Complete Mucosal Healing Research Articles

Rare Epiglottic Granulomatosis: Diagnostic Challenges and Therapeutic Implications.

We report a rare case of epiglottic granulomatosis with polyangiitis (GPA) in a 72-year-old woman presenting with 5 years of progressive dysphagia and dyspnea. Initial laboratory studies revealed leukocytosis (White Blood Cells 14.2 × 10³/µL), eosinophilia (8%), elevated inflammatory markers (C-Reactive Protein 42 mg/L, Erythrocyte Sedimentation Rate 78 mm/hour), and Proteinase 3 Anti-Neutrophil Cytoplasmic Antibody (PR3-ANCA) positivity (65 IU/mL). Laryngoscopy identified supraglottic edema with a right-sided mass, confirmed by Computed Tomography as localized epiglottic thickening without cartilage destruction. Histopathology of the biopsied lesion demonstrated necrotizing granulomas, vasculitis, and multinucleated giant cells, establishing the GPA diagnosis. Treatment with high-dose corticosteroids (1 mg/kg/day prednisone) and rituximab (375 mg/m²/week × 4) induced rapid symptom resolution within 2 weeks. Follow-up laryngoscopy at 1 month showed complete mucosal healing, and the patient remains recurrence-free during 18 month surveillance with maintenance immunosuppression (5 mg/day prednisone). This case highlights 3 critical insights: (1) isolated epiglottic GPA, although rare, should be considered in chronic upper airway obstruction unresponsive to conventional therapy; (2) PR3-ANCA serology and histopathology are indispensable for diagnosis; and (3) rituximab-based regimens achieve excellent outcomes in laryngeal GPA, but prolonged monitoring is essential given relapse risks. Our findings reinforce the need for multidisciplinary management of otolaryngologic GPA manifestations.

Histological healing in IBD: Ready for prime time?

Histological healing in IBD: Ready for prime time?

Role of E-Cadherin in Intestinal Stem Cells during Epithelial Repair Following Colitis Damage

Mucosal injury is critical for the pathogenesis of inflammatory bowel disease (IBD) and can develop into chronic inflammation. Current pharmaceutical therapeutic options for addressing IBD-associated inflammation are primarily focused on reducing inflammation. Treatment has not yet expanded to address the mucosal healing that is associated with a better prognosis and a reduced risk of surgery. Intestinal stem cells (ISCs) play a crucial role in regenerating epithelial tissue, which is essential for the complete healing of the mucosa. Although E-cadherin is crucial in various epithelial cells and cancers, research into its role in ISCs during regeneration after injury is limited. Therefore, our goal is to investigate E-cadherin's function in ISCs as a potential therapeutic target to promote mucosal healing. In this study, we hypothesized that the knockout of E-cadherin in Lgr5+ ISCs promotes cellular proliferation during regeneration, following colitis damage. The mice for tamoxifen-induced E-cadherin knockout in Lgr5+ ISCs were generated by crossbreeding Lgr5-CreERT and Cdh1fl/fl mice. Following the peak of dextran sodium sulfate (DSS)-induced colitis symptoms, E-cadherin was homologous or heterogeneous knocked out in ISCs through tamoxifen injection (100 mg/kg, three consecutive days) and compared with wild-type. The body weight, disease activity index (DAI), colon length, and histologic analyses were performed to evaluate the severity of injury and repair. No significant differences were observed in body weight, DAI, or colon length across the groups. However, both E-cadherin heterogeneous and homologous knockout during regeneration led to a marked reduction in epithelization. Simultaneously, the regenerative area was significantly larger in the knockout mice compared to the wild type. Additionally, immunofluorescence microscopy revealed an increase in Ki-67+ cells alongside decreased E-cadherin in the regenerative zone. Our findings suggest that E-cadherin knockout in ISCs during regeneration results in increased cell proliferation but does not lead to migration and differentiation, which are crucial to complete mucosal healing. Thus, upcoming research on the transient downregulation of E-cadherin in ISCs during early regeneration seeks to identify potential therapeutic targets for enhancing intestinal regeneration for patients with IBDs. Maryland Stem Cell Research Fund This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Complete mucosal healing prevents stricture progression after endoscopic balloon dilation in Crohn's disease.

Endoscopic balloon dilation (EBD) is an effective treatment for intestinal strictures in Crohn's disease (CD). However, restenosis often occurs and requires repeat EBD or surgery. Previous studies have seldom examined restenosis with respect to stricture diameter, leaving the factors contributing to post-EBD restenosis unclear. Our retrospective study indicated that complete mucosal healing significantly reduces restenosis after EBD in CD-related small intestinal strictures. This prospective study aimed to validate these findings by accurately measuring stricture diameters in patients with CD. We conducted a single-center prospective study of patients with CD and small intestinal strictures. The patients underwent an EBD session between June 2022 and December 2023. Stricture diameters were measured using a calibrated small-caliber-tip transparent hood. Multivariate analysis was performed to identify factors influencing stricture progression. This study included 41 patients (33 men). The number of strictures detected between sessions increased from 159 to 170. The average diameter of all strictures and the narrowest stricture per patient showed slight increases. However, 73% of patients experienced stricture progression. The presence of ulcers between sessions was identified as a significant risk factor for stricture progression (odds ratio 7.59, p=0.031). Patients achieving complete mucosal healing demonstrated a significant increase in the narrowest stricture diameter (+1.5mm, p=0.00089). Complete mucosal healing is crucial for preventing stricture progression after EBD in patients with CD-related small intestinal strictures.

