Proximal Ileum Research Articles

Discrimination of pediatric cryptogenic multifocal ulcerous stenosing enteritis from small bowel Crohn's disease and gastrointestinal tuberculosis: A retrospective study (with videos).

Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare entity that mimics various inflammatory strictures of the small intestine. Pediatric literature is scarce. We analyzed the clinical, radiological, endoscopic and histopathological features of children with CMUSE that differentiate it from small bowel Crohn's disease (SBCD) and gastrointestinal tuberculosis (GITB). CMUSE was diagnosed by the following criteria: (1) unexplained small bowel strictures with superficial ulcers, (2) chronic/relapsing ulcers of small bowel after resection, (3) no signs of systemic inflammation, (4) absence of other known etiologies of small bowel ulcers. SBCD and GITB were diagnosed based on standard criteria. The clinical features, laboratory parameters, radioimaging, endoscopy (including video capsule endoscopy [VCE], intra-operative endoscopy), histopathological features and treatment outcome were noted. Out of 48,CMUSE was diagnosed in 13 (27%) isolated small bowel and ileocecal strictures, while GITB and SBCD accounted for 41% and 21% cases, respectively. Common presentations were sub-acute obstruction (46%), obscure gastrointestinal bleeding (38%) and protein-losing enteropathy (38%). CMUSE patients had significantly longer disease duration compared to SBCD and GITB (p < 0.001). SBCD (90.0%) and GITB (85%) cases had elevated C-reactive protein (CRP), none with CMUSE had elevated CRP (p < 0.001). The disease was localized in jejunum (100%) and proximal ileum (56%) in CMUSE, ileocecal region (85%) in GITB, but evenly distributed in small intestine in SBCD. Endoscopy showed evenly placed, superficial, circumferential ulcers with strictures in CMUSE, deep linear ulcers in SBCD and circumferential ulcers in GITB. Upfront immunosuppression was given in four; three (75%) of them relapsed. Only surgery was done in three with one (25%) having relapse. Upfront surgery followed by immunosuppression was used in six, but all relapsed and two required repeat surgery. CMUSE is important but underdiagnosed in children. Lack of constitutional symptoms, normal inflammatory parameters and characteristic ulcers with strictures helped in differentiating CMUSE from GITB and SBCD.

Spatio-temporal dynamics of the human small intestinal microbiome and its response to a synbiotic

ABSTRACT Although fecal microbiota composition is considered to preserve relevant and representative information for distal colonic content, it is evident that it does not represent microbial communities inhabiting the small intestine. Nevertheless, studies investigating the human small intestinal microbiome and its response to dietary intervention are still scarce. The current study investigated the spatio-temporal dynamics of the small intestinal microbiome within a day and over 20 days, as well as its responses to a 14-day synbiotic or placebo control supplementation in 20 healthy subjects. Microbial composition and metabolome of luminal content of duodenum, jejunum, proximal ileum and feces differed significantly from each other. Additionally, differences in microbiota composition along the small intestine were most pronounced in the morning after overnight fasting, whereas differences in composition were not always measurable around noon or in the afternoon. Although overall small intestinal microbiota composition did not change significantly within 1 day and during 20 days, remarkable, individual-specific temporal dynamics were observed in individual subjects. In response to the synbiotic supplementation, only the microbial diversity in jejunum changed significantly. Increased metabolic activity of probiotic strains during intestinal passage, as assessed by metatranscriptome analysis, was not observed. Nevertheless, synbiotic supplementation led to a short-term spike in the relative abundance of genera included in the product in the small intestine approximately 2 hours post-ingestion. Collectively, small intestinal microbiota are highly dynamic. Ingested probiotic bacteria could lead to a transient spike in the relative abundance of corresponding genera and ASVs, suggesting their passage through the entire gastrointestinal tract. This study was registered to http://www.clinicaltrials.gov, NCT02018900.

Magnetic resonance enterography in diagnosing and monitoring of adult-onset IgA vasculitis (Henoch-Schönlein purpura) with gastro-intestinal involvement: Report of two cases

