Complete Mucosal Healing Research Articles

Broadening perspectives in the treatment of chronic pouchitis.

We present the case of a 64-year-old male diagnosed with corticosteroid-dependent ulcerative colitis in 1999, who underwent total proctocolectomy with a J-pouch in 2005. Three years later, he developed recurrent histologically confirmed pouchitis, with clinical worsening. Several therapies were tried, including Infliximab, which provided stability for six years, until the development of antibodies led to moderate pouchitis in the rectal stump. Attempts with Adalimumab, Vedolizumab, and Ustekinumab failed, leading to worsening cuffitis, pouchitis, and anastomotic stenosis. Tofacitinib was started at 10 mg/12h, leading to a >50% reduction in fecal calprotectin and a PDAI drop from 4 to 0 within four weeks. After reducing the dose to 5 mg/12h, disease control was maintained, and the patient remains asymptomatic after two years and seven months, with normal colonoscopy findings showing complete mucosal healing. Despite advances in treatment, around 15% of ulcerative colitis patients require surgery, and 30-50% of those develop acute or chronic cuffitis or pouchitis. Tofacitinib, a JAK inhibitor, is approved for ulcerative colitis but has shown inconsistent results in treating pouchitis and cuffitis. While some studies report a lack of efficacy, others show potential responses in refractory cases. More research with larger patient cohorts is needed to better understand the role of JAK inhibitors in this context.

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.

Modulation of stem cell fate in intestinal homeostasis, injury and repair

The mammalian intestinal epithelium constitutes the largest barrier against the external environment and makes flexible responses to various types of stimuli. Epithelial cells are fast-renewed to counteract constant damage and disrupted barrier function to maintain their integrity. The homeostatic repair and regeneration of the intestinal epithelium are governed by the Lgr5+ intestinal stem cells (ISCs) located at the base of crypts, which fuel rapid renewal and give rise to the different epithelial cell types. Protracted biological and physicochemical stress may challenge epithelial integrity and the function of ISCs. The field of ISCs is thus of interest for complete mucosal healing, given its relevance to diseases of intestinal injury and inflammation such as inflammatory bowel diseases. Here, we review the current understanding of the signals and mechanisms that control homeostasis and regeneration of the intestinal epithelium. We focus on recent insights into the intrinsic and extrinsic elements involved in the process of intestinal homeostasis, injury, and repair, which fine-tune the balance between self-renewal and cell fate specification in ISCs. Deciphering the regulatory machinery that modulates stem cell fate would aid in the development of novel therapeutics that facilitate mucosal healing and restore epithelial barrier function.

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

Endoscopic 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. This 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. Forty-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). Maintenance of complete mucosal healing is significantly associated with avoiding restenosis after EBD in CD-related small intestinal strictures.

P338 Transmural healing is not associated with less disability than complete endoscopic mucosal healing: a prospective study in a patient with Crohn's disease

Abstract Background Crohn's disease (CD) is associated with disability by affecting physical and emotional well-being, and by altering social interactions. In the era of treat to target, endoscopic remission has become the therapeutic target to prevent parietal destruction and disability. A deeper remission such as transmural healing would reduce long-term complications related to CD. The impact of transmural healing on disability is currently unknown. Methods We conducted a monocentric cross-sectional study between September 2019 and January 2022. Patients followed for CD in endoscopic remission (CDEIS &amp;lt;4) who underwent within &amp;lt; 4 weeks an intestinal ultrasound (IUS) and a disability assessment by an IBD-disk were consecutively included. Four groups were considered: (A) transmural healing defined by the combination of complete endoscopic healing (CDEIS=0) and ultrasound healing (bowel wall thickness (BWT) less than 3 mm), (B) complete endoscopic healing, (C) ultrasound healing and (D) no healing. Moderate to severe disability was defined as an overall score ≥ 40. Results A total of 85 patients were included. Forty-four (51.7%) were female, the median age and disease duration were respectively 38 years (interquartile range [IQR], 33-44) and 12.0 years (IQR, 5-20). There was no difference between the four groups in terms of age, sex, BMI, smoking status, disease location or phenotype or number of biologics failure. The median global IBD-Disk score was 25 (IQR, 9-41) and 24 patients (28.2%) had moderate to severe disability. Transmural healing (group A) was observed in 40 patients (47.1%). Moderate to severe disability was identified in 17.5% (7/40) of patients with transmural healing, 25% (4/16) with endoscopic healing, 44.4% (8/18) with ultrasound healing and 45.4 % (5/11) without healing. In univariate analysis, transmural healing reduced the risk of severe disability (group C vs A OR = 3.77, 95% CI [1.10, 13.45], p = 0.035), group D vs A OR = 3 .75, 95% CI [0.91, 17.12], p=0.063). There was no difference in terms of severe disability between patients with transmural healing and complete endoscopic healing (group B versus A OR = 1.57 95% CI [0.36, 6.23], p = 0.525). Conclusion Transmural healing did not provide any benefit in terms of disability compared to complete endoscopic healing. Mucosal healing therefore remains the objective to be achieved in order to reduce the risk of short-term disability.

