced by sex differences in insomnia severity or C-reactive protein levels. This study suggests insomnia symptoms may partially influence systemic inflammation in women with inflammatory bowel disease. Sex-specific psychological, immune and neuroendocrine pathways linking sleep to inflammation should be further elucidated.

Evaluation of deep remission in Crohn's disease (CD) can be challenging when the disease is confined to the small intestine. The aim of this study was to evaluate the effectiveness of through-the-scope EUS during double-balloon enteroscopy (DBE-EUS) in distinguishing small-bowel CD patients in endoscopic remission from those with active disease.

Patients who underwent DBE-EUS were divided into groups of endoscopic remission and endoscopic activity according to segmental Simple Endoscopic Score for Crohn's Disease (SES-CD). The thickness of small intestinal wall layers and other parameters were evaluated by EUS.

EUS using an ultrasonic catheter probe by DBE showed that the total wall thickness (TWT) and submucosal thickness (SMT) of the small intestine in the active group were significantly greater than those in the remission group (3.84 ± 1.02 mm vs 2.42 ± .25 mm and 1.23 ± .34 mm vs .79 ± .13 mm, respectively; P < .001). Cutoff values of 2.65 mm for TWT and .95 mm for SMT can distinguish active small-bowel CD from inactive disease (sensitivity 91.5% and specificity 80.8% and sensitivity 70.2% and specificity 88.6%, respectively). The correlation analysis revealed a significant positive correlation between TWT and SES-CD (r =.930, P < .001). Furthermore, TWT was strongly correlated with fecal calprotectin (r = .861, P < .001) and Crohn's Disease Activity Index (r = .805, P < .001). Similar results were observed for SMT.

EUS using an ultrasonic catheter probe during DBE is effective in evaluation of both mucosal and transmural healing in small-bowel CD patients. DBE-EUS could become an important tool in the management of patients with small-bowel CD.

Almost a third of patients with inactive inflammatory bowel disease (IBD) suffer from symptoms compatible with irritable bowel syndrome (IBS-like symptoms). The relation between these symptoms and diet in patients with IBD is not fully established. We aimed to assess associations between IBS-like symptoms and intake of macronutrients and fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) in patients with inactive IBD compared to an IBD-free background population.

Patients with IBD at one-year follow-up from the IBSEN III (Inflammatory bowel disease in South-Eastern Norway) study were compared to an IBD-free Norwegian background population (Tromsø7). A food frequency questionnaire (FFQ) was used to collect dietary data including FODMAP intake, which was compiled as gram/100 g of food and assessed in patients with active versus inactive IBD. Rome IV criteria were applied to define IBS-like symptoms in patients with inactive IBD.

A sample of 154 patients ≥40 years with inactive IBD was compared to 11078 adults from the IBD-free background population (Tromsø7). There were no significant associations between IBS-like symptoms and FODMAP and macronutrient intake, neither in patients with inactive IBD nor in the IBD-free background population. Patients with IBD ≥40 years had higher intake of fructans and total FODMAPs compared to the Tromsø7 sample. Intake of nutrients and FODMAPs was similar in patients with active IBD (n = 105), inactive IBD with IBS-like symptoms (n = 55), and without IBS-like symptoms (n = 197).

FODMAP and macronutrient intake were not associated with IBS-like symptoms in patients with inactive IBD one-year after diagnosis.

Inflammatory Bowel Disease (IBD) is a chronic digestive condition that requires continuous monitoring by healthcare professionals to determine appropriate therapy and manage short- and long-term complications. Telemedicine has become an essential approach for managing chronic conditions such as IBD, improving care accessibility and continuity, decreasing hospitalization rates, and optimizing patient follow-up. It enables rapid treatment adjustments and encourages patient self-management. Additionally, it reduces the burden on the healthcare system by decreasing unnecessary in-person visits and provides real-time support, thereby improving quality of life and clinical outcomes. The objective of this position statement by the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU) is to establish recommendations for the use of telemedicine in its different modalities (teleconsulting, telemonitoring, mobile applications and telepharmacy) for patients with IBD and address the legal, ethical, and technical aspects necessary for its proper implementation.

Serum C-reactive protein (CRP), leucine-rich alpha-2 glycoprotein (LRG), and fecal calprotectin (Fcal) are non-invasive markers used to assess Crohn's disease (CD) severity. However, the accuracy of these markers alone is often limited, and most previous reports have evaluated the efficacy of each marker individually. We aimed to improve the diagnostic performance of endoscopic remission (ER) of CD by combining these 3 markers.

We tested the diagnostic ability of various combinations of these 3 markers for endoscopic severity in 230 consecutive patients with CD from September 2014 to July 2023. The modified Simple Endoscopic Score for Crohn's disease (mSES-CD) was used to determine endoscopic severity.