Cumulative experience meets modern science: Remarkable effects of TongXieYaoFang formula on facilitating intestinal mucosal healing and secretory function.

Cumulative experience meets modern science: Remarkable effects of TongXieYaoFang formula on facilitating intestinal mucosal healing and secretory function.

P0250 Circulating blood matrix metalloproteinase (MMP)-10 and 12 can accurately predict mucosal healing in Inflammatory Bowel Disease (IBD) in a multi-centred prospective longitudinal cohort study (2020-2024)

Abstract Background Complete mucosal healing (CMH) is a key prognostic indicator of long-term remission in IBD. There are however, no early biomarkers of mucosal healing to allow for deeper biological studies and potential for treatment stratification. Here, we prospectively investigate the clinical utility of a novel custom-designed 21-proteomic PEA-Olink* Flex panel in blood to identify proteins with the propensity for mucosal healing. Methods In the multi-centre, prospective, longitudinal IBD study (www.musicstudy.uk), we used a custom selected 21-protein marker panel (based on roles in resolution of inflammation; Olink Flex [Figure 1]) in blood plasma (1µl), collected at timepoints T1, T2 and T3 (months 0, +3 and +6 respectively). This uses a proximity extension assay, allowing for highly specific and sensitive absolute protein quantification. All subjects had prospective endoscopic assessment T1→T2→T3 (follow-up mean 5.2 months). CMH was defined by a Mayo score of 0 in UC and SES-CD of 0 in CD. Statistical analysis was performed using R, adjusting for age and gender. A machine learning (ML) model using SHAP (SHapley Additive exPlanations) analysis was then applied to the data. Results A total of 239 blood samples from 81 IBD patients were analysed (median 37 years, 59% male; 37% UC) – all with paired endoscopic mucosal healing data. 27/81 patients (33%) achieved CMH at follow-up. Of 21 blood proteins, multivariate analysis showed MMP10 and MMP12 concentrations to be significantly associated with CMH at timepoint 3 (FDR p=0.02 for both) with AUC 0.68 and 0.64 respectively; comparable to faecal calprotectin (AUC 0.69) in predicting mucosal healing. Both proteins were significantly lower in the UC CMH group vs no CMH (p=0.01 respectively), with only MMP10 (p=0.02) being associated with CMH in CD alone. In UC, endoscopic severity score UCEIS at follow-up endoscopy, correlated strongly with MMP10 and MMP12 levels combined (p<0.001, r=0.62). In UC, ΔMMP10 levels over time were highly significant in predicting improvement in endoscopic scores; but not CD. Random Forest ML model (incorporating 80 clinical variables including drug treatment) to the 21 proteins from T1→T2→T3 predicted CMH with an AUC of 0.69. SHAP analysis identified MMP12 in the top 3 variables impacting the model’s prediction. Conclusion Our study identifies tissue remodelling proteins MMP-10 and 12 as biomarkers for CMH on par with faecal calprotectin. The ΔMMP10 expression in UC shows dynamic change, predicting mucosal healing with more significance over time. MMP-10 and 12 are involved in the tissue degradation and remodelling process of inflamed mucosa which may explain the reduction in blood levels as mucosal inflammation resolves. Further large-scale validation work is planned. References *PEA-Olink: Proximity Extension Assay

P1317 Oral microbiota is linked to the propensity for mucosal healing: A prospective oral-gut-stool microbiome analysis in IBD

Abstract Background The oral cavity is the second most complex human microbial niche and is the conduit through which initial gut microbial colonisation occurs during early life. While the gut microbiome is implicated in the pathogenesis of inflammatory bowel disease (IBD), the role of the oral microbiome remains underexplored. We aimed to characterise the oral-gut microbiome in IBD and its association with disease activity and complete mucosal healing (CMH), a key prognostic marker for long-term remission. Methods All patients with Crohn’s disease (CD) and Ulcerative Colitis (UC) were prospectively recruited via www.musicstudy.uk. We conducted a 3-stage experimental approach. (1) We profiled the oral microbiota in IBD vs healthy controls (HC) (CD = 34, UC = 24 and HC = 25). (2) We carried out trans-anatomical oral-ileal-stool microbial source tracking1 within the same patients at a single time-point (CD = 23; inflamed vs. non-inflamed mucosal samples), alongside longitudinal oral-stool sampling (CD = 32, UC = 17). (3) Our machine learning (ML) modelling integrated stool microbiota taxonomic profiles (CD = 53, UC = 11; sampled at 0, 3, and 6 months) with ~80 clinical variables to classify CMH using random forest, AdaBoost, XGBoost, logistic regression, and neural networks. Results 16S rRNA sequencing revealed significant divergence between IBD and HC oral microbiota (PCoA, Bray-Curtis; PERMANOVA, p=0.003). Active disease also differed from remission (PCoA, Bray-Curtis; PERMANOVA, p=0.01). Higher oral Veillonella abundances were associated with IBD; bacteria commonly enriched in the IBD gut. We determined within patient oral microbiota abundances in gut samples and found no difference between inflamed ileal mucosa compared to non-inflamed (p=0.52). Patients who did not achieve CMH exhibited significantly higher oral microbiota abundances in stool compared to those with CMH (β = 0.046, p=0.022, linear mixed-effects model). Oral microbiota abundances in stool correlated with clinical markers of disease activity, calprotectin (r = 0.23, p=0.009) and albumin (r = –0.28, p=0.002; Benjamini-Hochberg adjusted). ML models integrating stool microbiota taxonomic profiles and clinical variables outperformed clinical markers alone in predicting CMH (AUC: 0.79 vs. 0.55), indicating that the inclusion of stool microbiota features could be valuable in predicting CMH in the clinical setting. Conclusion Our data show distinct oral microbiota taxonomic profiles in IBD and active disease, with higher oral microbiota abundances in stool associated with lack of CMH. These findings highlight the oral microbiome as a potential upstream regulator of microbial-immune crosstalk from the site of IBD-inflammation.

