Bowel Crohn's Disease Research Articles

Diarrheal Illness

Diarrhea, qualitatively defined as an increase in stool frequency and liquid content, is a frequent complaint in patients presenting to emergency departments. Although most cases are uncomplicated viral infections, the most frequent causes of dangerous underlying entities are often not viral. In uncomplicated cases, laboratory testing for metabolic derangements is not required unless there are signs of moderate to severe dehydration or the patient has particular risks, such as chronic kidney disease. Secondary infections associated with antibiotic use (C difficile–associated diarrhea), other significant nosocomial exposures, recent international travel history, the presence of a nonintact immune system (HIV/AIDS, cancer/chemotherapy), and exposure to high-risk environments (including zoonotic exposures, outbreak-prone environments such as day care facilities) increase the likelihood of a bacterial or other infectious cause requiring either microbiologic testing or empirical antimicrobial treatments. Diarrhea is often present as a feature of clinically significant noninfectious conditions, including complications of inflammatory bowel diseases (Crohn disease and ulcerative colitis), overdoses, and withdrawal syndromes. In such cases, after hemodynamic stability has been ensured, advanced workup and treatment are guided by the underlying condition and antecedent risks, not the presence of diarrhea per se. Oral rehydration is the first step in management for mild dehydration caused by uncomplicated diarrhea. Intravenous fluids may be necessary in moderate to severe dehydration and in cases of electrolyte derangement requiring resuscitation where fluid choice and rate are paramount, as well as in patients who cannot tolerate oral intake. In cases of suspected bacteria-caused diarrhea, antibiotics, most often fluoroquinolones, reduce both the severity and duration of illness. In patients safe for home management, antidiarrheal agents such as loperamide may be used in uncomplicated and resolving cases. Probiotics appear safe in most cases and impart a small but clinically detectable decrease in the duration and severity of illness. Although there have been fears of bacterial outbreaks following natural disasters, improvements in local and global health efforts have led to decreases in cholera outbreaks, and typical viral causes of diarrhea are generally the most common causes. This review contains 4 figures, 5 tables and 32 references Key words: Clostridium difficile, diarrhea, infectious diseases, inflammatory bowel diseases, medication side effects, overdose syndromes, sepsis, traveler’s diarrhea, zoonotic infections

Surgical Management of Small Bowel Crohn's Disease.

Crohn's disease in the small bowel could present itself as an inflammatory stricture, a fibrotic stricture as penetrating disease or a combination of both. It is pertinent to differentiate the disease process as well as its extent to effectively manage the disease. Currently, a combination of medical and surgical therapies forms part of the treatment plan while the debate of which therapy is better continues. In managing the strictures, identification of the disease process through imaging plays a pivotal role as inflammatory strictures respond to anti-tumor necrosis factor (TNF) and biological agents, while fibrotic strictures require endoscopic or surgical intervention. Recent evidence suggests a larger role for surgical excision, particularly in ileocolic disease, while achieving a balance between disease clearance and bowel preservation. Several adaptations to the surgical technique, such as wide mesenteric excision, side to side or Kono-S anastomosis, and long-term metronidazole therapy, are being undertaken even though their absolute benefit is yet to be determined. Penetrating disease requires a broader multidisciplinary approach with a particular focus on nutrition, skincare, and intestinal failure management. The current guidance directs toward early surgical intervention for penetrating disease when feasible. Accurate preoperative imaging, medical management of active diseases, and surgical decision-making based on experience and evidence play a key role in success.

Childhood appendicitis and future risk of inflammatory bowel disease - A nationwide cohort study in Sweden 1973-2017.

AimThe aim of this study was to investigate the association between juvenile appendicitis, treated conservatively or with appendectomy, and adult risk of inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn's disease (CD). We used nationwide population data from more than 100,000 individuals followed for over four decades.MethodAll Swedish patients discharged with a diagnosis of appendicitis before the age of 16 years between 1973 to 1996 were identified. Everyone diagnosed with appendicitis was matched to an individual in the general population without a history of juvenile appendicitis (unexposed) of similar age, sex and region of residence. The study population was retrospectively followed until 2017 for any development of UC or CD. Cox proportional‐hazards models compared disease‐free survival time between exposed and unexposed individuals, also analysing the impact of treatment (conservative treatment versus appendectomy).ResultsThe final cohort consisted of 52,391 individuals exposed to appendicitis (1,674,629 person years) and 51,415 unexposed individuals (1,638,888 person years). Childhood appendicitis with appendectomy was associated with a significantly lower risk of adult IBD [adjusted hazard ratio (aHR) 0.48 (0.42–0.55)], UC [aHR 0.30 (0.25–0.36)] and CD [aHR 0.82 (0.68–0.97)]. Those treated conservatively had a lower risk of adult UC [aHR 0.29 (0.12–0.69)] but not CD [aHR 1.12 (0.61–2.06)] compared with unexposed individuals.ConclusionJuvenile appendicitis treated with appendectomy was associated with a decreased risk of adult IBD, both UC and CD. Those treated conservatively instead of with surgery had a lower risk of UC only. Our findings warrant more research on the role of the appendix and gut microbiota in the pathogenesis of IBD.

