Artificial intelligence and inflammatory bowel disease: Where are we going?

Inflammatory bowel diseases,namely ulcerative colitis and Crohn’s disease,are chronic and relapsing conditions that pose a growing burden on healthcare systems worldwide.Because of their complex and partly unknown etiology and pathogenesis,the management of ulcerative colitis and Crohn’s disease can prove challenging not only from a clinical point of view but also for resource optimization.Artificial intelligence,an umbrella term that encompasses any cognitive function developed by machines for learning or problem solving,and its subsets machine learning and deep learning are becoming ever more essential tools with a plethora of applications in most medical specialties.In this regard gastroenterology is no exception,and due to the importance of endoscopy and imaging numerous clinical studies have been gradually highlighting the relevant role that artificial intelligence has in inflammatory bowel diseases as well.The aim of this review was to summarize the most recent evidence on the use of artificial intelligence in inflammatory bowel diseases in various contexts such as diagnosis,follow-up,treatment,prognosis,cancer surveillance,data collection,and analysis.Moreover,insights into the potential further developments in this field and their effects on future clinical practice were discussed.

Fecal microbiota transplantation for the treatment of irritable bowel syndrome:A systematic review and meta-analysis

BACKGROUND Irritable bowel syndrome(IBS)is the most prevalent gastrointestinal disorder in developed countries and reduces patients’quality of life,hinders their ability to work,and increases health care costs.A growing number of trials have demonstrated an aberrant gut microbiota composition in IBS,also known as‘gut dysbiosis’.Fecal microbiota transplantation(FMT)has been suggested as a treatment for IBS.AIM To assess the efficacy and safety of FMT for the treatment of IBS.METHODS We searched Cochrane Central,MEDLINE,EMBASE and Web of Science up to 24 October 2022 for randomised controlled trials(RCTs)investigating the effectiveness of FMT compared to placebo(including autologous FMT)in treating IBS.The primary outcome was the number of patients with improvements of symptoms measured using a validated,global IBS symptoms score.Secondary outcomes were changes in quality-of-life scores,non-serious and serious adverse events.Risk ratios(RR)and corresponding 95%CI were calculated for dichotomous outcomes,as were the mean differences(MD)and 95%CI for continuous outcomes.The Cochrane risk of bias tool was used to assess the quality of the trials.GRADE criteria were used to assess the overall quality of the evidence.RESULTS Eight RCTs(484 participants)were included in the review.FMT resulted in no significant benefit in IBS symptoms three months after treatment compared to placebo(RR 1.19,95%CI:0.68-2.10).Adverse events were reported in 97 participants in the FMT group and in 45 participants in the placebo group(RR 1.17,95%CI:0.63-2.15).One serious adverse event occurred in the FMT group and two in the placebo group(RR 0.42,95%CI:0.07-2.60).Endoscopic FMT delivery resulted in a significant improvement in symptoms,while capsules did not.FMT did not improve the quality of life of IBS patients but,instead,appeared to reduce it,albeit non significantly(MD-6.30,95%CI:-13.39-0.79).The overall quality of the evidence was low due to moderate-high inconsistency,the small number of patients in the studies,and imprecision.CONCLUSION We found insufficient evidence to support or refute the use of FMT for IBS.Larger trials are needed.

生物制剂时代炎症性肠病的外科治疗

随着生物制剂的广泛应用,炎症性肠病(inflammatory bowel diseases,IBD)的治疗发生了巨大的变化.外科手术在治疗中仍然起到了必不可少的作用.且随着越来越多的患者接受生物制剂治疗,外科手术也需适应生物制剂时代对疾病产生的影响.本文旨在综述生物制剂时代外科治疗在IBD治疗中的作用,以及这些药物对围手术期的影响.

Secondary causes of inflammatory bowel diseases

Inflammatory bowel diseases(IBD),conventionally consist of Crohn’s disease(CD)and ulcerative colitis.They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors.The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis,which in turn is triggered due to exposure to various inciting environmental factors.But there is no clearly defined etiology of IBD and this type of disease is termed as“idiopathic IBD”,“classic IBD”,or“primary IBD”.We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions,and we consider this form of de novo IBD as“secondary IBD”.Currently known factors that are potentially responsible for giving rise to secondary IBD are medications;bowel altering surgeries and transplantation of organs,stem cells or fecal microbiome.Medications associated with the development of secondary IBD include;immunomodulators,anti-tumor necrosis factor alpha agents,anti-interleukin agents,interferons,immune stimulating agents and checkpoint inhibitors.Colectomy can in some cases give rise to de novo CD,pouchitis of the ileal pouch,or postcolectomy enteritis syndrome.After solid organ transplantation or hematopoietic stem cell transplantation,the recipient may develop de novo IBD or IBD flare.Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.

