P054 The impact of intestinal stenosis on the expression of Crohn’s disease in young mice with genetic predisposition

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S161-S161
Author(s):  
I Georgopoulos ◽  
E Mavrigiannaki ◽  
S Stasinopoulou ◽  
G Renieris ◽  
G NIkolakis ◽  
...  

Abstract Background In the majority of patients, the areas of the intestine affected in Crohn’s disease (CD) are the terminal ileum and less commonly the rectum. The terminal ileum is affected in the majority of genetic animal models of CD as well. Additionally, CD recurs at sites of tight anastomosis or strictures postoperatively. These observations lead to the assumption that increased intraluminal pressure related to the presence of a valve, sphincter or stenosis is associated with CD pathogenesis. We investigated the hypothesis that the creation of a partial intestinal stenosis could have an impact on disease severity, in a genetic animal model of CD (TNFΔare/+). TNFΔare/+ mice overexpress TNFα leading to a Crohn-like colitis in the terminal ileum. Methods Twenty-nine TNFΔare/+ mice, 6 weeks old, were divided into three intervention groups: stenosis, sham and control. In the stenosis group (n = 11), a partial small bowel obstruction was created via a novel triple suture technique, approximately 3 cm from the ileocecal valve. In the control group (n = 9), a loose single suture was placed at the aforementioned site to test the direct effect of the foreign material on the intestinal wall. The sham group (n = 9) received a sham operation. The triple suture stenosis was also performed on wild-type (WT) C57BL/6 mice (group WT, n = 9). 6 weeks post-surgery all animals were sacrificed and samples from the ileum 3 cm proximal and 3 cm distal to the intervention site were collected for histopathological evaluation. The Crohn-like changes were assessed using a modified colitis histological scoring system (based on Katakura et al., JCI 2005; 115: 695–702). Results Proximal to the intervention, the mean colitis score of stenosis group (10.18 ± 0.87) was significantly higher compared with sham (6.33 ± 0.97, p: 0.009) and control group (5.00 ± 0.91, p: 0.001). There was no difference between sham and control group (p: 0.332). No significant differences between the groups were reported distal to the intervention. The triple suture technique led to Crohn-like inflammatory lesions only in the TNFΔare/+ mice, as shown from the significantly increased score compared with WT mice proximal and distal to the stenosis (10.18 ± 0.87 vs. 0.67 ± 0.37, p < 0.001 and 9.20 ± 1.09 vs. 0.33 ± 0.24, p < 0.001). Conclusion The creation of a stenotic segment in the intestine of TNFΔare/+ mice, led to higher colitis score than expected. The probable mechanism is the increased intraluminal pressure proximal to the stenosis. This suggests that mechanical forces contribute as important co-factors in the pathophysiology of CD, in genetically predisposed populations.

Pathogens ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1119
Author(s):  
Agnieszka Krawczyk ◽  
Dominika Salamon ◽  
Kinga Kowalska-Duplaga ◽  
Tomasz Bogiel ◽  
Tomasz Gosiewski

The composition of bacteria is often altered in Crohn’s disease (CD), but its connection to the disease is not fully understood. Gut archaea and fungi have recently been suggested to play a role as well. In our study, the presence and number of selected species of fungi and archaea in pediatric patients with CD and healthy controls were evaluated. Stool samples were collected from children with active CD (n = 54), non-active CD (n = 37) and control subjects (n = 33). The prevalence and the number of selected microorganisms were assessed by real-time PCR. The prevalence of Candida tropicalis was significantly increased in active CD compared to non-active CD and the control group (p = 0.011 and p = 0.036, respectively). The number of Malassezia spp. cells was significantly lower in patients with active CD compared to the control group, but in non-active CD, a significant increase was observed (p = 0.005 and p = 0.020, respectively). There were no statistically significant differences in the colonization by archaea. The obtained results indicate possible correlations with the course of the CD; however, further studies of the entire archeobiome and the mycobiome are necessary in order to receive a complete picture.