Each of the 3 markers was correlated with mSED-CD (LRG: r = 0.69, CRP: r = 0.60, and Fcal: r = 0.67). A combination of 2 of the 3 markers did not increase the diagnostic accuracy of ER. However, by combining all 3 markers, the diagnostic ability for ER was improved in comparison to the diagnostic ability of the 3 individual markers, assuming that ER was obtained if 2 or 3 markers were negative. The sensitivity, specificity, and accuracy were 89%, 83%, and 86%, respectively. Additionally, we established a 2-step method using Fcal values after evaluating the 2 serum markers. This method was most useful for reducing both the patient burden and costs.

The newly established 2-step method allowed for a higher accuracy in the non-invasive diagnosis of ER when the 3 markers were combined.

The disease course of inflammatory bowel disease (IBD) is highly variable; early and precise identification of patients with poor outcomes is crucial. We aimed to classify the long-term disease course of IBD using biochemical markers and evaluate the clinical factors associated with different disease courses.

A latent class mixed model was employed to identify distinct trajectories of C-reactive protein (CRP) and fecal calprotectin (FCP) levels in 256 and 635 patients with Crohn's disease (CD) and ulcerative colitis (UC), respectively, from a tertiary hospital cohort. Multinomial logistic regression was used to evaluate the relationships between various trajectories and clinical variables.

Three trajectories were identified for CD and UC: class 1, early and sustained biochemical remission; class 2, delayed remission; and class 3, prolonged difficulty in achieving remission for > 5 years. For patients with CD, early immunomodulator initiation was associated with a high likelihood of belonging to class 1 in the CRP trajectory analysis, whereas early advanced therapy increased the probability of belonging to class 1 in the FCP trajectory analysis. CRP trajectory analysis showed no significant associations in patients with UC. Younger age at diagnosis and early immunomodulator initiation were associated with higher odds of being in class 2 or 3, whereas current smoking was associated with a high likelihood of being in class 1 in the FCP trajectory analysis.

Early aggressive medical treatment for CD may lead to long-term biochemical remission, whereas no similar association was observed in UC.

Gastrointestinal infections present major challenges to ruminant livestock systems, and gut health is a key constraint on fitness, welfare, and productivity. Fecal biomarkers present opportunities to monitor animal health without using invasive methods, and with greater resolution compared to observational metrics. Here we developed enzyme-linked immunosorbent assays for three potential fecal biomarkers of gut health in domestic ruminants: two immunological (total immunoglobulin [Ig]A and total IgG) and one inflammatory (lactoferrin). We analytically validated the assays, then evaluated whether they could be used as a biomarker of clinically diagnosed gastrointestinal pathologies in cattle (Bos taurus), and finally compared them with helminth fecal egg counts in sheep (Ovis aries). The analytes were detected above the lower limits of detection in cattle, sheep, and goats. Fecal IgA and lactoferrin were higher in cattle with infectious pathologies (strongyles, coccidiosis and symptomatic Johne's disease) compared to healthy controls. Lactoferrin was additionally higher in animals with infectious pathologies compared to noninfectious pathologies, and to asymptomatic Johne's cases. No significant relationships were found with sheep fecal egg counts. These initial findings suggest that fecal IgA and lactoferrin may be useful biomarkers of poor gastrointestinal health in cattle, and that fecal lactoferrin is specific to active inflammation caused by infectious agents. These could be incorporated into the growing suite of noninvasive ecoimmunological tools and used to understand ruminant gut health in a range of species. Applications include improving treatment regimens for gastrointestinal infections, and understanding wildlife physiological responses to infectious challenges.

Purpose: Fecal calprotectin (FC) is a Crohn's disease (CD) biomarker, although the impact of disease duration on its accuracy remains unclear. This study was aimed at investigating the effects of CD disease duration on FC. Methods: In this prospective, single-center, cross-sectional study, we performed 113 endoscopies and biomarker measurements. Endoscopy results were assessed using the simple endoscopic score for Crohn's disease (SES-CD), with an SES-CD ≤ 2 defined as endoscopic remission (ER). Cohort 1 was divided into short-term and long-term disease groups. The associations of the SES-CD with C-reactive protein and FC were analyzed. Results: The correlation coefficient of FC and the SES-CD was 0.670 for all cases. In Cohort 1, the correlation coefficient of FC and the SES-CD was > 0.670 for all subgroups of the short-term disease group (≤ 20 years). The correlation coefficient of FC and CD was < 0.670 for all subgroups of the long-term disease group (> 20 years). In Cohort 2, the correlation coefficients were > 0.670 (0.808) for the 0-4-year disease group and < 0.670 for the 5-14- and 15-40-year disease groups. The receiver-operating characteristic analysis performed to predict ER of all cases resulted in an area under the curve (AUC) of 0.8443, with large AUCs of 0.907, 0.816, and 0.770 observed for the 0-4-, 5-14-, and 15-40-year disease groups, respectively. Conclusions: FC was affected by CD duration, and it may be a useful biomarker of CD, especially in patients with a short disease duration.