Special issues in pediatric inflammatory bowel disease

The incidence of pediatric inflammatory bowel disease (IBD) is rising and recent advances in diagnostics and therapeutics have improved the care provided to these children. There are distinguishing features worth noting between early onset and adult onset IBD. Physical and psychosocial development remains a critical target for the comprehensive management of pediatric IBD. Children are not just little adults and consideration must be given to the stages of development and how these stages impact disease presentation and management. The final stage will be the transition from pediatric care to that of adult oriented care and special consideration must be given to make this a successful process. This review highlights special considerations in the management of the child with IBD.

Serologic and laboratory markers in prediction of the disease course in inflammatory bowel disease

The search for biologic markers that can assess the natural history and perhaps predict the course of individual's disease including response to treatments over time has become an important focus of inflammatory bowel disease research.The knowledge of an individual's prognosis can help physicians and patients make important management decisions and aid communication on risk and benefits of disease and treatment.

Microscopic features of colorectal neoplasia in inflammatory bowel diseases

The risk of developing dysplasia leading to colorectal cancer(CRC)is increased in both ulcerative colitis and Crohn’s disease.The prognosis of CRC may be poorer in patients with inflammatory bowel disease(IBD)than in those without IBD.Most CRCs,in general,develop from a dysplastic precursor lesion.The interpretation by the pathologist of the biopsy will guide decision making in clinical practice:colonoscopic surveillance or surgical management.This review summarizes features of dysplasia(or intraepithelial neoplasia)with macroscopic and microscopic characteristics.From an endoscopic(gross)point of view,dysplasia may be classified as flat or elevated(raised);from a histological point of view,dysplasia is separated into 3 distinct categories:negative for dysplasia,indefinite for dysplasia,and positive for dysplasia with low-or high-grade dysplasia.The morphologic criteria for dysplasia are based on a combination of cytologic(nuclear and cytoplasmic)and architectural aberrations of the crypt epithelium.Immunohistochemical and molecular markers for dysplasia are reviewed and may help with dysplasia diagnosis,although diagnosis is essentially based on morphological criteria.The clinical,epidemiologic,and pathologic characteristics of IBD-related cancers are,in many aspects,different from those that occur sporadically in the general population.Herein,we summarize macroscopic and microscopic features of IBD-related colorectal carcinoma.

Microbial dysbiosis in spouses of ulcerative colitis patients: any clues to disease pathogenesis?

A number of alterations have been found within the gutmicrobial profile of patients with inflammatory bowel diseases when compared with the healthy population; however, it is unclear whether such dysbiosis is the cause or simply the consequence of the disease state. In ulcerative colitis, the environment seems to play a crucial role in disease etiology since monozygotic twins show a concordance rate of only 8%-10%-though it is unclear whether it does so by acting through the microbiome. In this study, the authors investigated the influence of cohabitation on the gut microbial community in healthy partners of ulcerative colitis patients-with the intent of clarifying some of these issues. As expected, ulcerative colitis patients had a significant dysbiosis and alterations in microbial metabolism. Interestingly, these abnormal fecal microbial communities were relatively similar amongst patients and their spouses. Thus, this study shows that the microbial profile might be partially transferred from ulcerative colitis patients to healthy individuals. Whether this finding impacts on disease development or has any implication for the role of the microbiome in inflammatory bowel disease etiology remains to be determined.

What's hot in inflammatory bowel disease in 2011?

Ulcerative colitis and Crohn's disease(CD) are the two major forms of inflammatory bowel disease(IBD).In this highlight topic series of articles,the most recent advances in the IBD field are reviewed,especially the newly described cytokines,including the therapeutic implications for their manipulation.In addition,the interplay between the intestinal microbiota and the host is reviewed,including the role of defensins and dysbiosis in CD pathogenesis.Finally,the importance of the non immune systems such as endothelial cells and the hemostatic system are highlighted as new players in IBD pathogenesis.

