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Induction of remission in biologic-experienced individuals with moderate to severe Crohn’s disease (CD) can be a challenge. We hereby present a case of CD with secondary non-response to infliximab. Adding methotrexate and switching to ustekinumab plus methotrexate did not stop the inflammatory process. Therefore, combination therapy with two classes of biologics consisting of ustekinumab and adalimumab plus methotrexate was initiated. He achieved clinical remission in 4 weeks and remained on triple therapy for 6 months which was subsequently tailored to adalimumab/methotrexate combination therapy due to insurance restriction on ustekinumab. He remained in remission for the duration of follow-up, 14 months after initiation of triple therapy and 8 months after switching to methotrexate/adalimumab biologic monotherapy. Triple therapy with anti-TNF, IL-12/23 inhibitor and methotrexate could potentially be an option for induction of remission in biologic-experienced individuals with good initial clinical response to anti-TNF agents.

Crohn's Disease (CD), which usually leads to anal fistulas among patients, is the most important inflammatory bowel disease that causes morbidity in many people around the world. This review article proposes using MSCs as a hopeful therapeutic strategy for CD and anal fistula treatment in both preclinical and clinical conditions. Finally, darvadstrocel, a cell-based medication to treat complex anal fistulas in adults, as the only European Medicines Agency (EMA)-approved product for the treatment of anal fistulas in CD is addressed. Although several common therapies, such as surgery and anti-tumor necrosis factor-alpha (TNF-α) drugs as well as a combination of these methods is used to improve this disease, however, due to the low effectiveness of these treatments, the use of new strategies with higher efficiency is still recommended. Cell therapy is among the new emerging therapeutic strategies that have attracted great attention from clinicians due to its unique capabilities. One of the most widely used cell sources administrated in cell therapy is mesenchymal stem cell (MSC). This review article will discuss preclinical and clinical studies about MSCs as a potent and promising therapeutic option in the treatment of CD and anal fistula.

Background Infliximab (IFX) has been shown to be effective rescue therapy for hospitalized ulcerative colitis patients failing intravenous (IV) corticosteroids (CS). There is little evidence, however, describing its use in similar hospitalized Crohn's Disease (CD) patients. Study question To determine if IFX is an effective rescue therapy for IV CS resistant CD patients. Study design A retrospective study of inpatients with CD who received IFX as rescue therapy at 2 tertiary care hospitals from January 1, 2006, to December 31, 2016. Records were reviewed for demographics, disease activity, preadmission and inpatient treatment, surgical rates, and 30- and 90-day readmission rates. Measures and Outcomes: Efficacy of IFX as rescue therapy was defined by discharge without surgery and readmission rates. Only patients failing IV CS before IFX were included in the final analysis. Results Forty patients received IFX, of which 17 had failed IV CS. Four patients were receiving outpatient IFX therapy, but still received IV CS during hospitalization before IFX. The mean duration of IV CS therapy before IFX was 6.9 days. Of the 15 patients (88%) who responded to rescue IFX, the median hospital stay following IFX was 3 days (range 3-18 days). Readmission rates were 29% and 47% at 30 and 90 days respectively, without further surgeries noted. Conclusions In our series of hospitalized CD patients failing IV CS, those treated with IFX had low rates of urgent surgery and a generally rapid response to treatment, supporting IFX as an effective rescue therapy. By only including those with prior failure of IV CS, we have likely excluded patients for whom IFX was given in the hospital for reasons other than severe disease. Our results suggest that individuals with severe acute CD flare can be treated with early introduction of IFX, avoiding prolonged CS use, and hospitalization.

Patients with postoperative Crohn's disease are difficult to manage because of their risk of experiencing a more severe course, multiple symptom confounders, and poor sensitivity of symptomatic remission to rule out intestinal inflammation. In this group, data are lacking on biologic therapeutic efficacy, and recommendations are lacking for those with multiple medication failures. Novel noninvasive testing can simultaneously exclude alternate causes of symptoms (serum C4, fecal fat, small intestinal bowel overgrowth breath testing) and assess intestinal inflammation (fecal calprotectin, endoscopic healing index). In addition, endoscopy-based disease activity assessment and management are required. Endoscopy should be performed within 6 months of surgery, and aggressive disease activity monitoring can be considered with colonoscopy every 1-2 years subsequently to ensure late recurrence is detected. Patients with multiple resections should be screened for short bowel syndrome. Predictive biomarkers are needed to guide medication selection in this high-risk population. Postoperative prophylactic biologic therapy is prudent for patients with preoperative biologic failure. However, there are no high-quality data to guide which agent should be selected. Selecting biologics with an alternative mechanism of action in those who had failed a biologic with adequate drug concentrations and selection of different agents in those with previous intolerance are reasonable. Significantly more study is required to assess the efficacy of therapies in this setting.

Background/Aims:Crosstalk between the gut microbiota and bile acid plays an important role in the pathogenesis of gastrointestinal disorders. We investigated the relationship between microbial structure and bile acid metabolism in the ileal mucosa of Crohn’s disease (CD)., Methods:Twelve non-CD controls and 38 CD patients in clinical remission were enrolled. Samples were collected from the distal ileum under balloon-assisted enteroscopy. Bile acid composition was analyzed by liquid chromatography-mass spectrometry. The gut microbiota was analyzed by 16S rRNA gene sequencing., Results:The Shannon evenness index was significantly lower in endoscopically active lesions than in non-CD controls. β-Diversity, evaluated by the UniFrac metric, revealed a significant difference between the active lesions and non-CD controls (P=0.039). The relative abundance of Escherichia was significantly higher and that of Faecalibacterium and Roseburia was significantly lower in CD samples than in non-CD controls. The increased abundance of Escherichia was more prominent in active lesions than in inactive lesions. The proportion of conjugated bile acids was significantly higher in CD patients than in non-CD controls, but there was no difference in the proportion of primary or secondary bile acids. The genera Escherichia and Lactobacillus were positively correlated with the proportion of conjugated bile acids. On the other hand, Roseburia, Intestinibacter, and Faecalibacterium were negatively correlated with the proportion of conjugated bile acids., Conclusions:Mucosa-associated dysbiosis and the alteration of bile acid composition were identified in the ileum of CD patients. These may play a role in the pathophysiology of ileal lesions in CD patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Wuhan, China, in late 2019. Responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic, SARS-CoV-2 is one of three structurally similar beta-coronaviruses that can cause a strong upregulation of cytokines referred to as cytokine release syndrome (CRS). Unresolved CRS leads to respiratory symptoms, including pneumonia, and in more severe cases, acute respiratory distress syndrome (ARDS). Although COVID-19 is widely known for these hallmark respiratory symptoms, it also impacts the gut, causing gastrointestinal (GI) tract inflammation and diarrhea. COVID-19’s GI symptoms may be due to the high intestinal expression of angiotensin converting enzyme-2 receptors, which are for the binding of SARS-CoV-2 viral particles. Reports have shown that SARS-CoV-2 can be passed through fecal matter, with one study finding that 48.1% of COVID-19 patients expressed viral SARS-CoV-2 mRNA in their stool. Given that the GI tract is a target tissue affected by COVID-19, this causes concern for those with underlying GI pathologies, such as inflammatory bowel disease (IBD). Regrettably, there have been only limited studies on the impact of COVID-19 on gut health, and the impact of COVID-19 on intestinal inflammation among IBD patients remains unclear. In particular, questions regarding susceptibility to SARS-CoV-2 infection, clinical impact of COVID-19 on IBD, and the potential influence of age, sex, and immunosuppressant medications are still poorly understood. An improved understanding of these issues is needed to address the unique risks of COVID-19 among IBD patients, as well as the potential impact of SARS-CoV-2 on the host intestinal microbiota.

Patients with primary sclerosing cholangitis (PSC) commonly undergo ileal pouch-anal anastomosis (IPAA) for medically-refractory ulcerative colitis (UC) or colorectal dysplasia. Pouchitis develops more frequently in patients with PSC, potentially leading to increased morbidity. We aimed to assess clinical characteristics and treatment outcomes for pouchitis in patients with PSC compared to a matched, non-PSC cohort.All patients with PSC who underwent IPAA and were diagnosed with pouchitis (PSC-pouchitis) were identified. A matched cohort composed of non-PSC patients who underwent IPAA for UC and subsequently developed pouchitis (UC-pouchitis) was developed. Relevant demographic, clinical, endoscopic, histologic, and treatment data were collected and compared between groups.Of those with PSC-pouchitis (n=182), 53.9% and 46.1% underwent IPAA for medically-refractory disease and dysplasia, respectively, compared to 88.7% and 11.3% in the UC-pouchitis group (P.001). Patients with PSC-pouchitis were more likely to develop chronic pouchitis (68.1% vs 34.1%; P.001), have moderate-to-severe pouch inflammation (54.9% vs 32.4%; P.001), and prepouch ileitis (34.1% vs 11.5%; P.001) compared to UC-pouchitis. Of those with PSC-pouchitis, 50.6% and 17.6% developed chronic antibiotic-dependent or antibiotic-refractory pouchitis, respectively, compared to 25.8% and 7.7% with UC-pouchitis. There was no difference in treatment response between the two groups with use of thiopurines, anti-tumor necrosis factor agents, and newer biologics.PSC-associated pouchitis presents with a unique clinical phenotype, characterized by increased risk of chronic pouchitis, moderate-to-severe pouch inflammation, prepouch ileitis, and less response to conventional antimicrobial therapy.