Mucosal healing in Crohn's disease (CD) has been established as a crucial target of treatment, leading to long term remission and decrease in complication rates. Endoscopy still serves as the gold standard for assessment, particularly in the small bowel where balloon or capsule enteroscopy is frequently needed. However, these modalities are often unavailable, expensive, and invasive, posing risks to patients. Consequently, the identification of accessible and reliable biomarkers, especially in small intestinal CD, remains a challenge. The study by Ohno et al, published in this issue, further illuminates this field. It confirms the potential role of fecal biomarker leucine-rich α2 glycoprotein (LRG) and validates findings from previous smaller trials. Comparing to other markers LRG showed a much higher predictive value for mucosal healing of the small bowel, making it a useful option for small intestinal CD follow up. In this editorial, we explore the optimal marker of inflammation or mucosal healing in CD, particularly in the small bowel. We provide an overview of available conventional biomarkers and introduce several novel biomarkers, including an update on emerging technologies and innovations.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous inflammation of the colon and rectum. Accurate disease assessment is essential for effective treatment, with endoscopic evaluation, particularly the Mayo Endoscopic Score (MES), serving as a key diagnostic tool. However, MES measurement can be subjective and inconsistent, leading to variability in treatment decisions. Deep learning approaches have shown promise in providing more objective and standardized assessments of UC severity.

This study utilized publicly available endoscopic images of UC patients to analyze and compare the performance of state-of-the-art deep neural networks for automated MES classification. Several state-of-the-art architectures were tested to determine the most effective model for grading disease severity. The F1 score, accuracy, recall, and precision were calculated for all models, and statistical analysis was conducted to verify statistically significant differences between the networks.

VGG19 was found to be the best-performing network, achieving a QWK score of 0.876 and a macro-averaged F1 score of 0.7528 across all classes. However, the performance differences among the top-performing models were very small suggesting that selection should depend on specific deployment requirements.

This study demonstrates that multiple state-of-the-art deep neural network architectures could automate UC severity classification. Simpler architectures were found to achieve competitive results with larger models, challenging the assumption that larger networks necessarily provide better clinical outcomes.

Normalization of high-sensitivity C-reactive protein (hs-CRP) and fecal calprotectin (FCP) are suggested as intermediate treatment targets for Crohn's disease (CD). This analysis evaluates achievement of biomarker normalization and the relationship between improvements in biomarker concentrations and clinical and endoscopic outcomes among patients treated with risankizumab.

This post hoc analysis included patients with moderately to severely active CD and elevated baseline hs-CRP (>5 mg/L) or FCP (>250 µg/g) concentrations from the 12-week ADVANCE and MOTIVATE induction studies, and the 52-week FORTIFY maintenance study. We assessed the proportion of patients achieving biomarker normalization, defined as hs-CRP ≤5 mg/L and FCP ≤250 µg/g, and the association between achieving biomarker normalization and improved clinical and endoscopic outcomes.

Among 748 patients with elevated baseline hs-CRP or FCP concentrations, higher proportions of patients treated with risankizumab vs placebo achieved normalization of hs-CRP (Week 12: placebo, 17.5%; risankizumab 600 mg, 48.5%; Week 52: placebo, 29.5%; risankizumab 180 mg, 45.2%; risankizumab 360 mg, 40.8%) and FCP (Week 12: placebo, 9.1%; risankizumab 600 mg, 26.0%; Week 52: placebo, 28.0%; risankizumab 180 mg, 43.0%; risankizumab 360 mg, 44.0%; nominal p < 0.05 vs placebo for all comparisons). Achievement of both clinical or endoscopic outcomes and improvement of biomarker concentrations occurred at higher rates among patients treated with risankizumab vs placebo, regardless of prior exposure to biologic therapies.

Risankizumab treatment led to sustained normalization of inflammatory biomarkers with improved clinical and endoscopic results.

ADVANCE, NCT03105128; MOTIVATE, NCT03104413; FORTIFY, NCT03105102.

Inflammation is central in inflammatory bowel disease (IBD) pathogenesis. Because of diet's pro- and anti-inflammatory properties, multiple observational studies have explored the link between the dietary inflammatory potential and IBD-related outcomes. We aimed to systematically review the literature and provide a comprehensive overview of the dietary inflammatory potential and its association with the development and progression of IBD.

Literature was searched systematically on the 2nd of May 2024 in PubMed, Web of Science, Scopus, Cochrane Library, and Embase to identify the observational studies that explored the link between the dietary inflammatory potential and IBD-related outcomes. A higher dietary inflammatory potential was defined as the ability of a dietary pattern to promote inflammation in the body. Studies were included only if they quantified this using a dietary index, such as the dietary inflammatory index (DII) and the empirical dietary inflammatory pattern (EDIP). Two authors independently performed study selection and data extraction and assessed the risk of bias using the Newcastle-Ottawa scale.

Fourteen of the 165 identified records met the inclusion criteria. Seven investigated the risk of developing IBD, but with mixed results. Nine investigated the progression of IBD, which indicated that a higher dietary inflammatory potential contributed to higher disease activity and associated symptoms.

