Crohn's Disease Research Articles

Inflammatory bowel disease

Inflammatory bowel diseases, including Crohn disease and ulcerative colitis, have traditionally been diagnosed by performing an endoscopy. This approach is the standard method for diagnostics, but this invasive procedure isn't always the patient's preferred method.

Cost Effectiveness of Sequencing Vedolizumab as First-Line Biologic in Ulcerative Colitis and Crohn's Disease in Canada: An Analysis Using Real-World Evidence from the EVOLVE Study.

Vedolizumab is a gut-selective anti-lymphocyte trafficking biologic indicated for the treatment of adult patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD) in Canada. The objective of this study was to evaluate the cost effectiveness of treatment sequencing for UC and CD from a public healthcare payer perspective, leveraging new real-world evidence from the literature and the EVOLVE study, a retrospective chart review. Using separate decision tree/Markov models to assess cost effectiveness for UC and CD, two sequencing approaches were estimated for adult patients (≥ 18years) diagnosed with UC or CD who were biologic-naïve: vedolizumab as first-line biologic followed by anti-tumor necrosis factor (TNF)-α versus first-line anti-TNFα followed by vedolizumab. Treatment effectiveness (response and remission), surgery rates, dose escalation and regain of response and safety inputs were estimated from EVOLVE, a retrospective chart review of real-world data, and evidence synthesis from the literature, whereas costs and utilities were estimated from health technology assessment reports, clinical trials, and the literature. Biosimilar costs were used for anti-TNFα. Both models simulated a 5-year time horizon and discounted costs and outcomes at 1.5%. Probabilistic base-case analyses (n=10,000) reported total costs (2023 Canadian dollars) and quality-adjusted life-years (QALYs). Several scenario analyses were conducted to explore robustness of results. In UC, vedolizumab as a first-line biologic followed by anti-TNFα resulted in an incremental gain of 0.09 QALYs (2.46 vs. 2.55) and saved $7179 ($134,028 vs. $126,848), making this a dominant strategy compared with first-line anti-TNFα followed by vedolizumab. In CD, use of vedolizumab as a first-line biologic resulted in an incremental gain of 0.04 QALYs (3.35 vs. 3.39) at an incremental cost of $50,631 ($89,850 vs. $140,381) versus first-line anti-TNFα followed by vedolizumab (incremental cost-effectiveness ratio of $1,265,775 per QALY). Based on this analysis, sequencing vedolizumab as a first-line biologic prior to anti-TNFα in UC and CD provided additional clinical benefit to patients. In UC, vedolizumab as a first-line biologic also saved healthcare system costs compared with anti-TNFα, whereas in CD, vedolizumab provided incremental benefit at an incremental cost, which was not considered cost effective at a threshold of $50,000/QALY.

Enhancing radiologist's detection: an imaging-based grading system for differentiating Crohn's disease from ulcerative colitis

BackgroundDelayed diagnosis of inflammatory bowel disease (IBD) is common, there is still no effective imaging system to distinguish Crohn's Disease (CD) and Ulcerative Colitis (UC) patients.MethodsThis multicenter retrospective study included IBD patients at three centers between January 2012 and May 2022. The intestinal and perianal imaging signs were evaluated. Visceral fat information from CT images was extracted, including the ratio of visceral to subcutaneous fat volume (VSR), fat distribution, and attenuation values. The valuable indicators were screened out in the derivation cohort by binary logistic regression and receiver working curve (ROC) analysis to construct an imaging report and data system for IBD (IBD-RADS), which was tested in the validation cohort.ResultsThe derivation cohort included 606 patients (365 CD, 241 UC), and the validation cohort included 155 patients (97 CD, 58 UC). Asymmetric enhancement (AE) (OR = 87.75 [28.69, 268.4]; P < 0.001), perianal fistula (OR = 4.968 [1.807, 13.66]; P = 0.002) and VSR (OR = 1.571 [1.087, 2.280]; P = 0.04) were independent predictors of CD. VSR improved the efficiency of imaging signs (AUC: 0.929 vs. 0.901; P < 0.001), with a threshold greater than 0.97 defined as visceral fat predominance (VFP). In IBD-RADS, AE was the major criterion, VFP and perianal fistula were auxiliary criteria, and intestinal fistula, limited small bowel disease, and skip distribution were special favoring items as their 100% specificity. Grade 3 to 5 correctly classified most CD patients (derivation: 96.5% (352/365), validation: 98.0% (95/97)), and 98% of those were eventually diagnosed with CD (derivation: 97.8% (352/360), validation: 98.0% (95/97)).ConclusionsIBD-RADS can help radiologists distinguish between CD and UC in patients with suspected IBD.