DOP067 Selective JAK1 blockade with Upadacitinib is effective in immune checkpoint inhibitor-induced colitis

Abstract Background Immune checkpoint inhibitors (CPI) have transformed cancer outcomes, but frequently trigger autoimmune- like events, including life-threatening colitis. Current immunosuppressive treatments for CPI- colitis (CPI-c) incur significant side effects and may compromise CPI efficacy, highlighting the need for new therapies. Methods RNA sequencing was performed on colonic biopsies from patients with CPI-c (n=12), CPI (no colitis, n=6), healthy controls (n=13), and UC (n=12). Gene expression, pathway level (GSEA) and cellular composition were analysed. Cell-cell communication were analysed using a single-cell RNA sequencing reposited dataset. Colonic organoids from CPI-c and controls were cultured and treated with IFNg ± JAK1-STAT inhibition with Upadacitinib . The impact of JAK1 blockade was evaluated in vivo using pre-clinical models of CPI-c1. Colonic leukocytes were analysed by flow cytometry. Clinical and endoscopic outcomes were defined in five patients with treatment-refractory CPI-c, following treatment with Upadacitinib 45mg for 8 weeks. Results Gene expression profiling of colonic biopsies highlighted overactivity of the JAK1-dependent cytokine IFNg in CPI-c. IFNg responsive transcripts, including CXCL9, CXCL10, IDO1, GZMB and STAT1, were among the most upregulated transcripts, with IFNg signalling identified as the top enriched pathway. Cellular deconvolution revealed enrichment of TH1 and CD8+ memory cells. Cell-cell communication analysis indicated distinct dialogue mediated by IFNg between T-cell subsets in CPI-c, including TH17+PD1+ and epithelial cells, and inflammatory enterocytes. Colonic organoids from CPI-c patients retained high baseline expression of IFNg-responsive transcripts, and significantly over-expressed these following ex vivo stimulation with IFNg, which was corroborated at protein level. Upadacitinib treatment of stimulated organoids reversed these changes. In vivo administration of Upadacitinib significantly reduced pathological features and severity of CPI-c in preclinical models of disease. Encouraged by these findings, we treated 5 patients with severe, treatment refractory CPI-c with Upadacitinib. All achieved rapidly resolution of disease with complete mucosal healing, no adverse events, and favourable 9-month cancer outcomes were sustained. Conclusion IFNg signalling was highly upregulated in CPI-colitis patients, which was recapitulated in a novel CPI-c derived colonic organoid model and in vivo models of disease. Upadacitinib improved organoid morphology, reduced IFNg targets, and ameliorated CPI-c in mice. Moreover, Upadacitinib rapidly rescued treatment refractory patients highlighting its potential as a promising therapeutic approach in patients with severe disease.

P0323 Serum leucine-rich α2-glycoprotein (LRG) and Monocyte chemoattractant protein-1 (MCP-1) as Novel Biomarkers for Predicting Vedolizumab Response in Ulcerative Colitis Patients