The evidence suggested that a higher dietary inflammatory potential worsens the condition of IBD patients, while the link with the risk of developing the disease was less clear. To elucidate this, high-quality intervention studies are needed.

Ulcerative colitis (UC) is a lifelong chronic inflammatory disease that is characterized by the absence of specific markers for diagnosis and prognosis. TPM3 is an integral component of the thin filament, responsible for the structural stability of actin filaments and modulation of cytoskeletal function. This study investigated the regulatory role of TPM3 in UC and its potential mechanisms.

At the clinical level, TPM3 levels were assessed in serum and mucosal tissues of UC and other enteric disease. At the cellular level, the effects of TMP3 overexpressing lentivirus on Caco-2 cell phenotype and the barrier of IL-1β-induced UC model were explored. At the animal level, the effects of TMP3 overexpressing lentivirus on symptoms and colonic damage in a DSS-induced UC model were explored.

TPM3 expression in serum of UC patients was significantly lower than that of other enteric disease, and TPM3 levels in the intestinal mucosa showed a negative correlation with the Mayo score of UC patients. TPM3 overexpression alleviates IL-1β-induced apoptosis and inhibition of invasion and migration in UC model in vitro. In monolayer Caco-2 cells, TPM3 overexpression rescued the IL-1β-induced decrease in transepithelial electrical resistance and tight junction markers (ZO-1 and Occludin) and increase in permeability. In animal experiments, TPM3 overexpression increased body weight and colon length and decreased disease activity index in a DSS-induced UC model. In tissue staining, it alleviated pathological damage and upregulated Occuludin and TPM3 levels in the colon.

TPM3 levels correlated with UC disease course and TPM3 overexpression alleviated symptoms/phenotypes and barrier damage in UC models in vivo and in vitro. TPM3 may serve as a potential novel biomarker for UC diagnosis and prognosis.

Acute severe ulcerative colitis (ASUC) is a life-threatening medical emergency affecting over 20% of patients with ulcerative colitis (UC). Up to 40% of patients are refractory to intravenous corticosteroids (IVCS) and require rescue medical therapy or immediate colectomy. The potent Janus kinase (JAK) inhibitors, upadacitinib and tofacitinib, have proven efficacy in a randomised control trial setting for moderate-to-severe UC, but not ASUC. We describe a case series of sequential rescue therapy with JAK inhibitors following the failure of dose-intensified infliximab in corticosteroid-refractory ASUC. Six adult (>16 years old) patients received sequential rescue therapy with a JAK inhibitor (upadacitinib n = 5, tofacitinib n = 1) following failure of IVCS and dose-intensified infliximab at the Royal Brisbane and Women's Hospital (QLD, Australia) between October 2023 and April 2024. All patients met the Truelove and Witts criteria for ASUC on admission. Data were captured during admission and at 90-days post-discharge. Co-primary outcomes were 90-day colectomy-free survival and inpatient clinical response (<4 non-bloody stools per day) 72 h after JAK-inhibitor initiation. Secondary outcomes included 90-day clinical (PRO-2 score < 1) and biochemical (faecal calprotectin (FCP) < 150 µg/g and C-reactive protein (CRP) < 5 mg/L) corticosteroid-free remission and adverse events. Median CRP on admission was 100 mg/L (interquartile range (IQR) 58-105), median FCP 3400 µg/g (IQR 910-4950) and median Mayo Endoscopic Score 3. Four out of six patients had a clinical response within 72 h of sequential JAK-inhibitor rescue therapy. Two patients underwent emergent inpatient colectomy for refractory disease - one of whom developed post-operative sepsis. Among the four JAK-responders at 90 days, all achieved corticosteroid-free clinical remission and three achieved biochemical remission. No other adverse events were recorded. There is a promising role for JAK inhibitors as sequential rescue therapy following the failure of dose-intensified infliximab in select patients with corticosteroid-refractory ASUC.

Diagnosing and assessing Crohn's disease, which involves only the small bowel, is challenging. This study investigated the clinical value of combining double balloon enteroscopy with endoscopic ultrasound to evaluate this disease.

This single-center retrospective study included patients with Crohn's disease of the small intestine between October 2022 and October 2023. Relevant clinical data were collected. Double balloon enteroscopy and ultrasound endoscopy of the small intestine were performed.

Among the 50 patients, 10, 34, and 6 had mild, moderate, and severe active phase Crohn's disease, respectively. Ten patients scored between 1 and 4 points on the modified partial simple endoscopic score for Crohn's disease (mpSES-CD), 24 scored between 5 and 8 points, and 16 scored more than 8 points. Forty patients had thickening of the intestinal wall (total thickness, 4.14 ± 0.98 mm). Submucosal and intrinsic muscle layer thickening was primarily observed. Ten patients were in remission, and all mucosal-submucosal and submucosal-intrinsic muscle boundaries could be distinguished. Thirty-four patients had moderate-phase Crohn's disease, of whom 26 (76.47%) had distinguishable mucosal-submucosal boundaries, and 28 (82.35%) had distinguishable submucosal-intrinsic muscular boundaries. Of the six patients with severe phase Crohn's disease, four (66.67%) had distinguishable mucosal submucosal boundaries, and two (33.33%) had distinguishable submucosal-intrinsic muscular boundaries.