50% to 80% Crohn's disease (CD) and 10% to 30% ulcerative colitis (UC) patients require surgery over their lifetime. Biologic therapies may alter this natural history, but data on the effect of biologics on surgery rates in this patient population are mixed. We sought to investigate the influence of biologics on surgery prevalence in CD and UC.We used a commercial database (Explorys Inc, Cleveland, OH), which includes electronic health record data from 26 major integrated US healthcare systems. We identified all patients who were diagnosed with CD or UC that were treated with any biologics between 2015 and 2020. The primary outcome was to examine the association between biologics therapy and the prevalence of bowel resection. Also, we identified the factors associated with surgery in IBD patients on biologics.Of 32,904,480 patients in the database, we identified 140,540 patients with CD and 115,260 patients with UC, of whom 25,840 (18%) and 9,050 (7.8%) patients received biologics, respectively. The prevalence of intestinal resection was significantly lower in biologics-treated CD patients (9.3%) compared to those who did not receive biologics (12.1%) (p.001). Similarly, biologic-treated UC patients were significantly less likely to undergo colectomy (7.3%) compared to UC patients who did not receive biologic therapy (11.0%) (p.001). Tobacco use, Clostridium difficile infection, and perianal disease were associated with intestinal resection in CD. Colon neoplasm and Clostridium difficile infection were associated with colectomy in UC.In this study of a large healthcare administrative database, inflammatory bowel disease (IBD) patients treated with biologics were significantly less likely to undergo bowel resection when compared to those who never received biologics. This data suggests that biologics may impact surgical rates in IBD.

Background and aimsPost-colonoscopy colorectal cancers (PCCRCs) account for up to 50% of colorectal cancers (CRCs) in patients with inflammatory bowel disease (IBD). We investigated characteristics of IBD patients with PCCRC and their survival.MethodsWe identified IBD patients (ulcerative colitis [UC] and Crohn’s Disease [CD]) diagnosed with CRC from 1995 to 2015. We defined PCCRC as diagnosed between 6 and 36 months, and detected CRC (dCRC) as diagnosed within 6 months after colonoscopy. We computed prevalence ratios (PRs) comparing PCCRC vs. dCRC and followed patients from the diagnosis of PCCRC/dCRC until death, emigration, or study end. Mortality was compared using Cox proportional hazards regression models adjusted for sex, age, year of CRC diagnosis, and stage. The main analyses focused on patients with UC.ResultsAmong 23,738 UC patients undergoing colonoscopy, we identified 352 patients with CRC, of whom 103 (29%) had PCCRC. Compared with dCRC, PCCRC was associated with higher prevalence of metastatic cancer (33% vs. 20%; PR: 1.64, 95% confidence interval [CI]: 1.13-2.38), cancers exhibiting mismatch repair deficiency (79% vs. 56%; PR: 1.40, 95% CI: 1.13-1.72), and proximally located cancers (54% vs. 40%; PR: 1.34, 95% CI: 1.06-1.69). The one- and five -year adjusted hazard ratios (HRs) of death for PCCRC vs. dCRC among UC patients were 1.29 (95% CI: 0.77-2.18) and 1.24 [95% CI: 0.86-1.79), respectively.ConclusionThe characteristics of UC-related PCCRC suggest tumor biology as an important factor in the progression to cancer. However, the prognosis of PCCRC appears similar to that of dCRC.

Biologic treatment options for Crohn's disease (CD) are increasing and providers will need enhanced support in integrating these therapies into routine practice. Using phase 3 clinical trial programs in CD, we have previously built and validated clinical decision support tools for achieving clinical remission (CREM) with vedolizumab and ustekinumab in CD.1-4 We now aim to develop a clinical decision support tool for infliximab in CD.

Active lesions in the small bowel (SB) have been independently associated with poorer prognoses in patients with Crohn's disease (CD)1; however, there has been a lack of accurate and convenient screening methods. Past studies have found that serum levels of the glycoprotein leucine-rich α2 glycoprotein (LRG) correlates with endoscopic activity in ulcerative colitis,2,3 and this is now available for routine clinical use as a biomarker in patients with inflammatory bowel disease in Japan. LRG has not yet been thoroughly verified in CD, and we investigated whether it can be used as a serum biomarker for detecting SB mucosal activity in patients with CD.

Management of enterocutaneous fistulas in Crohn's disease is challenging. Most patients still need intestinal resection in the biologic era.The aim of this study was to evaluate the efficacy of endoscopic treatment for enterocutaneous fistulas.This is a retrospective study of medical records.This study was conducted in a single institution.All consecutive patients with Crohn's disease with an enterocutaneous fistula who underwent endoscopic fistula closure with the use of an over-the-scope clip or a hemostatic clip were included.The main outcome measured was the clinical success 3 months after the procedure, which was defined as the complete closure of all fistulas at physical examination and complete cessation of the drainage from the external opening, without surgery.Eight patients (men, 25%; median age 45 years [interquartile range, 33-51]) were followed. Fistulas were localized at the ileocolonic or colocolonic anastomosis in 7 patients and at the stomach in 1 patient. Seven patients were treated with an over-the-scope clip, and one was treated with a hemostatic clip. Technical success was achieved in all cases. Clinical success at 3 months was achieved in 75% of cases (6/8 patients). After a median 16-month (interquartile range, 13-23) follow-up, 3 of 8 (37.5%) patients had enterocutaneous fistula closure and 2 of 8 (25%) needed intestinal resection. No complications were observed.The retrospective nature, the small sample size of the study, and the heterogeneity of the population limit the interpretation of the results.Endoscopic treatment of enterocutaneous fistulas is feasible with a short-term effectiveness. Additional studies are needed to confirm these results. See Video Abstract at http://links.lww.com/DCR/B614.ANTECEDENTES:Es desafiante el manejo de las fístulas enterocutáneas en enfermedad de Crohn. En la era biológica, la mayoría de los pacientes todavía requieren de resección intestinal.OBJETIVO:Evaluar la eficacia por tratamiento endoscópico de fístulas enterocutáneas.ENTORNO CLINICO:Estudio retrospectivo de registros médicos.AJUSTE:Realizado en una sola institución.PACIENTES:Se incluyeron todos los pacientes consecutivos con fístula enterocutánea en enfermedad de Crohn, sometidos a cierre endoscópico de la fístula con clip sobre el endoscopio o clip hemostático.PRINCIPALES MEDIDAS DE VALORACION:El éxito clínico a los 3 meses después del procedimiento. Definido al examen físico, como el cierre completo de todas las fístulas y cese completo del drenaje por la abertura externa, sin cirugía.RESULTADOS:Se estudiaron a ocho pacientes (hombres, 25%, mediana de edad de 45 años (rango intercuartílico, 33-51)). En 7 pacientes, las fístulas se localizaron en la anastomosis ileocolónica o colocolónica y un paciente, en el estómago. Siete pacientes fueron tratados con clip sobre el endoscopio y uno con clip hemostático. Se logró éxito técnico en todos los casos. Se logró éxito clínico a los 3 meses en 75% de los casos (6/8 pacientes). Después de una mediana de 16 meses (rango intercuartílico, 13-23), de seguimiento 3/8 (37,5%) pacientes presentaron cierre de fístulas enterocutáneas y 2/8 (25%) requirieron resección intestinal. No se observaron complicaciones.LIMITACIONES:Estudio retrospectivo, pequeño tamaño de la muestra y heterogeneidad de la población, limitaron la interpretación de los resultados.CONCLUSIONES:Es posible el tratamiento endoscópico de fístulas enterocutáneas con efectividad a corto plazo. Se requieren nuevos estudios para confirmar estos resultados. Consulte Video Resumen en http://links.lww.com/DCR/B614. (Traducción-Dr. Fidel Ruiz Healy).

Background Mesentery thickening and enlarged lymphnodes are typical findings of Crohn's disease (CD), but their role is unknown. Aim of the present study was to evaluate their prevalence and significance on postoperative complications and long-term surgical recurrence after CD surgery. Methods 1272 consecutive, unselected patients were retrospectively reviewed, divided into 4 groups based on the presence or absence of a thickened mesentery and enlarged lymphnodes, and stratified for primary or recurrent surgical procedure. In all patients but those treated with strictureplasty the mesentery and lymphnodes were removed. Patients’ characteristics, peri-operative findings, and long-term recurrence were compared by univariate and multivariate analysis. Results Thickened mesentery and enlarged lymphnodes were not present in all cases, were typical of ileal location and penetrating behaviour, had a constant decrease over recurrences, were independent of either pre-operative medical therapy or surgical approach, did not increase the duration of surgery and complications, presented similar 20-years recurrence rate to normal mesentery and lymphnodes. Lymphopathy was associated to a worst nutritional status during disease recurrences. At multivariate analysis, age, location, and behaviour, but not mesenteric characteristics, were related to an increased risk of surgical recurrence. Conclusions This study provides new information on mesentery and lymphnodes in CD patients. Further studies are needed to clarify the appropriate surgical approach.

Intestinal fibrosis is considered an inevitable complication of Crohn’s disease (CD) that results in symptoms of obstruction and stricture formation. Endoscopic or surgical treatment is required to treat the majority of patients. Progress in the management of stricturing CD is hampered by the lack of effective antifibrotic therapy; however, this situation is likely to change because of recent advances in other fibrotic diseases of the lung, liver, and skin. In this review, we summarize data from randomized controlled trials (RCTs) of antifibrotic therapies in these conditions. Multiple compounds have been tested for antifibrotic effects in other organs. According to their mechanisms, they were categorized into growth factor modulators, inflammation modulators, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, intracellular enzymes and kinases, renin-angiotensin system (RAS) modulators, and others. From our review of the results from the clinical trials and discussion of their implications in the gastrointestinal tract, we have identified several molecular candidates that could serve as potential therapies for intestinal fibrosis in CD.