Isoleucine, an Essential Amino Acid, Induces the Expression of Human <i>β</i>Defensin 2 through the Activation of the G-Protein Coupled Receptor-ERK Pathway in the Intestinal Epithelia

Anti-microbial peptides are essential for the intestinal innate immunity that protects the intestinal epithelia from attacks by foreign pathogens. Human β-defensin (HBD) is one of the pivotal anti-microbial peptides that are expressed in the colonic epithelia. This study investigated the effect and the signaling mechanism of inducible β-defensin HBD2 by an essential amino acid, isoleucine (Ile) in colonic epithelial cells. Here we examined the expression level of HBD2 on induction of Ile in epithelial cells, and checked this pathway. HBD2 mRNA was induced by co-incubation with IL-1α and Ile in Caco2 cells, but not by Ile alone. An inhibitor of either ERK or Gi, a subunit of G-proteins, reduced the induction of HBD2 mRNA by Ile. The treatment with Ile also increased the intracellular calcium ion concentration, thus suggesting that the GPCR and ERK signaling pathway mediate the effects of Ile. These results indicate that an essential amino acid, Ile, enhances the expression of an inducible β-defensin, namely HBD2, by IL-1α through the activation of GPCRs and ERK signaling pathway. The administration of Ile may therefore represent a possible option to safely treat intestinal inflammation.

Effectiveness, safety, and drug sustainability of biologics in elderly patients with inflammatory bowel disease: A retrospective study

BACKGROUND Biologic therapy resulted in a significant positive impact on the management of inflammatory bowel disease(IBD) however data on the efficacy and side effects of these therapies in the elderly is scant.AIM To evaluate retrospectively the drug sustainability, effectiveness, and safety of the biologic therapies in the elderly IBD population.METHODS Consecutive elderly(≥ 60 years old) IBD patients, treated with biologics [infliximab(IFX), adalimumab(ADAL), vedolizumab(VDZ), ustekinumab(UST)] followed at the McGill University Inflammatory Bowel Diseases Center were included between January 2000 and 2020.Efficacy was measured by clinical scores at 3, 6-9 and 12-18 mo after initiation of the biologic therapy. Patients completing induction therapy were included. Adverse events(AEs) or serious AE were collected during and within three months of stopping of the biologic therapy.RESULTS We identified a total of 147 elderly patients with IBD treated with biologicals during the study period, including 109 with Crohn’s disease and 38 with ulcerative colitis. Patients received the following biologicals: IFX(28.5%), ADAL(38.7%), VDZ(15.6%), UST(17%). The mean duration of biologic treatment was 157.5(SD = 148) wk. Parallel steroid therapy was given in 34% at baseline,19% at 3 mo, 16.3% at 6-9 mo and 6.5% at 12-18 mo. The remission rates at 3, 6-9 and 12-18 mo were not significantly different among biological therapies. Kaplan-Meyer analysis did not show statistical difference for drug sustainability(P = 0.195), time to adverse event(P = 0.158) or infection rates(P = 0.973) between the four biologics studied. The most common AEs that led to drug discontinuation were loss of response, infusion/injection reaction and infection.CONCLUSION Current biologics were not different regarding drug sustainability, effectiveness, and safety in the elderly IBD population. Therefore, we are not able to suggest a preferred sequencing order among biologicals.