Abstract Background Close monitoring of disease activity is essential for the therapeutic management of inflammatory bowel disease. A minimally invasive and reliable serum biomarker is desirable, but its reliability and validity have not yet been fully evaluated. The purpose of this study (UMIN000043185) was to investigate the utility of leucine-rich α-2-glycoprotein (LRG) in the management of vedolizumab therapy in patients with ulcerative colitis (UC), and to identify mucosal signatures and surrogate biomarkers by using serum cytokine and mucosal transcriptome analysis. Methods Serum LRG, C-reactive protein (CRP), serum Mucosal Vascular Addressin Cell Adhesion Molecule 1(MadCAM1), serum vedolizumab levels, 19 serum cytokines, and fecal calprotectin (fCal) were measured over 54 weeks (week 0, 2, 6, 14, 30, and 54) (n=21). Clinical remission (Mayo score <= 2, all subscore < = 1) and mucosal healing (Mayo endoscopic subscore <= 1) at week 14 were compared between the clinical remission (CR) group (n=11) and non-clinical remission (non-CR) group (n=10), and between the mucosal healing (MH) group (n=14) and non-mucosal healing (non-MH) group (n=7). Differentially expressed gene (DEG) extraction was performed by stratifying data at week 0 and comparing two groups: CR (n=10) and non-CR (n=3), and complete MH (Mayo endoscopic subscore = 0) (n=8) and non-complete MH (n=6) at week 14. Results Serum LRG concentrations were significantly lower in CR group compared to the non-CR group at week 0 (19.0 vs. 29.0 ug/mL, p=0.027) and week 6 (13.4 vs. 19.6 ug/mL, p=0.034) and significantly lower in MH group compared to the non-MH group at week 6 (13.7 vs. 21.6 ug/mL, p=0.033). In contrast, there were no significant differences in serum CRP and fecal calprotectin levels at any time point for either CR or MH. Serum MCP-1 levels showed significant differences between CR and non-CR at week 0 (609.0 vs 403.4 pg/mL, p=0.0018), between MH and non-MH at week 0 (587.2 vs 358.9 pg/mL, p<0. 001), week 6 (606.9 vs 451.6 pg/mL, p=0.015). DEGs extracted from colon tissue included LRG1 and LRG-related cytokines, MCP-1, reflecting the effect of vedolizumab treatment. Conclusion Both serum LRG (lower in CR/ MH group) and serum MCP-1 (higher in CR/MH group) were suggested to be promising predictive biomarkers of vedolizumab treatment response in patients with UC. Further studies are needed to assess their reliability and validity as indicators of treatment effectiveness.

P0342 Quantitative faecal immunochemical test (qFIT) is comparable to calprotectin as a biomarker of IBD: Prospective longitudinal analysis of disease activity and endoscopic mucosal healing

Abstract Background Quantitative faecal immunochemical test (qFIT) to detect stool haemoglobin is used for colorectal cancer screening at a population level in UK (& Europe) with high patient acceptability due to its ease of use and relative low cost . We evaluate the clinical utility of qFIT with faecal calprotectin (fCal) in IBD. Methods UC and CD patients from the prospective, multi-centre longitudinal MUSIC study (2020-2024; www.musicstudy.uk) were included. qFIT and fCal samples were collected every three months at five time points. qFIT analysis was conducted using the HM-JACKarc automated analyser. Blinded qFIT results were compared with physician global assessment, clinical indices (HBI, SCCAI)*, and endoscopic findings. All patients had active disease at baseline, with a repeat colonoscopy at timepoint 3 to assess for complete mucosal healing (CMH), defined as Mayo-score or SES-CD of 0 in UC and CD respectively. Results 357 qFIT results were analysed from 124 patients (58 colonic CD/ 66 UC). qFIT was significantly higher in active disease compared to remission (n=227 vs. 130; 100µgHb/g vs 2.5 µgHb/g; p<0.001). The ability of qFIT to predict active disease was higher in those with UC than colonic CD AUC 0.77 and 0.69 respectively (in 179 UC /178 CD samples). Optimal threshold for predicting remission was <14µgHb/g, with a sensitivity of 0.73, specificity of 0.66. 27 qFIT results from ileal CD patients showed no significant difference between active disease and remission (p=0.2). 339 qFIT results had paired FCal results. The ability of fCal to predict active disease was higher in UC than colonic CD with AUC of 0.82 and 0.77 respectively. For both IBD types, the AUC was 0.81 [Figure 1]. The optimal fCal level was 240 µg/g for remission, with a sensitivity of 0.76 and specificity of 0.72. Combining qFIT and fCal improved prediction of remission to an AUC of 0.82. qFIT performed better than fCal at predicting mucosal inflammation with an AUC 0.74 vs. 0.67 respectively. In 76 UC patients, Mayo endoscopy scores were paired with mean qFIT levels, showing a correlation: score 0 = 32 µgHb/g, score 1 = 181 µgHb/g, score 2 = 217 µgHb/g, and score 3 = 295 µgHb/g (one-way ANOVA, p = <0.001). 20 patients (from 52) achieving CMH, showed significant reduction in qFIT using paired T-test (107 vs 37 µgHb/g, p=0.026). In the 32 patients with ongoing inflammation, qFIT remained high (213 vs. 170 µgHb/g, p=0.23). Conclusion qFIT is comparable to fCal as a biomarker of IBD activity. With its superior patient acceptability and intrinsic test qualities, it should be considered as routine clinical test in IBD. Further large scale validation is warranted to establish its clinical utility. References *AUC – Area Under Curve **HBI-Harvey Bradshaw Index ***SCCAI – Simple Colitis Activity Index

P0488 The course of Crohn’s Disease in the Biologics Era: an in depth Single-Center Tertiary Cohort Study in Belgium