BackgroundIgA vasculitis (IgAV) is a small vessel vasculitis affecting children and, less commonly, adults; in the latter, gastro-intestinal (GI) involvement occurs in up to 50% of cases. Diagnosis is made with computed tomography, ultrasonography and endoscopy, but no data have been to date published about the use of magnetic resonance enterography (MRE). Aim of the workThis work reports two leading cases of adult-onset IgAV with GI involvement in which MRE was used at baseline and during follow-up. Case reportThe first case was for a 55-year old male presenting with microhematuria and elevated markers of inflammation at admission. MRE evidenced jejunum and proximal ileum diffuse and asymmetric thickening and hypervascularization. Leukocytoclastic vasculitis and glomerulonephritis with IgA deposit were evidenced at skin and renal biopsy, respectively. At one-year follow-up, a relapse was suspected: microhematuria and proteinuria were found at routine urinalysis, while MRE findings were similar to the ones at baseline. The second case was for a 49-year old male previously treated with methotrexate for mild seronegative arthritis, reporting hematochezia and worsening of arthralgias. Inflammatory bowel disease (IBD) was suspected and colonoscopy revealed diffuse mucosal hyperemia. Computerized tomography of the terminal ileum appeared thickened and edematous, while skin biopsy showed leukocytoclastic vasculitis with IgA infiltrate. The patient was successfully treated with oral prednisone and, after two months from discharge, MRE was negative. ConclusionIgAV may occur in adults and presenting with GI involvement may be particularly severe, mimicking IBD. MRE is a promising tool in diagnosing and monitoring IgAV.

Efficacy of exclusive enteral nutrition on the mucosal healing of different gastrointestinal segments in children with Crohn's disease.

To investigate the association between disease location and segmental mucosal healing (SMH) following exclusive enteral nutrition (EEN) in children with Crohn's disease (CD). Treatment-naive pediatric patients with endoscopically active CD treated with EEN alone as induction therapy were retrospectively enrolled from January 1, 2017 to June 30, 2022. Thesimpleendoscopic score for CD (SES-CD) was employed to score disease activity in theupper gastrointestinal (GI) tract (esophagus, stomach, duodenum), rectum, left colon, transverse colon, right colon, and terminal ileum. While the Lewis score assessed that of the small bowel from the jejunum to the proximal ileum (except the terminal ileum). The variation in the total scores for each segment and SES-CD subscores for each ileocolonic segment from baseline to 1 year after EEN therapy and the segmental endoscopic outcomes and potential predictors associated with SMH for the segments scored by SES-CD were evaluated. Overall, 82 children with CD were enrolled. Except for the upper GI segment, scores in other segments declined significantly from baseline to EEN completion (all P < 0.001). We analyzed 486 segments (79, 80, 81, 82, 82 and 82 from upper GI tract, terminal ileum, right colon, transverse colon, left colon, and rectum) and found that the segmental SES-CD at baseline (odds ratio [OR] 0.62, 95% confidence interval [CI] 0.55-0.70, P < 0.001) and upper GI location (OR 0.25, 95% CI 0.11-0.55, P = 0.001) were associated with SMH at EEN completion. Disease location of the upper GI segment in pediatric CD was associated with SMH following EEN therapy.

P049 The lipidome of creeping fat in Crohn’s disease points towards a harmful microenvironment

Abstract Background A pathognomonic observation in Crohn’s disease (CD) is the existence of mesenteric adipose tissue (MAT) wrapping around the inflamed and fibrotic intestine, so-called creeping fat. The etiology of this phenomenon is unclear, and both a protective and harmful role in disease pathogenesis and progression have been proposed. Given this conflicting evidence, we aimed to further unravel the role of creeping fat by extensive profiling of its lipidome. Methods We prospectively included 22 CD patients who underwent an ileocecal resection with ileocolonic anastomosis (Table 1). Perioperatively paired adipose tissue samples were collected from 3 locations: (1) creeping fat, (2) MAT close to the proximal unaffected ileum, and (3) MAT far from the diseased ileum, defined as near the base of the ileocecal artery (Fig. 1A). The lipidome of all 66 samples was profiled by quantitative mass spectrometry (targeted C18 LC-MS/MS and HILIC LC-MS/MS; Lipometrix core KU Leuven). This approach enables the detection of mediator lipids, and membrane and storage lipids, of which the latter group represents more complex chemical structures and thus a higher diversity in classification and number of species. Data analysis and paired Wilcoxon rank- sum tests were performed with Python and R 4.3.2. Results Across all CD adipose tissue samples, we detected 38 mediator lipid species, and 456 membrane and storage lipid species . When paired-wise comparing creeping fat with MAT far from the diseased ileum, we observed a significant decrease in 16 lipid mediators (p&amp;lt;0.05), namely arachidonic acid (AA), docosahexaenoic acid (DHA), 4 epoxy and 10 hydroxy mediator lipids; with hydroxy mediator X being the top downregulated in creeping fat (fold change (FC)=-2.11, p=0.0003) (Fig. 1B). While AA and DHA are (semi)-essential fatty acids and function as precursors, the other 8 decreased lipids in creeping fat are known to be anti-inflammatory, and 3 (incl. mediator X) are also anti-fibrotic. The lipid mediator profile of MAT close to the proximal unaffected ileum was similar to that of creeping fat, except for a pro-inflammatory lipid being increased in creeping fat (FC=2.30, p=0.004) (Fig. 1B). Lastly, when evaluating the membrane and storage lipid abundances both at species level (sum notation; fatty acyl composition) and at class level, no paired-wise differences among the three adipose tissue locations were found (p&amp;gt;0.05). Conclusion In this pilot lipidomics study, we did not observe any changes in storage or membrane lipids in creeping fat as compared to paired unaffected MAT. In contrast, a decrease in anti-inflammatory and anti-fibrotic lipid species along with an increase in a pro-inflammatory species points towards a harmful microenvironment within creeping fat.