TOpClass Class 4 Perineal Crohn's Disease: A Systematic Review and Meta-analysis of Perineal Wound Complication After Proctectomy in Crohn's Patients.

Nonhealing perineal wounds have been reported to be common after proctectomy for Crohn's disease (CD). We performed a systematic review and meta-analysis of perineal wound healing after proctectomy for CD and assessed the risk factors for nonhealing. A comprehensive literature search was conducted in PubMed, Embase, and Scopus databases from 2010 to 2023, and articles reporting perineal wound healing rates after proctectomy for CD were included. Data on study characteristics and proportion of healed wounds, and risk factors, were extracted. Random-effects meta-analysis was performed to estimate the pooled proportion and 95% CIs using the "meta" package in R. Heterogeneity was assessed using the I2 statistic. We identified 501 articles, of which 252 remained after de-duplication. After screening, 4 retrospective cohort studies involving 333 patients were included. Across the 4 studies, the pooled proportion of completely healed perineal wounds at 6 months was 65% (95% CI 52%-80%), and 70% (95% CI 60%-83%) at 12 months. Significant heterogeneity was found between studies (I2 = 86% at 6 months). Three studies examined risk factors for impaired healing after proctectomy. One study identified preoperative perineal sepsis as the only independent factor associated with impaired healing (P = .001) on multivariable analysis. In 1 study, male sex, shorter time from diversion to proctectomy, and higher preoperative C-reactive protein levels were all associated with delayed healing in univariate analysis. Another study found that close rectal dissection was associated with significantly lower healing rates than total mesorectal excision (P = .01). Prior use of tumor necrosis factor inhibitors was not associated with wound healing outcomes. This meta-analysis revealed complete perineal healing in only 70% of patients 12 months after proctectomy for CD. This highlights knowledge gaps, including the identification of modifiable risk factors and methods for preventing or as rescue therapy, such as vacuum-assisted closure and flap reconstruction, for nonhealing perineal wounds after proctectomy for CD. Poor perineal wound healing outcomes are likely related to imperfectly understood underlying inflammatory dysregulation and systemically impaired wound healing in patients with CD.

Worldwide research trends in Crohn's disease treatment over the past 2decades: a bibliometric analysis.

The treatment of Crohn's disease (CD) has received widespread attention in clinical practice, but there is currently a lack of quantitative evaluation of the literature published in this field. This study aimed to describe the development trends and research hotspots of CD treatment through bibliometric analysis. Publications related to CD treatment published from 2004 to 2023 were searched in the WoSCC. Microsoft Office Excel 2021 was used for the analysis and visualization of the annual number of publications. CiteSpace was used to visualize the collaboration networks of authors, institutions, and countries, as well as to construct a reference timeline visualization map and identify keywords with the strongest citation bursts. The bibliometric analysis included 25,608 publications between 2004 and 2023. The most productive year was 2021. The United States of America (n = 7,891) and the University of California System (n = 939) are the country and institution with the most published papers, respectively. Among the 97,564 authors, Peyrin-Biroulet, Laurent (n = 424) published the most articles. The core journals were Inflammatory Bowel Diseases, Journal of Crohns and Colitis, Alimentary Pharmacology and Therapeutics, etc. The timeline view showed that "#5 JAK Inhibitor" was the most recent topic. The keywords that burst and persist from 2020 to 2023 include "ustekinumab" and "vedolizumab". An increasing number of researchers are dedicating their efforts to exploring the treatment of CD, with the United States making the largest contribution to this field. Currently, the research hotspots predominantly involve drug therapy including ustekinumab, vedolizumab, and JAK inhibitors. Our study provides valuable information for scholars studying CD treatment.

Interpreting modern randomized controlled trials of medical therapy in inflammatory bowel disease.

Treatment options for the medical management of inflammatory bowel disease (IBD) have expanded substantially over the past decade. Multiple classes of advanced therapies, including both monoclonal antibodies and novel oral small molecules, are now available for the treatment of moderately-to-severely active Crohn's disease and ulcerative colitis, highlighted by the approvals of the first IL23p19 antagonists, selective Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators. These advances have been accompanied by the identification of novel targets and the rapid growth in both the number and size of IBD clinical trials. Over a dozen landmark randomized controlled trials (RCTs) have been completed in the past 5 years, including the first head-to-head biologic trials, the first combination biologic studies, and multiple phase III registrational trials of novel compounds with new co-primary and composite end points that will change the treatment landscape for years to come. Importantly, the methodology of RCTs in IBD has evolved substantially, with new trial designs, evaluation of unique patient populations, and different types of efficacy and safety end points being key innovations. In this Review, we provide a comprehensive evaluation of how modern RCTs of IBD medical therapies have evolved and the implications for their appraisal that will help guide the application of these data to clinical practice.

