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Background: The injection of allogeneic adipose tissue-derived mesenchymal stem cells (MSC) into anal fistulas in patients with Crohn's disease has never been evaluated in "real-life" conditions in France. Methods: We prospectively studied the first patients receiving MSC injections at our center and undergoing 12 months of follow-up. The primary endpoint was the clinical and radiological response rate. The secondary endpoints were symptomatic efficacy, safety, anal continence, quality of life (Crohn's anal fistula-quality of life scale, CAF-QoL), and predictive factors of success. Results: We included 27 consecutive patients. The complete clinical and radiological response rates at M12 were 51.9% and 50%, respectively. The combined complete clinical–radiological response (deep remission) rate was 34.6%. No major adverse effects or changes in anal continence were reported. The perianal disease activity index decreased from 6.4 to 1.6 (p < 0.001) for all patients. The CAF-QoL score also decreased from 54.0 to 25.5 (p < 0.001). At the end of the study, M12, the CAF-QoL score was significantly lower only in patients with a complete combined clinical–radiological response relative to those without a complete clinical–radiological response (15.0 versus 32.8, p = 0.01). Having a multibranching fistula and infliximab treatment were associated with a combined complete clinical–radiological response. Conclusions: This study confirms reported efficacy data for the injection of MSC for complex anal fistulas in Crohn's disease. It also shows a positive impact on the quality of life of patients, particularly those for whom a combined clinical–radiological response was achieved. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to evaluate the real‐life clinical and radiological efficacy of darvadstrocel injection into complex perianal fistulas in Crohn's disease. Secondary endpoints were to assess symptomatic efficacy, adverse effects and factors associated with complete combined clinical‐radiological response (deep remission). Methods: After marketing the product in France, all first patients treated consecutively were included. A complete clinical response was defined by a complete closure of all external openings with no discharge on pressure. A complete radiological response (MRI), evaluated at least after six months of follow‐up, was defined by a completely fibrotic sequela without abscess. A deep remission was defined as the association of a complete clinical response with a complete radiological response. Results: A total of 43 patients were included (M/F: 22/21, median age 37 [26–45] years). The fistulas were already drained with seton(s) and were on biologic treatment. After a median follow‐up of 383 (359–505) days, 28 (65%) patients showed a clinical response (22 complete and 6 partial) and 16 (37%) achieved a deep remission. The Perineal Disease Activity Index decreased significantly after treatment: 39 (91%) patients reported symptomatic improvement in terms of discharge, pain, and induration, and 28 (65%) no longer had any perineal symptoms. No severe adverse events were reported. A short history of Crohn's disease <3 years was significantly associated with deep remission (OD 4.5 [1.0–19.1], p = 0.04). Conclusion: Darvadstrocel injection resulted in a clinical response for two thirds of patients and deep remission for one third. A shorter duration of Crohn's disease was associated with deep remission. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic and disabling diseases that affect patient health-related quality of life (HRQoL). IBD patients are frequently exposed to high levels of stress and psychological distress. Biological drugs have been proven to reduce inflammation, hospitalization, and most of the complications that characterize IBDs; their potential contribution to patients' HRQoL remains to be explored. Aim: To evaluate and compare any change in the HRQoL and markers of inflammation in IBD patients undergoing biological drugs (infliximab or vedolizumab). Material and Methods: A prospective observational study was conducted on a cohort of IBD patients, aged >18 years, who were prescribed with infliximab or vedolizumab. Demographic and disease-related data at baseline were collected. Standard hematological and clinical biochemistry parameters, including C-reactive protein (CRP), white blood cells count (WBC), erythrocytes sedimentation rate (ESR), and α1 and α2 globulins were measured after a 12-h fast at baseline (T0), after 6 weeks (T1), and at 14 weeks (T2) of biological treatment. Steroid use, disease activity as measured by the Harvey–Bradshaw index (HBI) and partial Mayo score (pMS) for the CD and UC, respectively, were also recorded at each timepoint. The Short Form 36 Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT-F), and Work Productivity and Activity Impairment–General Health Questionnaire (WPAI:GH) were administered to each patient at baseline, T1, and T2 to address the study aims. Results: Fifty eligible consecutive patients (52% with CD and 48% with UC) were included in the study. Twenty-two patients received infliximab and twenty-eight received vedolizumab. We noted a significant reduction in the CRP, WBC, α1, and α2 globulins from T0 to T2 (p = 0.046, p = 0.002, p = 0.008, and p = 0.002, respectively). Participants showed a significant decrease in steroid administration during the observation period. A significant reduction in the HBI of CD patients at all three timepoints and a similarly significant decrease in the pMS of UC patients from baseline to T1 were recorded. Statistically significant changes were observed in all questionnaires during follow-up as well as an overall improvement in the HRQoL. The interdependence analysis carried out between the biomarkers and the scores of the individual subscales showed a significant correlation between the variation (Δ) of the CRP, Hb, MCH, and MCV with physical and emotional dimensions of the SF-36 and FACIT-F tools; work productivity loss expressed by some of the WPAI:GH items negatively correlated with the ΔWBC and positively with the ΔMCV, ΔMCH, and Δ α1 globulins. A sub-analysis according to the type of treatment showed that patients receiving infliximab experienced a more pronounced improvement in their HRQoL (according to both SF-36 and FACIT-F) compared with patients receiving vedolizumab. Conclusions: Both infliximab and vedolizumab played an important role in contributing to the improvement of the HRQoL in IBD patients by also reducing inflammation and, consequently, steroid use in patients with an active disease. HRQoL, being one of the treatment goals, should also be assessed when taking charge of IBD patients to assess their clinical response and remission. The specific correlation between the biomarkers of inflammation and life's spheres, as well as their possible role as clinical markers of HRQoL, should be further investigated. [ABSTRACT FROM AUTHOR]