Small bowel Crohn's disease: optimal modality for diagnosis and monitoring.

This paper reviews different imaging options for small bowel (SB) Crohn's disease (CD) patients. In total, 80% of patients suffering from CD have SB involvement, being the exclusive manifestation in 30% of cases. As the proximal disease is related to poor response to treatment, a higher rate of stenosis and a greater need for surgical treatment, a SB assessment should be performed. This evaluation should be done not only once the disease has been diagnosed but periodically. The former to determine the extent of the disease, and the latter according to a treat-to-target strategy. Available techniques such as magnetic resonance imaging, intestinal ultrasound and capsule endoscopy (CE) have shown good accuracy parameters in CD patients. Cross-sectional studies are superior for penetrating and stricturing disease, whereas CE is excellent for proximal involvement and mucosal healing. Local expertise and availability may lead the election between techniques, nevertheless, they should not be considered as competitors but as complementary tools. SB involvement in CD patients is frequent and related to poorer outcomes. Hence, SB evaluation should be screened after diagnosis and routinely during the follow-up.

The Joints Manifestation of Inflammatory Bowel Diseases

Joint manifestations of inflammatory bowel diseases (IBD) are observed in 30% of cases. Their largest share is in total forms of ulcerative colitis (UC) 85-90% and Crohn's disease (CD) involving the colon 30-35% or large and small intestines 60%. The pathogenesis of articular manifestations remains unclear. The importance of increased permeability of the intestinal wall, which is noted in patients with UC and CD, is discussed, as a result of which the components of the membrane wall of bacteria enter the bloodstream. These components act as peptide antigens that can lead to the development of arthritis. Contacting the molecules of histocompatibility complexes and further activating T-lymphocytes, peptides lead to joint inflammation. From the point of view of a rheumatologist, the articular manifestations of IBD are classified as seronegative spondyloarthropathies. During 2013-2020, we studied the frequency of treatment of patients with IBD with extraintestinal articular manifestations for examination to a rheumatologist. We analyzed the ratio of the number of patients with IBD having joints manifestations, which were confirmed and diagnosed by a rheumatologist or consulted in the areas of a gastroenterologist and a surgeon-proctologist. All patients who turned to a rheumatologist with joints manifestations over the years were referred by a gastroenterologist (38%), surgeon-proctologist (14%) and these extraintestinal manifestations of IBD were suspected and confirmed by a rheumatologist (48%). The need for a differentiated approach to the treatment of peripheral arthritis and any axial skeletal lesions is noted, the role of 5-aminosalicylic acid (5-ASA) drugs, steroidal and non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressant and biological drugs in the treatment of articular syndrome in IBD is evaluated. It is indicated that patients with IBD having of joints manifestations should be observed jointly by a rheumatologist, gastroenterologist and a proctologist. Regional or granulomatous ileitis is a chronic bowel disease (Crohn's disease) that covers all the layers of the intestinal wall (transmural lesions), and sometimes spreads to the mesentery, regional lymph nodes affecting both the small and large intestines, but most often localized in the terminal section of a thin guts (regional, terminal ileitis). These diseases can be accompanied by damage to the peripheral joints, spine, or joints and spine. The clinical manifestations of the joint syndrome in both processes are the same. The pathogenesis of the intestinal process and joint damage has not been fully established, but it is believed that many mechanisms participate in it, and in particular, toxic, immune, autoimmune. In the blood of patients, antibodies to the cells of the intestinal mucosa, lymphocytotoxin antibodies, circulating immune complexes, in which, possibly, antigenic components of intestinal microbes, etc., are also present. In Crohn's disease, articular manifestations usually occur in childhood and adolescence. The development of peripheral arthritis in these diseases is usually not associated with the carriage of the histocompatibility antigen B27. Ankylosing spondylitis is more common in men than in women (3: 1). This disease usually develops in people who have HLA B27. Articular changes with regional ileitis occur more often in patients with other extraintestinal manifestations of the processes - with ulcers of the oral mucosa, exacerbate erythema nodosum, gangrenous pyoderma.