P328 Holistic well-being as Patient-reported outcomes (PROs) in translational IBD research: Prospective capture of CUCQ32 as study endpoints for mechanistic biomarker MUSIC/GIDAMPs study.

Abstract Background There is increasing recognition of ‘holistic’ wellbeing as a key target in the management of IBD. Patient-reported outcomes (PROs) capture the impact of IBD on social, emotional and general wellbeing. Recently, regulatory bodies such as FDA/EMA mandates the study of PROs in interventional clinical trials. However, the role of PROs has never been investigated as a potential end-point in translational scientific research in IBD Methods CUCQ32 is a 32-question form that captures well-being of IBD patients including aspects of fatigue/anxiety/sexual/emotional health – score range from 0-272 (↑score correlating with worse quality QoL). We prospectively captured CUCQ32-PROs in our on-going MUSIC (Cohort 1) and GI-DAMPs (Cohort 2) IBD biomarker studies (www.musicstudy.uk) based in Edinburgh, Glasgow and Dundee (2018-present, ~total n=700 patients recruited). MUSIC is a prospective 12-month longitudinal study (over 5 time points) following active IBD patients in response to current drug treatment whilst GI-DAMPs is a cross-sectional study across IBD disease activity at one-time point. CUCQ32-PROs has been recorded since 2021 with 163 data-points captured. CUCQ32 were filled independently by patients. Results In IBD, CUCQ32-PROs scores were high with medians of 113 (IQR of 67.5-152.2) and 132 (IQR of 91-179) in Cohorts 1 and 2 respectively. In MUSIC Cohort 1, CUCQ32 decreased in response to treatment 113→62→58→45→30 over 3-monthly intervals. CUCQ32 scores are significantly correlated to clinical indices of disease activity, SCCAI for UC (Cohort 1, p=0.003/Cohort 2, p&amp;lt;0.001) and HBI for CD (Cohort 1, p&amp;lt;0.001/Cohort 2, p&amp;lt;0.001). Of interest, no correlation was observed with CRP and faecal calprotectin. Notably, although overall CUCQ32 scores associated with active disease, those deemed in ‘clinical remission’ continue to have high score (median 154 vs. 87 respectively, p=0.06). High CUCQ32 scores were observed even in those achieving complete mucosal healing (defined as either endoscopic SESCD or UCEIS score of 0) from longitudinal prospective endoscopic follow-up; median decrease from 116 (baseline) to 55 (6-months SESCD/UCEIS =0), paired data available in n=14 patients. There is no statistical correlation with endoscopic mucosal healing (p=0.6; in 34 patients). Conclusion Although patient wellbeing improved with medical treatment in IBD and PROs are correlated with clinical indices of IBD activity, high CUCQ32 (thereby poor quality of life) scores were observed in traditional categorisation of ‘clinical remission’. This suggests a far-reaching impact of IBD beyond gut-related signs/symptoms. Our current work incorporates PROs into our scientific biomarker studies and molecular analyses) and will be the first in IBD, to our knowledge.