Background: Recent advances in biologics have provided new insights into the clinical course of asthma, including disease modification, clinical remission (CR), and deep remission (DR). However, the extent to which biologics achieve CR and DR in severe asthma patients is poorly understood. Methods: To assess the achievement rate and predictors of CR and DR using long-term biologics, we retrospectively evaluated 54 severe asthma patients recently started on biologics. "CR" denotes the achievement of all three criteria: (1) absence of asthma symptoms, (2) no asthma exacerbations, and (3) no use of oral corticosteroids. DR denoted CR plus (4) normalized pulmonary function and (5) suppressed type 2 inflammation. Results: CR and DR achievement rates were 68.5% and 31.5%, respectively. Compared with the non-deep remission group, the DR group had higher adult-onset asthma rates (94.1% vs. 70.3%, p = 0.078), shorter asthma duration (5 vs. 19 years, p = 0.006), and higher FEV1 (91.5% vs. 71.5%, p < 0.001). There were no significant differences in the Asthma Control Questionnaire scores, exacerbation frequency, or type 2 inflammation at baseline between groups. Asthma duration combined with FEV1 can stratify the achievement rates of CR and DR. Conclusions: the early introduction of biologics in severe asthma patients may help achieve CR and DR. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) patients included in the Tailored Treatment With Infliximab for Active Crohn's Disease (TAILORIX) trial started infliximab in combination with an immunosuppressant for 1 year. The aim of the present study was to determine the long-term disease course beyond the study period. We compared the outcomes of patients who did or did not reach the primary end point of the TAILORIX trial, defined as sustained corticosteroid-free clinical remission from weeks 22 through 54, with no ulcers on ileocolonoscopy at week 54. The primary outcome of this follow-up study was the progression-free survival of CD defined by anal or major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment. The 95 patients (median disease duration, 4.5 mo; interquartile range, 1.0–56.6 mo) analyzed, including 45 (47%) who achieved the primary end point, were followed up for a median duration of 64.2 months (interquartile range, 57.6–69.9 mo) after the end of the study period. There was no significant difference in CD progression-free survival at 1, 3, and 5 years between patients who achieved the TAILORIX primary end point and patients who did not (P =.64). No difference was observed between both groups for each component of CD progression: anal surgery, major abdominal surgery, CD-related hospitalization, or the need for a new systemic CD treatment. Achieving a sustained clinical remission off steroids with complete endoscopic remission in this cohort of 95 patients with early CD was not associated with less disease progression. Prospective trials to define the therapeutic goals that change the natural history of CD and prevent complications are needed. [ABSTRACT FROM AUTHOR]

Background and Aims: 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 (TTS) endoscopic ultrasound (EUS) during Double-balloon enteroscopy (DBE) in distinguishing small-bowel CD patients in endoscopic remission from those with active disease., Methods: 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). Thickness of small intestinal wall layers and other parameters were evaluated by EUS., Results: EUS using the ultrasonic catheter probe via 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 (TWT 3.84±1.02 vs 2.42±0.25mm, SMT 1.23±0.34 vs 0.79±0.13mm, respectively, p<0.001). Cut-off values of 2.65 mm for TWT and 0.95 mm for SMT can distinguish active small-bowel CD from inactive disease (Sensitivity 91.5%, Specificity 80.8% and Sensitivity 70.2%, Specificity 88.6%, respectively). The correlation analysis revealed a significant positive correlation between TWT and SES-CD (r=0.930, p<0.001). Furthermore, TWT was strongly correlated with FC (r=0.861, p<0.001) and CDAI (r=0.805, p<0.001). Similar results were observed for SMT., Conclusions: 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., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Background: Mucosal healing (MH) is an established treatment goal in inflammatory bowel disease (IBD). However, various definitions of MH exist. We aimed to identify how MH is defined in randomized controlled trials (RCTs) in ulcerative colitis (UC) and Crohn's disease (CD)., Methods: We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD., Results: One hundred forty-four studies were included, 72 in UC and 72 in CD, published between 1997 and 2023. In UC, 64% (46/72) RCTs reported MH as an endpoint. 12 definitions of MH were found, from endoscopic assessment alone (35/46; 76%) to the more recent combination of histology and endoscopy (10/46; 22%). 96% (44/46) of studies used the Mayo Endoscopic Subscore. In CD, reporting of MH lagged behind UC, with only 12% (9/72) of trials specifically defining MH as an endpoint, 7 as "absence of ulceration," 2 as Simplified Endoscopic Score for CD score ≤2 or 0. Histological assessment was performed in 3 RCTs of CD. Centralized reading of endoscopy was used in 48% (35/72) of RCTs of UC and 22% (16/72) of CD. Only 1 RCT included transmural healing as an endpoint., Conclusions: A standard definition of MH in IBD is lacking. Definitions have evolved particularly in UC, which now includes the addition of histological evaluation. Transmural healing holds promise as a future target in CD. We support a greater standardization of definitions as we expect endpoints to become increasingly stringent and multimodal with computers automating the assessment., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Patients with Crohn's disease (CD) are at risk of progressing from inflammatory to stricturing and penetrating phenotypes. The influence of the depth of remission on the risk of progression has not been adequately evaluated., Methods: A retrospective cohort study including surgically naïve CD patients with inflammatory phenotype evaluated concomitantly by magnetic resonance enterography and colonoscopy. The degree of remission was correlated with the risk of progressing to stricturing and penetrating phenotypes., Results: Three hundred nineteen CD patients were included: 27.0% with transmural remission, 16.0% with isolated endoscopic remission, 14.4% with isolated radiologic remission, and 42.6% without remission. Patients with transmural remission presented the lowest rates of phenotype progression (1.2%), with a significant difference compared to isolated radiologic remission (10.9%, p = 0.019), to isolated endoscopic remission (19.6%, p ≤ 0.001), and to no remission (46.3%, p ≤ 0.001). In multivariate regression analysis, transmural remission (OR 0.017 95% CI 0.002-0.135, p < 0.001), isolated radiologic remission (OR 0.139 95% CI 0.049-0.396, p < 0.001), and isolated endoscopic remission (OR 0.301 95% CI 0.123-0.736, p = 0.008) resulted in lower rates of phenotype progression compared to no remission. No patient with transmural or isolated radiologic remission progressed to penetrating phenotypes., Conclusion: The degree of bowel remission correlates with the risk of phenotype progression. Patients with transmural remission are at the lowest risk of progressing to stricturing and penetrating phenotypes., (© 2024 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: While mucosal healing (MH) and transmural healing (TH) predict relevant clinical outcomes in Crohn's disease (CD), little is known about the real significance and clinical impact of deep remission (DR). Objectives: To better explore the concept of DR, toward a direct correlation between MH, TH, and biomarkers. Design: Real-world observational longitudinal study to evaluate the rate of clinical remission (CR), MH and TH, and the fecal calprotectin (FC)/C-reactive protein (CRP) levels in all consecutive CD patients on biologics. Methods: A receiver operating characteristic (ROC) curve was constructed to define the best FC and CRP cut-offs associated with MH and TH. Finally, patients achieving CR, MH, and TH, in association with the target FC/CRP values, were considered in DR. Results: Among 118 CD patients, CR, MH, and TH were achieved in 62.7, 44.1, and 32.2%, respectively. After 2 years, the mean FC levels decreased from 494 ± 15.4 μg/g to 260 ± 354.9 μg/g (p < 0.01). Using the ROC curve analysis, an FC cut-off value of 94 μg/g was associated with both MH [sensitivity: 94.2%, specificity: 84.8%, positive predictive value (PPV): 83.05%, negative predictive value (NPV): 94.92%, area under the curve (AUC): 0.95] and TH (sensitivity: 92.1%, specificity: 70%, PPV: 64.4%, NPV: 94.9%, AUC: 0.88). CRP < 5 mg/L was associated with both MH (sensitivity: 96.1%, specificity: 62.1%, PPV: 66.7%, NPV: 95.35%, AUC: 0.85) and TH (sensitivity: 97.4%, specificity: 52.5%, PPV: 52%, NPV: 95.35%, AUC: 0.78). When considering CD patients with concomitant CR, MH, and TH associated with an FC < 94 μg/g and CRP < 5 mg/L, this association was found identified in 33 patients (27.9%). Conclusion: An FC < 94 μg/g and a normal CRP are associated with CR, MH, and TH and could be included in the definition of DR in association. So by definition, DR could be achieved in approximately 30% of CD patients during maintenance treatment with biologics. [ABSTRACT FROM AUTHOR]