The mpSES-CD and Harvey-Bradshaw Index correlate well. Endoscopic ultrasound can determine disease severity by measuring each bowel wall layer's thickness and observing the distinction between the layers. This combination of techniques can compensate for the shortcomings in diagnosing the depth of the vertical infiltration of Crohn's disease using white-light endoscopy.

Small bowel Crohn's disease (SBCD) is increasingly treated with biological therapies. Predicting response or remission (RoR) for individual patients is difficult and complicates treatment strategy. We aimed to determine if motility magnetic resonance imaging (mMRI) is superior to CRP and fecal calprotectin (FC) for the prediction of RoR at 1 year in patients commencing biologics for SBCD.

Prospective, multicenter (n = 13) cohort study of patients with active non-stricturing SBCD requiring anti-TNFα or anti-IL-12/23 treatment. We measured mMRI and CRP at baseline and post-induction (visit 2: 12-30 weeks), and FC in a subset. RoR was assessed at 1 year using clinical and structural magnetic resonance enterography parameters. We compared sensitivity, specificity, and area under the receiver operating characteristic curve (ROC-AUC) of changes in mMRI and CRP to predict RoR at 1 year. Secondary outcomes compared mMRI with FC, and prediction of improved quality of life (QoL).

Eighty-six participants completed all assessments. Stable or improved mMRI at visit 2 was more sensitive than normalization of CRP for RoR (mMRI:71.0%, 95%CI 52.0-85.8; CRP:45.2%, 95%CI 27.3-64.0%, P = .008) but less specific (mMRI:30.9%, 95%CI 19.1-44.8; CRP:67.3%, 95%CI 53.3-79.3%, P < .001). There was no significant difference in ROC-AUC (mMRI:0.48; CRP:0.53, P = .65). Similar results were obtained for FC. None of mMRI, CRP, or FC predicted patient QoL at 1 year.

Although improved mMRI is more sensitive than CRP and FC to predict RoR at 1 year, it is less specific. No factor predicted patient QoL. Motility MRI remains a marker of disease activity at given timepoints.

Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration.

Participants with IBD were monitored for 40 to 130 minutes with a proprietary wearable sensor device used to measure C-reactive protein, interleukin-6, and calprotectin. Sensor response using electrochemical impedance spectroscopy and serum samples were measured on the same day. The Mann-Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed.

A total of 33 subjects were enrolled. Expression of calprotectin was significantly elevated in the active cohort compared with the remission cohort in perspiration (P < .05; median = 906.69 ng/mL; active 95% confidence interval [CI], 466.0-1833 ng/mL; remission 95% CI, 328.4-950.8 ng/mL), serum (median = 1860.82 ng/mL; active 95% CI, 1705-2985 ng/mL; remission 95% CI, 870.2-1786 ng/mL), and stool (P < .05; median = 126.74 µg/g; active 95% CI, 77.08-347.1 µg/g; remission 95% CI, 5.038-190.4 µg/g). Expression of CRP in perspiration and serum was comparable between the active and remission cohorts (perspiration: P > .05; median = 970.83 pg/mL; active 95% CI, 908.7-992 pg/mL; remission 95% CI, 903.3-991.9 pg/mL; serum: median = 2.34 µg/mL; active 95% CI, 1.267-4.492 µg/mL; remission 95% CI, 1.648-4.287 µg/mL). Expression of interleukin-6 in perspiration was nonsignificant in the active cohort compared with the remission cohort and was significantly elevated in serum (perspiration: P < .05; median = 2.13 pg/mL; active 95% CI, 2.124-2.44 pg/mL; remission 95% CI, 1.661-2.451 pg/mL; serum: median = 1.15 pg/mL; active 95% CI, 1.549-3.964 pg/mL; remission 95% CI, 0.4301-1.257 pg/mL). Analysis of the linear relationship between perspiration and serum calprotectin (R2 = 0.7195), C-reactive protein (R2 = 0.615), and interleukin-6 (R2 = 0.5411) demonstrated a strong to moderate relationship across mediums.

We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.

Crohn's disease (CD) is a chronic, inflammatory bowel disease with a wide range of presentations, including perianal disease. Presentation is variable, ranging from skin tags to complex fistulas, strictures, and nonhealing wounds. Symptoms of perianal CD can be devastating and may impact quality of life. Optimal management requires coordinated medical and surgical therapy. When possible, conservative treatment of perianal disease should be attempted. However, surgical treatment is often required, and some patients may ultimately require total proctocolectomy with permanent diversion due to the severity of disease. Even with close attention and treatment, disease can be recurrent, and complications of treatment are sometimes worse than the initial presentation. Novel treatments, including use of mesenchymal stem cells and autologous fat grafting, hold some promise, but are not yet widely available. Thorough knowledge of treatment options, careful patient selection, coordination between medical and surgical providers, and setting realistic expectations are important in the successful treatment of difficult perineal CD.

