bluuebunny/crossref_metadata_2025_split huggingface dataset:
A101 USTEKINUMAB LEVELS MEASURED DURING INDUCTION ARE ASSOCIATED WITH CLINICAL AND BIOCHEMICAL OUTCOMES AT WEEK 12 OF TREATMENT IN CROHN’S DISEASE
Authors: Walshe M , Borowski K , Boland K , Rho S , Stempak J , Silverberg M 
Published: February 2020

Abstract

Background
Therapeutic drug monitoring (TDM) helps guide use of anti-TNF drugs in IBD patients. In addition, higher anti-TNF levels during induction therapy have been shown to be associated with better clinical and endoscopic outcomes. The role of TDM for more novel biologics such as ustekinumab (an anti- IL-12/23 antibody used to treat Crohn’s disease) remains to be elucidated.

Aims
We set out to investigate correlations between ustekinumab drug levels measured during induction with clinical and biochemical outcomes in patients with Crohn’s disease.

Methods
Patients with Crohn’s disease commencing treatment with ustekinumab were recruited from a single tertiary referral centre. Standard weight-based induction dosing was used. TDM was performed at week 2 and week 6 following IV induction dose. A drug-tolerant assay (Prometheus) was used. Kruskal-Wallis test was used to examine association between induction dose and ustekinumab levels. CDAI, CRP, and faecal calprotectin (FCP) were measured at week 12. Pearson correlation co-efficient was used to assess the relationship between ustekinumab levels and i)CDAI ii)CRP and iii)FCP at week 12.

Results
A total of 38 ustekinumab levels in 21 patients were measured. Week 2 ustekinumab levels were available for 17 patients, 16 (94.1%) of whom had levels of greater or equal to 25μg/mL. (1 patient had a level of 19.5μg/mL.) Week 6 ustekinumab levels were available for 21 patients; median 15μg/mL (IQR 9.9–21.3). No patients had detectable antibodies to ustekinumab. There was no significant association between absolute induction dose and week 6 ustekinumab levels; p=0.46.
Of the 21 patients with week 6 levels, CDAI, CRP and FCP were available for 18, 18 and 16 patients respectively; Median CDAI 103(IQR 42–249), median CRP 2.3mg/L(IQR 1.0–11.3), median FCP 269μg/g(IQR109-932).
There was a significant negative correlation between week 6 ustekinumab levels and CDAI; r=-.609, p=0.007. A negative correlation between week 6 ustekinumab levels and FCP was also significant; r=-.526, p=0.037. There was no significant correlation between week 6 ustekinumab levels and CRP; r=-.259, p=0.298.

Conclusions
We have demonstrated inter-patient variation in drug pharmacokinetics at week 6 following induction dose of ustekinumab in patients with Crohn’s disease. Drug levels at week 6 are significantly associated with clinical and biochemical markers of disease activity (CDAI, faecal calprotectin) at week 12. Measurement of week 6 ustekinumab levels may aid early identification of patients at risk of primary non-response to ustekinumab.

Funding Agencies
Testing provided by Prometheus
A109 CELIAC DISEASE IS A RARE CAUSE OF BENIGN DUODENAL STRICTURE
Authors: Balubaid I , Khanna N 
Published: February 2020

Abstract

Background
Benign duodenal stricture is an uncommon problem encountered by gastroenterologists. The most common cause is peptic ulcer disease (PUD). With the diagnosis and eradication of H. Pylori, early diagnosis of PUD and the use of PPIs to treat upper gastrointestinal inflammation, the incidence of benign duodenal stricture has dramatically decreased. Patients with duodenal stricture may present with early satiety, nausea, vomiting and weight loss. We present the case of a man with a refractory web-like stricture in the second part of the duodenum (D2) caused by Celiac disease.