Background & Aims Mucosal healing is associated with better outcomes in Crohn’s disease (CD). Colonoscopy is invasive and poorly tolerated. Bowel ultrasound (US) is a noninvasive tool that increasingly is being used for CD assessment. We assessed the predictive role of baseline bowel US findings on disease course in a large prospective cohort of CD patients for 12 months. Methods Ileocolonic CD consecutive patients were followed up for 12 months after performing bowel US. The negative course of CD, defined as the need for steroids and/or change of therapy and/or hospitalization and/or the need for surgery, was assessed. We evaluated this composite end point and subsequently considered each individual end point separately. Predictors of negative disease course were analyzed by logistic regression analysis. Results There were 225 ileal and/or colonic CD consecutive patients included in the study. We analyzed the association between baseline bowel US parameters and endoscopic activity (defined as a Simplified Endoscopic Activity score for CD > 2) to set up a noninvasive quantitative ultrasound-based score (bowel ultrasound score). The multivariable analysis identified the following independent predictors of a worse outcome throughout the 12-month period as follows: bowel ultrasound score greater than 3.52 (odds ratio [OR], 6.97; 95% CI, 2.87–16.93; P Conclusions Bowel US predicts the 12-month course in CD.

BACKGROUND: Disability in patients with medically refractory ulcerative colitis (UC) after total proctocolectomy (TPC) with ileal pouch anal anastomosis (IPAA) is not well understood. The aim of this study was to compare disability in patients with IPAA vs medically managed UC, and identify predictors of disability. METHODS: This was a multi-center cross-sectional study performed at five academic institutions in New York City. Patients with medically or surgically treated UC were recruited. Clinical and socioeconomic data were collected and the inflammatory bowel disease disability index (IBD-DI) was administered to eligible patients. Predictors of moderate-severe disability (IBD-DI≥35) were assessed in univariable and multivariable models. RESULTS: A total of 94 patients with IPAA and 128 patients with medically managed UC completed the IBD-DI. Among patients with IPAA and UC, 35 (37.2%) and 30 (23.4%) had moderate-severe disability, respectively. Patients with IPAA had significantly greater IBD-DI scores compared to patients with medically managed UC (29.8 vs 17.9, p

Despite pharmacological advances, strictures in Crohn's Disease (CD) continues to be an important problem that leads in a high percentage of patients to undergo endoscopic and/or surgical treatments. There are currently no clinical scores or diagnostic tools that allow predicting which patients will develop this complication, and when a stricture is diagnosed, it is usually already well established and clinically relevant. The current role of pharmacological treatment is limited to treat inflammation and once there is significant fibrosis, the only therapeutic options are endoscopic and/or surgical. To establish a correct therapeutic algorithm and based on the current scientific evidence available, the Spanish Group Working on Crohn's Disease and Ulcerative Colitis (GETECCU) has decided to conduct this position statement on the treatment of strictures in CD. This document embraces the three mentioned therapeutic approaches, medical, endoscopic and surgical. Recommendations and therapeutic algorithms are established to help us to choose the most appropriate option based on the characteristics of the stricture and the patient.

Background and Aims We conducted a systematic review and meta-analysis to summarize emerging data on the safety and effectiveness of dual biologic therapy in combination or with tofacitinib in patients with refractory inflammatory bowel disease (IBD). Methods Through a systematic search of multiple electronic databases through November 9, 2020, we identified cohort studies or case series (>10 patients) reporting the safety and effectiveness of simultaneous use of biologic agents in combination or with tofacitinib in patients with IBD. Rates of adverse events, clinical remission, and endoscopic remission were synthesized using pooled data, and we identified factors associated with successful dual therapy. Results We identified 30 studies reporting 288 trials of dual biologic or small molecule therapy in 279 patients (76% Crohn’s disease; median duration of treatment 24 weeks (IQR25-IQR75 1332)). The main indications for dual therapy included medically refractory IBD (81%) and concurrent extra-intestinal manifestations or rheumatologic disease (12%). The most common combinations of dual therapy included tumor necrosis factor-α antagonists & anti-integrins (48%), ustekinumab & anti-integrins (19%); 61% of patients had previously failed at least one of the two therapies used in combination. Over a median follow-up of 32 weeks (IQR25-IQR75 24-52), pooled rates of adverse and serious adverse events were 31% (95% CI, 13%-54%) and 6.5% (95% CI, 2.1%-13.1%); pooled rates of clinical and endoscopic remission were 59% (95% CI, 42%-74%), and 34% (95% CI, 23%-46%), respectively. 12% (95% CI, 4%-24%) of patients required surgery. Rates of success were higher in patients on dual therapy due to EIM. Heterogeneity was not significant for endoscopic response (P = .88, I2 = 0%), endoscopic remission (P = .44, I2 = 0%), and malignancy (P = .87, I2 = 0%). However, significant heterogeneity existed for other outcomes. Conclusions Dual biologic or small molecule therapy may be a possible option in highly selected, refractory IBD patients at specialized centers. Higher quality combination of therapies with a significant improvement in the quality of data is required prior to more widespread use.

Non-steroidal antiinflammatory drugs (NSAIDs) are currently one of the most widely used drugs. The use of NSAIDs is associated with gastrointestinal toxicity, affecting both upper gastrointestinal tract (peptic ulcer disease) and lower gastrointestinal tract (NSAID-induced enteropathy). NSAIDs use has been associated with an increased risk of clinical relapse in inflammatory bowel disease patients. In this article, we review the upper and lower gastrointestinal toxicity of NSAIDs, with a focus on the risks and specific data of these drugs in inflammatory bowel disease patients, giving recommendations for its appropriate use in the clinical practice. Although evidence is scarce, short-term use of NSAIDs appears to be safe, and the data available suggest that selective COX-2 inhibitors are the safer option. NSAIDs should be avoided as long-term treatment or with high doses, especially in patients with active inflammation.

No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD.RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation.Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p0.0001).Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

The aims of this study were to describe the trends in the behavior of pediatric CD during the last decade and to describe the seasonal variation of disease presentation.Patients under 18 years old and diagnosed between 2009 and 2019 were included. The clinical, endoscopic, histological, and laboratory data were collected from the medical records. We analyzed the trends of these parameters according to the year and season of diagnosis.654 patients were included in the study. The number of incident CD cases increased yearly. Patients diagnosed between 2015 and 2019 were younger at diagnosis (OR 2.53, p = 0.02), had more perianal diseases (OR: 2.30, p 0.0001) and more granulomas (OR: 1.61, p = 0.003), but fewer eosinophils (OR: 0.35, p 0.0001) and less chronic lymphoplasmacytic infiltrate (OR: 0.56, p = 0.008) as compared to the 2009-2014 cohort. There was fewer CD diagnosis during winter. Patients diagnosed in the fall had lower PCDAIs, less failure to thrive and less extensive digestive involvement. Colonic disease was significantly more frequent during summer and fall.The clinical and histological phenotype of CD has changed over time and there are important seasonal trends in the frequency and severity on disease behavior suggesting possible disease triggers.

BackgroundOrofacial granulomatosis [OFG] is a rare syndrome that may be associated with Crohn’s disease [CD]. We aimed to characterise this relationship and the management options in the biologic era.MethodsThis multicentre case series was supported by the European Crohn’s and Colitis Organisation [ECCO], and performed as part of the Collaborative Network of Exceptionally Rare case reports [CONFER] project. Clinical data were recorded in a standardised collection form.ResultsThis report includes 28 patients with OFG associated with CD: 14 males (mean age of 32 years, ±12.4 standard deviation [SD]) and 14 females [40.3 years, ±21.0 SD]. Non-oral upper gastrointestinal tract involvement was seen in six cases and perianal disease in 11. The diagnosis of OFG was made before CD diagnosis in two patients, concurrently in eight, and after CD diagnosis in 18. The distribution of OFG involved the lips in 16 cases and buccal mucosa in 18. Pain was present in 25 cases, with impaired swallowing or speaking in six. Remission was achieved in 23 patients, notably with the use of anti-tumour necrosis factors [TNFs] in nine patients, vedolizumab in one, ustekinumab in one, and thalidomide in two. A further five cases were resistant to therapies including anti-TNFs.ConclusionsOFG associated with CD may occur before, concurrently with, or after the diagnosis of CD. Perianal and upper gastrointestinal [UGI] disease are common associations and there is a significant symptom burden in many. Remission can be obtained with a variety of immunosuppressive treatments, including several biologics approved for CD.

Staphylococcus schleiferi has rarely been reported to cause pyogenic spondylitis. A 42-year-old man had been treated for Crohn's disease with immunosuppressive agents and home parenteral nutrition via a central vein (CV) port. The patient was admitted to our hospital, presenting with neck pain and a fever. A neurological examination showed slight weakness in his left-hand muscles, and he was diagnosed with pyogenic spondylitis of C6 and C7 vertebral bodies due to catheter-related blood stream infection caused by S. schleiferi. An early diagnosis by magnetic resonance imaging, CV port removal and antibiotic therapy targeting S. schleiferi improved his symptoms.