Clinical Assessment of the Treatment of 18 Cases of Denosumab-related Osteonecrosis of the Jaw （DRONJ）

This study aimed to evaluate the treatment outcome of osteonecrosis of the jaw （ONJ） in 18 patients receiving only denosumab. The patients comprised 11 males and seven females, with a median age of 82.5 years and mean age of 77.9 years. Fifteen patients were cancer patients with bone metastasis and three had osteoporosis. Stage 2 was the most common stage （77.8％）. Of the 18 patients, surgical treatment was performed in five patients, while purely conservative treatment was performed in 13. Surgical treatment achieved complete mucosal healing in 100％ （5/5） and was significantly correlated with treatment outcome on univariate analysis. In purely conservative treatment, two patients achieved complete mucosal healing and two patients achieved partial ONJ resolution. The treatment efficacy rate of conservative treatment was 30.8％ （4/13）. In four patients who were effectively treated by conservative treatment, their sequestrums detached spontaneously and epithelialized after a median of 12.5 months and mean of 15 months of discontinuing denosumab. ONJ progressed or was unchanged in five patients even after discontinuation of denosumab treatment. It may take a long time even if conservative treatment is successful. We recommend surgical treatment even for denosumab related osteonecrosis of the jaw when patients can tolerate surgery.

Association between Mucosal Healing and Lipid Profiles in Patients with Ulcerative Colitis: A Cross-Sectional Study

Introduction: Recent meta-analysis showed that ulcerative colitis (UC) is a risk factor for cardiovascular disease (CVD). Dyslipidemia is a well-established risk factor for CVD. However, evidence regarding inflammatory bowel disease (IBD), including UC and lipid profiles, is limited. Additionally, no study has assessed the association between endoscopic activity and lipid profiles in patients with IBD. Therefore, we aimed to clarify the association between mucosal healing (MH) and lipid profiles in patients with UC. Methods: A total of 221 Japanese patients with UC were enrolled in this analysis. Total cholesterol (T-chol), triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were divided into tertiles (high, moderate, and low) based on the distributions, respectively. Self-administered questionnaire was used to obtain information regarding medication for dyslipidemia. Complete MH and MH are based on Mayo endoscopic subscore 0 and 0–1, respectively. Results: The percentage of complete MH was 30.8%. In patients without medication for dyslipidemia, high HDL-C (>66 mg/dL) was significantly positively associated with complete MH (adjusted odds ratio [OR] 2.58, 95% CI: 1.04–6.64, p for trend = 0.037). In patients with nonproctitis, a positive association between HDL-C and complete MH was found (adjusted OR 3.54, 95% CI: 1.22–11.01, p for trend = 0.020). T-chol and TG were not associated with MH, regardless of medication for dyslipidemia. Conclusions: Complete MH was significantly positively associated with HDL-C in UC patients without medication for lipid. The disease extent might affect the association between complete MH and HDL-C.