Small Bowel Crohn's Disease Recurrence is Common After Total Proctocolectomy for Crohn's Colitis.

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 age <18 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 edad <18 (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).

Crown disease with extrainterinal manifestations in the form of granulematous alveolitis

Objective: To present a clinical description of the observation of a patient with Crohn’s disease (CD) with extraintestinal manifestations in the form of granulomatous alveolitis.Materials and Methods: A brief review of the literature on the current understanding of the prevalence and clinical manifestations of lung lesions in inflammatory bowel diseases (IBD) and CD, as well as a description of a patient with this pathology with the results of autopsy is presented.Results: The rare presence of granulomatous lung lesions in a patient with CD was proved.Conclusion: Difficulties in the differential diagnosis and treatment of CD lung lesions are shown. In particular, suspicion of tuberculous lesion, lung abscess creates potential risks of generalization of the process when using such therapeutic effects as glucocorticosteroids, cytostatics, immunosuppressants, biological genetically engineered drugs and active surgical intervention. The authors hope that the described observation will alert doctors in terms of possible systemic pulmonary lesions in CD.

CT or MR Enterography to Assess Response During Vedolizumab Therapy for Small Bowel Crohn's Disease.

To describe response to therapy of small bowel (SB) Crohn's disease (CD) at CT or MR enterography (CTE/MRE) in patients on vedolizumab. Patients with SB CD who underwent CTE/MRE exams greater than 12 months apart on vedolizumab therapy were included. Length (in cm) and inflammation severity (EMBARK score) of inflamed SB segments were assessed. Changes in inflammation length of 3.4cm or greater or inflammation severity of 2 EMBARK points or greater was categorized as response or progression, as appropriate, with development of newly inflamed segments, strictures, or penetrating complications also indicating progression. Patients not meeting the criteria for response or progression were categorized as having stable disease. Of 36 SB CD patients, the large majority had prior surgery (86%; 31), anti-TNF use (92%; 33), and internal penetrating (78%; 28) disease. Thirty-two patients had paired baseline and follow-up CTE/MRE exams without interval surgery, with clinical response observed in 24/32 (75%). Based on imaging response criteria, 22% (7/32; 95% CI: 9%-40%) had response, 50% (16/32; 95% CI: 32%-68%) were stable, and 28% (9/32; 95% CI: 14%-47%) had disease progression. Fifty-six percent of (18/32; 95% CI: 38%-74%) patients had clinical improvement with response or stable disease by imaging. Patients with stable disease had shorter median baseline lengths of SB inflammation (P = .012). Proportion of patients with colonic inflammation, perianal disease, or penetrating complications did not change. Most patients on vedolizumab for over 12 months demonstrated response or stable SB disease when using objective cross-sectional radiologic imaging criteria using CTE/MRE.

Association between autism spectrum disorder and inflammatory bowel disease: A systematic review and meta‐analysis

Children with autism spectrum disorder (ASD) are frequently diagnosed with co-occurring medical conditions including inflammatory bowel disease (IBD). To investigate the association, we conducted a systematic review registered in PROSPERO (ID:CRD42021236263) with a random-effects meta-analysis. We searched PubMed, Embase, and PsycInfo (last search on January 25, 2021), and manually searched relevant publications. We included observational studies measuring the association between ASD and IBD. The primary outcome was the association (odds ratio, OR) between ASD and later development of IBD. Sensitivity analyses were conducted by quality, confounding adjustment, and study design. We performed meta-regression analyses and assessed heterogeneity, publication bias, and quality of studies with the Newcastle-Ottawa Scale. Overall, we included six studies consisting of eight datasets, including over 11 million participants. We found that ASD was significantly associated with subsequent incident IBD (any IBD, OR=1.66, 95% confidence interval[CI]=1.25-2.21, p< 0.001; ulcerative colitis, OR=1.91, 95%CI=1.41-2.6, p< 0.001; Crohn's disease, OR=1.47, 95%CI=1.15-1.88, p =0.002). ASD and IBD were also associated regardless of temporal sequence of diagnosis (any IBD, OR=1.57, 95%CI=1.28-1.93, p< 0.001; ulcerative colitis, OR=1.7, 95%CI=1.36-2.12, p< 0.001; Crohn's disease, OR=1.37, 95%CI=1.12-1.69, p =0.003). Sensitivity analyses confirmed the findings of the main analysis. Meta-regression did not identify any significant moderators. Publication bias was not detected. Quality was high in four datasets and medium in four. In conclusion, our findings highlight the need to screen for IBD in individuals with ASD, and future research should identify who, among those with ASD, has the highest risk of IBD, and elucidate the shared biological mechanisms between ASD and IBD. LAY SUMMARY: This systematic review and meta-analysis of eight observational datasets found that individuals with autism spectrum disorder (ASD) are more likely to develop any inflammatory bowel disease, ulcerative colitis, or Crohn's disease. Our findings highlight the need to screen for inflammatory bowel disease in patients with ASD and elucidate the shared biological mechanisms between the two disorders.