Total proctocolectomy with ileal pouch-anal anastomosis has become the standard procedure for patients with medically refractory ulcerative colitis, although a subset will develop de novo Crohn's disease.In this study, we investigated the association of preoperative C-reactive protein levels with the development of de novo Crohn's disease after ileal pouch-anal anastomosis.A prospectively maintained database of patients undergoing ileal pouch-anal anastomosis was reviewed.Preoperative C-reactive protein levels were compared between patients who developed de novo Crohn's disease and those who did not. De novo Crohn's disease was defined as small-bowel inflammation proximal to the ileal pouch or perianal disease identified more than 3 months after ileostomy closure. To minimize the heterogeneity of the timing of preoperative C-reactive protein measurement and the severity of ulcerative colitis, only hospitalized patients who had proctocolectomy for severe ulcerative colitis were included in the study.Development of de novo Crohn's disease was analyzed.Of 105 patients, 23 (22%) developed de novo Crohn's disease. Having C-reactive protein in the third tertile significantly increased the risk of developing de novo Crohn's disease (HR 3.44, 95% CI 1.10- 10.70, p = 0.03) compared to in the first tertile. In a multivariable model, a C-reactive protein in the third or second tertile vs the first tertile and younger age was associated with the development of de novo Crohn's disease.Limited to only hospitalized patients with severe ulcerative colitis.In hospitalized patients undergoing ileal pouch-anal anastomosis for medically refractory ulcerative colitis, higher preoperative C-reactive protein levels appear to increase the risk of developing de novo Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B750.LA MAGNITUD DE LA ELEVACIÓN PREOPERATORIA DE LA PROTEÍNA C REACTIVA SE ASOCIA CON APARICIÓN DE UNA ENFERMEDAD DE CROHN DE NOVO DESPUÉS DE UNA ANASTOMOSIS DE BOLSA ILEAL AL ANO EN PACIENTES CON COLITIS SEVERAANTECEDENTES:La proctocolectomía total con anastomosis bolsa ileal-anal se ha convertido en el procedimiento estándar para los pacientes con colitis ulcerativa refractaria al tratamiento médico, aunque un subgrupo desarrollará una enfermedad de Crohn de novo.OBJETIVO:En este estudio investigamos la asociación de los niveles de proteína C reactiva preoperatoria con el desarrollo de la enfermedad de Crohn de novo, después de la anastomosis bolsa ileal-anal.DISEÑO:Se revisó una base de datos recolectada en forma prospectiva, de pacientes sometidos a anastomosis bolsa ileal-anal.PACIENTES:Se compararon los niveles de proteína C reactiva preoperatoria entre los pacientes que desarrollaron la enfermedad de Crohn de novo y los que no la desarrollaron. La enfermedad de Crohn de novo se definió como una inflamación del intestino delgado proximal a la bolsa ileal o una enfermedad perianal identificada más de 3 meses después del cierre de la ileostomía. Para minimizar la heterogeneidad del momento de la medición de la proteína C reactiva preoperatoria y la gravedad de la colitis ulcerativa, solo se incluyeron en el estudio los pacientes hospitalizados que se sometieron a una proctocolectomía por colitis ulcerativa grave.PRINCIPALES MEDIDAS DE RESULTADO:se analizó el desarrollo de la enfermedad de Crohn de novo.RESULTADOS:De 105 pacientes, 23 (22%) desarrollaron enfermedad de Crohn de novo. Tener una proteína C reactiva en el tercer tercil aumentó significativamente el riesgo de desarrollar la enfermedad de Crohn de novo (HR 3,44, IC del 95%: 1,10-10,70, p = 0,03) en comparación con el primer tercil. En un modelo multivariable, una proteína C reactiva en el tercer o segundo tercil frente al primer tercil y una edad más joven se asoció con el desarrollo de la enfermedad de Crohn de novo.LIMITACIONES:Limitado solo a pacientes hospitalizados con colitis ulcerativa grave.CONCLUSIONES:En pacientes hospitalizados sometidos a anastomosis bolsa ileal-anal por colitis ulcerativa refractaria al tratamiento médico, niveles más elevados de proteína C reactiva preoperatoria parecen aumentar el riesgo de desarrollar enfermedad de Crohn de novo. Consulte Video Resumen en http://links.lww.com/DCR/B750. (Traducción-Eduardo Londoño-Schimmer).

Surgical intervention for Crohn's disease involving the colon is often a total proctocolectomy with end ileostomy. There are limited data regarding postoperative small bowel recurrence rates in the recent era.The purpose of this study was to determine the rate of small bowel Crohn's disease recurrence following total proctocolectomy and secondarily define risk factors for disease recurrence.This was a retrospective cohort study.The study was conducted at four hospitals within a single healthcare system.Patients were those with Crohn's disease undergoing total proctocolectomy with end ileostomy between 2009-2019.Main outcome measures were clinical, endoscopic, radiographic, and/or surgical Crohn's disease recurrence.In total, 193 patients were included with a median follow-up of 1.8 years (IQR 0.4-4.6). Overall, 74.6% (n = 144) of patients had been previously exposed to biologic therapy, and 51.3% (n = 99) had a history of small bowel Crohn's disease. Postoperatively, 14.5% (n = 28) of patients received biologic therapy. Crohn's disease recurrence occurred in 23.3% (n = 45) of patients with an estimated median 5-year recurrence rate of 40.8% (95% CI' 30.2-51.4). Surgical recurrence occurred in 8.8% (n = 17) of patients with an estimated median 5-year recurrence rate of 16.9% (95% CI' 8.5-25.3). On multivariable analysis, prior small bowel surgery for Crohn's disease (HR 2.61; 95% CI' 1.42-4.81) and Crohn's diagnosis at age18 years (HR 2.56; 95% CI' 1.40-4.71) were associated with Crohn's recurrence. In patients without prior small bowel Crohn's disease, 14.9% (n = 14) had Crohn's recurrence with an estimated 5-year overall recurrence rate of 31.1% (95% CI' 13.3-45.3) and 5-year surgical recurrence rate of 5.7% (95% CI' 0.0-12.0).The study was limited by its retrospective design and lack of consistent follow-up on all patients.Greater than one third of patients who underwent total proctocolectomy for Crohn's disease were estimated to have small bowel Crohn's recurrence at 5 years after surgery. Patients with a history of small bowel surgery for Crohn's and diagnosis at any early age may benefit from more intensive postoperative surveillance and consideration for early medical prophylaxis. See Video Abstract at http://links.lww.com/DCR/B762.ANTECEDENTES:La cirugia para la enfermedad de Crohn que involucra el colon es a menudo una proctocolectomía total con ileostomía terminal. Hay datos limitados con respecto a las tasas de recurrencia posoperatoria de la enfermedad de Crohn del intestino delgado en la actualidad.OBJETIVO:Buscamos determinar la tasa de recurrencia de la enfermedad de Crohn del intestino delgado después de la proctocolectomía total y, en segundo lugar, definir los factores de riesgo de recurrencia de la enfermedad.DISEÑO:Estudio de cohorte retrospectivo.ENTORNO CLINICO:Cuatro hospitales de un mismo sistema sanitario.PACIENTES:Pacientes con enfermedad de Crohn sometidos a proctocolectomía total con ileostomía terminal entre 2009-2019.PRINCIPALES MEDIDAS DE VALORACIÓN:Recurrencia clínica, endoscópica, radiográfica y / o quirúrgica de la enfermedad de Crohn.RESULTADOS:Se incluyeron 193 pacientes con un seguimiento promedio de 1,8 años (IQR 0,4-4,6). El 74,6% (n = 144) de los pacientes habían recibido previamente terapia biológica y el 51,3% (n = 99) tenían antecedentes de enfermedad de Crohn del intestino delgado. Después de la operación, el 14,5% (n = 28) de los pacientes recibieron terapia biológica. La recurrencia de la enfermedad de Crohn ocurrió en el 23,3% (n = 45) de los pacientes con una tasa de recurrencia media estimada a los 5 años del 40,8% (IC del 95%: 30,2-51,4). La recidiva quirúrgica se produjo en el 8,8% (n = 17) de los pacientes con una tasa de recidiva media estimada a los 5 años del 16,9% (IC del 95%: 8,5-25,3). En el análisis multivariable, la cirugía previa del intestino delgado para la enfermedad de Crohn (HR 2,61, IC del 95%: 1,42-4,81) y el diagnóstico de Crohn a la edad18 (HR 2,56, IC del 95%: 1,40-4,71) se asociaron con la recurrencia de Crohn. En pacientes sin enfermedad previa de Crohn del intestino delgado, el 14,9% (n = 14) tuvo recurrencia de Crohn con una tasa de recurrencia general estimada a 5 años del 31,1% (IC del 95%: 13,3-45,3) y una tasa de recurrencia quirúrgica a 5 años del 5,7% (IC del 95%: 0,0-12,0).LIMITACIONES:Diseño retrospectivo, falta de seguimiento constante de todos los pacientes.CONCLUSIONES:Se estimó que más de un tercio de los pacientes que se sometieron a proctocolectomía total tenían recurrencia de Crohn del intestino delgado a los 5 años después de la cirugía. Los pacientes con antecedentes de cirugía por enfermedad de Crohn del intestino delgado y diagnóstico a una edad temprana pueden beneficiarse de una vigilancia posoperatoria más intensiva y la consideración de una profilaxis médica temprana. Consulte Video Resumen en http://links.lww.com/DCR/B762. (Traducción- Dr. Ingrid Melo).