The relationship between the disease activity of ulcerative colitis and fatigue is unclear. We investigated how reaching deep remission versus remaining in active disease influenced the severity of fatigue. We included 149 consecutive patients in a longitudinal study. Patients were re-examined after 3 months of conventional treatment and dichotomized into A: Active disease or B: Deep remission. The Partial Mayo Score (PMS) was recorded in all patients. Fatigue was rated using the fatigue visual analog scale (fVAS), Fatigue Severity Scale (FSS), and Short Form-36 Vitality Subscale (SF-36vs). A control group of 22 age and sex-matched healthy subjects were included as controls for patients reaching deep remission. After 3 months there were no significant differences in fVAS, FSS and SF-36vs scores in patients with active disease compared to patients reaching deep remission, when adjusting for baseline fatigue scores. Patients in remission based on MES-UC scores had no significant reduction in fatigue scores, whereas patients in remission based on PMS had all three fatigue scores reduced. However, patients reaching deep remission still had higher fVAS and lower SF-36vs scores compared to healthy control subjects. After 3 months of conventional treatment there were no differences in fatigue severity in patients reaching deep remission compared with patients still having active disease. Fatigue was more pronounced in patients in deep remission than in healthy subjects, and was associated with subjective and not objective measures of disease activity. This indicates that other potent factors than inflammation influence fatigue in UC. [ABSTRACT FROM AUTHOR]

Deep remission should be induced early in the disease course of Crohn's disease (CD), because it significantly prevents disease progression. Identifying predictors of deep remission before treatment is important to guide therapeutic strategy. Little is known about the predictors of infliximab-induced deep remission in treatment-naïve patients with isolated small bowel CD. We aimed to investigate the predictors of infliximab-induced deep remission in these patients. From January 2015 to December 2019, all consecutive treatment-naïve patients with isolated small bowel CD who started infliximab induction therapy (5 mg/kg at week 0, 2, and 6) and underwent capsule endoscopy (CE) at week 14 were retrospectively included. Deep remission was defined as clinical remission in combination with CE-identified mucosal healing. Logistic regression was used to investigate the predictors of 14-week deep remission. Ninety-one patients were included. At week 14 after infliximab induction therapy, deep remission was found in 42 patients. Multivariate logistic regression analysis showed that a moderate-to-severe endoscopic disease [odds ratio (OR), 0.28; p =.01] and the presence of fibrofatty proliferation (OR, 0.26; p =.04) at baseline were independently associated with a decreased possibility of deep remission. In treatment-naïve patients with isolated small bowel CD, a moderate-to-severe endoscopic disease and the presence of fibrofatty proliferation at baseline reduce the possibility of infliximab-induced deep remission. Patients with such risk factors may need more aggressive treatment at the beginning of induction therapy to promote deep remission at an early stage. [ABSTRACT FROM AUTHOR]

Introduction: The ultimate indicator of adherence to a gluten-free diet is the demonstration of mucosal healing. However, the need for histological reassessment is subject to controversy among “experts”. The aim of this study was to evaluate celiac patients who underwent histological reevaluation after starting a gluten-free diet in order to identify those with histological remission and associated factors. Methods: This retrospective study included patients who agreed to a histological reassessment after apparent clinical and serological remission and reported at least 12 months of diet adherence. In all cases, informed consent was signed for upper endoscopy. Results: A total of 69 patients were included. In 67.9% of cases, the diagnosis was made in the context of “classic” symptomatology, 17% had “nonclassical” presentation, and 15.1% were in latent phase. 69.2% of the diagnoses were initially suspected by serology. Endoscopically, 11.8% of the patients did not present suggestive features macroscopically, and a histological grade of Marsh IIIa–c was observed in 75.5% of all cases. The histological findings were normalized in 37.7%, which was associated with the presence of lower Marsh score values at diagnosis (p = 0.014) and lower DEXA T-score values (p = 0.038). A histological improvement was observed in 55 patients (≥2 grades in 37 cases), which was related to the initial transferrin saturation (p = 0.027) and with higher Marsh scores at diagnosis (p = 0.007). Conclusion: Even under a gluten-free diet, celiac histology normalization is difficult to obtain and appears to be independent of most clinical and serological findings at diagnosis. Patients with less severe histological levels at diagnosis reach remission more easily, but only represent the ­minority of the population.