Role of bowel ultrasound in the management of postoperative Crohn's disease

The use of biological and immunosuppressive therapy in Crohn's disease(CD) changed favorably the course of the disease and is currently suggested in the prevention of clinical recurrence. Symptomatic exacerbation is a feature of the natural course of the disease. Endoscopic recurrence may occur earlier than clinical manifestations and its rate is still high ever since the first year after surgery. The severity of mucosal lesions is highly predictive of a new flare of the disease so that the early detection of recurrence warrants strong therapeutic changes or a closer monitoring of the case. Endoscopy is at present the gold-standard technique for the diagnosis and grading of recurrence severity, but is poorly accepted by patients for its invasiveness. A simple and easy repeatable examination able to detect early signs of recurrence could be useful in the follow-up as an alternative or as a backing in the choice of the right timing for endoscopy in questionable cases. The use of bowel ultrasound(B-US) in the management of CD has grown in the past twenty years. Its accuracy in the real time detection of the disease and its complications, known since the 80's, together with the non-invasiveness, low cost and wide availability of the technique have influenced the extension of its clinical use in many referral centers in Europe. The latest generation of ultrasound scannersallows a precise and reproducible morphological assessment of the intestinal tract and the surrounding tissues and enables a complete evaluation of the disease. This review analyzes the literature history about B-US in the diagnosis of postoperative recurrence of CD and outlines the clinical implications of its use. Published works confirm a very good accuracy of B-US in the diagnosis of CD recurrence compared to endoscopy, also in the early phase. B-US shows a good correlation with Rutgeert's score grading, but does not prove significant association with C-reactive protein or CD Activity Index values. A wider use of B-US in the daily practice could allow to set a prompt diagnosis and an earlier and targeted treatment, probably sparing more invasive tests.

Diet of patients after pouch surgery may affect pouch inflammation

AIM:To investigate the diet of pouch patients compared to healthy controls,and to correlate pouch patients’diet with disease behavior.METHODS:Pouch patients were recruited and prospectively followed-up at the Comprehensive Pouch Clinic at the Tel Aviv Sourasky Medical Center.Pouch behavior was determined based on clinical,endoscopic and histological criteria.Healthy age-and sex-matched volunteers were selected from the"MABAT"Israeli Nutrition and Public Health Governmental Study and served as the control group.All the participants completed a 106-item food frequency questionnaire categorized into food groups and nutritional values based on those used in the United States Department of Agriculture food pyramid and the Israeli food pyramid.Data on Dietary behavior,food avoidance,the use of nutritional supplements,physical activity,smoking habits,and body-mass index(BMI)were also obtained.Pouch patients who had familial adenomatous polyposis(n=3),irritable pouch syndrome(n=4),or patients whose pouch surgery took place less than one year previously(n=5)were excluded from analysis.RESULTS:The pouch patients(n=80)consumed significantly more from the bakery products food group(1.2±1.4 servings/d vs 0.6±1.1 servings/d,P<0.05)and as twice as many servings from the oils and fats(4.8±3.4 servings/d vs 2.4±2 servings/d,P<0.05),and the nuts and seeds food group(0.3±0.6 servings/d vs 0.1±0.4 servings/d,P<0.05)compared to the controls(n=80).The pouch patients consumed significantly more total fat(97.6±40.5 g/d vs 84.4±39 g/d,P<0.05)and fat components[monounsaturated fatty acids(38.4±16.4 g/d vs 30±14 g/d,P<0.001),and saturated fatty acids(30±15.5 g/d vs 28±14.1 g/d,P<0.00)]than the controls.In contrast,the pouch patients consumed significantly fewer carbohydrates(305.5±141.4 g/d vs 369±215.2 g/d,P=0.03),sugars(124±76.2 g/d vs 157.5±90.4 g/d,P=0.01),theobromine(77.8±100 mg/d vs 236.6±244.5 mg/d,P<0.00),retinol(474.4±337.1μg/d vs 832.4±609.6μg/d,P<0.001)and dietary fibers(26.2±15.4 g/d vs 30.7±14 g/d,P=0.05)than the controls.Comparisons of the food consumption of the patients without(n=23)and with pouchitis(n=45)showed that the former consumed twice as many fruit servings as the latter(3.6±4.1 servings/d vs 1.8±1.7 servings/d,respectively,P<0.05).In addition,the pouchitis patients consumed significantly fewer liposoluble antioxidants,such as cryptoxanthin(399±485μg/d vs 890.1±1296.8μg/d,P<0.05)and lycopene(6533.1±6065.7μg/d vs 10725.7±10065.9μg/d,P<0.05),and less vitamin A(893.3±516μg/d vs1237.5±728μg/d,P<0.05)and vitamin C(153.3±130 mg/d vs 285.3±326.3 mg/d,P<0.05)than the patients without pouchitis.The mean BMI of the pouchitis patients was significantly lower than the BMI of the patients with a normal pouch:22.6±3.2 vs 27±4.9(P<0.001).CONCLUSION:Decreased consumption of antioxidants by patients with pouchitis may expose them to the effects of inflammatory and oxidative stress and contribute to the development of pouchitis.