Background: Mirikizumab is a humanized monoclonal antibody targeting interleukin 23p19 with demonstrated efficacy in psoriasis and ulcerative colitis. We investigated the safety and efficacy of mirikizumab in patients with moderate-to-severe Crohn's disease (CD). Methods: Patients (N = 191) were randomized (2:1:1:2) to receive placebo (PBO), 200, 600, or 1000 mg mirikizumab, administered intravenously (IV) every 4 weeks. Patients who received mirikizumab and achieved ≥1 point improvement in Simple Endoscopic Score-CD at Week 12 (rerandomized maintenance cohort) were rerandomized to continue their induction IV treatment (combined IV groups [IV-C]) or receive 300 mg mirikizumab subcutaneously (SC) every 4 weeks. Nonrandomized maintenance cohort included endoscopic nonimprovers (1000 mg) and PBO patients (PBO/1000 mg) who received 1000 mg mirikizumab IV from Week 12. The primary objective was to evaluate superiority of mirikizumab to PBO in inducing endoscopic response (50% reduction from baseline in Simple Endoscopic Score-CD) at Week 12. Results: At Week 12, endoscopic response was significantly higher by the predefined 2-sided significance level of 0.1 for all mirikizumab groups compared with PBO (200 mg: 25.8%, 8/31, 95% confidence interval [CI], 10.4–41.2, P = .079; 600 mg: 37.5%, 12/32, 95% CI, 20.7–54.3, P = .003; 1000 mg: 43.8%, 28/64, 95% CI, 31.6–55.9, P < .001; PBO: 10.9 %, 7/64, 95% CI, 3.3–18.6). Endoscopic response at Week 52 was 58.5% (24/41) and 58.7% (27/46) in the IV-C and SC groups, respectively. Frequencies of adverse events (AE) in the mirikizumab groups were similar to PBO. Through Week 52, frequencies of treatment-emergent AEs were similar across all groups. Frequencies of serious AE and discontinuations due to AE were higher in the nonrandomized maintenance cohort. Conclusion: Mirikizumab effectively induced endoscopic response after 12 weeks in patients with moderate-to-severe CD and demonstrated durable efficacy to Week 52. A detailed summary can be found in the Video Abstract. ClinicalTrials.gov, Number: NCT02891226

Background Patients with inflammatory bowel diseases (IBD), specifically those treated with anti-tumor-necrosis-factor (TNF)α biologics are at high risk for vaccine preventable infections. Their ability to mount adequate vaccine responses is unclear. Aim To assess serologic responses to mRNA-COVID-19 vaccine, and safety profile, in patients with IBD stratified according to therapy, compared to healthy controls (HC). Methods Prospective, controlled, multi-center Israeli study. Subjects enrolled received two BNT162b2 (Pfizer/BioNTech) doses. Anti-spike antibodies levels and functional activity, anti-TNFα levels and adverse events (AEs) were detected longitudinaly. Results Overall 258 subjects: 185 IBD (67 treated with anti-TNFα, 118 non-anti-TNFα), and 73 HC. After the first vaccine dose all HC were seropositive, while ∼7% of patients with IBD, regardless of treatment, remained seronegative. After the second dose all subjects were seropositive, however anti-spike levels were significantly lower in anti-TNFα treated compared to non-anti-TNFα treated patients, and HC (both P, Graphical abstract

Very early onset inflammatory bowel disease (VEO-IBD) represents approximately 25% of cases of IBD-like colitis occurring during childhood and, by definition, it is characterized by an onset prior to 6 years of age. This subgroup of patients presents significant differences from IBD occurring in older children and in adults, including a more severe clinical course, a reduced responsiveness to conventional IBD therapy, and a greater proportion of cases featuring an underlying monogenic disorder. Histological findings from gastro-intestinal (GI) biopsies are characterized by an IBD-like, apoptotic or enterocolitis-like pattern, complicating the differential diagnosis with other pediatric diseases involving GI tract. Moreover, individuals with monogenic disorders may develop significant comorbidities, such as primary immunodeficiency (PID), impacting treatment options. Without an appropriate diagnosis, the clinical course of VEO-IBD has greater potential for escalated treatment regimens involving extensive surgery, more intensive medical therapies and, even more important, inadequate recognition of underlying monogenic defect that may lead to inappropriate (sometimes fatal) therapy. For these reasons, an adequate context leading to an appropriate diagnosis is imperative, calling for a close collaboration between pediatricians, pathologists, geneticists, and immunologists.

Background and Aims Starting biologic treatment early in the course of inflammatory bowel disease (IBD) may be associated with higher efficacy, especially in Crohn's disease (CD). Methods This was a systematic review and individual-patient data meta-analysis of all placebo-controlled trials of biologics approved for IBD at study inception (October 2015), using Vivli data-sharing platform. The primary outcome was the proportional biologic/placebo treatment effect on induction of remission in patients with short-duration (≤18 months) vs long-duration disease (>18 months) analyzed separately for CD and ulcerative colitis (UC). We used meta-regression to examine the impact of patients' characteristics on the primary outcome. Results We included 25 trials, testing infliximab, adalimumab, certolizumab, golimumab, natalizumab, or vedolizumab (6168 patients with CD and 3227 patients with UC). In CD, remission induction rates were higher in pooled placebo and patients in active arms with short-duration disease of ≤18 months (41.4% [244 of 589]) compared with disease duration of >18 months (29.8% [852 of 2857], meta-analytically estimated odds ratio, 1.33; 95% confidence interval, 1.09–1.64). The primary outcome, proportional biologic/placebo treatment effect on induction of remission, was not different in short-duration disease of ≤18 months (n = 589, odds ratio, 1.47; 95% confidence interval, 1.01–2.15) compared with longer disease duration (n = 2857, odds ratio, 1.43; 95% confidence interval, 1.19–1.72). In UC trials, both the proportional biologic/placebo remission-induction effect and the pooled biologic-placebo effect were stable, regardless of disease duration. Primary outcome results remained unchanged when tested using alternative temporal cutoffs and when modeled for individual patient's covariates, including prior anti–tumor necrosis factor exposure. Conclusions There are higher rates of induction of remission with biologics and with placebo in early CD, resulting in a treatment to placebo effect ratio that is similar across disease durations. No such relationships between disease duration and outcomes was found in UC. PROSPERO registration: CRD42018041961.

Background and Aims We conducted a retrospective cohort study comparing the risk of serious infections between patients treated with tumor necrosis factor-a (TNFa) antagonists vs. vedolizumab in patients with inflammatory bowel diseases (IBD). Methods Using an administrative claims database, we identified patients with IBD who were new-users of either TNFa antagonists or vedolizumab between 2014-2018 and had insurance coverage for at least 1y before and after treatment initiation. We compared the risk of serious infections (infections requiring hospitalization) between patients treated with vedolizumab or TNFa antagonists using marginal structural Cox proportional hazard models adjusted for baseline disease characteristics, healthcare utilization, comorbidities, and time-varying use of corticosteroids, immunomodulators and opiates. Results We included 4881 patients treated with TNFa antagonists (age, 41 ± 15y, 60% with Crohn’s disease [CD]) of whom 434 developed serious infections over 5786 person-year [PY] follow-up, and 1106 patients treated with vedolizumab (age, 44 ± 16y, 39% with CD) of whom 86 developed serious infections over 1040-PY follow-up. Vedolizumab was associated with 46% lower risk of serious infections as compared with TNFa antagonists in patients with ulcerative colitis (HR,0.54 [95% CI,0.35-0.83), but no significant differences were observed in patients with CD (HR,1.30 [0.80-2.11]). Vedolizumab was associated with lower risk of extra-intestinal serious infections in patients with UC, but higher risk of gastrointestinal serious infections in patients with CD. Conclusions In an observational study of patients with IBD, vedolizumab was associated with lower risk of serious infections as compared with TNFa antagonists, in patients with UC, but not in patients with CD.