Protein-losing enteropathy: is it Crohn's disease?

Case of a 24-year-old woman presenting due to edema in lower extremities. The patient had had infectious mononucleosis three weeks prior and had medical history of suspicion of Crohn's disease (CD) (due to a non-specific ileocolitis in a colonoscopy/EnteroRM). No ongoing medication. Laboratory evaluation unveiled hypoproteinemia with severe hypoalbuminemia, no renal abnormalities. A PLE was assumed, with post-infectious or CD being the most likely culprits. Alternative causes were extensively excluded. A videocapsule revealed white-tipped or granular villi, some white nodular villi and diffuse edema of the mucosa, and multiple extensive erosions and superficial ulcers in the jejunum and proximal ileum, not suggestive of CD. A push enteroscopy revealed unspecific histopathology. After incomplete response to enteral nutrition, corticotherapy was initiated resulting in sustained improvement. A follow-up Ileocolonoscopy and double balloon enteroscopy revealed no abnormalities. Six months post-treatment, the patient remains asymptomatic, with unremarkable laboratory results and no need for medication.

Use of double-balloon endoscopy and an endoscopic scoring system to assess endoscopic remission in isolated small bowel Crohn's disease after treatment with infliximab.

It is unclear how clinical and endoscopic factors affect the attainment of endoscopic remission (ER) in patients with small bowel Crohn's disease (SB-CD) who are infliximab-naïve. We aimed to identify the effect of different factors on attaining ER using double-balloon endoscopy (DBE) evaluation. A single-center retrospective observational study was conducted from 1 January 2018 to 30 November 2022. Among 262 patients who were screened for isolated SB-CD by baseline DBE, 108 patients were assessed for effectiveness during maintenance infliximab therapy by a second DBE evaluation. DBE findings before and after infliximab therapy were compared. ER was defined as a simple endoscopic score for CD (SES-CD) below 3, and segmental ER as SES-CD activity of 0. Multivariate regression with calculations of odds ratios (OR) was used to determine the impact of different factors on attaining ER. In all, 41 patients (38.0%) achieved ER. An elevated C-reactive protein at week 6 was independently associated with a decreased probability of ER [OR: 0.86, 95% confidence interval (CI) = 0.75-0.98, p = 0.03]. Segmental ER of the terminal ileum, rather than the proximal ileum, was associated with a higher rate of ER (60.9% versus 38.2%, p = 0.01). High baseline SES-CD (⩾16) was unrelated to overall ER. For patients with disease in the terminal ileum, those with moderate/severe disease were less likely to attain segmental ER than those with mild disease [adjusted odds ratios (aOR): 0.27, 95% CI: 0.09-0.83, p = 0.02]. A large ulcer in the terminal ileum was associated with a lower rate of segmental ER (aOR: 0.18, 95% CI: 0.06-0.56, p = 0.01). For infliximab-naïve patients with SB-CD, the overall severity of the endoscopic score was unrelated to attainment of ER. Patients were less likely to attain segmental ER if they had greater endoscopic inflammation or larger ulcers in the terminal ileum.

A NEW EIMERIA SPECIES (APICOMPLEXA: EIMERIIDAE) PARASITIZING COMMERCIAL CHUKAR PARTRIDGES (ALECTORIS CHUKAR) IN SOUTHERN ONTARIO.