Current State of Scientific Knowledge on Curcumin Encapsulation and Applications.

The yellow pigment curcumin has long been used in traditional medicine for its anti-inflammatory, antibacterial and antioxidant activities. Over the past half-century, scien-tific investigations have shown that curcumin is endowed with additional health benefits be-cause it can modify key molecular targets associated with a number of pathologies, such as diabetes, cancer, and arthritis, in addition to cardiovascular, multiple sclerosis, Alzheimer's, and Crohn's diseases. However, this molecule has several disadvantages, such as low bioavail-ability and solubility, severe oxidative destruction, light sensitivity, fast systemic clearance and breakdown at alkaline pH levels. To address these drawbacks, several methods of micro-encapsulation employing a variety of shell materials have been investigated. These techniques contributed toward the increase of curcumin's solubility and stability against heat, light, oxy-gen, and an alkaline pH. The various shell materials and methods used to microencapsulate this chemical are the main topics of this review. The use of microencapsulated curcumin in food, medicine, and cosmetics is also discussed in more detail. Recent relevant research from the last few years has been given in this area, along with future difficulties.

Emerging Nanoparticle-Based Herbal Drug Delivery Systems for Colon Targeting Therapy

Abstract: Herbal medications hold a dominant position in the pharmaceutical sector due to their well-established therapeutic effects and extremely low negative effects. Besides, herbal remedies are easily available and highly economical. However, to circumvent the issue of poor bioavailability, the combinatorial strategy of incorporating herbal medicines and nano-technology is useful. The phytoconstituents molded in novel nanocarriers such as polymeric nanoparticles, polymeric micelles, liposomes, solid lipid nanoparticles, nanostructured lipid carriers, nanoemulsions, gold nanoparticles, etc., have been extensively investigated as they are the most promising approach for colon-targeting drug delivery systems. Although plant-based medicines have been developed for decades, there is enormous research interest in the development of an effective plant-derived delivery system for the incorporation of phytocon-stituents into various nanomaterials to overcome potential challenges related to solubility, bioavailability, and stability issues. The encapsulation of phytoconstituents in a novel nanocarrier is a promising approach to improving the bioavailability, stability, and therapeutic efficacy of herbal medicines. The herbal nanomedicines are used as a promising tool for tar-geted delivery to the colon, with potentially effective outcomes for the treatment of colonic diseases, viz., ulcerative colitis, diverticulitis, Crohn's disease, shigellosis, constipation, co-lonic polyps, colon cancer, etc. This article presents a comprehensive survey of recent find-ings and patents by innovators working exclusively on nanoparticles for the delivery of phy-tomedicines for colon targeting.

Human Amniotic Epithelial Stem Cells Promote Colonic Recovery in Experimental Colitis via Exosomal MiR-23a-TNFR1-NF-κB Signaling.

Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease, manifests as chronic intestinal inflammation with debilitating symptoms, posing a significant burden on global healthcare. Moreover, current therapies primarily targeting inflammation can lead to immunosuppression-related complications. Human amniotic epithelial stem cells (hAESCs), which exhibit low immunogenicity and ethical acceptability, have gained attention as potential therapeutics. In this study, it is demonstrated that their encapsulation in a hydrogel and administration via anal injection enhanced the colonic mucosal barrier repair in a murine colitis model induced by dextran sodium sulfate during the recovery phase. The underlying mechanism involved the release of exosomes from hAESCs enriched with microRNA-23a-3p, which post-transcriptionally reduced tumor necrosis factor receptor 1 expression, suppressing the nuclear factor-κB pathway in colonic epithelial cells, thus played a key role in inflammation. The novel approach shows potential for IBD treatment by restoring intestinal epithelial homeostasis without the immunosuppressive therapy-associated risks. Furthermore, the approach provides an alternative strategy to target the key molecular pathways involved in inflammation and promotes intestinal barrier function using hAESCs and their secreted exosomes. Overall, this study provides key insights to effectively treat IBD, addresses the unmet needs of patients, and reduces related healthcare burden.