Background. In recent years, there has been high interest in the prevalence of small intestinal bacterial overgrowth (SIBO) syndrome in various populations. Chronic inflammatory bowel disease (IBD) is known to be a heterogeneous group of disorders, with a high degree of geographical variability in terms of symptoms, nature of progression, clinical manifestations, or combination with other types of pathologies. Since the involvement of the intestinal microbiome plays an important role in the etiopathogenesis of inflammatory bowel disease, the combination of SIBO and IBD is increasingly being considered and studied recently. Since the symptoms of both pathological conditions are significantly echoed, and therefore exacerbated by the combination, the manifestations of malnutrition become more pronounced, which negatively affects the nutritional status of patients with IBD. The purpose of the study is to determine the frequency of SIBO in patients with IBD depending on the nosological forms and to investigate its effect on clinical and laboratory indicators of nutritional status and clinical manifestations. Materials and methods. We examined 100 patients with IBD, aged 19 to 79 years, on average (42.54 ± 1.50) years, including 70 patients with ulcerative colitis (UC), and 30 — with Crohn’s disease (CD). All patients underwent general clinical examination, anthropometric measurements, general and biochemical blood tests (with the determination of total protein, albumin, prealbumin). To characterize the state of the small intestine microbiota (presence of SIBO), all patients underwent a hydrogen breath test with glucose loading using a Gastro+ Gastrolyzer gas analyzer from Bedfont Scientific Ltd (UK). Results. The analysis of SIBO frequency showed the changes in the state of the small intestinal microflora in 45 % of patients with IBD. The prevalence of SIBO was higher in the group of patients with CD — 53.3 % (16) than in the group with UC — 41.4 % (29). The presence of SIBO in the group of patients with UC had statistical significance and a direct correlation with the duration of the disease — (9.3 ± 6.2) versus (2.9 ± 3.1) years (p = 0.001, r = 0.55). There was a decrease in weight and body mass index (BMI) in patients with SIBO, especially in patients with Crohn’s disease, and accounted for (19.8 ± 3.5) kg/m2. There was a significant difference between the levels of total protein in patients with SIBO and without it, both in the basic group and in the group of UC: (65.8 ± 8.4) vs. (70.2 ± 8.2) g/l (p = 0.009, r = –0.232) and (66.5 ± 8.3) vs. (70.7 ± 7.4) g/l (p = 0.029), respectively, and albumin levels were reduced in both nosological groups. No relationship was found between the severity of abdominal pain and the presence of SIBO. When SIBO was detected, the manifestations of flatulence significantly prevailed in patients with UC — 75.8 % (n = 22), and diarrheal syndrome in patients with CD — 75 % (n = 12). Conclusions. The obtained results indicate a high prevalence of SIBO in patients with IBD. Patients with CD suffered from SIBO more often (53.3 %) than patients with UC (41.4 %) (with a predominance of patients with severe disease). A direct correlation of SIBO with the disease duration in patients with UC (r = 0.55, р < 0.05) was revealed, which is explained by the violation of physiological barriers that prevent the emergence of SIBO, due to more episodes of exacerbation, long-term use of drugs and concomitant pathology with time. The negative impact of SIBO on nutritional status manifested in weight loss, reduced BMI and other anthropometric (mid-upper arm circumference, mid-arm muscle circumference, triceps skinfold) and laboratory (total protein, albumin, prealbumin) parameters in these patients. The most common symptoms in patients with IBD with SIBO were abdominal pain, diarrhea, and flatulence that reflected the typical clinical picture of SIBO., Актуальність. Останніми роками спостерігається висока зацікавленість щодо поширеності синдрому надлишкового бактеріального росту (СНБР) у тонкому кишечнику в різних популяціях. Відомо, що хронічні запальні захворювання кишечника (ХЗЗК) є гетерогенною групою розладів із високим ступенем географічної мінливості щодо симптомів, характеру прогресування, клінічних проявів або зі сполученням з іншими типами патологій. Зважаючи на те що участь мікробіому кишечника відіграє важливу роль в етіопатогенезі запальних захворювань кишечника, поєднання СНБР та ХЗЗК все частіше розглядається та досліджується останнім часом. Оскільки симптоматика обох патологічних станів значно перекликається, а отже і посилюється при поєднанні, прояви мальнутриції стають більш вираженими, що негативно впливає на нутритивний статус пацієнтів із ХЗЗК. Мета дослідження: визначити частоту СНБР в осіб із ХЗЗК залежно від нозологічних форм та дослідити його влив на клініко-лабораторні показники нутритивного статусу та клінічні прояви. Матеріали та методи. Було обстежено 100 пацієнтів із ХЗЗК віком від 19 до 79 років (у середньому (42,54 ± 1,50) року), у тому числі 70 осіб із неспецифічним виразковим колітом (НВК), 30 — із хворобою Крона (ХК). Усім хворим були проведені загальноклінічне обстеження, антропометричні вимірювання, загальний та біохімічний аналізи крові (із визначенням загального білка, альбуміну, преальбуміну). Для характеристики стану мікробіоти тонкого кишечника (наявності СНБР) усім хворим проведений водневий дихальний тест із навантаженням глюкозою з використанням газоаналізатора Gastro+ Gastrolyzer компанії Bedfont Scientific Ltd (Великобританія). Результати. Аналіз частоти виявлення СНБР показав, що зміни у стані мікрофлори тонкої кишки спостерігались у 45 % пацієнтів із ХЗЗК. Поширеність СНБР виявилася вищою в групі пацієнтів із ХК — 53,3 % (16), ніж у групі з НВК — 41,4 % (29). Наявність СНБР у групі хворих на НВК мала статистичну значущість та прямий кореляційний зв’язок із тривалістю захворювання — (9,3 ± 6,2) проти (2,9 ± 3,1) року (р = 0,001, r = 0,55). Спостерігалося зниження ваги та індексу маси тіла в пацієнтів із СНБР, особливо в осіб із ХК: так, середній показник індексу маси тіла в цих хворих становив (19,8 ± 3,5) кг/м2. Виявлено вірогідну різницю між рівнями загального білка у хворих із СНБР та без нього як у загальній групі, так і в групі НВК: (65,8 ± 8,4) проти (70,2 ± 8,2) г/л (р = 0,009, r = –0,232) та (66,5 ± 8,3) проти (70,7 ± 7,4) г/л (р = 0,029) відповідно, а також були знижені рівні альбуміну в обох нозологічних групах. Не виявлено залежності між вираженістю абдомінального болю та наявністю СНБР. При виявленому СНБР прояви метеоризму значно переважали у хворих на НВК — 75,8 % (n = 22), а діарейний синдром у пацієнтів із ХК — 75 % (n = 12). Висновки. Отримані результати свідчать про високу поширеність СНБР у пацієнтів із ХЗЗК. Пацієнти з ХК страждали від СНБР частіше (53,3 %), ніж пацієнти з НВК (41,4 %) (із переважанням хворих із тяжким ступенем вираженості). Виявлено прямий кореляційний зв’язок СНБР із тривалістю захворювання в осіб із НВК (r = 0,55; р < 0,05), що пояснюється порушенням фізіологічних бар’єрів, які попереджають виникнення СНБР, внаслідок більшої кількості епізодів загострення, тривалого прийому медичних препаратів та приєднання супутньої патології з часом. Негативний вплив СНБР на нутритивний статус проявлявся в зниженні маси тіла, індексу маси тіла та інших антропометричних (окружність середньої частини плеча, окружність м’язів плеча, товщина шкірно-жирової складки) та лабораторних (загальний білок, альбумін, преальбумін) параметрів у цих пацієнтів. Найчастішими симптомами в пацієнтів із ХЗЗК із СНБР були абдомінальний біль, діарейний синдром та метеоризм, що явно відображало типову клінічну картину СНБР.

Growing evidence suggests that there are similar pathological mechanisms and closely related pathogenic risk factors for inflammatory bowel disease (IBD) and Parkinson's disease (PD). However, the epidemiological features of these two diseases are different. This review systematically evaluated the relationship between inflammatory bowel diseases and Parkinson's disease risk. We searched PubMed, Embase, and Cochrane databases to retrieve observational studies of IBD and PD published from inception to October 2019. Nine observational studies, involving 12,177,520 patients, were included in the final analysis. None of the studies had Newcastle–Ottawa Scale scores that suggested a high risk of bias. After adjusting for confounders and excluding heterogeneous studies, the overall risk of PD was significantly higher in IBD patients than in the general population (adjusted risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.15–1.34, P < 0.001). A meta-analysis of the temporal relationship revealed that the incidence of IBD was significantly increased before (adjusted hazard ratio [HR] = 1.26, 95% CI: 1.18–1.35, P < 0.001) and after (adjusted RR = 1.40, 95% CI: 1.20–1.80, P < 0.001) PD diagnosis. After excluding a heterogeneous study, the pooled risk of PD development in patients with ulcerative colitis (adjusted HR = 1.25, 95% CI: 1.13–1.38, P < 0.001) or Crohn's disease (adjusted HR = 1.33, 95% CI: 1.21–1.45, P < 0.01) was significantly increased. Subgroup analysis revealed no significant differences in risk between men (adjusted HR = 1.23, 95% CI: 1.10–1.39) and women (adjusted HR = 1.26, 95% CI: 1.10–1.43); however, older (> 65 years old) IBD patients (adjusted HR = 1.32, 95% CI: 1.17–1.48) may have a higher risk than younger (≤ 65 years old) patients (adjusted HR = 1.24, 95% CI: 1.08–1.42). Patients with IBD who were not treated with anti-tumor necrosis factor-α or azathioprine had significantly higher PD risk (adjusted HR = 1.6, 95% CI: 1.2–2.2). Thus, our meta-analysis indicates a certain correlation between IBD and PD, and suggests that IBD may moderately increase PD risk regardless of sex, especially in patients over 65 years of age. Moreover, early anti-inflammatory therapies for IBD might reduce the risk of developing PD. Our findings suggest an urgent need for an individualized screening strategy for patients with IBD. However, most studies included in this paper were observational, and more randomized controlled trials are needed to confirm the precise association between IBD and PD.

Summary Pouchitis, Crohn's disease of the pouch, cuffitis, polyps, and extraintestinal manifestations of inflammatory bowel disease are common inflammatory disorders of the ileal pouch. Acute pouchitis is treated with oral antibiotics and chronic pouchitis often requires anti-inflammatory therapy, including the use of biologics. Aetiological factors for secondary pouchitis should be evaluated and managed accordingly. Crohn's disease of the pouch is usually treated with biologics and its stricturing and fistulising complications can be treated with endoscopy or surgery. The underlying cause of cuffitis determines treatment strategies. Endoscopic polypectomy is recommended for large, symptomatic inflammatory polyps and polyps in the cuff. The management principles of extraintestinal manifestations of inflammatory bowel disease in patients with pouches are similar to those in patients without pouches.