Background: Allogenic adipocyte stem cells represent an unprecedented opportunity for regenerative therapy to treat Crohn anal fistulas. Apart from the results of one 8-year-old trial, scientific evidence remains scarce., Methods: Data from consecutive patients treated with darvadstrocel for Crohn anal fistulas were reviewed at 6 first tertiary reference centers. The judgment criteria combined asymptomatic status plus clinical occlusion of the fistula tract and MRI-confirmed healing of the tract (no inflammation and/or disappearance of the tract). Both clinical and MRI-confirmed healing of the tract defined a deep remission. Clinical remission was defined by an absence of complaint, occlusion of all external openings, and no fistula discharge., Results: A total of 116 patients were extracted (median follow-up after cell stem injection: 11 [6-14] months). No severe adverse events were reported after surgery except for subsequent anal surgery in 29 (25%) patients. Fifty-one (44%) patients had clinical remission defined by the absence of complaints, the occlusion of all external openings, and the presence of no fistula discharge. Deep remission was observed in 23 (29%) patients. Patients with clinical remission more often received combined therapy (immunosuppressant antitumor necrosis factors) than those with no improvement (31 of 51 [61%] vs 23 of 65 [35%]; P = .007). Regression analysis showed that high fistulas (odds ratio, 3.8 [1.1-12.5]; P = .03) and younger age (<38 years, odds ratio, 2.3 [1.0-58;4]; P = .02) were associated with a better outcome., Conclusions: Allogeneic stem cell treatment of Crohn's anal fistulas results in complete remission in less than half of patients, with a significant reintervention rate., (© The Author(s) 2024. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The concept of disease clearance has been proposed as a potential target in ulcerative colitis (UC). We conducted a systematic review to investigate the role of disease clearance, defined as a composite outcome including simultaneous clinical, endoscopic, and histologic remission of disease in the management of patients with UC. Based on the literature data, statements regarding disease clearance were developed and voted on by the members of the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD) according to a Delphi methodology. A definition of disease clearance was proposed to standardize its use in clinical practice and clinical trials and to provide practical recommendations for its implementation as a therapeutic target in UC., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background Deep remission in patients with UC has relied on initial achievement of biochemical, endoscopic, and/or histological remission. We evaluated persistent symptomatic remission and endoscopic healing (EH: Mayo endoscopy score [MES] 0 or 1) on consecutive endoscopic examinations as a durable treatment endpoint. Methods In a retrospective cohort study, we estimated and compared cumulative risk of clinical relapse in patients with persistent EH, with and without persistent histological remission and depth of EH, among adults with active UC treated-to-target of symptomatic remission and EH who achieved and maintained symptomatic remission and EH over two serial endoscopic assessments. We also explored risk of relapse in patients with persistent EH whose therapy was de-escalated. Results Of 270 patients who initially achieved EH with treatment-to-target, 89 maintained symptomatic remission and EH on follow-up endoscopy [interval between EH1 and EH2, 16 months]. On follow-up after EH2 [median, 19 months], 1-year cumulative risk of relapse in patients with persistent EH was 11.5%, and with persistent histological remission was 9.5%. Seventeen patients with persistent EH, who underwent de-escalation of therapy, did not have an increased risk of relapse as compared with patients who continued index therapy [5.3% vs 14%, p  = 0.16]. Conclusions Patients with active UC treated-to-target of clinical remission, who achieve and maintain symptomatic remission and EH over consecutive endoscopies, have a low risk of relapse, particularly in a subset of patients who simultaneously achieve histological remission. Persistent EH should be examined as a treatment endpoint suggestive of deep remission. [ABSTRACT FROM AUTHOR]

Background & Aims: Histological remission (HR) has been recently demonstrated as the last therapeutic goal in ulcerative colitis (UC), but it is unknown whether and how it may occur. Our aim was to assess the histology during the follow-up of an UC population in deep remission under treatment with adalimumab (ADA). Methods: We performed a retrospective study on 22 UC patients who were in deep remission and followed-up while receiving therapy with ADA. Colonoscopy in those patients was performed every year. Four-quadrant biopsies every 10 cm were obtained during each colonoscopy and assessed by hematoxylin and eosin stain. Histological activity was classified using the Geboes scale. Results: A total of 22 patients were enrolled in the study. The mean follow-up of those patients was 28±7 months, and 2,592 biopsy specimens in total were taken during 108 colonoscopies performed during the follow-up. At the beginning of the follow-up, histological inflammation was found in 15/22 (68.2%) of patients in deep remissio while receiving maintenance ADA therapy, 8/22 (36.4%) of them with Geboes score =3.1. At the end of the follow-up, when patients were still in deep remission while receiving maintenance ADA therapy, only 4 patients (18.2%) had at least one biopsy specimen with evidence of any histological inflammation during the follow-up; only two patients (9.1%) had Geboes score =3.1. Conclusions: Our study shows for the first time that UC patients in deep remission under ADA may reach HR, but it seems slower than other clinical or endoscopic goals. [ABSTRACT FROM AUTHOR]