P032 Clinical Usefulness of Double Balloon Enteroscopy in Patients With Established or Suspected Small Bowel Crohn's Disease.

The diagnosis of isolated small bowel Crohn's disease (CD) can be challenging. Symptoms are non-specific and both imaging and capsule endoscopy (CE) may be misleading as several diseases may mimic CD. Double balloon enteroscopy (DBE) allows a more extensive endoscopic and histologic evaluation of the small bowel. Our aim was to describe the diagnostic utility and impact of DBE on management of patients with known CD and in patients with suspected/rule-out CD. Retrospective review of our institution's DBE database from February 2009 to May 2013. Adult patients referred for DBE for further evaluation of known or suspected CD (due to symptoms, abnormal imaging and/or CE) were included. Patient demographics, clinical characteristics, imaging and CE results, prior DBE, indication for DBE, DBE findings, DBE adverse events, pathology findings, final diagnosis, treatment prior and post DBE and follow-up DBE were abstracted from the electronic medical record. A total of 108 patients were included, 61 (56%) females, mean age 52 years (range 20-83). Indications for DBE included: disease activity assessment/therapeutic in 10 patients with established diagnosis of CD and for diagnostic purposes in 98 patients with suspected CD (31 patients due to abnormal imaging, 29 due to abnormal CE and 26 due to both abnormal imaging and CE). Upper, lower, bidirectional upper and lower, and stomal DBE were performed in 21, 24, 62 and 1 patients, respectively. DBE revealed active disease in 8/10 patients with known CD with one patient undergoing dilation of a stricture. Changes in management were recommended for all patients with active disease - start thiopurine (2), optimize thiopurine dose (1), start biologics (3) change biologics (1), systemic steroids (1) and budesonide (1). The patient who underwent stricture dilation ultimately required surgery. A definitive diagnosis of CD (both endoscopic and histologic) was reached in only 39/98 (40%) patients who were referred for suspected CD. Changes in management were recommended in 32/39 (82%) patients. Interestingly, 24/98 patients had been diagnosed with CD at outside institutions and were recommended to initiate therapy for CD. Of these, CD was confirmed in only 15/24 (63%) patients. Adverse events included perforation in 1 patient (1%) who required surgical management and mouth swelling/abrasion in 3 patients (3%). Follow-up DBE to re-assess disease activity was performed in 10/49 (20%) patients with definitive diagnosis of CD, average time between procedures 4.5 years (range 0.7-11.6). One patient with CD was diagnosed with lymphoma 2.4 years after initial DBE. Changes in management were recommended in 6 patients: de-escalation of therapy (3, two underwent surgery), start thiopurine and/or biologic (2) and switch biologics (1). No complications were seen at follow-up DBE. DBE is a useful technique to confirm a diagnosis in patients who have suspected CD and can help establish a diagnosis of several diseases that may mimic CD on CT scan or CE. Additionally, DBE in patients with established diagnosis of small bowel CD is an effective tool to assess disease activity and guide therapy. Serious complications are infrequent.

Open versus minimally invasive small bowel resection for Crohn's disease: a NSQIP retrospective review and analysis.