Background and aims Fecal calprotectin (FC) is a non-invasive biomarker used in inflammatory bowel disease (IBD) management and risk stratification of non-specific gastrointestinal symptoms. Leukocyte esterase is an inexpensive and widely available point-of-care inflammatory marker present on urinalysis test strips. We aim to assess the diagnostic accuracy of fecal leukocyte esterase (FLE) relative to FC and endoscopy and demonstrate its use as an alternative biomarker for IBD. Methods In this prospective cohort study, 70 patients who had FC ordered as part of standard clinical care also received FLE testing. FLE levels were compared to various FC cut-off values and endoscopy and pathology findings as gold standard. Results As the FC cut-off increased from 50 to 500 μg/g, FLE sensitivity increased from 67% to 95% while the specificity decreased from 86% to 76%. The area under the receiver operating characteristic (AUROC) increased from 0.79 to 0.90. An FLE of ≥1+ had the best test characteristics. Amongst patients who underwent endoscopic evaluation, FLE demonstrated an identical sensitivity (75%) and specificity (86%) to FC in predicting endoscopic inflammation. AUROC was 0.80 for FLE and 0.85 for FC with an optimal cut-off of ≥2+ and 301 μg/g, respectively. When used to distinguish between active IBD and no/inactive IBD patients, FLE had a sensitivity of 84% and specificity of 90%, comparable to the 84% and 83%, respectively, of FC. AUROC was 0.88 for FLE and 0.91 for FC with an optimal cut-off of ≥2+ and 145 μg/g, respectively. Conclusion FLE demonstrates adequate correlation and comparable accuracy to FC in predicting endoscopic inflammation and distinguishing between patients with active versus inactive IBD.

Mucosal healing (MH) has become a therapeutic goal in Crohn's Disease (CD), but its frequent evaluation in endoscopic examination is fraught with several limitations. There is an increasing demand to replace invasive procedures with noninvasive markers of CD.To assess the clinical importance of the recently developed Mucosal Inflammation Noninvasive Index (MINI) in newly diagnosed paediatric Crohn's Disease patients.Out of 60 consecutive newly diagnosed paediatric CD patients, 55 were enrolled in the study. The study examined the relationship between Simple Endoscopic Score for CD (SES-CD), Paediatric Crohn's Disease Activity Index (PCDAI), laboratory findings and the newly developed MINI index.Out of the 55 paediatric patients involved in the study, ileocolonoscopy was successful in 42 patients. In this group there was a strong positive correlation between MINI and PCDAI (The newly developed MINI index is a simple and intuitive clinimetric score that can be considered a useful tool in assessing mucosal inflammation among newly diagnosed paediatric CD patients.

Background Capsule endoscopy (SBCE) has developed a relevant role in patients with established Crohn's Disease (CD). However, evaluation of the impact in clinical management has been scarce. Aims To evaluate therapeutic impact of SBCE in an 11-year real-life cohort of known CD patients. Methods Retrospective single center study including all patients with established CD submitted to SBCE procedure from 01/01/2008 to 31/12/2019. Patency capsule was used in selected patients. Small bowel mucosal inflammation was quantified using Lewis score. Therapeutic impact was defined as a change in CD-related treatment recommended based on SBCE results. Patients were assigned to four groups regarding SBCE indication: staging, flare, post-op and remission. Results From the 432 SBCE performed 87.5% were conclusive. Active disease was present in 63.7 of patients; 41.6% mild inflammation and 21.9% moderate-to-severe activity. A change of management was guided by SBCE in 51.3% of procedures: 199 (46.1%) escalation and 23 (5.3%) de-escalation, with significant changes in all groups. Escalation increased with disease activity: 57.8% in mild and 89.5% in moderate-to-severe disease. De-escalation was conducted in 13.9% procedures with mucosal healing and 1.1% with mild disease. Conclusion SBCE is a useful tool for guiding therapeutic management in CD patients both for treatment escalation and de-escalation.

Background & Aims Treatment of patients with inflammatory bowel diseases (IBD; Crohn’s disease (CD), ulcerative colitis (UC) who have a prior history of cancer pose a unique challenge. The impact of Vedolizumab (VDZ) on the risk of new or recurrent cancers in patients with a previous malignancy is unknown. Methods This was a retrospective study of patients with IBD with a history of current or prior cancer who were subsequently initiated on VDZ, tumor necrosis factor α antagonists (anti-TNF), or had no immunosuppressive therapy after the index cancer diagnosis. The occurrence of a new primary cancer or recurrent cancer was ascertained on follow-up. Multivariable Cox-proportional hazard models were used to determine the independent effect of post-cancer treatment on new/recurrent cancer. Results The study included 96 patients exposed to VDZ after a prior diagnosis of cancer who were compared to 184 and 183 patients exposed to anti-TNF or no immunosuppressive therapy, respectively. The most common primary cancer were solid tumors (50%). Over a median of 6.2 person-years of follow-up, 18 patients on VDZ developed new (7) or recurrent (11) cancer corresponding to a rate of 22 per 1000 person-years after cancer diagnosis. In a multivariable Cox-model, after adjusting for confounders, there was no increase in the risk of new or recurrent cancer with VDZ (HR 1.38 95% CI 0.38 – 1.36) or anti-TNF therapy (HR 1.03, 95% CI 0.65 – 1.64), when compared to no IS. Conclusions Neither Vedolizumab nor TNF-antagonists were associated with increased risk of new or recurrent cancers in patients with prior malignancy.

Background Crohn’s disease (CD)-related rectovaginal fistulas (RVFs) and anovaginal fistulas (AVFs) are rare, debilitating conditions that present a substantial disease and treatment burden for women. This systematic literature review (SLR) assessed the burden of Crohn’s-related RVF and AVF, summarizing evidence from observational studies and highlighting knowledge gaps. Methods This SLR identified articles in PubMed and Embase that provide data and insight into the patient experience and disease burden of Crohn’s-related RVF and AVF. Two trained reviewers used pre-specified eligibility criteria to identify studies for inclusion and evaluate risk of bias using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for observational studies. Results Of the 582 records identified, 316 full-text articles were assessed, and 16 studies met a priori eligibility criteria and were included. Few epidemiology studies were identified, with one study estimating the prevalence of RVF to be 2.3% in females with Crohn’s disease. Seven of 12 treatment pattern studies reported that patients had or required additional procedures before and/or after the intervention of interest, demonstrating a substantial treatment burden. Seven of 11 studies assessing clinical outcomes reported fistula healing rates between 50 and 75%, with varying estimates based on population and intervention. Conclusions This SLR reports the high disease and treatment burden of Crohn’s-related RVF and AVF and identifies multiple evidence gaps in this field. The literature lacks robust, generalizable data, and demonstrates a compelling need for substantial, novel research into these rare and debilitating sequelae of CD. Registration The PROSPERO registration number for the protocol for this systematic literature review is CRD42020177732.

Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) that is usually the consequence of chronic inflammation. Although the currently available anti-inflammatory therapies have had little impact on intestinal fibrosis in Crohn’s disease (CD), increased understanding of the pathophysiology and the development of therapies targeting fibrogenic pathways hold promise for the future. One of the critical challenges is how reduction or reversal of intestinal fibrosis should be defined and measured in the setting of clinical trials and drug approval. The International Organization for Inflammatory Bowel Disease (IOIBD) organized a workshop in Amsterdam, The Netherlands, on December 19(th) and 20(th), 2018 in an attempt to review the current knowledge of the biological background, diagnosis, treatment of intestinal fibrosis and clinical trial endpoints. Basic and clinical scientists discussed the pathophysiology of intestinal fibrosis, the current status of biomarkers and imaging modalities in stenosing CD, and recent clinical studies in this area. Researchers from outside of the IBD field presented advances in the understanding of fibrotic processes in other organs, such as the skin, liver and lungs. Lastly, the design of clinical trials with antifibrotic therapy for IBD was discussed, with priority on patient populations, patient reported outcomes (PROs) and imaging. This report summarizes the key findings, discussions and conclusions of the workshop.

Summary Background The Crohn's disease exclusion diet (CDED) with partial enteral nutrition is effective for induction of remission in children with mild-to-moderate Crohn's disease. We aimed to assess the CDED in adults with Crohn's disease. Methods We did an open-label, pilot randomised trial at three medical centres in Israel. Eligible patients were biologic naive adults aged 18–55 years with mild-to-moderate Crohn's disease (defined by a Harvey–Bradshaw Index score of 5–14 points), a maximal disease duration of 5 years, with active disease on colonoscopy, or imaging with elevated inflammatory markers (C-reactive protein >5 mg/L or faecal calprotectin concentration >200 μ/g). Patients were randomly assigned (1:1) to CDED plus partial enteral nutrition or CDED alone for 24 weeks. Randomisation was via block randomisation (block sizes of six) using sealed, numbered, and opaque envelopes. Patients and investigators were aware of which group patients were assigned to due to the nature of the different interventions. The primary endpoint was clinical remission, defined as a Harvey–Bradshaw Index score of less than 5 at week 6. The primary endpoint was assessed in the intention-to-treat (ITT) population, which included all patients who used the dietary therapy for at least 48 h. We report results of the final analysis. This trial is registered with ClinicalTrials.gov , NCT02231814 . Findings Between Jan 12, 2017, and May 11, 2020, 91 patients were screened, of whom 44 were randomly assigned to the CDED plus partial enteral nutrition group (n=20) or CDED alone group (n=24). 19 patients in the CDED plus partial enteral nutrition group and 21 patients in the CDED alone group received the allocated intervention for at least 48 h and thus were included in the ITT analysis. At week 6, 13 (68%) of 19 patients in the CDED plus partial enteral nutrition group and 12 (57%) of 21 patients in the CDED group had achieved clinical remission (p=0·4618). Among the 25 patients in remission at week 6, 20 (80%) were in sustained remission at week 24 (12 patients in the CDED plus partial enteral nutrition group and eight in the CDED alone group). 14 (35%) of 40 patients were in endoscopic remission at week 24 (eight patients in the CDED plus partial enteral nutrition group and six in the CDED alone group). No serious adverse events or treatment-related adverse events were reported in either group. Interpretation CDED with or without partial enteral nutrition was effective for induction and maintenance of remission in adults with mild-to-moderate biologic naive Crohn's disease and might lead to endoscopic remission. These data suggest that CDED could be used for mild-to-moderate active Crohn's disease and should be assessed in a powered randomised controlled trial. Funding Azrieli Foundation and Nestle Health Science.