Background and aims: A multicentre, retrospective, non-interventional, patient chart review study was conducted to investigate deep (DR) and histological remission rates during maintenance therapy with biological agents in inflammatory bowel disease (IBD). Methods: We reviewed clinical, endoscopic, and histological findings, and laboratory markers such as C-reactive protein (CRP) and faecal calprotectin (FC) on average of nine years after the initiation of anti-TNF-therapy. DR was defined as no clinical symptoms (The physicians' global assessment scores; PGA = 0) with endoscopic remission (the Simple Endoscopic Score for Crohn's Disease [SES-CD] ≤ 2 or Mayo endoscopic subscore ≤1). Histological activity was defined as normal if only architectural alterations without cellularity changes occurred. Results: Of 117 IBD patients on maintenance therapy, 72 (62%; CD n = 55 [56%], UC n = 17 [85%]) patients were in DR. Of patients in DR, 76% were also in histological remission. 77% of patients remained on initiated biological treatment. UC patients achieved DR significantly more often than CD patients (p =.016). Both median CRP and FC levels were significantly lower in patients with DR. Conclusion: Reassuringly, almost two thirds of the IBD patients on maintenance therapy with biological agents maintained DR in the long-term, and more than two thirds of patients in DR achieved also histological remission. CD patients in DR had fewer surgical operations due to CD than patients not achieving DR. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor ( EGFR) tyrosine kinase inhibitors ( TKIs) have changed the treatment strategy for EGFR-mutant lung cancers; however, resistance usually occurs due to a secondary mutation, T790M, in EGFR. Combination therapy using afatinib and cetuximab has had good results in lung tumors harboring EGFRT790M mutations in clinical trials. The effect of bevacizumab, an antivascular endothelial growth factor ( VEGF) antibody, combined with EGFR- TKIs has also been investigated. We hypothesized that the dose of afatinib and cetuximab could be reduced by combination with bevacizumab and that the triplet therapy may result in better tumor inhibition with tolerable toxicity. Using a xenograft mouse model with H1975-harboring EGFRL858R+T790M and RPC-9-harboring EGFR19DEL+T790M, we tested the efficacy of the triplet therapy with a modified dose of afatinib, cetuximab, and bevacizumab, and compared this therapy to single and double therapies. Triplet therapy with afatinib, cetuximab, and bevacizumab induced pathological complete remission in xenograft tumors with H1975 and RPC-9 cells versus tumors treated with single or double therapies. We saw no body weight loss in the mice. The triple therapy induced a significant reduction in CD31-positive vascular endothelial cells and increased cleaved caspase-3-positive cells in the tumors. This suggests that one mechanism underlying the deep remission could be suppression of neovascularization and induction of apoptosis by intensive inhibition of driver oncoproteins and VEGF. These results highlight the potential of afatinib, cetuximab, and bevacizumab to induce deep remission in tumors harboring EGFRT790M mutations. Therefore, clinical trials of this combination therapy are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Deep remission, defined as clinical remission with mucosal healing (MH), with anti-tumor necrosis factor (TNF)-α agents is a new target for therapy in Crohn's disease (CD). Provided that the efficacy of infliximab (IFX) for induction of MH in CD has been demonstrated, there are much less data for adalimumab (ADA), and none concerning MH on histopathological examination. Aim: To assess the impact of biological therapy with ADA on both endoscopic and histopathological MH in paediatric patients with CD. Material and methods: Twenty-three children (10 boys and 13 girls) aged 13.0 ±9.3 years with moderate to severely active CD diagnosed at the mean age of 5.5 ±0.83 years were included into the study. Seven (30.4%) patients had been previously treated with infliximab and switched to ADA due to intolerance or loss of response. Colonoscopy and gastroscopy with sample collection were performed in all patients before and after induction treatment with ADA. Clinical activity of the disease was assessed using the Paediatric Crohn's Disease Activity Index (PCDAI), and the endoscopic activity was scored using the Simple Endoscopic Score (SES-CD). Histological changes were evaluated by a self-adapted numerical scoring system. Results: Four (17.4%) patients reached clinical remission (PCDAI ⩽ 10). When comparing data at baseline and at a week after ADA treatment, a significant decrease was observed in median PCDAI and in SES-CD score between the initial and control colonoscopies. We reported a decrease in histological scale, which was not statistically significant. A correlation was found between PCDAI and SES-CD score. Conclusions: Biological therapy with ADA has a positive impact on endoscopic mucosal healing in paediatric patients with CD, which is not associated with histological evidence of suppression of inflammation. Endoscopic MH correlates better than microscopic one with clinical remission. [ABSTRACT FROM AUTHOR]

Discontinuation of anti–tumor necrosis factor-α treatment (anti-TNF) (infliximab and adalimumab) in patients with inflammatory bowel disease (IBD) is associated with a high relapse risk that may be influenced by endoscopic activity at the time of stopping. We assessed the relapse rate after anti-TNF withdrawal in patients with endoscopic healing and studied predictors of relapse including the depth of endoscopic healing. This was a multicenter, prospective study in adult patients with Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU), with ≥6 months of corticosteroid-free clinical remission (confirmed at baseline) and endoscopic healing (Mayo <2/SES-CD <5 without large ulcers), who discontinued anti-TNF between 2018 and 2020 in the Netherlands. We performed Kaplan-Meier and Cox regression analyses to assess the relapse rate and evaluate potential predictors: partial (Mayo 1/SES-CD 3–4) versus complete (Mayo 0/SES-CD 0–2) endoscopic healing, anti-TNF trough levels, and immunomodulator and/or mesalamine use. Among 81 patients (CD: n = 41, 51%) with a median follow-up of 2.0 years (interquartile range, 1.6–2.1), 40 patients (49%) relapsed. Relapse rates in CD and UC/IBDU patients were comparable. At 12 months, 70% versus 35% of patients with partial versus complete endoscopic healing relapsed, respectively (adjusted hazard rate [aHR], 3.28; 95% confidence interval [CI], 1.43–7.50). Mesalamine use was associated with fewer relapses in UC/IBDU patients (aHR, 0.08; 95% CI, 0.01–0.67). Thirty patients restarted anti-TNF, and clinical remission was regained in 73% at 3 months. The relapse risk was high after anti-TNF withdrawal in IBD patients with endoscopic healing, but remission was regained in most cases after anti-TNF reintroduction. Complete endoscopic healing and mesalamine treatment in UC/IBDU patients decreased the risk of relapse. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Treatment targets of ulcerative colitis (UC) have evolved to include not only endoscopic but also histologic remission. However, the concept of histological activity is still in its early days. We aimed to capture the attitudes toward UC histology and the uptake of standardized reporting of endoscopy and histology of UC in daily practice., Methods: We conducted a cross-sectional survey of physicians involved in the care of inflammatory bowel disease worldwide. The survey included 21 questions divided into three sections. The first recorded demographics, specialty, and level of experience of participants; the second covered clinical practices and attitudes toward the use and reporting of endoscopy; and the third covered histology., Results: In total, 359 participants from 60 countries and all levels of experience completed the survey. UC histology was used by nearly all respondents (90.5%) for initial diagnosis, by 72% to monitor disease course, by 62.4% to determine the microscopic extension, by 59.9% to confirm deep remission when considering to stop treatment, and 42.3% to increase/optimize treatment. Nevertheless 77.2% of participants reported that no standard histological index was available in their daily practice. Instead, endoscopy reports included the Mayo Endoscopic score in 90% of cases. The majority of respondents welcomed as useful or very useful an artificial intelligence system to automate scoring of endoscopy (69%) or histology (73%)., Conclusion: UC histology reports are less standard than endoscopy reports, although most physicians consider histological activity useful when managing UC and would welcome artificial intelligence systems to automate endoscopic and histological scoring., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background & Aims: Recently, treatment goals in inflammatory bowel disease (IBD) in clinical trials have shifted from mainly symptom-based to more mucosa-driven. Real world data on treatment priorities are lacking. We aimed to investigate the current practice and most commonly used definitions of IBD treatment targets among Dutch gastroenterologists. Methods: Dutch gastroenterologists were asked to participate in a computer-based nation-wide survey. We asked questions on demographics, opinion and current practice regarding IBD treatment targets. Results: Twenty-four percent (134/556) of the respondents completed the survey. For both Crohn's disease (CD) (47.3%, 61/129) and ulcerative colitis (UC)(45%, 58/129) the main treatment goal was to achieve and maintain deep remission, defined as clinical, biochemical and endoscopic remission. Seventy-six percent of the participants use mucosal healing (MH) as a potential treatment target for IBD, whereas 22.6% use histological remission. There is no single definition for MH in IBD. The majority use Mayo score ≤ 1 in UC (52%) and 'macroscopic normal mucosa' in CD (66%). Conclusion: More stringent and mucosa-driven treatment targets as 'deep remission' and 'mucosal healing' have found traction in clinical practice. The most commonly used definition for MH in routine practice is endoscopic MAYO score ≤ 1 in UC and 'macroscopic normal mucosa' in CD. [ABSTRACT FROM AUTHOR]