A commercial producer hatching and rearing chukar partridges (Alectoris chukar) in Ontario, Canada had flocks experiencing coccidiosis. Microscopic analysis of Eimeria species isolated from a field sample indicated the presence of 2 distinct oocyst morphotypes; the most abundant species was determined to be Eimeria chapmani, based on oocyst morphology and sequence-based genotyping, and the less abundant, second Eimeria sp. was an undescribed parasite. Oocysts of the unknown Eimeria sp. were large and oval-shaped; dimensions averaged 27.9 μm by 17.0 μm (shape index = 1.65 μm). Oocysts contained at least 1 polar granule and 4 almond-shaped sporocysts with average dimensions measuring 12.5 μm by 6.9 μm (shape index = 1.83). Each sporocyst featured a Stieda body, sub-Stieda body, and sporocyst residuum; a sporocyst contained 2 sporozoites that each possessed a small anterior refractile body and a larger posterior refractile body. Virtually all oocysts sporulated after 24 hr when suspended in potassium dichromate at room temperature (22 C) on a rotary platform. Experimental infections with various doses of oocysts demonstrated elevated parasite shedding from birds gavaged with higher challenge doses; fecundity generally decreased in heavier infections. The approximate prepatent period of the parasite was 4-5 days (unsporulated oocysts observed histologically at 90 hr postinfection and in feces by day 5) and patency lasted until day 12 postinfection. To characterize the endogenous development of the Eimeria sp., tissues were collected at 8 regions along the intestinal tract (including the ceca and rectum) every 6 hr throughout the estimated prepatent period. Parasites were observed to infect the descending and ascending duodenum, midjejunum, proximal and distal ileum, and the ceca. The endogenous stages identified included intracellular sporozoites, 3 generations of merogony, and gametogonic stages. Sequences of the mitochondrial genome (GenBank MW934555) and nuclear 18S ribosomal DNA (GenBank MW934259) were obtained using polymerase chain reaction amplification for Sanger sequencing, and these were unique from all published sequences on GenBank. Molecular data, in conjunction with the unique biology of the Eimeria sp. isolated from the chukar partridge flock, support that this coccidium is new to science.

PSI-A-2 Effects of Microencapsulated Zinc Oxide on Nursery Pig Growth Performance and Intestinal Morphology

Abstract The inclusion of pharmacological levels of zinc oxide (ZnO) has been used to enhance the health and performance of piglets immediately post-weaning for decades, but there is consumer and regulatory pressure to limit this practice. Microencapsulation can allow for a more targeted release and better utilization of zinc oxide, thus making it a viable alternative to conventional ZnO. The objective of this experiment was to evaluate the impact of a microencapsulated ZnO on growth performance and intestinal morphology in newly weaned pigs. A total of 300 nursery pigs (DNA 200 x 400; initially 6.03 ± 0.08 kg BW) were allotted in a completely randomized design to one of five dietary treatments: 1) Negative control (basal diet with no added ZnO); 2) basal diet + 3,000 ppm added Zn from ZnO in phase 1 and 2,000 ppm added Zn from ZnO in phase 2; 3) basal diet + 400 ppm added Zn from ZnO; 4) 3,000 ppm added Zn from microencapsulated ZnO in phase 1 and 2,000 ppm added Zn from microencapsulated ZnO in phase 2; and 5) 400 ppm added Zn from microencapsulated ZnO in phases 1 and 2. Pigs were fed treatment diets from d 0 to 28, and a common diet was fed to all pigs from d 29 to 42. To determine average daily gain (ADG), average daily feed intake (ADFI), and feed efficiency (G:F), pigs and feeders were weighed weekly. On d 28, 6 piglets per treatment were euthanized to collect small intestinal samples. Tissue samples were fixed in formalin, stained with hematoxylin and eosin, and slides were then evaluated for villi height (VH) and crypt depth (CD) on 10 villi per sample. Data were analyzed using the GLIMMIX procedure of SAS. There was no evidence of differences (P &amp;gt; 0.05) in ADG, ADFI or G:F for the entire treatment period (d 0 to 28); however, pigs fed the negative control or a diet with microencapsulated ZnO had improved (P &amp;lt; 0.0001) ADG and ADFI during the common period compared with pigs fed conventional ZnO. There was no evidence of differences (P &amp;gt; 0.05) in the VH and CD of both proximal and distal ileum samples. Results indicate the need for further investigation of the use of M-ZnO in post weaned nursery pigs.

Enhancing the Differentiation between Intestinal Behçet's Disease and Crohn's Disease through Quantitative Computed Tomography Analysis.

Behçet's disease (BD) behaves similarly to Crohn's disease (CD) when the bowel is involved. Computed tomography enterography (CTE) can accurately show intestinal involvement and obtain body composition data. The objective of this study was to evaluate whether CTE could improve the ability to distinguish between intestinal BD and CD. This study evaluated clinical, laboratory, endoscopic, and CTE features on first admission. Body composition analysis was based on the CTE arterial phase. The middle layers of the L1-L5 vertebral body were selected. The indicators assessed included: the area ratio of visceral adipose tissue (VAT)/subcutaneous adipose tissue (SAT) (VSR) in each layer, the total volume ratio of VAT/SAT, the quartile of VAT attenuation in each layer and the coefficient of variation (CV) of the VAT area for each patient was also calculated. Two models were developed based on the above indicators: one was a traditional model (age, gender, ulcer distribution) and the other was a comprehensive model (age, gender, ulcer distribution, proximal ileum involvement, asymmetrical thickening of bowel wall, intestinal stenosis, VSRL4, and CV). The areas under the receiver operating characteristic (ROC) curve of the traditional (sensitivity: 80.0%, specificity: 81.0%) and comprehensive (sensitivity: 95.0%, specificity: 87.2%) models were 0.862 and 0.941, respectively (p = 0.005).