2006 ◽  
Vol 63 (9) ◽  
pp. 787-792 ◽  
Author(s):  
Leposava Lukic-Kostic ◽  
Jasna Jovic ◽  
Slobodan Sekulovic

Background/aim: Crohn's disease (CD) is a chronic granulomatous inflammatory disease of unknown etiology, involving any part of the gastrointestinal tract, and frequently followed by extra intestinal manifestations. The use of ultrasonography plays a significant role in diagnosing this disease, as well as in monitoring the effects of the therapy. The aim of this study was to assess the use of ultrasonographic diagnostics in the patients with moderate serious and the mild form of CD. Methods. The study involved 30 patients both sexes with CD of moderate form determined using the standard diagnostics, according to the Crohn's Disease Activity Index - CDAI ranging from 220?400. The patients were divided into two groups with CDAI > 320 (Ia), and CDAI between 220 and 320 (Ib), respectively. The Control group was made of 19 patients with the mildly active stage of the disease and the CDAI values in the range from 100?220. The patients were submitted to an ultrasonographic examination of the terminal ileum affected with CD in order to determine the length of the affected segment of intestine, the thickness of the wall, the changes of the structure of the wall, the changes of the surrounding mesenterium with the enlarged lymph nodes. CD complications, abscesses, and enteroenteral fistulas were investigated, too. Results. The comparison of the ultrasonographic findings of the three groups revealed that more serious clinical laboratory image of CD significantly correlated with the higher length of the affected segment (p < 0.001), higher thickness of the wall (p < 0.001), the higher number and the larger lymph nodes of the mesenterium (p < 0.001). Only the most serious patients were found to have abscess of the ileocecal area (Ia ? 40%). There was no difference found between the groups regarding the occurrence of enteroenteral fistulas. Conclusion. Considering the obtained results and data from the literature, it could be concluded that an ultrasonographic examination of the ileocecal area plays an important role in the diagnostic procedure in the management of a patient with CD. Of particular significance is the possibility to use this examination in monitoring the effects of the therapy in patients with CD.


2020 ◽  
Vol 13 ◽  
pp. 175628482093941
Author(s):  
Adriana Ribas Andrade ◽  
Tania Rubia Flores da Rocha ◽  
Carmen Lucia Ortiz-Agostinho ◽  
Iêda Nishitokukado ◽  
Alexandre Sousa Carlos ◽  
...  

Background: As Crohn’s disease (CD) is associated with a high risk of thromboembolic events (TE), including patients with subclinical inflammation, we aim to evaluate the correlation between the impact of endoscopic activity (EA) in the coagulation profiling of CD patients while in clinical remission. Methods: From 164 consecutive CD patients included in clinical remission [Crohn’s disease activity index (CDAI) < 150], 75 were in the EA group [Simplified Endoscopic Score for CD (SES-CD) ⩾ 7], 89 were in the endoscopic remission (ER) group (SES-CD ⩽ 2), and 50 were included as healthy controls in the study. Blood samples were analyzed for tissue factor (TF), factor VIII (FVIII), thrombomodulin (TM), ADAMTS-13, von Willebrand factor (VWF), and endogenous thrombin potential (ETP), as well as collecting data regarding risk factors for TE and CD profile. Results: Mean plasma TF activity showed significantly higher levels in the EA group when compared with the ER and control groups (127 pM versus 103 pM versus 84 pM; p = 0.001), although the VWF:Ag (160% versus 168% versus 110%; p = 0.001), VWF/ADAMTS-13 (191 versus 219 versus 138; p = 0.003), FVIII (150% versus 144% versus 90%; p = 0.001) and TM (5.13 ng/ml versus 4.91 ng/mL versus 3.81 ng/ml; p < 0.001) were only increased in CD regardless of EA status when compared with controls. Lastly, ETP with and without TM remained the same in all three groups. Conclusions: CD patients in clinical remission with EA present endothelial lesion inducing TF exposure and subsequent coagulation cascade activation. Recommended thromboprophylaxis for EA outpatient subgroups will require additional investigation in order to be validated.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S154-S154
Author(s):  
A Spinelli ◽  
S Lönnfors ◽  
L Avedano ◽  
D Bojic