Many patients with Crohn's Disease will require surgical resection. While many studies have described outcomes following ileocecectomy, few have evaluated surgical resection of other portions of small bowel. We sought to compare open and minimally invasive surgery (MIS) approaches for small bowel resection excluding ileocecectomy of patients with Crohn's Disease using the National Surgical Quality Improvement Program (NSQIP) database. The NSQIP database was queried for patients with Crohn's disease or complications related to Crohn's disease who underwent segmental small bowel resection utilizing open or minimally invasive approaches between 2012 and 2018. Patients requiring ileocecectomy or diagnosed with ascites, disseminated cancer, pre-operative sepsis, ASA class 5, and patients requiring mechanical ventilation were excluded. The association of pre-operative variables including patient demographic information and comorbidities with surgical approach were examined using Fishers exact test. Intraoperative, and 30-day post-operative outcomes were compared between the groups using both univariate and multivariate logistical regression models. SAS was used for data analysis with p < 0.05 considered significant. After exclusions, we found 1697 patients with Crohn's disease who underwent segmental small bowel resection, 1252 of whom underwent open surgery and 445 of whom underwent MIS. After adjusting for possible confounders with multivariable analysis, patients who underwent MIS had a lower incidence of wound events (surgical site, organ space, or deep wound infection, or dehiscence), post-operative bleeding, need for return to the operating room, and shorter total hospital length of stay despite longer operative times compared with open surgery. This retrospective review of NSQIP shows that minimally invasive small bowel resection is associated with equivalent or improved morbidity over open surgery in select patients with small bowel Crohn's Disease. We show that in select patients minimally invasive small bowel resection can be safe and performed for patients with isolated small bowel Crohn's disease.

P077 Incidence of Colonic Strictures - A Systematic Review and Meta-analysis.

Intestinal strictures are a complication of the inflammatory bowel diseases (IBD, including ulcerative colitis (UC) and Crohn's disease (CD)) that can lead to bowel obstruction and therapy failure. Intestinal strictures occurring after long-standing tissue damage and repair are more frequently reported in CD, but colonic strictures can occur in UC. However, there is a paucity of literature that comprehensively summarizes the available information regarding the incidence and etiology of colonic strictures in UC. The aim of this study was to perform a systematic review and meta-analysis of published reports on the incidence of colonic strictures in UC patients. Four independent reviewers performed a comprehensive review of all original articles describing the incidence of colonic strictures in UC published from inception to June 2021. Primary outcomes were (1) overall incidence of colonic strictures; (2) 10-year incidence of colonic strictures; and (3) incidence of colonic strictures containing high-grade dysplasia (HGD) or colorectal cancer (CRC). Subgroup analysis was performed to compare the outcomes between the pre-biologic era and post-biologic era. The meta-analysis was performed and the statistics were 2-tailed. Finally, probability of publication bias was assessed using funnel plots and with Egger's test. Eleven studies reporting on a total of --- patients with colonic strictures were included in the analysis after comprehensive search. This yielded a pooled colonic stricture incidence rate of 5.4% (95% confidence interval (CI) 3.7-7.8). The incidence rate of colonic strictures was lower in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (2.6% vs 6%; p = 0.14). The pooled 10-year colonic stricture rate was 3.2% (95% CI 1.5-6.8). The pooled 10-year incidence rate of colonic strictures was lower in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (1% vs 1.8%; p = 0.1). The pooled incidence of strictures with associated high-grade dysplasia (HGD) or colorectal cancer (CRC) was 21.9% (95% CI 12.2-36.5). The incidence rate of HGD or CRC in colonic strictures was higher in the post-biologic era compared to the pre-biologic era but the difference was not statistically significant (23.6% vs 20.4%; p = 0.79). This systematic review and meta-analysis on the incidence of colonic strictures in UC showed that the overall pooled incidence and 10-year incidence of colonic strictures in UC are low. There was a trend towards lower incidences of UC strictures in the post-biologic era, although the differences did not reach statistical significance. While the overall incidence of colonic strictures, in UC is low, a high proportion of colonic strictures are associated with HGD or CRC, even in the biologic era. Therefore, this study provides further support for importance of stricture biopsy and surgical evaluation for colectomy in the UC patient with colonic stricture.

Interspecies variation in hominid gut microbiota controls host gene regulation.

SUMMARYThe gut microbiome exhibits extreme compositional variation between hominid hosts. However, it is unclear how this variation impacts host physiology across species and whether this effect can be mediated through microbial regulation of host gene expression in interacting epithelial cells. Here, we characterize the transcriptional response of human colonic epithelial cells in vitro to live microbial communities extracted from humans, chimpanzees, gorillas, and orangutans. We find that most host genes exhibit a conserved response, whereby they respond similarly to the four hominid microbiomes. However, hundreds of host genes exhibit a divergent response, whereby they respond only to microbiomes from specific host species. Such genes are associated with intestinal diseases in humans, including inflammatory bowel disease and Crohn’s disease. Last, we find that inflammation-associated microbial species regulate the expression of host genes previously associated with inflammatory bowel disease, suggesting health-related consequences for species-specific host-microbiome interactions across hominids.