Resumen Objetivo La ecografia intestinal se considera una alternativa para la evaluacion de la recurrencia posquirurgica (RPQ) de la enfermedad de Crohn. El objetivo de este estudio es evaluar la correlacion entre los hallazgos ecograficos y endoscopicos. Metodos Se recogieron de forma retrospectiva los datos de pacientes con enfermedad de Crohn y reseccion ileocecal en los que se habia realizado una colonoscopia y una ecografia intestinal para la deteccion de RPQ. La RPQ se evaluo empleando el indice de Rutgeerts (IR). Los hallazgos ecograficos analizados fueron el grosor de la pared intestinal, la hiperemia parietal por Doppler, la desestructuracion del patron de capas y la proliferacion fibrograsa. Resultados Se incluyo a un total de 31 pacientes, 15 (48,4%) sin recurrencia (IR? Conclusiones En nuestra experiencia, la ecografia tiene una alta rentabilidad diagnostica para la deteccion de RPQ y puede considerarse en muchas ocasiones como una alternativa valida y no invasiva a la ileocolonoscopia.

ObjectiveIn newly diagnosed paediatric patients with moderate-to-severe Crohn’s disease (CD), infliximab (IFX) is initiated once exclusive enteral nutrition (EEN), corticosteroid and immunomodulator therapies have failed. We aimed to investigate whether starting first-line IFX (FL-IFX) is more effective to achieve and maintain remission than conventional treatment.DesignIn this multicentre open-label randomised controlled trial, untreated patients with a new diagnosis of CD (3–17 years old, weighted Paediatric CD Activity Index score (wPCDAI) >40) were assigned to groups that received five infusions of 5 mg/kg IFX at weeks 0, 2, 6, 14 and 22 (FL-IFX), or EEN or oral prednisolone (1 mg/kg, maximum 40 mg) (conventional). The primary outcome was clinical remission on azathioprine, defined as a wPCDAI Results100 patients were included, 50 in the FL-IFX group and 50 in the conventional group. Four patients did not receive treatment as per protocol. At week 10, a higher proportion of patients in the FL-IFX group than in the conventional group achieved clinical (59% vs 34%, respectively, p=0.021) and endoscopic remission (59% vs 17%, respectively, p=0.001). At week 52, the proportion of patients in clinical remission was not significantly different (p=0.421). However, 19/46 (41%) patients in the FL-IFX group were in clinical remission on azathioprine monotherapy without need for treatment escalation vs 7/48 (15%) in the conventional group (p=0.004).ConclusionsFL-IFX was superior to conventional treatment in achieving short-term clinical and endoscopic remission, and had greater likelihood of maintaining clinical remission at week 52 on azathioprine monotherapy.Trial registration numberClinicalTrials.gov Registry (NCT02517684).

A 14-year-old girl presented to the ophthalmology clinic with progressive diminution of vision, redness, pain and photophobia in both eyes for the last 1 month. She had abdominal pain, diarrhoea and weight loss during that period. Ocular examination revealed features of anterior uveitis, vitritis and retinal vasculitis. In view of gastrointestinal symptoms, abdominal imaging was done, which showed multiple enhancing bowel wall thickening with skip lesions in the terminal ileum and ascending colon. Colonoscopy showed ulcers in the ascending colon, caecum and terminal ileum. Histopathology revealed microgranulomas in lamina propria and submucosal granulomas suggestive of Crohn’s disease. The patient was started on topical steroid eye drops and oral budesonide and mesalazine. Her vision improved after 3 weeks and bowel symptoms attained remission after 8 weeks, and at present, she is doing well.

Crohn's disease (CD) is chronic recurrent bowel disease of unknown etiology, characterized by segmental transmural granulomatous inflammation, mainly with the development of local and systemic complications. Despite the active development of conservative therapy methods, the number of drug-resistant forms of CD and complications of the disease requiring surgical treatment continues to increase. The article reflects modern scientific ideas about the methods of diagnosis, conservative and surgical treatment of CD in children.

Background This retrospective study aimed to investigate the usefulness of the optimized kiloelectron volt (keV) for virtual monoenergetic imaging (VMI) combined with iodine map in dual-energy computed tomography enterography (DECTE) in the diagnosis of Crohn’s disease (CD). Methods Seventy-two patients (mean age: 41.89 ± 17.28 years) with negative computed tomography enterography (CTE) were enrolled for investigating the optimized VMI keV in DECTE by comparing subjective and objective parameters of VMIs that were reconstructed from 40 to 90 keV. Moreover, 68 patients (38.27 ± 15.10 years; 35 normal and 33 CD) were included for evaluating the diagnostic efficacy of DECTE iodine map at the optimized VMI energy level and routine CTE for CD and active CD. Statistical analysis for all data was conducted. Results Objective and subjective imaging evaluations showed the best results at 60 keV for VMIs. The CT values of the normal group, active subgroup, and CD group during the small intestinal phase at routine 120 kVp or 60 keV VMI had significant differences. The diagnostic efficacy of an iodine map was the best when NIC = 4% or fat value = 45.8% for CD, whereas NIC P Conclusions VMI at 60 keV provided the best imaging quality on DECTE. NIC and fat value provided important basis for active CD evaluation. Routine CTE combined with VMI at 60 keV improved the diagnostic efficiency for CD.

Differentiation of Crohn’s disease (CD) from intestinal tuberculosis (ITB) is a big challenge to gastroenterologists because of their indistinguishable features and insensitive diagnostic tools. A non-invasive biomarker is urgently required to distinguish ITB/CD patients particularly in India, a TB endemic region, where CD frequency is increasing rapidly due to urbanization. Among the three differentially expressed miRNAs obtained from small RNA transcriptomic profiling of ileocaecal/terminal ileal tissue of ITB/CD patients (n = 3), only two down-regulated miRNAs, miR-31-5p, and miR-215-5p showed comparable data in qRT-PCR. Out of which, only miR-215-5p was detectable in the patient’s plasma, but there was no significant difference in expression between ITB/CD. On the other hand, miR-375-3p, the pulmonary TB specific marker was found in higher amount in the plasma of ITB patients than CD while reverse expression was observed in the ileocaecal/terminal ileal tissues of the same patients. Next, using Bioplex pro-human cytokine 48-plex screening panel, only three chemokines, Eotaxin-1/CCL11, SDF-1α/CXCL12, and G-CSF have noted significantly different levels in the serum of ITB/CD patients. ROC analysis has revealed that compared to a single molecule, a combination of miR-375-3p + Eotaxin-1/CCL11 + SDF-1α /CXCL12 + G-CSF showed a better AUC of 0.83, 95% CI (0.69–0.96) with 100% specificity and positive predictive value while sensitivity, negative predictive value, and accuracy were 56%, 69%, and 78% respectively in distinguishing ITB from CD. This study suggests that a combination of plasma markers shows better potential in differentiating ITB from CD than a single marker and this panel of markers may be used for clinical management of ITB/CD patients.

Background The anti-inflammatory effect of exclusive enteral nutrition on the gut of children with Crohn’s disease is rapidly lost after food reintroduction. This study assessed disease dietary triggers following successful treatment with exclusive enteral nutrition. Methods Nutrient intake, dietary patterns and dietary biomarkers in faeces (gluten immunogenic peptides, undigestible starch, short chain fatty acids) were assessed in 14 children with Crohn’s disease during early food reintroduction, following exclusive enteral nutrition. Groups above (Group A) and below (Group B) the median levels of faecal calprotectin after food reintroduction were assigned for comparative analysis. Results Intakes of fibre, gluten-containing cereals and red and processed meat were significantly higher in Group A than Group B; (median [Q1, Q3], g/day; Fibre: 12.1 [11.2, 19.9] vs. 9.9 [7.6, 12.1], p = 0.03; Red and processed meat: 151 [66.7, 190] vs. 63.3 [21.7, 67], p = 0.02; gluten-containing cereals: 289 [207, 402] vs. 203 [61, 232], p = 0.035). A diet consisting of cereals and meat products was predictive (92% accuracy) of higher faecal calprotectin levels after food reintroduction. In faeces, butyrate levels, expressed as absolute concentration and relative abundance, were higher in Group A than Group B by 28.4 µmol/g (p = 0.015) and 6.4% (p = 0.008), respectively. Levels of gluten immunogenic peptide and starch in faeces did not differ between the two groups. Conclusions This pilot study identified potential dietary triggers of gut inflammation in children with Crohn’s disease after food reintroduction following treatment with exclusive enteral nutrition. Trial registration: Clinical trials.gov registration number: NCT02341248; Clinical trials.gov URL: https://clinicaltrials.gov/ct2/show/NCT02341248 (retrospectively registered).