Significance of low level infliximab in the absence of anti-infliximab antibodies

AIM:To evaluate the prevalence of double negative(DN)sera and the mechanisms responsible for DN status.METHODS:Sera of inflammatory bowel disease patients treated with infliximab(IFX)were tested for drug/antibodies to infliximab(ATI)trough levels and the proportion of DN results was compared between a commercially available double antigen ELISA(with labeled IFX as the detection antibody)and an antilambda ELISA(with anti-human lambda chain detection antibody).Repeat testing with lower than customary serum dilution(1:10)was performed.Patients with DN status were matched with IFX+/ATI-controls and were followed-up for subsequent development of nontransient ATI to investigate if DN status precedes ATI.RESULTS:Of 67 sera obtained at time of loss of response,only 6/67(9%)were DN by anti-lambda ELISA compared to 27/67(40%)with double antigen ELISA(P<0.001,Fisher’s Exact test).Of the latter27 sera,22%were also DN by anti-lambda ELISA,whereas 44%were actually IFX positive(IFX+ATI-),30%were ATI positive(IFX-ATI+)and 4%were double positive(IFX+ATI+).Re-testing using a 1:10 dilution converted most DN results into IFX+and/or ATI+status.Patients with DN status had shorter survival free of non-transient ATI compared with matched controls(log rank test,P<0.001).In 9/30(30%)of these patients,non transient ATI occurred before and after the event at which the DN serum was obtained,supporting the view that a DN result may represent aparticular time-point along the two curves of ATI titer rise and infliximab drug level decline.CONCLUSION:DN status may result from false negative detection of IFX or ATI by double antigen ELISA,suggesting a transitional state of low-level immunogenicity,rather than non-immunological clearance.

Intestinal ischemic manifestations of SARS-CoV-2:Results from the ABDOCOVID multicentre study

BACKGROUND Intestinal ischemia has been described in case reports of patients with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)disease(coronavirus disease 19,COVID-19).AIM To define the clinical and histological,characteristics,as well as the outcome of ischemic gastrointestinal manifestations of SARS-CoV-2 infection.METHODS A structured retrospective collection was promoted among three tertiary referral centres during the first wave of the pandemic in northern Italy.Clinical,radiological,endoscopic and histological data of patients hospitalized for COVID-19 between March 1st and May 30th were reviewed.The diagnosis was established by consecutive analysis of all abdominal computed tomography(CT)scans performed.RESULTS Among 2929 patients,21(0.7%)showed gastrointestinal ischemic manifestations either as presenting symptom or during hospitalization.Abdominal CT showed bowel distention in 6 patients while signs of colitis/enteritis in 12.Three patients presented thrombosis of main abdominal veins.Endoscopy,when feasible,confirmed the diagnosis(6 patients).Surgical resection was necessary in 4/21 patients.Histological tissue examination showed distinctive features of endothelial inflammation in the small bowel and colon.Median hospital stay was 9 d with a mortality rate of 39%.CONCLUSION Gastrointestinal ischemia represents a rare manifestation of COVID-19.A high index of suspicion should lead to investigate this complication by CT scan,in the attempt to reduce its high mortality rate.Histology shows atypical feature of ischemia with important endotheliitis,probably linked to thrombotic microangiopathies.

硫唑嘌呤治疗炎症性肠病——大小剂量选择原则

硫唑嘌呤是治疗炎症性肠病的主要药物,其疗效与剂量呈正相关,但高剂量易造成更多副反应。关于中国患者硫唑嘌呤合适的剂量一直存在争论,文章对硫唑嘌呤的合适使用剂量进行探讨阐述,以期指导临床合理用药。

A rare case of epiploic appendagitis in a patient affected by ulcerative colitis on vedolizumab therapy

Introduction Epiploic appendagitis(EA)is an acute inflammation of the pedunculated mesenteric fat attached to the colonic surface,distinguished into two forms:primary EA,seemingly elicited by local ischaemic factors;and secondary EA(SEA),elicited by the inflammation of the adjacent organs,with diverticulitis being the most common trigger[1].Few case series have described the association between SEA and inflammatory bowel disease(IBD);however,information about clinical,laboratory and imaging findings,outcomes,and the impact of IBD-specific therapy were not reported.We first report the case of a woman affected by ulcerative colitis(UC)who developed a SEA during vedolizumab therapy(Figure 1A).