Combination of transjugular intrahepatic portosystemic shunt and antegrade through-the-TIPS coil embolization for bleeding mixed-type ectopic ileal varices

A 61-year-old man with alcoholic cirrhosis and a history of severe cholecystitis leading to secondary thrombosis of the recanalized paraumbilical vein was admitted to our hospital for recurrent gastrointestinal bleeding and severe anemia. Capsule endoscopy and CT angiography detected profuse bleeding in the proximal ileum from ectopic ileal varices. Hepatic venous-portal gradient (HVPG) measurement was consistent with severe portal hypertension. Persistent bleeding despite transjugular intrahepatic portosystemic shunt (TIPS) placement required a combined approach with antegrade through-the-TIPS coil embolization of the ileal varices.

Gallstone Ileus With Persistent Cholelithiasis and Choledocholithiasis.

Gallstone ileus is an uncommon but well-described occurrence in general surgery. However, discrepancy regarding optimal surgical management with 1 or 2 stage operation is still debated. This case report presents a 73-year-old woman who presented to the emergency department (ED) with a small bowel obstruction due to a gallstone lodged in a portion of the proximal ileum. The patient was also noted to have persistent cholelithiasis and cholecystoduodenal fistula. A single-stage surgery involving enterolithotomy, cholecystectomy, fistula repair, and cholangioscopy was performed. The patient progressed well and was discharged home without recurrent symptoms. Therefore, in a hemodynamically stable patient with persistent cholelithiasis or choledocholithiasis, it is reasonable to perform a definitive single-stage operation.

Gallstone Ileus, A Rare Yet Deadly Cause of Small Bowel Obstruction

Introduction:Gallstone ileus is a rare cause of intestinal obstruction. It commonly affects older patients with significant medical conditions. This disease has a high mortality rate (12-17%), hence should be an important diagnosis to consider, especially as the geriatric population grows worldwide.Method: Case Report:84-year old gentleman, with diabetes and ischemic heart disease, presented with diarrhea, vomiting and fever for one day. He was febrile, tachycardic and hypotensive. There was lower abdominal tenderness with guarding. Labs done revealed metabolic acidosis with a raised lactate along with raised inflammatory markers. Impression was intra-abdominal sepsis, with a need to rule out mesenteric ischemia. He underwent CTAP which revealed gallstone ileus. The gallbladder was collapsed and pneumobilia was present in keeping with fistulation. Dilated small bowel loops were present with a transition point at the distal jejunum or proximal ileum, where there are two gallstones. Patient underwent exploratory laparotomy. There was an obstructing large gallstone 100cm from the DJ flexure. After removal of gallstone and decompression, the bowel was pink with areas of bruising. Patient was hypotensive intra-operatively likely contributed by septic shower, requiring dual vasopressors. He was transferred to the ICU post-operatively and developed cardiogenic shock with type 2 respiratory failure precipitated by sepsis. He demised on Day 2 post-operatively.Results:Gallstone ileus is caused by intestinal impaction of a gallstone that has migrated through a cholecystoenteric fistula. The classic radiologic sign of gallstone ileus is Rigler's triad. This is only picked up 15% of the time on plain abdominal x-rays. Early CT scans can reveal Rigler triad up to 80% of the time. Surgical management remains the cornerstone of treatment.Conclusion:Gallstone ileus remains a diagnostic challenge as patients present with non-specific signs and symptoms. It is prudent for emergency physicians to consider this disease in elderly patients who present with small bowel obstruction.

Multi-parametric MRI in the diagnosis and scoring of gastrointestinal acute graft-versus-host disease