Clinical features of 44 patients with small bowel Crohn's disease.

At present, there are many studies on Crohn's disease of terminal ileum and colon, but few studies on Crohn's disease of small intestine alone. This study aims to analyze the clinical features and therapeutic effect of small bowel in adult patients with Crohn's disease so as to strengthen the diagnosis and treatment for this disease. From July 1, 2015 to October 31, 2018, patients with small bowel Crohn's disease at Department of Gastroenterology, Third Xiangya Hospital of Central South University, were enrolled. At the same time, patients' demographics and clinical data were collected. A total of 44 patients were small bowel Crohn's disease. Among them, 40 patients were male. The age at diagnosis was (35.8±10.3) years old and disease duration was (35.2±59.5) months. The subtypes included 29(65.9%) of ileum, 7(15.9%) of jejunum, 8(18.2%) of ileum with jejunum. There were 27(61.4%) of stricture behavior, 4(9.1%) of penetrating behavior, and 13(29.5%) of non-stricture and non-penetrating behavior. Endoscopic visible stricture (29/85, 34.1%) was common, followed by longitudinal ulcers (27/85, 31.8%). Non-caseate granulomatous were found in 2 cases (4.5%). The score of Crohn's disease activity index was correlated to hemoglobin, hematocrit, and erythrocyte sedimentation rate (all P<0.05). Among the most common symptom of abdominal pain (34/44, 77.3%), 11 patients (25.0%) developed complications (eg. intestinal obstruction) during the follow-up, and 66.7% of patients treated with mesalazine had complications. Patients with ileum account for a large proportion in patients with small bowel Crohn's disease. Stricture is more common in small bowel Crohn's disease. Stricture and longitudinal ulcer are more common under enteroscopy. Crohn's disease activity index is correlated to hemoglobin, red blood cell specific volume, and erythrocyte sedimentation rate. The most common complication is intestinal obstruction. Mesalazine is less effective on small bowel Crohn's disease.

Multidetector computed tomography: a corner stone imaging modality in evaluation of acute small bowel diseases

BackgroundThe diagnosis of acute small bowel diseases is one of the challenging issues that confronted by the radiologists so accurate diagnosis is essential to determine the appropriate way of management. CT has become the preferred imaging tool to evaluate acute small bowel diseases. Our study aimed to assess the role of MDCT in evaluation of acute abdomen secondary to small bowel origin by identification and differentiation between different acute small bowel pathologies.ResultsThirty-eight patients presented with acute abdomen of small bowel origin from June 2019 to September 2019. The mean age of incidence was 48 ± 19 years ranged from 4 to 88 years. Males represented by 23 patients (60.5%). Acute exacerbation of inflammatory bowel diseases (Crohn’s disease) represented by (34.2%), small bowel obstruction (31.6%), ischemic bowel diseases (21.1%), small bowel perforation (10.5%) and infectious (TB enteritis) small bowel disease (2.6%). MDCT had an overall high sensitivity (97.3%) in assessment of acute small bowel diseases in correlation with post-operative data and follow-up response to management.ConclusionsMDCT is a reliable diagnostic imaging tool for assessment of patients with acute abdomen secondary to small bowel origin with high-efficiency in differentiation between different pathological entities that causing acute abdomen.

Features of inflammatory bowel diseases in St. Petersburg and peculiarities of basic therapy in the regional healthcare system: cross-sectional study results