Calcitonin gene-related peptide promotes epithelial reparative and anti-colitic functions of IL-4 educated human macrophages.

Interleukin-4 activated human macrophages (M(IL4) promote epithelial wound healing and exert an anti-colitic effect in a murine model. Blood monocyte-derived M(IL4)s from healthy donors and individuals with Crohn's disease had increased mRNA expression of the calcitonin gene-related peptide (CGRP) receptor chain, RAMP1, raising the issue of neural modulation of the M(IL4)s reparative function. Thus, human (MIL4)s were treated with CGRP and the cells phagocytotic, epithelial wound repair and anti-colitic functions were assessed. Initial studies confirmed up-regulation of expression of the CGRP receptor, which was localized to the cell surface and was functional as determined by CGRP-evoked increases in cAMP. M(IL4,CGRP)s had increased mannose receptor (CD206) and FcgRIIa (CD32a) mRNA expression, a subtle, but significant increase in phagocytosis, and decreased chemokine production following exposure to E. coli. When delivered systemically (106 cells, ip.) to oxazolone-treated rag1-/- mice, M(IL4,CGRP) had an anti-colitic effect superior to M(IL4)s from the same blood donor. Conditioned medium (CM) from M(IL4,CGRP) had increased amounts of TGFb and increased wound-healing capacity compared to matched M(IL4)-CM in the human CaCo2 epithelial cell line in vitro wounding assay. Moreover, M(IL4,CGRP)s displayed increased cyclooxygenase (COX)-1 and prostaglandin D2, and CM from M(IL4,CGRP)s treated with indomethacin or SC-560 to inhibit COX1 activity failed to promote repair of wounded CaCo2 cell monolayers. These data confirm the human M(IL4)s' anti-colitic effect that was enhanced by CGRP, and may be partially dependent on macrophage COX1/PDG2 activity. Thus, input from neurone-derived molecules is a local modifier capable of boosting the anti-colitic effect of autologous M(IL4) transfer.

Risk factors affecting relapse after discontinuation of biologics in children with Crohn's disease who maintained deep remission.

Biologics are important therapeutic agents for pediatric Crohn's disease. Discontinuation of biologics is known to increase the relapse rate up to 71.4% in these patients; however, their long-term use increases the risk of opportunistic infections and causes economic burden and psychological fatigue. Therefore, taking a drug holiday is meaningful, even if the biologics cannot be completely discontinued. This study aimed to analyze the risk factors affecting relapse after discontinuation of biologics in children with Crohn's disease. We retrospectively reviewed the data of 435 children with Crohn's disease who visited a single health center between March 2013 and March 2021. Subsequently, we analyzed data from the patients who discontinued biologics after deep remission. Among the enrolled patients, 388 were followed up for ≥2 years, and of these, 357 were administered biologics. A total of 103 patients discontinued biologics after deep remission, subsequently 31 maintained remission and 72 relapsed. The shorter the duration of biologic treatment (odds ratio of 0.444, P = 0.029), the higher the ESR (odds ratio of 1.294, P = 0.009) and fecal calprotectin (odds ratio of 1.010, P = 0.032), and the less histological remission at the time of discontinuation of biologics (odds ratio of 0.119, P = 0.026), the greater the risk of relapse after discontinuation of biologics. We identified factors associated with relapse after discontinuation of biologics. The results suggest that biologics can be discontinued in the absence of these factors after deep remission. However, because the relapse rate may increase after the discontinuation of biologics, close monitoring is important, and if necessary, re-administration of biologics should be actively considered.

Association of Crohn’s Disease and Hepatic Cirrhosis Post-Primary Sclerosing Cholangitis: A Case Report

Primary sclerosing cholangitis (PSC) is a distinct entity associated with inflammatory bowel disease (IBD). We report the case of a 49-year-old patient with ileocecal Crohn’s disease of the stenosing phenotype, presenting with perianal lesions in the form of fistulas, who was diagnosed with PSC complicated by hepatic cirrhosis following the development of clinical and biological cholestasis, as well as his first ascitic decompensation. After initiating treatment with azathioprine for Crohn's, he experienced significant abdominal pain, ascites, and jaundice, leading to further investigations. MRI revealed bile duct stenosis, and endoscopic procedures confirmed portal hypertension. After excluding secondary causes, a diagnosis of PSC was made. Treatment with methotrexate and ursodeoxycholic acid resulted in clinical improvement. The discussion emphasizes the rare but notable association between Crohn's disease and PSC, outlining diagnostic challenges and management strategies. It highlights the poor prognosis linked to PSC, including risks of cirrhosis and colorectal cancer, with recommendations for regular monitoring and surveillance for dysplasia in patients with both conditions. Overall, the study underscores the need for careful management and ongoing research into effective treatments for this challenging dual diagnosis.