Abstract Background Since 1999, Biologics have become a cornerstone in the management of Crohn’s Disease (CD), enabling complete mucosal healing in a significant proportion of patients, with measurable changes in major outcomes in large phase III/IV clinical trials. This holds true particularly when patients were exposed early at diagnosis to biologics, as reported in the recent PROFILE study. However, their real-world impact on the long-term course of the disease remains uncertain. This retrospective study aims to characterize the natural history of CD before and during the biologic era, in a single tertiary center in Belgium. Methods Based on inclusion criteria, 516 CD patients were included and stratified in two subpopulations, according to the date of CD diagnosis (before or after 1999). All events were recorded from date of diagnosis to maximum follow-up (FU), to achieve high granularity, from disease characteristics to treatment adaptations. Statistical analyses were performed using Prism. Results Among 516 CD patients included, 87 and 429 were diagnosed before and after 1999, respectively. There was no significant difference in demographics or disease characteristics at diagnosis. Patients diagnosed after 1999 were exposed to biologics for a larger portion of their FU compared to those diagnosed before 1999 [51% vs 11%, p<0.0001]. At maximum FU, more patients diagnosed before 1999 had progressed to B2/B3 phenotypes (69% vs 39%, p<0.0001), reflecting their longer disease duration compared to patients diagnosed after 1999 (Median FU 27 years [22-30] vs 12 years [6-15], p<0.0001). Indeed, 10 years after CD diagnosis, disease progression to B2/B3 phenotypes was similar in both groups (27% vs 23%, p=0.6), (Figure 1a). Changes in phenotype were diagnosed sooner in patients diagnosed after 1999 compared to those diagnosed before 1999 (Median 4.8 years [1.8-9.9] vs 12.3 years [6-16.8], p<0.0001] (Figure 1b). They were also operated sooner than patients diagnosed before 1999 (Median 5.9 years [2.1-10.2] vs 12.5 years [6.6-18.2], p<0.0001] (Figure 1c). Conclusion The proportion of patients progressing to a B2/B3 phenotype at 10 years of disease course is similar for CD patients diagnosed before and during the Biological Era. The detection of complications occured earlier in patients diagnosed after 1999, which suggests a shift toward more proactive monitoring since the advent of biologics. Based on these findings, it remains uncertain whether biological therapies have significantly altered the course of the disease and phenotype progression in CD patients. However, while these results are based on objective outcomes, they do not fully capture the impact of biological treatments on patients quality of life and disease burden.

Budesonide Induces Favourable Histologic and Symptomatic Recovery in Patients with Non-responsive and Refractory Coeliac Disease When Given in an Open Capsule Format

IntroductionNon-responsive coeliac disease (NRCD), where symptoms and enteropathy persist despite a prolonged gluten-free diet (GFD), is common. Refractory coeliac disease (RCD), characterised by malabsorption and extensive enteropathy, is rare but serious. In both, treatment options are limited. Topical budesonide may help and an open capsule format promoting proximal small intestinal delivery may be advantageous.AimTo describe the effect of budesonide and its presentation on mucosal healing, symptoms, and tolerability in NRCD and RCD.MethodsA retrospective cohort study of NRCD and RCD patients who received budesonide for enteropathy despite a strict GFD for over 12 months. Primary outcome was improvement in histology. Symptoms and adverse treatment effects were recorded.Results50 patients with NRCD (n = 14; 86% F), RCD type 1 (n = 30; 60% F), and RCD type 2 (n = 6 based on aberrant duodenal T cells; 33% F) were identified. Common RCD symptoms were diarrhoea (68%), fatigue (40%), and weight loss (34%). 16 received closed capsule budesonide (CCB) 9 mg OD and 35 open capsule budesonide (OCB) 3 mg 3 times a day. Complete and partial mucosal healing was significantly higher after OCB compared to CCB (p < 0.001, Mann–Whitney U test). Symptom improvement was also significantly higher after OCB compared to CCB (p = 0.002, Mann–Whitney U test). Side effects were mild and self-limiting and were reported in 25% of both cohorts.ConclusionOCB was well tolerated and associated with improvements in enteropathy (83%) and symptoms (90%) in NRCD and RCD. Our findings support OCB as the preferred 1st-line therapy for NRCD and RCD type 1.

Could MRONJ Be Related to Osimertinib Monotherapy in Lung Cancer Patients after Denosumab Suspension?

Medication-related osteonecrosis of the jaws is the most frequent complication in patients treated or in therapy with antiresorptive/antiangiogenetic drugs. The list of medications possibly related to MRONJ onset is constantly growing; we aimed to report on a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (Osimertinib) as possibly responsible for bilateral maxillary necrosis onset in the herein-described case. In June 2023, an oncologic patient with two different maxillary bone exposures was referred to our attention. His medical history revealed a two-year Denosumab regimen along with Osimertinib, the latter not suspended before teeth extractions. The clinicians performed a sequestrum removal and bone debridement after three cycles of antibiotic therapy. Histologic examinations confirmed the clinical diagnosis of MRONJ excluding a metastatic occurrence, while complete mucosal healing was achieved after 15 days. The patient suspended Denosumab for more than six months before teeth extraction for MRONJ prevention; hence, failure to discontinue Osimertinib led us to consider it a possible etiological factor. From a literature analysis, only one case has already been published reporting a possible Osimertinib-related occurrence of MRONJ in lung cancer patients. Our case is a further report that could be intended as an alert both for oncologists and dentists to share decisions about the oral management of such patients together, also informing them about this possible risk. Also, this report could trigger in the scientific community the necessity to evaluate further guidelines for similar doubtful cases in which the drug interaction, the mono-suspension, and the possible removable prosthesis-related additional trauma should be considered causes or con-causes.