Background. Inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) are serious problem in modern gastroenterology, as these diseases affect the working population, have a progressive chronic course, a high risk of disabling complications and require significant costs for the drug management.Aim. We wanted to assess the inflammatory bowel diseases structure and features of the use of basic drugs in outpatient and inpatient treatment in St. Petersburg, Russia.Materials and methods. A cross-sectional study was performed. Data about drug therapy, disease features and demographic from 42 outpatient institutions and from 6 city hospitals for the period 2018–2020 in St. Petersburg was collected. The analysis included data from 617 patients with ulcerative colitis and 455 patients with Crohn’s disease.Results. The median age of patients with ulcerative colitis was 44 years, which was statistically significant more than with Crohn’s disease (39 years). In ulcerative colitis, the left-sided localization of colon lesions (56%) prevailed over total colitis (23%) and proctitis (21%) In Crohn’s disease, the prevalence of ilecocolitis (36%) was approximately equal to the prevalence of colitis (35%), the frequency of terminal ileitis was significantly less (26%), other variants of gastrointestinal lesions were found in 3% cases. In Crohn’s disease compared to ulcerative colitis, the proportion of patients with mild disease was similar (36.6% and 38.2% respectively), but in in Crohn’s disease the frequency of severe disease there was more than three times compared to ulcerative colitis. There has been a significantly higher incidence of surgery in the past for Crohn’s disease compared to ulcerative colitis (14.8% and 2.6%, respectively). The vast majority of patients (more than 80%) received therapy with oral 5-aminosalycilic acid drugs. Topical formulas of 5-aminosalycilic acid drugs in ulcerative colitis were prescribed in about 50% of cases (it was significantly less than commonly used in Crohn’s disease). Corticosteroids were used in the treatment of 16.6% of ulcerative colitis patients and in 24.4% Crohn’s disease patients. In both diseases in the conditions of inpatient treatment, this group of drugs was used several times more often than in outpatient observation. Immunosuppressants (tyopurines, methotrexate) were administered in 6.9% ulcerative colitis patients with and in 17.0% Crohn’s disease patients.Conclusion. Clinical features of inflammatory bowel diseases in St. Petersburg and the features of basic therapy in comparison with the nationwide indicators in Russia demonstrate similar trends. The key problem points of therapy of inflammatory bowel diseases remains the widespread use of drugs of the group of 5-aminosalycilic acid in Crohn’s disease, insufficient use of rectal forms of 5-aminosalycilic acid in ulcerative colitis, a relatively small frequency of use of immunosupressors to maintain remission in Crohn’s disease. The solution to the problem of optimizing the therapy of patients with inflammatory bowel diseases within the framework of routine practice includes educational activities, as well as the creation of a regional register of patients with inflammatory bowel diseases in St. Petersburg.

Does exclusive enteral nutrition reduce the rate of stoma formation in patients requiring ileocolic resection for Crohn's disease? A single center experience.

Nutrition has a role in achieving and maintaining remission in Crohn's disease. The aim of this study was to determine the impact of a strategy of steroid-avoidance and Exclusive Enteral Nutrition (EEN) for 6 weeks (with a minimum of 4 weeks) in adult patients presenting with acute small bowel Crohn's disease followed by an interval ileocolic resection 4-6 weeks later. Retrospective review of prospectively collected data. Patients were administered exclusive enteral nutrition (EEN) for at least 4 weeks prior to surgery. 24 EEN patients included. Median age of 45 (range 23-73). 17/24 patients tolerated Modulen for at least 4 weeks, 5 were switched to Ensures and 2 a liquid diet. 6 patients underwent surgery earlier than planned. Prior to surgery, there was no change in the mean BMI, albumin increased from a mean of 36g/L (range 25-43) to 40g/L (range 30-48). CRP levels decreased by a mean of 35.8mg/L overall. 19 (79%) of operations were performed laparoscopically. 6 of the cases were re-do operations. All but 3 patients avoided a stoma at the time of the original operation. There were 5 post-operative complications: 1 anastomotic leak in a patient with a BMI of 42, 3 cases of paralytic ileus and 2 wound infections. Median length of stay was 7 days (range 3-76 days). Only 2 patients were readmitted within the 30-day post-operative period. The pre-operative use of EEN appears to avoid unnecessary stoma formation with acceptable clinical outcomes.

CAR directs T cell adaptation to bile acids in the small intestine.

Bile acids are lipid-emulsifying metabolites synthesized in hepatocytes and maintained in vivo through enterohepatic circulation between the liver and small intestine1. As detergents, bile acids can cause toxicity and inflammation in enterohepatic tissues2. Nuclear receptors maintain bile acid homeostasis in hepatocytes and enterocytes3, but it is unclear how mucosal immune cells tolerate high concentrations of bile acids in the small intestine lamina propria (siLP). CD4+ T effector (Teff) cells upregulate expression of the xenobiotic transporter MDR1 (encoded by Abcb1a) in the siLP to prevent bile acid toxicity and suppress Crohn's disease-like small bowel inflammation4. Here we identify the nuclear xenobiotic receptor CAR (encoded by Nr1i3) as a regulator of MDR1 expression in T cells that can safeguard against bile acid toxicity and inflammation in the mousesmall intestine. Activation of CAR induced large-scale transcriptional reprogramming in Teff cells that infiltrated the siLP, but not the colon. CAR induced the expression of not only detoxifying enzymes and transporters in siLP Teff cells, as in hepatocytes, but also the key anti-inflammatory cytokine IL-10. Accordingly, CAR deficiency in T cells exacerbated bile acid-driven ileitis in T cell-reconstituted Rag1-/- orRag2-/-mice, whereas pharmacological activation of CAR suppressed it. These data suggest that CAR acts locally in T cells that infiltrate the small intestine to detoxify bile acids and resolve inflammation. Activation of this program offers an unexpected strategy to treat small bowel Crohn's disease and defines lymphocyte sub-specialization in the small intestine.