Impact of inflammatory bowel diseases on the intimate lives of youths: Creating a brief screening questionnaire.

The objectives were to describe the challenges faced by youths with inflammatory bowel disease (IBD) in their intimate lives before the onset of sexual activity and develop a screening tool to detect early difficulties. We conducted a cross-sectional qualitative study via semi-structured interviews with 15-19-year-olds diagnosed with IBD. To be eligible for inclusion, these adolescents had to respond having not yet started their sexual life. This led to a collaborative development of a detection tool with a multidisciplinary team to evaluate adolescents' intimate life stage and to early screen difficulties. Fifteen subjects were recruited. Among them eight were males, 10 were followed for Crohn's disease while five were followed for ulcerative colitis. The median age was 16 years. Nine out of fifteen teenagers felt unprepared and reluctant for intimate relationship. Teenagers who have started their romantic journey, expressed satisfaction with their intimate lives, but the possibility of experiencing diarrhea or abdominal pain during intimate moments may be a concern. The study highlights a general reluctance among adolescents with IBD to engage in intimate relationships, and IBD symptoms may be a concern for intimate life. It resulted in the creation of a brief detection tool allowing clinicians to early screen and address intimate life issues, fostering better support for this vulnerable group's challenges.

Advances in Colon-Targeted Drug Delivery Systems: Innovative Strategies for Treating Colonic Disorders and Prospects for the Future.

Colon-specific targeting delivery systems have drawn a great deal of attention because they represent potential vehicles for treating colonic disorders like diverticulitis, colitis, salmonellosis, Crohn's disease, etc. with less systemic adverse effects as well as for the better oral delivery of many therapeutics that are prone to enzymatic and acidic deterioration in the upper GI tract. Smart polymeric delivery systems in particular have been investigated as "intelligent" delivery systems capable of releasing entrapped pharmaceuticals at the proper time & site of action in response to certain physiological stimuli. The creation of novel polymers & crosslinkers with improved biodegradability and biocompatibility would expand and enhance applications now in use. The development of polymeric systems could result in more precise and programmable drug delivery/therapies. In addition, newer advancements have led to the development of numerous ground-breaking techniques for directing a medication molecule to the colon. This review highlighted formulation techniques pH-dependent, time-dependent, enzyme sensitive, magnetically dependent, ligand-receptor mediated, and microflora-activated systems. Moreover, several methods have been put forth that make use of the innovative idea of such delivery systems, and mechanisms in which the release of drugs is regulated by pH and time as well as pH and the colon's bacteria.

Role of glucocorticoid receptor beta in the development of steroid resistance

Glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs for the treatment of inflammatory diseases, despite the fact that the resistance to them is increasing due to various circumstances. GC insensitivity is an important clinical issue that is associated with life-threatening disease progression. Currently, there is no reliable biomarker that can be used to define steroid resistance. According to several studies, increased expression of the glucocorticoid receptor beta (GR-β) isoform is associated with steroid resistance. The purpose of this review is to analyse the correlation between GR-β expression and the occurrence of steroid therapy-resistant diseases and to determine its potential as a biomarker. This review summarizes studies that point out increased GR-β expression in steroid-resistant groups of patients compared to steroid-sensitive groups. Articles included in the review focus on asthma, nasal polyposis, ulcerative colitis, and other chronic inflammatory diseases in which resistance to steroid therapy is observed. GR-β levels have also been shown to be elevated in patients with allergic rhinitis, Crohn's disease and rheumatoid arthritis. In most studies, higher levels of GR-β were detected in peripheral blood mononuclear cells (PBMC) by reverse transcription polymerase chain reaction (RT-PCR). Increased expression of GR-β is mostly associated with steroid resistance. Thus, it can potentially be used as a biomarker of steroid resistance-related disorders.

Evaluating genetic insights into ulcerative colitis and anxiety: Limitations and future directions.

We reviewed the study by He et al, which investigates the genetic correlation between ulcerative colitis (UC) and anxiety using bidirectional Mendelian randomization. This study reveals a genetic link between UC and anxiety, diverging from prior research associating higher anxiety with Crohn's disease. While the study's use of large-scale genome-wide association studies data is commendable, it faces limitations such as single nucleotide polymorphism selection biases, lack of multiple testing corrections, and a reliance on European populations. Future research should address these limitations, incorporate diverse populations, and explore psychotherapeutic interventions to improve UC management and patient outcomes.