An Unusual Case of Chest Pain and Pyrexia

Question: A 44-year-old man with tearing retrosternal pain for 2 weeks was admitted to our department. A day before the onset of symptoms, he had pharyngalgia, cough, sputum production, moderate pyrexia, and fatigue, which he thought was due to a common cold. He then had sudden-onset severe chest pain, which lasted 4 to 6 seconds and occurred every 30 seconds, with acid reflux and heartburn. The patient had consumed nothing after the start of the symptoms until this consultation. He denied emesis, hematemesis, melena, dysphagia, odynophagia, history of esophageal disease, eating hurriedly, ingestion of hot or rough food, anticoagulants, or foreign body. His medical history was significant for alcohol consumption (100 g/d) for more than 20 years. He visited a local hospital and underwent chest computer tomography (CT); however, the diagnosis was unclear, and an attempt to insert a nasogastric tube failed. The patient visited another hospital, and a CT scan revealed dilation of the esophageal lumen and thickening of the esophageal wall, with exudation in the periesophageal areas and lung fields. Esophagoscopy revealed a large depressed lesion at 20 cm from the incisors, measuring 1 cm in diameter and covered with pus. The background esophageal mucosa was severely inflamed and edematous. Contrast esophagography performed a week later showed accumulation of contrast medium in the middle and lower esophagus, which formed a sac-like shadow beside the esophagus, without communication with the thoracic or gastric cavity. The patient was treated conservatively, and his symptoms were partially relieved. Because the pathogenesis was still unknown, the patient was referred to our institution for further evaluation. What is the correct diagnosis and management of this condition? See the Gastroenterology website (www.gastrojournal.org) for more information on submitting to Gastro Curbside Consult According to his medical history from other hospitals, normal electrocardiography and cardiac enzyme levels excluded the diagnosis of myocardial infarction; absence of hypertension and no abnormalities in aortic anatomy disclosed by means of contrast CT argued against aortic dissection; absence of emesis and no extravasation of contrast medium demonstrated by contrast esophagography excluded Boerhaave’s syndrome. Then contrast chest CT scan, which revealed thickening and liquid accumulation in the middle and lower esophageal wall, with little extra-esophageal air leakage and pneumonia (Figures A and B), and upper endoscopy (Figures C and D) were performed. A diagnosis of spontaneous intramural esophageal dissection (SIED) complicated by infectious esophagitis and pneumonia was made. SIED is a rare disease entity characterized by transverse and longitudinal separation of the mucosal and submucosal layers from the esophageal wall. Sudden onset of severe retrosternal chest pain, odynophagia, dysphagia, and hematemesis are the most common symptoms. Contrast esophagography and chest CT are the preferred methods to establish the diagnosis, and endoscopy also proved to be safe and useful in this condition. In most cases, conservative treatment has a good prognosis. Endoscopic interventions and surgery are alternative therapies when patients are refractory to conservative management or when complex complications occur.1Khil E.K. Lee H. Her K. Spontaneous intramural full-length dissection of esophagus treated with surgical intervention: multidetector CT diagnosis with multiplanar reformations and virtual endoscopic display.Korean J Radiol. 2014; 15: 173-177Crossref PubMed Scopus (4) Google Scholar,2Jung K.W. Lee O.J. Extensive spontaneous submucosal dissection of the esophagus: long-term sequential endoscopic observation and treatment.Gastrointest Endosc. 2002; 55: 262-265Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar The patient was treated conservatively and discharged on day 35. Seven weeks later, follow-up endoscopy showed complete mucosal healing (Figure E), and he was asymptomatic at the time of writing (August 1, 2022).

Association between socioeconomic status and mucosal healing in Japanese patients with ulcerative colitis: a cross-sectional study

ObjectiveSocioeconomic status is a risk factor for worse outcomes in many diseases. However, evidence on the association between socioeconomic status and clinical outcome in patients with ulcerative colitis (UC) is...

S2521 Sevelamer: An Underreported Cause of Enteritis and Colitis

Introduction: Hyperphosphatemia is a common metabolic derangement in patients with end-stage renal disease (ESRD). In addition to dietary constraints, phosphate binders are needed to treat hyperphosphatemia. Sevelamer is the most used resin-based phosphate binder and can crystallize to form concretions. Crystals formed by other resin-based binders such as polystyrene sulfonate (kayexalate) are a well-known cause of gastrointestinal (GI) mucosal injury. However, sevelamer is an underreported culprit. Here, we describe a case of ileitis and colitis caused by sevelamer crystals. Case Description/Methods: A 65-year-old male veteran with ESRD, secondary hyperparathyroidism treated with sevelamer, and cocaine abuse was admitted for abdominal pain and bloody diarrhea for 3 days. CT scan of the abdomen and pelvis revealed inflammation of the ileum and rectosigmoid. He was started on ciprofloxacin and metronidazole. Stool studies were negative. A colonoscopy revealed an ulcerated and erythematous terminal ileum (TI) between 15cm and 7cm proximal to the ileocecal valve. There was mild ulceration and erythema in the ascending colon. The worst ulceration was between 40cm to 30cm from the anal verge with additional ulceration seen in the rectosigmoid. The colonic mucosa between the ulcerations were normal appearing. Biopsies taken from the TI, ascending colon, and descending colon revealed chronic ileitis and colitis with ulceration, granulation tissue associated crystals, crypt abscess, and fibrinopurulent debris and negative for infection or malignancy. A review the medication reconciliation confirmed no exposure to kayexalate and, thus, concluded that sevelamer was the cause. The patient was advised to stop taking sevelamer. A follow up colonoscopy 6 months later revealed complete mucosal healing (Figure). Discussion: GI mucosal injury is a rare and underrecognized adverse effect of sevelamer. A limited number of reported cases describe a range of symptoms such as nausea, vomiting, constipation, dysentery, and acute abdomen requiring surgery. The enteritis and colitis caused by sevelamer can be overlooked and presumed to be infectious or ischemic etiology. The pathology can also be missed because of misidentification or failure to identify crystals on histology. Increased awareness of this underreported complication of sevelamer is important for these reasons and for directing appropriate therapy with cessation of this medication in the setting of enteritis or colitis.Figure 1.: H&E stain showing fibrinopurulent exudate (ischemic /acute erosive pattern colitis) and the presence of Sevelamer crystals.