Mucosal healing (MH) is now considered as a major treatment goal in clinical trials and clinical practice for patients with inflammatory bowel disease (IBD). MH is associated with sustained clinical remission, steroid-free remission, and reduced rates of hospitalization and surgery. There is a well-known disconnect between clinical symptoms and mucosal lesions that is more pronounced in CD. More stringent therapeutic goals have been discussed recently such as deep remission defined as clinical remission associated with MH. Recent international guidelines from the IOIBD recommended deep remission as a treatment goal in clinical practice. However there is no validated definition of deep remission in IBD. Also, the efficacy of available drugs to induce and maintain deep remission in IBD is poorly known. Finally, whether deep remission is the best way to modify the course of IBD and whether it should be achieved before considering drug de-escalation have to be formally evaluated in upcoming disease-modification trials. [ABSTRACT FROM AUTHOR]

Introduction: The clinical efficacy of infliximab (IFX) for induction of remission in both adults and children with active Crohn's disease (CD) has been well documented. Recently, so-called "deep remission" defined as mucosal healing has become the ultimate endpoint of the most recent therapeutic advances for CD. However, endoscopic evidence of mucosal healing is not necessarily associated with histological evidence of suppression of inflammation. Aim: Since data on that issue are limited, especially in the paediatric population, the aim of this study was to assess the impact of induction therapy with IFX on deep microscopic remission in paediatric patients with CD. Material and methods: Fifty-six children (32 boys and 24 girls) aged 13.0 ±9.3 years with moderate to severely active CD diagnosed at the mean age of 5.5 ±0.83 years were included into the study. Colonoscopy and gastroscopy with sample collection were performed in all patients before and after three injections of IFX. Clinical activity of the disease was assessed using the Paediatric Crohn's Disease Activity Index (PCDAI), and the endoscopic activity was scored using the Simple Endoscopic Score (SES-CD). Histological changes were evaluated by a previously described numerical scoring system. Results: Thirty-nine (69.6%) patients reached clinical remission (PCDAI ≤ 10). When comparing data at baseline and at week 10, a significant decrease was observed in median PCDAI, and in SES-CD score between the initial and control colonoscopies. We also reported a decrease in histological scale. However, the difference was not statistically significant (p = 0.63). Three (5.4%) patients had a score of zero in the control histological examination. The correlation was found only between histological score and SES-CD score. Clinical remission correlated better with mucosal healing expressed by a decrease in SES-CD score than with microscopic changes. Conclusions: Biological therapy with infliximab enables mucosal healing in paediatric patients with CD, which is not necessarily associated with histological evidence of suppression of inflammation. Mucosal healing correlates better than microscopic healing with clinical remission. [ABSTRACT FROM AUTHOR]

Incidence of Crohn's disease (CD) continues to rise, especially in regions where previously it was not common. Particularly in children, therapy of this condition could be very problematic, since disease presentation and course are more severe than in adults. Nowadays, deep remission (with mucosal - and preferably - transmural healing) represents the major therapeutic goal. Despite enormous progress in development of new drugs, there is yet no cure for CD and no therapy with 100% success. Patients and families should be informed from the beginning about the unpredictability of CD course. Delayed diagnosis could impair a successful therapy, patients presenting with already severe forms of CD. Available medical tools [i.e., exclusive enteral nutrition - EEN, corticoids, anti-tumour-necrosis-factor (TNF) agents] may work well in induction of clinical remission in most patients, however mucosal healing could be obtained especially with EEN and anti-TNF. For prevention of relapses, immunomodulators and anti-TNF could be useful, but long-term deep remission is achieved in less than 50% of patients. Many patients still require surgery and there is no effective therapy to prevent post-surgical recurrence. Most therapies have adverse reactions and benefits and risks should be always discussed with patients and families. Other therapeutic issues that have to be taken into consideration are correction of nutritional deficits, with restoring growth (including bone growth and density) and development, improvement of quality of life and maximization of adherence to therapy. We discuss difficulties in treating CD children, based on the experience of the 2nd Department of Pediatrics, Cluj- Napoca, Romania (1998-2015). [ABSTRACT FROM AUTHOR]