USEFULLNESS OF SERUM LEUCINE-RICH ALPHA2-GLYCOPROTEIN AND FECAL CALPROTECTIN ASSURROGATE MARKERS IN ULCERATIVE COLITIS

Abstract BACKGROUND AND AIM Serum Leucine-rich alpha-2 glycoprotein (LRG) was identified as a novel biomarker for rheumatoid arthritis and IBD by using a proteomics approach. Several studies have suggested that serum LRG levels and fecal calprotectin (fCal) were correlated with clinical activities in patients with ulcerative colitis (UC). We compared utility of these biomarkers for monitoring disease activity in UC. METHODS A single-center observational study was conducted at Kyushu University Hospital. A total of 101 patients who underwent colonoscopy during the period from February to December 2021 were enrolled. The associations between endoscopic and histological activity and biomarkers were investigated. Endoscopic activity was defined as Mayo endoscopic score (MES) of 1 or less for mucosal healing and 0 for complete mucosal healing. For histological activity (n=90), Geboes score of 2 or less was defined as histological remission. RESULTS Subjects ranged in age from 16 to 80 years (35 males and 66 females). There were 63 cases of total colitistype, 32 cases of left-sided colitis type, and 6 cases of proctitis type. The MES at enrollment were as follows: MES 0 in 41 cases, MES 1 in 33 cases, MES 2 in 19 cases, and MES 3 in 8 cases. In comparison between the mucosal healing and non-mucosal healing groups, LRG was significantly lower in the mucosal healing group (p&amp;lt;0.0001). The correlation coefficient of LRG with MES was r=0.614 (p&amp;lt;0.0001), which was higher than that of fCal, r=0.414 (p&amp;lt;0.0001). In ROC analysis with mucosal healing as the outcome, the AUC and cut-off value of LRG were 0.781 and 17.9 μg/ml, respectively, and for fCal were 0.850 and 396 μg/g, respectively. In the ROC analysis with complete mucosal healing as the outcome, the AUC for LRG was 0.690, which was lower than the AUC of 0.846 for fCal . When compared by histological remission, LRG was lower in the histological remission group (p&amp;lt;0.001). In the ROC analysis with histological remission as the outcome, the AUC for LRG was 0.722 (cutoff value 14.2 μg/ml) and for fCal was 0.837 (cutoff value 119 μg/g). CONCLUSION Both LRG and fCal are valuable biomarkers reflecting disease activity in UC.

P366 Risk factors and outcomes of chronic antibiotic-refractory pouchitis in Korean ulcerative colitis patients: a single center retrospective study

Abstract Background Chronic inflammation of the pouch after total proctocolectomy with ileal pouch-anal anastomosis (IPAA) remains a morbid complication in ulcerative colitis (UC). The goal of this study was to investigate risk factors and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with UC. Methods This was a single center retrospective study on patients with UC who underwent total proctocolectomy with IPAA at Asan Medical Center in Korea between January 1987 and December 2022. CARP was defined as failure to respond to a 4-week course of a single antibiotic, needing more than 4 weeks of therapy with 5-aminosalicylates, steroids, immunomodulators or biologics/small molecules, while chronic antibiotic-dependent pouchitis (CADP) was defined as more than 3 episodes of pouchitis per year or persistent symptoms requiring long-term antibiotics to maintain disease remission. Primary outcomes were endoscopic remission defined as complete mucosal healing of chronic pouchitis and pouch failure defined as the requirement of diverting loop ileostomy or pouch excision. Univariable and multivariable logistic regression analysis were used to identify risk factors of CARP. Results A total of 251 patients were included and 232 were analyzed (Male, 57.3%; Current smoker, 13.4%; Median age at surgery, 44 years; Disease duration at surgery, 4 years; Previous exposure to biologics/small molecules, 23.7%; Extra-intestinal manifestations, 8.2%; Preoperative cytomegalovirus infection, 19.4%). The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). The median time from surgery to chronic pouchitis was 48 months (interquartile range 23.5–100.0). Among 74 patients (31.9%) with chronic pouchitis, 31 patients (13.4%) were CARP and 43 patients (18.5%) were CADP. The most frequent endoscopic phenotype according to Chicago classification was focal inflammation of the pouch in all groups (chronic pouchitis, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to have concomitant probiotics compared with CADP (29.0% vs 72.1%; p&amp;lt;0.01). Endoscopic remission rate in chronic pouchitis, CARP, and CADP were 14.9% (11/74), 9.7% (3/31), and 18.6% (8/43), respectively (Table 1). Pouch failure rate in chronic pouchitis, CARP, and CADP were 13.5% (10/74), 16.1% (5/31), and 11.6% (5/43), respectively (Table 1). In a multivariable analysis, current smoking status was positively associated with CARP development (OR: 3.56; 95% confidence interval 1.33–9.52; p=0.01). Conclusion Current smoker with UC who underwent IPAA had a higher risk of CARP. Concomitant use of probiotics was less likely to be associated with developing CARP.

Histologic features and predicting prognosis in ulcerative colitis patients with mild endoscopic activity.