Prior studies indicate that serum calprotectin (SC) and plasma calprotectin (PC) can be used as biomarkers in Crohn's disease (CD). The aim of this study was to investigate the diagnostic accuracy of SC and PC in patients with a clinical suspicion of CD.

This biobank study included patients from a prospective, blinded, multicenter study examining minimally invasive modalities for diagnosing CD. Patients had a standardized work-up including ileocolonoscopy, pan-enteric capsule endoscopy, and blood samples within a 2-week period. Plasma and serum were stored at - 80 °C until further analysis. A routine C-reactive protein (CRP) was measured on the same day. Pan-endoscopy served as reference standard.

126 patients entered the study, and 58 (46.0%) were diagnosed with CD. Patients with CD had a median PC of 0.37 mg/L (IQR 0.20-0.70) compared to 0.29 mg/L (IQR 0.16-0.41) in non-CD patients (p = 0.03). The median SC was 1.09 mg/L (IQR 0.80-1.80) and 0.93 mg/L (IQR 0.66-1.25), respectively (p = 0.01). Receiver operating characteristics curves showed an AUC of 0.63 (CI 0.53-0.73) for SC and 0.61 (CI 0.51-0.71) for PC for detection of CD, which was inferior to that of CRP (AUC = 0.76, CI 0.68-0.85) (p < 0.02). None of the biomarkers reflected the endoscopic severity of CD.

Although levels of PC and SC are elevated in patients with CD, diagnostic accuracies are inferior to CRP. SC and PC are not reliable as stand-alone blood-based biomarkers for diagnosing CD and selecting patients for endoscopy.

An ideal test to evaluate the inflammatory burden in ulcerative colitis is still an unmet need. Fecal calprotectin (FCP) and C-reactive protein (CRP) have significant limitations. Plasma calprotectin (PC) seems to be promising in inflammatory diseases, but its value in IBD is still to be determined. Our aim was to assess whether PC correlates with inflammatory activity in UC.

Prospective single center cohort study. Consecutive patients previously diagnosed with UC undergoing endoscopy were included (June 2021-September 2022). Demographic, clinical, analytical (CRP, PC and FCP), endoscopic and histologic data was collected at the time of colonoscopy. PC was assessed with Gentian Calprotectin Immunoassay and, in a subgroup of patients, also with QUANTA Flash Circulating Calprotectin from INOVA.

Inclusion of 98 patients (60.2% male) with a median age 49 (38-61) years. The extent of colitis was distal in 12 (12.2%), left-sided in 49 (50%), and extensive in 37 (37.8%). Mesalazine was taken by 65 (66.3%) patients, with biologic monotherapy used in 24 (24.5%) and combination therapy in 6 (6.1%). Clinical, endoscopic and histological remission were detected, in 56 (57.1%), 48 (49%) and in 55 (56.1%) patients, respectively. Comparing MES 0/1 vs MES 2/3, a statistically significant difference was found with PC, CRP and FCP. Concerning endoscopic (MES=1) and histological (GS<2) remission, FCP was the only biomarker able to detect these outcomes. PC (Gentian) and PCi (INOVA) were highly correlated with CRP.

PC has low value in distinguishing patients in remission from patients with endoscopic or histologic activity in UC. This essential role must continue be played by FCP.

Inflammatory bowel disease (IBD) is a condition of unknown origin. It does not have a definite cure and its response to various treatments can be evaluated based on symptom-based measures, invasive procedures, or biomarker levels, highlighting the need for an accurate biomarker. Since C-reactive protein (CRP) and fecal calprotectin have their shortcomings, the need for a novel biomarker remains critical. Systematic searches of PubMed, Scopus, Web of Science, and Embase were performed In January 2024. PROSPERO number is CRD42024507383. We assessed the accuracy of leucine-rich alpha-2 glycoprotein (LRG) in identifying disease activity among patients with IBD using a bivariate diagnostic random-effects model. Fourteen studies involving 1794 individuals conducted in Japan were selected for our systematic review. The sensitivity and specificity of LRG levels for detecting disease activity were analyzed in patients with IBD and in two subgroups (ulcerative colitis and Crohn's disease). The synthesized sensitivity and specificity were 75.4% [95% confidence interval (CI), 68.9-80.9%] and 77.3% (95% CI, 69.9-83.2%), respectively, in patients with IBD, 73.1% (95% CI, 62.7-81.5%) and 81.9% (95% CI, 73.9-87.8%), respectively, in patients with CD, and the secondary analysis of the ulcerative colitis subgroup showed a pooled sensitivity and specificity of 72.8 and 59.7%, respectively. Our systematic review and meta-analysis demonstrated that LRG could be useful in detecting IBD activity. It is superior for detecting disease activity, especially in patients with normal CRP levels. The LRG was more accurate in monitoring disease activity in patients with CD than in patients with IBD.