Background Mucosal healing is increasingly recognised as an important treatment goal in Crohn's disease (CD). Data from colonic disease shows improved long-term outcomes in patients achieving complete mucosal healing. Little is currently known of this with regard to ileitis which is increasingly diagnosed using capsule endoscopy (SBCE). This is the first study to prospectively assess mucosal healing and deep remission rates following 52 weeks of therapy in a cohort of symptomatic small bowel CD patients commencing immunomodulator or biologic therapy. Methods Baseline demographics, quality of life questionnaires and Harvey Bradshaw Index were collected along with C-reactive protein & calprotectin. Capsule endoscopy Crohn's disease activity (CECDAI) index was used to assess ileitis severity. All parameters were reassessed at week 52. Results at baseline & week 52 were compared using univariate analysis, p < 0.05 considered significant. Results In total, 108 capsule procedures were performed on 43 patients. Based on the CECDAI, 39 (90%) demonstrated active small bowel CD at baseline with 28 (65%) undergoing 52 week assessment. In total, 12 (42%) participants achieved complete mucosal healing and deep remission by 52 week assessment (p < 0.0001 95% CI − 0.62 to − 0.22). Despite overall impressive mucosal healing rates, patients with strictures were less likely to demonstrate a decrease in CECDAI and were more likely to have symptoms. Conclusion In patients with active small bowel CD symptomatic and biochemical response to treatment appears to be mirrored by endoscopic remission in 42% of individuals. Strictures identified prior to therapy appear to be a poor indicator for success of treatment. [ABSTRACT FROM AUTHOR]

Background & Aims Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. Methods We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. Results Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 μg/g; interquartile range, 136–696 μg/g) than those without active histologic inflammation (68 μg/g; interquartile range, 30–172 μg/g) ( P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. Conclusions Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin. [ABSTRACT FROM AUTHOR]

Background: Clinical remission and endoscopic mucosal healing are the main treatment targets in patients with ulcerative colitis (UC). Recently, the concept of disease clearance has been proposed as a potential target in UC., Objective: We aimed to evaluate the impact of disease clearance on long-term outcomes in UC patients., Methods: A multicenter retrospective cohort study was conducted at the Humanitas Research Hospital-IRCCS (Italy) and at the Nancy University Hospital (France) between 2014 and 2021. Disease clearance in UC was defined as simultaneous clinical (partial-Mayo score ≤2), endoscopic (endoscopic-Mayo score = 0), and histological (Nancy index = 0) remission, and patients were monitored over a long-time follow-up (≥12 months), to compare the occurrence of negative outcomes., Results: A total of 494 patients with UC was included in the study (269, 54.4% males). Disease clearance was present in 109 patients (22.1%) at baseline. Median follow up was 24 months. Patients with disease clearance were associated to a significantly lower risk of UC-related hospitalization compared with the control group (5.5% vs. 23.1%; p < 0.001) at last observation. Similarly, a lower rate of surgeries was detected in patients with disease clearance at baseline compared with those without (1.8% vs. 10.9%; p = 0.003). The Kaplan Meier curves confirmed that patients with disease clearance at baseline had a lower risk of hospitalization (log-rank p < 0.0001) and surgery (log-rank p < 0.00095)., Conclusion: In UC patients with early disease clearance are at significant lower risk for hospitalization and surgery. Disease clearance should be considered as a new composite outcome., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC. on behalf of United European Gastroenterology.)

There is uncertainty regarding the optimal duration of treatment with azathioprine (AZA) in ulcerative colitis (UC) and Crohn's disease (CD). We analyzed the clinical course and predictors of relapse after AZA withdrawal in patients in sustained deep remission. A prospective study was performed on patients who stopped their treatment with AZA while being in steroid-free, extended deep remission (normal clinical, endoscopic, and histologic indexes, C-reactive protein, and fecal calprotectin [FC]). Standard biochemical tests and FC were measured at 3 and 6 months, then every 6 months. Bowel ultrasounds and ileocolonoscopy were performed every 6 and 12 months, respectively. Multivariate analysis for predictors of relapse was performed using a Cox proportional hazards model and hazard ratios were calculated. Spearman nonparametric correlation test was also used. The accuracy of significant predictors was calculated. Fifty-seven patients with inflammatory bowel disease stopped AZA after median 7 years (range, 5–19) and were followed up for median 50 months (range, 25–85). Twenty-six patients (18/31 UC, 8/26 CD; P =.003) relapsed, within a median 15 months (range, 2–37). FC was the only variable significantly correlated with later relapse of both diseases (UC: hazard ratio, 3.3; 95% confidence interval, 1.2–10; CD: hazard ratio, 4.5; 95% confidence interval, 1.4–12.5). The sensitivity, specificity, and positive and negative predictive values of FC were 50%, 100%, 100%, and 59% in UC and 50%, 94%, 80%, and 81% in CD. More than half patients with UC and one-third of patients with CD relapse after AZA withdrawal despite previous deep remission. FC positivity is associated with high risk of relapse, allowing early correction of the therapeutic strategy. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: The ultimate indicator of adherence to a gluten-free diet is the demonstration of mucosal healing. However, the need for histological reassessment is subject to controversy among "experts". The aim of this study was to evaluate celiac patients who underwent histological reevaluation after starting a gluten-free diet in order to identify those with histological remission and associated factors., Methods: This retrospective study included patients who agreed to a histological reassessment after apparent clinical and serological remission and reported at least 12 months of diet adherence. In all cases, informed consent was signed for upper endoscopy., Results: A total of 69 patients were included. In 67.9% of cases, the diagnosis was made in the context of "classic" symptomatology, 17% had "nonclassical" presentation, and 15.1% were in latent phase. 69.2% of the diagnoses were initially suspected by serology. Endoscopically, 11.8% of the patients did not present suggestive features macroscopically, and a histological grade of Marsh IIIa-c was observed in 75.5% of all cases. The histological findings were normalized in 37.7%, which was associated with the presence of lower Marsh score values at diagnosis ( p = 0.014) and lower DEXA T-score values ( p = 0.038). A histological improvement was observed in 55 patients (≥2 grades in 37 cases), which was related to the initial transferrin saturation ( p = 0.027) and with higher Marsh scores at diagnosis ( p = 0.007)., Conclusion: Even under a gluten-free diet, celiac histology normalization is difficult to obtain and appears to be independent of most clinical and serological findings at diagnosis. Patients with less severe histological levels at diagnosis reach remission more easily, but only represent the -minority of the population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 by S. Karger AG, Basel.)