Feature Pyramid Network Based Spatial Attention and Cross‐Level Semantic Similarity for Diseases Segmentation From Capsule Endoscopy Images

ABSTRACTAs an emerging technology that uses a pill‐sized camera to visualize images of the digestive tract. Wireless capsule endoscopy (WCE) presents several advantages, since it is far less invasive, does not need sedation and has less possible complications compared to standard endoscopy. Hence, it might be exploited as alternative to the standard procedure. WCE is used to diagnosis a variety of gastro‐intestinal diseases such as polyps, ulcers, crohns disease, and hemorrhages. Nevertheless, WCE videos produced after a test may consist of thousands of frames per patient that must be viewed by medical specialists, besides, the capsule free mobility and technological limits cause production of a low quality images. Hence, development of an automatic tool based on artificial intelligence might be very helpful. Moreover, most state‐of‐the‐art works aim at images classification (normal/abnormal) while ignoring diseases segmentation. Therefore, in this work a novel method based on Feature Pyramid Network model is presented. This approach aims at diseases segmentation from WCE images. In this model, modules to optimize and combine features were employed. Specifically, semantic and spatial features were mutually compensated by spatial attention and cross‐level global feature fusion modules. The proposed method testing F1‐score and mean intersection over union are 94.149% and 89.414%, respectively, in the MICCAI 2017 dataset. In the KID Atlas dataset, the method achieved a testing F1‐score and mean intersection over union of 94.557% and 90.416%, respectively. Through the performance analysis, the mean intersection over union in the MICCAI 2017 dataset is 20.414%, 18.484%, 11.444%, 8.794% more than existing approaches. Moreover, the proposed scheme surpassed the methods used for comparison by 29.986% and 9.416% in terms of mean intersection over union in KID Atlas dataset. These results indicate that the proposed approach is promising in diseases segmentation from WCE images.

Gastrointestinal: Leveraging intestinal ultrasound to guide endoscopic closure of the internal opening of a vesico-sigmoid fistula in ileo-colonic Crohn's disease.

Gastrointestinal: Leveraging intestinal ultrasound to guide endoscopic closure of the internal opening of a vesico-sigmoid fistula in ileo-colonic Crohn's disease.

Defining mucosal healing in randomized controlled trials of inflammatory bowel disease: A systematic review and future perspective.

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). We searched MEDLINE, EMBASE, and the Cochrane library from inception to December 2023 for phase 2 and 3 RCTs of advanced therapies in IBD. 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. 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.

Enhanced Transcription of Human Endogenous Retroviruses and TRIM28 Downregulation in Patients with Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) includes patients affected by Crohn's disease or ulcerative colitis. IBD is thought to be a chronic immune-mediated disease, but its origin remains elusive, and this limits new therapeutic approaches. Human endogenous retroviruses (HERVs) originate from ancestral infections and represent 8% of the human genome. HERVs are no longer infectious, but some retroviral sequences can be activated, and their aberrant expressions have been implicated in inflammatory and autoimmune disorders. HERV transcription is regulated by TRIM28 and SETDB1, which are also directly involved in epigenetic processes and modulation of the immune response. Using a PCR real-time Taqman amplification assay, we assessed, for the first time, the transcription levels of pol genes of HERV-H, -K, and -W families of env genes of syncytin 1 (SYN1), SYN2, and HERV-W, as well as of TRIM28 and SETDB1 in the whole blood of 48 patients with Crohn's disease (CD), 20 with ulcerative colitis (UC), and in healthy controls (HC) of comparable age. The transcriptional levels of HERV-H-pol (p = 0.0003) and HERV-K-pol (p = 0.001) were significantly higher in IBD patients compared with HC, with no differences between patients with CD and UC. No significant differences were found for the remaining HERVs between IBD patients and HC. The transcript levels of TRIM28 were significantly downregulated in IBD patients (p < 0.001), without differences between CD and UC, while the SETDB1 levels were preserved. The enhanced transcription of HERV-H-pol and HERV-K-pol, as well as the impaired activation of TRIM28, were not influenced by clinical disease activity and type of treatment. The overexpression of HERVs and impaired transcription of TRIM28 in patients affected by CD or UC suggest that they might be the main actors in the pathophysiology of IBD, opening the way to innovative targeted interventions.