Serum free thiols (SFTs) reflecting oxidative stress appear to correlate with inflammatory bowel disease (IBD) activity. We aimed to evaluate the performance of SFTs concentrations vs endoscopic and histological activity, compare SFTs with established biomarkers, and identify clinical and laboratory parameters independently associated with SFT levels in IBD patients.

Patients with confirmed IBD undergoing routine ileocolonoscopy for activity assessment were prospectively recruited, with serum samples obtained concurrently for SFTs and routine bloods, plus fecal calprotectin and immunochemical tests were collected ±30 days from ileocolonoscopy. Endoscopic activity was assessed via established indices and histological activity graded as inactive/mild/moderate. Receiver-operating characteristic curve analyses were utilized to assess performance of SFTs vs endoscopic activity, and multiple regression analysis was used to identify factors associated with SFT levels.

A total of 141 (80 Crohn's disease, 61 ulcerative colitis) patients were recruited. Median SFTs were significantly lower in moderate vs inactive/mild endoscopic activity (309 µM vs 433/471 µM, respectively; P < .01). There was no significant difference in median SFTs across inactive/mild/moderate histological activity. SFTs achieved higher sensitivity than C-reactive protein in predicting moderate, endoscopically active disease (89% vs 78%; area under the curve, 0.80 each) yet was outperformed by fecal calprotectin (100%; area under the curve, 0.93). Advancing age and increasing albumin levels were independently associated with SFT levels, and thus are possible confounders.

This prospective study has demonstrated the potential of SFTs as a serum biomarker in IBD. It was more sensitive than C-reactive protein, yet less sensitive than fecal biomarkers for prediction of endoscopically active IBD.

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, impose an escalating burden on healthcare systems globally, with a rising prevalence contributing to increased costs. This study explored healthcare utilisation patterns and its drivers amongst IBD patients in an outpatient clinic.

A longitudinal cohort study was conducted at a Dutch academic teaching hospital. IBD patients ( n  = 180) were followed for 1 year and were categorised based on disease activity and consultation frequency. Healthcare utilisation was assessed through consultations and laboratory tests. Patient-reported outcomes and biochemical disease activity were measured, and subsequently the reasons for consultations were analysed.

The frequency of outpatient healthcare utilisation exceeded the recommended IBD care guidelines by two-fold. Comorbidities were the leading reason for consultations (40.4%), followed by remission induction, medication changes and pending test results. Moreover, clinical disease activity, reported problems with self-care, daily activities and pain were predictive of an increase in annual consultations.

This study identified factors influencing healthcare utilisation in IBD outpatients. Personalised care pathways using eHealth technologies have the potential to reduce unnecessary consultations and optimise resource allocation.

Oral formulation is the ideal treatment method for inflammatory bowel disease (IBD) therapy, but the mucosal damage and diarrhea symptoms impede the drug retention around the inflammatory region, severely limiting IBD therapeutic efficacy. To address this, an oral astaxanthin (Ast) precise delivery formulation is developed with the selective Ast anchoring around the inflammatory region by the novel lactoferrin (LF)-responsive flocculation. This formulation also heightens the apparent solubility of Ast with the minimized edible safety risks for the edible raw materials. For in vivo IBD therapy, the precise delivery formulation exhibits remarkable outcomes, including a significant increase in colon length and a 100% survival rate. Furthermore, it is verified that the mechanism of treatment is primarily attributed to the improved immunoregulation, epithelial repair, and gut microbiota remodeling after the LF-responsive flocculation. This effective inflammatory-responsive delivery design is instructive and valuable to develop more precise delivery systems for IBD therapy.

Ulcerative colitis (UC) is an incurable disease represented by relapse and remission. Noninvasive biomarkers are required to predict disease activation. This study aimed to identify noninvasive biomarkers, such as the c-reactive protein-albumin (CRP/ALB) ratio, platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR), that might forecast disease activation in UC.

This retrospective study included 443 participants: 192 patients with active UC, 166 in remission, and 85 healthy controls. Mayo Endoscopic Subscore was employed to assess endoscopic disease activity. Serum CRP, erythrocyte sedimentation rate (ESR), ALB levels, and complete blood count characteristics were documented. Three ratios of inflammation-related indicators were identified as CRP/ALB, PLR, and NLR.

A positive correlation was found between ESR, CRP, neutrophil count, platelet count, levels of CRP/ALB, PLR, NLR, and endoscopic activity. The CRP/ALB ratio demonstrated more efficacy than the NLR and PLR in differentiating the UC patients from the controls (p = 0.007, p = 0.003, respectively) and the active group from the remission group (p < 0.001, p < 0.001, respectively). Regression analysis revealed that the CRP/ALB was significantly able to distinguish active UC from the remission group and the controls (p < 0.001, p < 0.001, respectively).

The CRP/ALB ratio could be useful as an independent predictive biomarker for disease activity in UC.

Crohn's disease (CD) is a chronic inflammatory disorder with periods of exacerbation and remission. We aim to evaluate the systemic immune-inflammation index (SII) as a prognostic biomarker in CD and its utility in predicting disease activity and severity.