Infliximab (IFX), as a drug of first-line therapy, can alter the natural progression of Crohn's disease (CD), promote mucosal healing and reduce complications, hospitalizations, and the incidence of surgery. Perianal fistulas are responsible for the refractoriness of CD and represent a more aggressive disease. IFX has been demonstrated as the most effective drug for the treatment of perianal fistulizing CD. Unfortunately, a significant proportion of patients only partially respond to IFX, and optimization of the therapeutic strategy may increase clinical remission. There is a significant association between serum drug concentrations and the rates of fistula healing. Higher IFX levels during induction are associated with a complete fistula response in these patients. Given the apparent relapse of perianal fistulizing CD, maintenance therapy with IFX over a longer period seems to be more beneficial. It appears that patients without deep remission are at an increased risk of relapse after stopping anti-tumor necrosis factor agents. Thus, only patients in prolonged clinical remission should be considered for withdrawal of IFX treatment when biomarker and endoscopic remission is demonstrated, especially when the hyperintense signals of fistulas on T2-weighed images have disappeared on magnetic resonance imaging. Fundamentally, the optimal timing of IFX use is highly individualized and should be determined by a multidisciplinary team., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interests., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Pan-enteric capsule endoscopy (PCE) is effective for assessment of small intestinal and colonic Crohn's disease (CD) in pediatric patients. We aimed to determine whether PCE can be used to monitor mucosal healing and deep remission, in a treat to target strategy for pediatric patients with CD. We performed a prospective study of 48 children with a diagnosis of CD at a tertiary care pediatric gastroenterology unit; 46 patients were included in the final analysis. Biomarker, imaging, and PCE analyses were performed at baseline and after 24 and 52 weeks. Small bowel and colonic mucosal healing were defined by Lewis scores <135 and simple endoscopic score for CD ≤1, respectively. Clinical remission was defined as defined as a pediatric CD activity index score <10 and biomarker-based remission based on normal levels of biomarkers; deep remission was defined as a combination of clinical remission, biomarker-based remission, and mucosal healing. Treatments were adjusted based on findings from PCE (imaging was considered only for patients with negative findings from PCE). Therapies were introduced, optimized, switched, or combined at the discretion of treating clinicians. The primary outcome was the ability of PCE to assess mucosal healing and deep remission at 3 timepoints and to guide a treat to target strategy. PCE detected inflammation in 34 patients (71%) at baseline, 22 patients (46%) at week 24, and 18 patients (39%) at week 52 (P for comparison among timepoints <.05). Findings from PCE led to a change in therapy for 34 patients (71%) at baseline and 11 patients (23%) at 24 weeks, whereas only 2 patients with negative results from PCE (4%) changed therapies based on findings from imaging. When the treat to target strategy was applied, proportions of patients with mucosal healing and deep remission increased from 21% at baseline, to 54% at week 24, to 58% at week 52 (P for comparison among timepoints <.05); 2 patients (4%) did not respond to treatment. In a prospective study of 48 children with CD, we found a treat to target strategy, based on findings from PCE, to significantly increase the proportions of patients with mucosal healing and deep remission. Clinical Trial.gov no: NCT03161886. [ABSTRACT FROM AUTHOR]

Background: There is a need to use noninvasive markers in refining the management of ulcerative colitis to reduce the number of unnecessary colonoscopies, which facilitates the follow-up of activity and the response to treatment., Aim: Postulation of a sensitive, specific, simple and noninvasive score to monitor disease activity in ulcerative colitis., Methods: A case-control study was conducted: 168 patients with ulcerative colitis, 40 healthy individuals, and 60 patients for validation. Patients were divided into new diagnosis ( n = 50), clinical remission ( n = 60), and relapse ( n = 58). The main outcome measures if the score correlates with clinical, endoscopic and histopathological characteristics and if it correlates with deep remission., Results: A scoring system was established composed of lactoferrin at a cutoff of 148.5 μg/mL, neutrophil lymphocyte ratio at a cutoff of 2.35, erythrocyte sedimentation rate at the first hour at a cutoff of 29.5 mm/h, C-reactive protein at a cutoff of 3.85 mg/L, mean platelet volume at a cutoff of 8.8 fL, fecal white blood cells at a cutoff of 9 cells/HPF, and fecal red blood cells at a cutoff of 6 cells/HPF. A score ≥5 can detect 94% of cases of UC as determined by the receiver operating characteristic curve with a sensitivity of 94% and a specificity 100%, AUC 0.92, SE 0.05, p = 0.001, 95% CI 0.82-1.1. In the validation group, it identified severely affected patients with a sensitivity of 95% and a specificity of 85.7%., Conclusions: This easily applied and reproducible noninvasive activity score showed high performance in predicting disease activity and deep remission in ulcerative colitis.

Crohn's disease (CD) represents a chronic transmural inflammatory condition of the gastrointestinal tract, which usually leads to structural damage and significant disability. Deep remission - defined by both clinical and endoscopic remission, signifying mucosal healing - represents the current endpoint in the treat-to-target strategy, significantly improving patients' long-term outcomes. Transmural healing (TH) could be a more effective target, but this possibility remains unclear. This narrative review aims to critically review and summarize the available literature relating TH to long-term outcomes, being the first of its kind and to the best of the author's knowledge. A systematic literature search (from inception to March 31 2018) was performed, using multiple databases, and identifying seven full-text manuscripts. In those studies, long-term favorable outcomes (≥ 52 wk) included sustained clinical remission, as well as fewer therapeutic changes, CD-related hospitalizations, and surgeries. Despite heterogeneous design and methodological limitations, six of the studies demonstrated that TH or intestinal healing (TH plus mucosal healing) were predictive for the aforementioned favorable outcomes. Therefore, TH may become a reasonable therapeutic target and be included in the concept of deep remission. Further prospective, well-designed, multicenter trials aiming to better define the role of TH in personalized therapy for CD and to determine the long-term influence of TH on bowel damage and disability are warranted., Competing Interests: Conflict-of-interest statement: The author has no potential conflicts of interest relevant to this publication.