Protocol for an open-label feasibility study for a randomised controlled trial of vitamin D supplementation in Crohn\u2019s Disease patients with vitamin D deficiency: D-CODE Feasiblity study

BackgroundCrohn's disease (CD) is a principal form of inflammatory bowel disease, affecting approximately 1 in every 650 people in the UK. Vitamin D deficiency is common in approximately 57.7% of CD patients; with anaemia occurring in about 43% of patients. There is growing evidence that supplementing CD patients who are vitamin D deficient may be effective in reducing the severity of CD symptoms and reducing iron-deficiency anaemia. Nevertheless, National Institute for Health and Care Excellence guidance regarding the management of CD does not address vitamin D deficiency in these patients. The aims of the study are (1) to determine the prevalence of vitamin D deficiency in adults with CD in Birmingham, UK and (2) to assess the feasibility of conducting a multi-site randomised controlled trial in adult patients with CD and vitamin D deficiency.MethodsD-CODE consists of two parts—a screening study and an open-label randomised controlled feasibility study.Vitamin D screeningThree hundred patients, 18 years or older with CD will have a dried blood spot test to measure vitamin D levels. Dietary and sun exposure data will be collected. Eligible patients with low levels of vitamin D will be invited to participate in the feasibility study.Feasibility studyFifty participants with CD and vitamin D deficiency will be randomised to receive either a low (400 IU daily for 24 weeks) or high (3200 IU daily for 12 weeks then vitamin D3 800 IU daily for 12 weeks) dose of vitamin D3 oral supplementation.Patient-reported outcomes (Inflammatory Bowel Disease Questionnaire, EQ-5D-5L and Crohn’s Disease Activity Index Score) will be collected at weeks 0 and 24. Biochemical monitoring will take place at weeks 0, 12 and 24 and will measure 25-hydroxyvitamin D, corrected calcium, albumin, parathyroid hormone, hepcidin, other vitamin D metabolites, iron studies and C-reactive protein. Faecal calprotectin will be measured at weeks 0 and 24.DiscussionA key aspect of D-CODE is the identification of vitamin D deficiency prior to supplementation. It is hoped that this feasibility study will lead to a definitive trial that will investigate the benefits of treating vitamin D deficiency in patients with CD.Trial registrationThe trial has been registered with EudraCT number 2018-003910-42, ClinicalTrials.gov identifier NCT03718182 and ISRCTN number 15717783.

Diagnostic Accuracy of Fecal Calprotectin for the Detection of Small Bowel Crohn's Disease through Capsule Endoscopy: An Updated Meta-Analysis and Systematic Review.

Background/AimsThe diagnosis of small bowel Crohn’s disease with negative ileocolonoscopic findings has been challenging. Fecal calprotectin (FC) has been used to detect colonic inflammation, but its efficacy for detecting small bowel inflammation is less established. We performed an updated meta-analysis to evaluate the diagnostic accuracy of FC to detect active small bowel inflammation observed during capsule endoscopy.MethodsWe conducted a systematic literature search for studies that evaluated the correlation between small bowel inflammation and FC in patients with suspected/established Crohn’s disease. We calculated the pooled sensitivity, specificity, and diagnostic odds ratios (DORs) and constructed hierarchical summary receiver operating characteristic curves for FC cutoffs of 50, 100, and 200 µg/g.ResultsFourteen studies were eligible for the final analysis. The DORs of all FC cutoffs were significant. The highest DOR was observed at 100 µg/g (sensitivity, 0.73; specificity, 0.73; and DOR, 7.89) and was suggested as the optimal diagnostic cutoff. If we analyzed only studies that included patients with suspected Crohn’s disease, the DOR was 8.96. If we analyzed only studies that included patients with a Lewis score ≥135 as a diagnostic criterion for active disease, the DOR was 10.90.ConclusionsFC has significant diagnostic accuracy for detecting small bowel inflammation, and an FC cutoff of 100 µg/g can be used as a tool to screen for small bowel Crohn’s disease. (Gut Liver 2021;15-741)