This retrospective study analyzed CD patients using the Harvey-Bradshaw index (HBI) for disease stratification and the Simple Endoscopic Score for Crohn's Disease (SES-CD) for post-treatment evaluation. Data analysis was conducted using R software. Serological indices underwent predictive analysis through the receiver operating characteristic (ROC) curve. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression identified independent prognostic factors to construct nomograms. Model validation was performed using the Concordance index (C-index), calibration analysis and decision curve analysis (DCA).

In this study, 254 patients with Crohn's disease (CD) were enrolled, including 171 males and 83 females, with ages ranging from 13 to 74. SII was significantly elevated in active CD (p<0.001), correlating with disease severity (p<0.001). Although SII decreased in patients with mucosal healing (p<0.001), its prognostic accuracy (AUC=0.719) was lower than other biomarkers. However, SII emerged as an independent predictor for CD activity and severity with higher efficacy (AUC=0.774 and 0.807). The CD activity and severity prediction nomograms showed high C-indices (0.8038 and 0.8208), indicating strong predictive performance.

SII is a valuable biomarker for assessing CD severity and monitoring mucosal healing post-treatment. The SII-based nomograms offer a reliable model for evaluating CD progression, aiding in personalized treatment approaches and enhancing clinical decision-making. We recommend randomized controlled trials (RCTs) or studies with larger sample sizes to improve the model.

Inflammatory bowel diseases (IBD) including Crohn's disease (CD) and ulcerative colitis (UC) are chronic, relapsing conditions characterized by dysregulated immune responses and persistent intestinal inflammation. This review aims to examine new potential therapeutic targets in IBD starting from the STRIDE-II statements. Key targets now include clinical remission, endoscopic remission, and biomarker normalization (such as C-reactive protein and fecal calprotectin). Moreover, histologic remission, transmural remission, and in the future molecular targets are emerging as important indicators of sustained disease control. The treatment goals for inflammatory bowel disease are varied: to relieve symptoms, prevent permanent intestinal damage, promote inflammation remission, and minimize complications. Consequently, the therapeutic targets have evolved to become broader and more ambitious. Integrating these advanced therapeutic targets has the potential to redefine IBD management by promoting deeper disease control and improved patient outcomes. Further research is essential to validate these strategies and optimize their clinical implementation.

Stool characteristics may change depending on the endoscopic activity of ulcerative colitis (UC). We developed a deep learning model using stool photographs of patients with UC (DLSUC) to predict endoscopic mucosal inflammation.

This was a prospective multicenter study conducted in 6 tertiary referral hospitals. Patients scheduled to undergo endoscopy for mucosal inflammation monitoring were asked to take photographs of their stool using smartphones within 1 week before the day of endoscopy. DLSUC was developed using 2,161 stool pictures from 306 patients and tested on 1,047 stool images from 126 patients. The UC endoscopic index of severity was used to define endoscopic activity. The performance of DLSUC in endoscopic activity prediction was compared with that of fecal calprotectin (Fcal).

The area under the receiver operating characteristic curve (AUC) of DLSUC for predicting endoscopic activity was 0.801 (95% confidence interval [CI] 0.717-0.873), which was not statistically different from the AUC of Fcal (0.837 [95% CI, 0.767-0.899, DeLong P = 0.458]). When rectal-sparing cases (23/126, 18.2%) were excluded, the AUC of DLSUC increased to 0.849 (95% CI, 0.760-0.919). The accuracy, sensitivity, and specificity of DLSUC in predicting endoscopic activity were 0.746, 0.662, and 0.877 in all patients and 0.845, 0.745, and 0.958 in patients without rectal sparing, respectively. Active patients classified by DLSUC were more likely to experience disease relapse during a median 8-month follow-up (log-rank test, P = 0.002).

DLSUC demonstrated a good discriminating power similar to that of Fcal in predicting endoscopic activity with improved accuracy in patients without rectal sparing. This study implies that stool photographs are a useful monitoring tool for typical UC.

Over the past decades, an increased importance has been given to gastrointestinal (GI) endoscopy in the management of children with inflammatory bowel diseases (IBD), considering that mucosal healing has been recognized as the optimal endpoint in the treat-to-target paradigm. The recent advances in technology and anesthesia have facilitated the comprehensive evaluation of the GI tract. In this review, we will discuss the role of ileocolonoscopy, upper GI endoscopy, and device-assisted enteroscopy in the work-up and management of pediatric Crohn's disease (CD) and ulcerative colitis, with particular attention on non-invasive endoscopic techniques, such as wireless capsule endoscopy. We will also analyze the most commonly used endoscopic scoring systems, including small bowel scoring systems and endoscopic recurrence grading of neo-terminal ileum CD. Moreover, we will focus on the endoscopic management of complications, such as strictures, that commonly require surgery. Lastly, we will discuss cancer surveillance in children with IBD, with particular consideration of the role of high-definition endoscopic equipment and chromoendoscopy in dysplasia detection rates.