We aimed to evaluate the histologic features predictive of prognosis and correlate them with endoscopic findings in patients with ulcerative colitis (UC) having complete or partial mucosal healing (MH). We prospectively collected and reviewed data from patients with UC who underwent colonoscopy or sigmoidoscopy with biopsy. Complete and partial MH were defined as Mayo endoscopic subscores (MESs) of 0 and 1, respectively. Histologic variables, including the Nancy index (NI), predicting disease progression (defined as the need for medication upgrade or hospitalization/surgery), were evaluated and correlated with endoscopic findings. Overall, 441 biopsy specimens were collected from 194 patients. The average follow-up duration was 14.7 ± 7.4 months. There were 49 (25.3%) and 68 (35.1%) patients with MESs of 0 and 1, respectively. Disease progression occurred only in patients with an MES of 1. NI ≥ 3 was significantly correlated with disease progression during follow-up. Mucosal friability on endoscopy was significantly correlated with NI ≥ 3 (61.1% in NI < 3 vs. 88.0% in NI ≥ 3; p = 0.013). Histological activity can help predict the prognosis of patients with UC with mild endoscopic activity. Mucosal friability observed on endoscopy may reflect a more severe histological status, which can be a risk factor for disease progression.

Autologous stem cell transplantation with low-dose cyclophosphamide to improve mucosal healing in adults with refractory Crohn’s disease: the ASTIClite RCT

Some text in this abstract has been reproduced from Lindsay J, Din S, Hawkey C, Hind D, Irving P, Lobo A, et al. OFR-9 An RCT of autologous stem-cell transplantation in treatment refractory Crohn’s disease (low-intensity therapy evaluation): ASTIClite. Gut 2021;70(Suppl. 4):A4. Background Treatment-refractory Crohn’s disease is characterised by chronic symptoms, poor quality of life and high costs to the NHS, and through days of work lost by patients. A previous trial of autologous haematopoietic stem cell transplant (HSCT) failed its end point of medication-free clinical remission for 3 months with no evidence of disease activity, and reported high toxicity. Subsequent studies suggest that HSCT achieves complete mucosal healing in 50% of patients, and that toxicity likely relates to the cyclophosphamide dose. Objectives The primary objective was to assess the efficacy of HSCTlite (HSCT with low-dose cyclophosphamide) compared with standard care for inducing regression of intestinal ulceration in patients with refractory Crohn’s disease at week 48. Secondary objectives included the assessment of disease activity, quality of life and regimen safety. Mechanistic objectives included immune reconstitution after HSCTlite. Design Two-arm, parallel-group randomised controlled trial with a 2 : 1 (intervention : control) allocation ratio. Setting Nine NHS trusts (eight trusts were recruitment sites; one trust was a treatment-only site). Participants Adults with treatment-refractory Crohn’s disease, for whom surgery was inappropriate or who had declined surgery. Interventions The intervention treatment was HSCTlite using cyclophosphamide, and the control was any current available treatment for Crohn’s disease, apart from stem cell transplantation. Main outcomes The primary outcome was treatment success at week 48 [mucosal healing (Simple Endoscopic Score for Crohn’s Disease ulcer subscore of 0) without surgery or death], assessed by central readers blinded to allocation and timing of assessment. Key secondary outcomes were clinical remission, Simple Endoscopic Score for Crohn’s Disease scores at week 48, change in Crohn’s Disease Activity Index scores and safety. Results The trial was halted owing to Suspected unexpected serious adverse events that took place after randomising 23 patients (HSCTlite arm, n = 13; usual-care arm, n = 10). Ten out of the 13 patients randomised to the HSCTlite arm received the intervention and nine (one death) reached the 48-week follow-up. In the usual-care arm 9 out of the 10 patients randomised reached the 48-week follow-up (one ineligible). The primary outcome was available for 7 out of 10 HSCTlite patients (including the patient who died) and six out of nine usual-care patients. Absence of endoscopic ulceration without surgery or death was reported in three out of seven (43%) HSCTlite patients, compared with zero out of six (0%) usual-care patients. Centrally read Simple Endoscopic Score for Crohn’s Disease scores [mean (standard deviation)] were 10.8 (6.3) and 10.0 (6.1) at baseline, compared with 2.8 (2.9) and 18.7 (9.1) at week 48, in the HSCT and usual-care arms, respectively. Clinical remission (Crohn’s Disease Activity Index scores of &lt; 150) occurred in 57% and 17% of patients in the HSCTlite and usual-care arms, respectively, at week 48. Serious adverse events were more frequent in the HSCTlite arm [38 in 13 (100%) patients] than in the usual-care arm [16 in 4 (40%) patients]. Nine suspected unexpected serious adverse reactions were reported in six HSCTlite patients, including three cases of delayed renal failure due to proven thrombotic microangiopathy. Two HSCTlite patients died. Conclusions Within the limitations of reduced patient recruitment and numbers of patients assessed, HSCTlite meaningfully reduced endoscopic disease activity, with three patients experiencing resolution of ulceration. Suspected unexpected serious adverse reactions, particularly relating to thrombotic microangiopathy, make this regimen unsuitable for future clinical use. Limitations The early trial closure prevented complete recruitment, and the impact of the coronavirus pandemic prevented completion of some study investigations. Small participant numbers meant analysis could only be descriptive. Future work Owing to undetermined aetiology of thrombotic microangiopathy, further trials of HSCTlite in this population are not considered appropriate. Priorities should be to determine optimal treatment strategies for patients with refractory Crohn’s disease, including those with a stoma or multiple previous resections. Trial registration This trial is registered as ISRCTN17160440 and EudraCT 2017-002545-30. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme, a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 3. See the NIHR Funding and Awards website for further award information.