Ozone Infiltration for Osteonecrosis of the Jaw Therapy: A Case Series.

Medication-related osteonecrosis of the jaw (MRONJ) is a serious adverse reaction, mainly due to bone-modifying agents (BMA), and it is a potentially painful and debilitating condition. To date, the literature has reported a 90% rate of successful outcomes for MRONJ patients undergoing surgical treatment. Particularly for patients with advanced disease stages who are unsuitable for surgery, prolonged medical treatment is required, with a consequent risk of the overuse of antibiotics and antibiotic resistance. The aim of this study is to evaluate the efficiency and safety of ozone, via oral mucosal infiltrations, in seven cancer patients with MRONJ, who are not eligible for surgery. The protocol (OZOPROMAF) consists of intratissue injections of an oxygen ozone (O2O3) mixture, which is applied until formation of a sequestrum and clinical healing. Follow-up was scheduled to confirm the healing of MRONJ and radiological evaluations by CBCT were planned. In order to assess the level of pain, a questionnaire including the Numeric Rating Scale for Pain (NRS Pain) was administered on the first visit, one day after treatment, and one week after treatment. After an application of OZOPROMAF, all patients reported discomfort for some hours, probably due to soft tissue pressure around the infiltration site. Thereafter, the discomfort subsided within 6–8 h. Complete mucosal healing of MRONJ occurred within a number of cycles ranging from 7 to 16. Complete resolution with an improvement in bone condition was observed in all patients. The MRONJ lesions of all patients healed after 18–24 months. The authors of this study contend that these preliminary results suggest the efficiency and safety of the O2O3 mixture. However, further research is required to confirm the efficacy of the O2O3 mixtures in MRONJ treatment, at least for patients who are unsuitable for surgery.

Fluorescence-guided surgery for osteoradionecrosis of the jaw: a retrospective study

ObjectiveOsteoradionecrosis of the jaw (ORNJ) is one of the most severe head and neck complications in patients treated with radiotherapy. The goal of treatment is to suppress ORNJ progression. Currently, surgical removal of necrotic bone is an effective management approach for advanced stages. In this study, we present our experience in managing ORNJ using fluorescence-guided surgery.MethodsNineteen ORNJ lesions in 15 hospitalized patients were treated with fluorescence-guided surgery. We retrospectively reviewed patients’ demographic data, comorbidities, local preceding event, location, ORNJ stage, and treatment outcomes with a median follow-up of 12 months.ResultsTwelve lesions (63%) were treated surgically under tetracycline fluorescence, and seven lesions (37%) were surgically treated under auto-fluorescence. Overall, four lesions (21%) achieved complete mucosal healing, eight lesions (42%) showed partial mucosal healing with bone exposure and no signs or symptoms of inflammation, and seven lesions (37%) were progressive. The results showed that either healing or ORNJ stabilization was achieved in 63% of lesions (n = 12).ConclusionFluorescence-guided surgery can be beneficial in curing or stabilizing ORNJ. However, randomized clinical trials are needed to confirm these findings.