Abstract Background Perianal involvement in Crohn’s disease (CD), including fistulas, ulcers, abscesses, strictures and cancer, can lead to a significant, occasionally debilitating impairment in the patients‘ short- and long-term quality of life (QoL). Perianal fistulae can cause symptoms such as leakage, rectal pain, swelling, pain with bowel movements, and fever, which may significantly affect a patient’s social performance, sexual function and normal life activities. Fistulae are a relatively common CD complication: around 35% of CD patients have at least one fistula, while the majority of CD fistulas are complex. Still, few studies have assessed the impact of complex perianal fistulae (CPF) on the QoL of CD patients from the patient perspective. Methods A questionnaire assessing the effect of CPF on the QoL of CD patients was developed by patient representatives and medical experts. It consisted of 43 questions about history and activity of CD and CPF, treatment experiences, self-reported level of being informed about the disease, past and current symptoms, self-reported impact on QoL, emotions related to the disease, impact and restrictions on close relationships and social life, sexual activity, professional life and work absence. The survey was launched online on the European Federation of Crohn’s and ulcerative colitis Associations (EFCCA) website on July 15, 2019 (remains open until December 2019) and shared to national patient associations through the EFCCA network. Both CD patients with and without CPF were invited to participate in order to have a control group of patients for data analysis. The self-selective, anonymous survey was offered in English, French, German, Greek, Hebrew, Italian, Polish, Portuguese, Romanian, Spanish and Slovenian. Results On November 20, 2019, there were 788 responses from CD patients with and without CPF. There may have been selection bias as the survey is self-selective, only available online and in a limited amount of languages. Considering the retrospective aspect of some questions, recall bias may also have affected some of the responses. Regardless, the data collected will allow a comparison between CD patients with and without CPF, and between patients in different countries, in important, patient-relevant QoL aspects. Conclusion The collected data will be analysed in early 2020. The results will provide valuable insights into the often unspoken burden in the life of CD patients with CPF and potentially help in making treatment decisions for CD patients suffering from CPF.


Author(s):  
Neeraj Narula ◽  
Emily C L Wong ◽  
Parambir S Dulai ◽  
John K Marshall ◽  
Jean-Frederic Colombel ◽  
...  

Abstract Background and Aims There is paucity of evidence on the reversibility of Crohn’s disease [CD]-related strictures treated with therapies. We aimed to describe the clinical and endoscopic outcomes of CD patients with non-passable strictures. Methods This was a post-hoc analysis of three large CD clinical trial programmes examining outcomes with infliximab, ustekinumab, and azathioprine, which included data on 576 patients including 105 with non-passable strictures and 45 with passable strictures, as measured using the Simple Endoscopic Score for Crohn’s Disease [SES-CD]. The impact of non-passable strictures on achieving clinical remission [CR] and endoscopic remission [ER] was assessed using multivariate logistic regression models. CR was defined as a Crohn’s Disease Activity Index [CDAI] &lt;150, clinical response as a CDAI reduction of ≥100 points, and ER as SES-CD score &lt;3. Results After 1 year of treatment, patients with non-passable strictures demonstrated the ability to achieve passable or no strictures in 62.5% of cases, with 52.4% and 37.5% attaining CR and ER, respectively. However, patients with non-passable strictures at baseline were less likely to demonstrate symptom improvement compared with those with passable or no strictures, with reduced odds of 1-year CR (adjusted odds ratio [aOR] 0.17, 95% CI 0.03–0.99, p = 0.048). No significant differences were observed between patients with non-passable strictures at baseline and those with passable or no strictures in rates of ER [aOR 0.82, 95% CI 0.23–2.85, p = 0.751] at 1 year. Conclusions Patients with non-passable strictures can achieve symptomatic and endoscopic remission when receiving therapies used to treat CD, although they are less likely to obtain CR compared with patients without non-passable strictures. These findings support the importance of balancing the presence of non-passable strictures in trial arms.