ObjectivesAcute gastrointestinal graft-versus-host disease (GI-aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). Diagnosis relies on clinical, endoscopic, and pathological investigations. Our purpose is to assess the value of magnetic resonance imaging (MRI) in the diagnosis, staging, and prediction of GI-aGVHD-related mortality.MethodsTwenty-one hematological patients who underwent MRI for clinical suspicion of acute GI-GVHD were retrospectively selected. Three independent radiologists, blinded to the clinical findings, reanalyzed MRI images. The GI tract was evaluated from stomach to rectum by analyzing fifteen MRI signs suggestive of intestinal and peritoneal inflammation. All selected patients underwent colonoscopy with biopsies. Disease severity was determined on the basis of clinical criteria, identifying 4 stages of increasing severity. Disease-related mortality was also assessed.ResultsThe diagnosis of GI-aGVHD was histologically confirmed with biopsy in 13 patients (61.9%). Using 6 major signs (diagnostic score), MRI showed 84.6% sensitivity and 100% specificity in identifying GI-aGVHD (AUC = 0.962; 95% confidence interval 0.891–1). The proximal, middle, and distal ileum were the segments most frequently affected by the disease (84.6%). Using all 15 signs of inflammation (severity score), MRI showed 100% sensitivity and 90% specificity for 1-month related mortality. No correlation with the clinical score was found.ConclusionMRI has proved to be an effective tool for diagnosing and scoring GI-aGVHD, with a high prognostic value. If larger studies will confirm these results, MRI could partly replace endoscopy, thus becoming the primary diagnostic tool for GI-aGVHD, being more complete, less invasive, and more easily repeatable.Key Points• We have developed a new promising MRI diagnostic score for GI-aGVHD with a sensitivity of 84.6% and specificity of 100%; results are to be confirmed by larger multicentric studies.• This MRI diagnostic score is based on the six MRI signs most frequently associated with GI-aGVHD: small-bowel inflammatory involvement, bowel wall stratification on T2-w images, wall stratification on post-contrast T1-w images, ascites, and edema of retroperitoneal fat and declivous soft tissues.• A broader MRI severity score based on 15 MRI signs showed no correlation with clinical staging but high prognostic value (100% sensitivity, 90% specificity for 1-month related mortality); these results also need to be confirmed by larger studies.

SMALL BOWEL OBSTRUCTION DUE TO MECKELS DIVERTICULUM: A CASE REPORT

Meckels diverticulum is the most common congenital anomaly of the small intestine. It results from incomplete obliteration of the vitelline duct leading to the formation of a true diverticulum of the small intestine which is usually located on the antimesenteric border of the ileum. This case report presents the diagnosis and management of a small bowel obstruction due to Meckels diverticulum in a 70-year-old patient. To identify the cause of the small bowel obstruction, The patient underwent computed tomography (CT) scan of her abdomen and pelvis which showed mild dilatation of the small bowels, particularly in the distal jejunum and proximal ileum with no transition point was seen on the CT scan. During the laparotomy, it was revealed a gross distension of the small bowel, and the distal portion of the ileum was markedly compressed by an internal hernia twisted around a giant Meckels diverticulum with a mesodiverticular artery in an area 50 cm from the tip of the ileum.

Gastrointestinal permeability and inflammatory status of preweaning dairy calves in response to decreasing the ratio of n-6 to n-3 fatty acid in milk replacer

The ratio of n-6 to n-3 fatty acid (FA) is between 2 and 10 times higher in milk replacer (MR) than in whole milk, which may promote inflammation and compromise the integrity of the intestinal epithelium. To evaluate how decreasing the n-6:n-3 FA ratio of MR affects gastrointestinal (GIT) permeability and inflammatory status, 30 dairy calves (2.8 ± 1.06 d of age; mean ± standard deviation) were randomly assigned to be fed an MR with an n-6:n-3 FA ratio of 40:1 (CON; 29.3% crude fat of DM; n = 15) or 6.5:1 (n-3; 29.1% crude fat of DM; n = 15). Calves were fed 7.0 L/d in 2 meals. Calves were weighed and fecal consistency was analyzed weekly. On d 22, calves were administered Cr-EDTA, lactulose, and d-mannitol to assess GIT permeability. Blood and total urine were sequentially collected for 6 and 24 h, respectively, and analyzed for marker content. Whole blood collected 4 h after the meal was subjected to an ex vivo lipopolysaccharide (LPS) challenge to evaluate cytokine secretion from blood cells. Calves were euthanized on d 25 for collection of intestinal tissue samples. Tissue samples were processed to assess FA composition by gas chromatography, histomorphology by bright-field microscopy, and gene expression of tight junction proteins, lipid metabolism enzymes, and immune molecules by real-time quantitative PCR. Data were analyzed using PROC GLIMMIX in SAS (version 9.4, SAS Institute Inc.). Growth performance and fecal consistency were unaffected. Calves fed MR with a lower ratio of n-6 to n-3 FA had 2-fold higher n-3 FA contents and 2-fold lower ratios of n-6 to n-3 FA in proximal jejunum and ileum tissues. Total urinary recovery (0-24 h relative to marker administration) and plasma concentrations of the markers were unaffected. Expression of TJP1 tended to be higher in proximal jejunum tissue and lower in ileum tissue of n-3 calves. The expression of TLR4 and TNFA tended to be higher and CD14 was higher in ileum tissue of n-3 calves. Plasma concentrations of interleukin-4 were decreased in response to the ex vivo LPS challenge in n-3 calves. Histomorphology and GIT permeability were largely unaffected by treatment. Furthermore, the inclusion of linseed and algae oil may promote inflammation, as suggested by greater concentrations of the acute-phase proteins haptoglobin and serum amyloid A postprandially, demonstrating that fat sources should be evaluated for their suitability for MR formulations. Understanding how MR composition affects dairy calf health may improve nutritional strategies on farm.