Amino acid-based enteral nutrition is effective for pediatric Crohn's disease: a multicenter prospective study.

Exclusive enteral nutrition (EEN) therapy effectively induces remission in pediatric Crohn's disease (CD). However, this may depend on the type of enteral formula used. Moreover, data on the efficacy of amino acid-based EEN are limited. Thus, we aimed to prospectively evaluate the efficacy of amino acid-based formulas for EEN in pediatric patients with active CD. Patients with active CD aged between 6 and 17 years were recruited into this prospective study from four hospitals in China between March 2019 and December 2021. Patients received EEN for 8 weeks. Inflammatory and nutrition-associated indices were evaluated at 0, 4, and 8 weeks after treatment. Paired t-tests and Wilcoxon signed-rank tests were used to compare continuous and categorical variables before and after intervention, respectively. Twenty-four patients were included in the analysis. After an 8-week intervention period, the CD activity index significantly decreased (26.3 ± 12.2 vs 7.1 ± 8.3, P < 0.001). Most patients (66.7%) achieved complete clinical remission. Among the 22 patients who had ulcers and erosions diagnosed endoscopically at baseline, 10 (45.5%) achieved complete mucosal healing. The degree of thickening of the intestinal wall was significantly reduced after EEN intervention, with a transmural healing rate of 42.9%. Furthermore, the serum inflammatory markers decreased and there was a significant improvement in the nutrition-related indices (P < 0.05). There were no severe adverse effects. Amino acid-based EEN is effective and safe for treating pediatric-onset CD. Studies with larger sample sizes and mechanistic and follow-up studies are required to further validate these findings.

A Treat-to-Target Strategy Guided by Pan-Enteric Evaluation in Children With Crohn's Disease Improves Outcomes at 2 Years.

It is uncertain whether a treat-to-target approach could be an effective strategy for improving outcomes in children with Crohn's disease (CD). Previously, we reported mucosal healing (MH) and deep remission rates throughout the intestinal tract by performing 3 pan-enteric capsule assessments and using a treat-to-target strategy over 52 weeks in children with CD. This report describes the outcomes of this approach at 104 weeks. Children with known CD who completed the 52-week protocol repeated pan-enteric capsule endoscopy (PCE) at 104 weeks. Results at weeks 52 and 104 were compared, and long-term outcomes between patients, with and without MH, were calculated using an intention-to-treat analysis of clinical relapse, need for steroids, treatment escalation, hospitalization, and surgery. Of the previous study cohort of 48 patients, 46 (96%) were available for this extension study (28 [61%] of 46 with MH and 18 [39%] of 46 without MH at 52 weeks). When evaluated at 104 weeks, MH was maintained in 93% of patients with MH at 52 weeks. In the intention-to-treat analysis, complete MH at 52 weeks was associated with reduced risk of steroid use (log-rank P < .0001), treatment escalation (log-rank P < .0001), hospitalization (log-rank P < .0001), and clinical relapse (log-rank P < .0001). When a PCE-based, treat-to-target strategy is employed, MH is sustainable (93%) over a 1-year period and is correlated with improved patient outcomes, including reduced need for steroids, treatment escalation, hospitalization, and clinical relapses at 104 weeks.ClinicalTrials.gov number: NCT03161886.

Maintenance of complete mucosal healing is associated with avoiding restenosis after endoscopic balloon dilation of Crohn's disease‐related small intestinal strictures

BackgroundEndoscopic balloon dilation (EBD) is an effective, minimally invasive treatment for Crohn's disease (CD) related intestinal strictures. However, restenosis frequently occurs and requires repetitive EBD or surgical resection. Since previous studies could not evaluate restenosis based on stricture diameter, factors affecting restenosis after EBD were unclear. This study aimed to identify these factors by precisely measuring the diameter of small intestinal strictures in patients with CD.MethodsThis single‐center retrospective study enrolled patients with CD with de novo small intestinal strictures who underwent two double‐balloon enteroscopy sessions (EBD and follow‐up) between January 2016 and October 2021. Clinical and endoscopic data were obtained from electronic medical records. A calibrated small‐caliber‐tip transparent hood was used to precisely measure stricture diameters. Multivariate analysis was performed to identify factors associated with restenosis.ResultsForty‐eight patients (37 male) were analyzed. The total number of strictures detected decreased from 162 to 143. The mean diameter of all strictures and the narrowest stricture in each patient increased significantly from 8.6 to 9.8 mm and from 7.6 to 8.7 mm, respectively. Thirty‐two (67%) patients developed endoscopic restenosis. Multivariate analysis showed that the presence of ulcers at the follow‐up session was a risk factor for restenosis (odds ratio 9.4, p = 0.01). Patients with complete mucosal healing at both sessions (n = 21) showed significant improvement in the narrowest stricture (+1.7 mm, p = 0.001).ConclusionsMaintenance of complete mucosal healing is significantly associated with avoiding restenosis after EBD in CD‐related small intestinal strictures.