2019 ◽  
Vol 26 (7) ◽  
pp. 1050-1058 ◽  
Author(s):  
Robert P Hirten ◽  
Ryan C Ungaro ◽  
Daniel Castaneda ◽  
Sarah Lopatin ◽  
Bruce E Sands ◽  
...  

Abstract Background Crohn’s disease recurrence after ileocolic resection is common and graded with the Rutgeerts score. There is controversy whether anastomotic ulcers represent disease recurrence and should be included in the grading system. The aim of this study was to determine the impact of anastomotic ulcers on Crohn’s disease recurrence in patients with prior ileocolic resections. Secondary aims included defining the prevalence of anastomotic ulcers, risk factors for development, and their natural history. Methods We conducted a retrospective cohort study of patients undergoing an ileocolic resection between 2008 and 2017 at a large academic center, with a postoperative colonoscopy assessing the neoterminal ileum and ileocolic anastomosis. The primary outcome was disease recurrence defined as endoscopic recurrence (&gt;5 ulcers in the neoterminal ileum) or need for another ileocolic resection among patients with or without an anastomotic ulcer in endoscopic remission. Results One hundred eighty-two subjects with Crohn’s disease and an ileocolic resection were included. Anastomotic ulcers were present in 95 (52.2%) subjects. No factors were associated with anastomotic ulcer development. One hundred eleven patients were in endoscopic remission on the first postoperative colonoscopy. On multivariable analysis, anastomotic ulcers were associated with disease recurrence (adjusted hazard ratio [aHR] 3.64; 95% CI, 1.21–10.95; P = 0.02). Sixty-six subjects with anastomotic ulcers underwent a second colonoscopy, with 31 patients (79.5%) having persistent ulcers independent of medication escalation. Conclusion Anastomotic ulcers occur in over half of Crohn’s disease patients after ileocolic resection. No factors are associated with their development. They are associated with Crohn’s disease recurrence and are persistent.


Author(s):  
Ioannis Georgopoulos ◽  
Eleftheria Mavrigiannaki ◽  
Sotiria Stasinopoulou ◽  
Georgios Renieris ◽  
Georgios Nikolakis ◽  
...  

2021 ◽  
Vol 10 (4) ◽  
pp. 720
Author(s):  
Adam Benjafield ◽  
Liesl Oldstone ◽  
Leslee Willes ◽  
Colleen Kelly ◽  
Carlos Nunez ◽  
...  

There are currently few data on the impact of mask resupply on longer-term adherence to positive airway pressure (PAP) therapy. This retrospective analysis investigated the effects of mask/mask cushion resupply on the adherence to PAP versus no resupply. Deidentified patient billing data for PAP supply items were merged with telemonitoring data from Cloud-connected AirSense 10/AirCurve 10 devices via AirViewTM (ResMed). Eligible patients started PAP between 1 July 2014 and 17 June 2016, had ≥360 days of PAP device data, and achieved initial U.S. Medicare adherence criteria. Patients who received a resupply of mask systems/cushions (resupply group) were propensity-score-matched with those not receiving any mask/cushion resupply (control group). A total of 100,370 patients were included. From days 91 to 360, the mean device usage was 5.6 and 4.5 h/night in the resupply and control groups, respectively (p < 0.0001). The proportion of patients with a mean device usage ≥4 h/night was significantly higher in the resupply group versus the control group (77% vs. 59%; p < 0.0001). The therapy termination rate was significantly lower in the resupply group versus the control group (14.7% vs. 31.9%; p < 0.0001); there was a trend toward lower therapy termination rates as the number of resupplies increased. The replacement of mask interface components was associated with better longer-term adherence to PAP therapy versus no resupply.


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