Gastrointestinal structure and function of preweaning dairy calves fed a whole milk powder or a milk replacer high in fat

The composition of milk replacer (MR) for calves greatly differs from that of bovine whole milk, which may affect gastrointestinal development of young calves. In this light, the objective of the current study was to compare gastrointestinal tract structure and function in response to feeding liquid diets having a same macronutrient profile (e.g., fat, lactose, protein) in calves in the first month of life. Eighteen male Holstein calves (46.6 ± 5.12 kg; 1.4 ± 0.50 d of age at arrival; mean ± standard deviation) were housed individually. Upon arrival, calves were blocked based on age and arrival day, and, within a block, calves were randomly assigned to either a whole milk powder (WP; 26% fat, DM basis, n = 9) or a MR high in fat (25% fat, n = 9) fed 3.0 L 3 times daily (9 L total per day) at 135 g/L through teat buckets. On d 21, gut permeability was assessed with indigestible permeability markers [chromium (Cr)-EDTA, lactulose, and d-mannitol]. On d 32 after arrival, calves were slaughtered. The weight of the total forestomach without contents was greater in WP-fed calves. Furthermore, duodenum and ileum weights were similar between treatment groups, but jejunum and total small intestine weights were greater in WP-fed calves. The surface area of the duodenum and ileum did not differ between treatment groups, but the surface area of the proximal jejunum was greater in calves fed WP. Urinary lactulose and Cr-EDTA recoveries were greater in calves fed WP in the first 6 h post marker administration. Tight junction protein gene expression in the proximal jejunum or ileum did not differ between treatments. The free fatty acid and phospholipid fatty acid profiles in the proximal jejunum and ileum differed between treatments and generally reflected the fatty acid profile of each liquid diet. Feeding WP or MR altered gut permeability and fatty acid composition of the gastrointestinal tract and further investigation are needed to understand the biological relevance of the observed differences.

Comparison between CT-enterography and MR-enterography for the diagnosis of right-sided deep infiltrating endometriosis of the bowel

ObjectiveTo compare computed tomography-enterography (CTE) and magnetic resonance-enterography (MRE) in the detection of right-sided bowel deep infiltrating endometriosis (DIE). Materials and MethodsFifty women with DIE who underwent preoperatively CTE and MRE were included. CTE and MRE were first analyzed separately by two independent readers who analyzed five bowel segments (cecum, appendix, ileocecal junction, distal ileum and proximal small bowel [i.e., proximal ileum and jejunum]) for the presence of DIE and then interpreted in consensus. CTE, MRE and CTE with MRE were compared in terms of sensitivity, specificity and accuracy. Interobserver agreement was assessed with kappa (κ) test. ResultsUsing the reference standard 25 out 250 bowel segments were involved by DIE in 18 women and 225 were free of DIE. Sensitivity, specificity, and accuracy of CTE were 60% (95% confidence interval [CI]: 39–79), 93% (95% CI: 89–96) and 90% (95% CI: 85–93) for Reader 1, respectively, and 52% (95% CI: 31–72), 99% (95% CI: 97–100) and 94% (95% CI: 91–97) for Reader 2, with no differences in sensitivity (P = 0.564) and specificity (P = 0.181) between readers and fair interobserver agreement (κ = 0.37). For MRE these figures were 52% (95% CI: 31–72), 92% (95% CI: 88–95) and 88% (95% CI: 84–92) for Reader 1 and 60% (95% CI: 39–79), 99% (95% CI: 96–100) and 95% (95% CI: 91–97) for Reader 2, with no differences in sensitivity (P = 0.157) and specificity (P = 0.061) between readers and fair interobserver agreement (κ = 0.31). Significant differences in sensitivity (20%; 95% CI: 7–41) were found between CTE + MRE vs. CTE alone for Reader 1 and vs. MRE alone for Reader 2 (P = 0.041 for both) ConclusionCTE and MRE have not different sensitivities and convey only fair interobserver agreement but are highly specific for the diagnosis of right-sided bowel DIE. CTE and MRE are complementary because they improve the detection of DIE implants when used in combination.

P248 The diagnostic accuracy of Intestinal ultrasound for assessing disease activity in the proximal ileum and jejunum in children with Crohn’s disease: Preliminary results of a prospective study

Abstract Background Crohn’s disease (CD) is an inflammatory bowel disease (IBD) involving mainly the small intestine and the colon. Current imaging modalities such as magnetic resonance enterography (MRE) to assess disease activity in the small bowel are expensive and are often poorly tolerated by children. Intestinal ultrasound (IUS) is a non-invasive and well tolerated monitoring tool for assessing disease activity in colon and terminal ileum. In children the diagnostic accuracy of IUS for proximal bowel has not been systematically studied. In this study we assess the diagnostic accuracy of IUS compared to MRE for the proximal ileum and jejunum in the paediatric population. Furthermore we aim to establish which IUS features are the best predictors for IBD activity in the proximal ileum and jejunum. Methods Paediatric CD patients were prospectively enrolled and underwent MRE and IUS within 7 days. MRE-images were scored using the segmental grading system by Tielbeek et al. The ultrasonographer was blinded for the MRE results and the paediatric radiologist who assessed the MRE images was blinded for IUS results. Results Forty-two paediatric CD patients underwent IUS paired with MRE until now. Eighty-four bowel segments were available for analyses. In total 24 bowel segments had mild (n=12) to moderate severe (n=12) disease activity based on MRE. The AUROC of BWT for moderate severe disease was 0.78 (95% CI 0.61-0.95). A cut-off value of BWT &amp;gt;2.5 mm showed had a specificity of 90%. A cut-off value of BWT &amp;lt;1.7 mm showed had a sensitivity of 91%. Of the affected segments 12 had increased Doppler signal and 13 showed mesenteric fat proliferation. No regression analysis was performed since the number of inflamed segments was too low. Conclusion IUS is an promising tool to non-invasively assess disease activity in the proximal ileum and jejunum. Our preliminary results suggest that a cut-off for BWT &amp;lt; 2,5mm IUS can be used to demonstrate disease activity. A lager sample size to perform regression analysis and to assess other IUS features for disease activity is currently being collected.

DOP33 Single-cell analysis identifies pathological fibroblasts as a new therapeutic target to prevent intestinal fibrosis in Crohn’s disease.

Abstract Background Recurrent episodes of intestinal inflammation and tissue remodeling progressively result in fibro-stenosis and bowel obstruction in Crohn’s disease (CD). This irreversible end-stage complication is the main indication for surgical intervention but is often associated with postoperative recurrence of inflammation and repeated tissue resection. Methods To understand transmural inflammation-induced fibro-stenosis, full-thickness ileum from CD patients (n=10) undergoing ileocecal resection were profiled using single-cell RNA sequencing (scRNA seq) on 10x Genomics platform. Our tissue sampling strategy aimed at recapitulating different disease stages from the same patient including normal ileum, chronic active inflammation and stenotic ileum, allowing a better definition of cell heterogeneity, inter-cellular communication, and tissue organization in CD. Healthy ileum from CRC patients (n=5) undergoing right hemicolectomy were included as external control. Flow cytometry (FACS) was carried out to confirm scRNA seq findings. For functional validation, intestinal fibroblasts were co-cultured with NicheNet-predicted cytokines and FACS-sorted myeloid supernatants. Finally, the chronic dextran sulfate sodium (DSS)-induced colitis model was used to validate the transcription regulation in activated fibroblasts. Results Using scRNA seq, we identified a specific subset of activated fibroblasts during chronic inflammation and fibrosis. FACS showed increasing FAP+ fibroblasts in both inflamed and stenotic ileum, compared to control ileum and proximal ileum (p&amp;lt;0.01). Computational methods predicting ligand-receptor signaling suggest that fibroblast activation is mostly mediated by myeloid cell-derived inflammatory signals resulting in collagen deposition and tissue fibrosis. Intestinal fibroblasts co-cultured with inflammatory monocyte supernatant and predicted ligands expressed higher protein levels of FAP, COL3A1 and showed signs of EMT transformation. Furthermore, stimulated intestinal fibroblasts secreted higher levels of ECM proteins, including COL1 (p&amp;lt;0.001), and COL3A1 (p&amp;lt;0.005). After inhibiting an EMT-related transcription factor identified in the activated fibroblasts, collagen expression and extracellular matrix accumulation were decreased in fibroblasts. Finally, inhibition of EMT transformation in chronic DSS colitis resulted in reduced ECM deposition, compared to vehicle mouse (p&amp;lt;0.05). Conclusion Our findings suggest that inflammatory monocytes mediate local activation of fibroblasts promoting excessive collagen deposition. We furthermore show that targeting activated fibroblasts was able to reduce tissue remodeling and may therefore prevent fibrostenosis in CD.