Aims
To describe a rare endoscopic finding in a patient with Celiac disease

Methods
Case report with literature review

Results
We present a case of a 64 year old male was referred for consideration of duodenal stenting of a refractory stricture in the second part of the duodenum D2. The patient had a 1 year history of abdominal pain, early satiety and weight loss (10 lbs). He also reported intermittent episodes of diarrhea. Investigations included a CT scan of the abdomen which showed a stricture at the level of proximal D2 described as a “duodenal band”. Previous attempts at balloon dilation had not resulted in prolonged symptomatic or endoscopic improvement. Testing for H. Pylori was negative and he did not use NSAIDs.
Upper endoscopy was performed to assess the stricture prior to consideration of stenting. This showed a tight web-like stricture in proximal D2. The stricture was balloon dilated up to 16.5 mm, enabling the endoscope to pass beyond it. The mucosa in D2 was atrophic with flattening of the folds and scalloping. There was no inflammation seen. Biopsies from D2 revealed moderate villous blunting and intraepithelial lymphocytosis. Celiac serology testing was abnormal, with an anti-tTG Ab level of 32 RU/ml which confirmed the diagnosis of Celiac disease. The balloon dilation and gluten-free diet resulted in resolution of his symptoms. Follow up endoscopy revealed normalization of his duodenal folds and biopsies. In addition, anti-tTG Ab level was normalized. Although stricture improved with prolonged patency, he still has mild recurrence of his stricture requiring balloon dilation on an annual basis.

Conclusions
This case describes a very uncommon complication of Celiac disease. The likely pathophysiology involves inflammation and potentially ulceration from Celiac disease, resulting in a benign stricture. There have been a few case reports describing duodenal strictures as a complication of Celiac disease. Treatment involves a gluten-free diet and endoscopic therapy. More severe cases of obstruction would likely require surgical intervention. In our case, the gluten-free diet and balloon dilation were successful and duodenal stenting was not necessary. Given the possibility of Celiac disease as a cause of duodenal stricture, it would be reasonable to biopsy D2 and check anti-tTG Ab in cases of duodenal stricture.

Funding Agencies
None
A112 ANGIOEDEMA,A RARE YET AN IMPORTANT CAUSE OF ABDOMINAL PAIN. A CASE STUDY AND LITERATURE REVIEW
Authors: Almalki F M , Cino M , Betschel S , Sasson A N 
Published: February 2020

Abstract

Background
Abdominal pain is a common gastroenterological symptom with an extensive deferential diagnoses. Angioedema is an important cause to remember after the more common causes have been excluded.It is caused by a deficiency in the inhibitor of the first component of classical complement pathway and is divided into hereditary or acquired.Acquired angioedema is associated with autoimmune or lymphoproliferative neoplasms.The clinical features of both include recurrent,self-limiting and circumscribed edema affecting the subcutaneous tissue of the upper respiratory airways and gastrointestinal tract.

Aims
We describe an interesting case of acquired angioedema presenting with recurrent abdominal pain. We also systematically review the current literature on this rare entity.

Methods
A search of electronic databases was performed inclusive to September 2019, for all studies and reviews of patients with acquired angioedema manifested as recurrent attacks of abdominal pain.
Results:
Case Report: 65 year old lady ho has an at least 2 year long history of abdominal pain and bloating associated on some occasions with nausea and vomiting.She presented to our emergency department in August,2018 with a day history of severe generalized abdominal pain and was found to have circumferential thickening,edema with mucosal hyperenhancement involving the distal segment of the small bowel.Splenomegaly was noted on that study.A double balloon enteroscopy was planned,but ultimately cancelled as her ileitis had resolved.The patient was discharged home as her pain resolved with conservative management which included intravenous fluid, pain medications and antiemetics.She then represented to the hospital on September 16, 2019 severe abdominal pain and throat tightness associated with shortness of breath. Again,noted was an extremely short segment of ileum with mucosal edema and hyperenhancement which resolved on a repeat CT scan done during that admission on September 18th, 2019.In light of the patient’s symptoms,CT scan findings,progressive anemia, thrombocytopenia and splenomegaly. It was thought that her abdominal pain is related to secondary to angioedema driven by a lymphoproliferative process as evident by the splenomegaly and worsening cytopenia. A bone marrow was done which revealed clonal B, so the diagnosis of lymphoma was made. The patient’s C1 esterase was 0.2 with reduced functional activity.CH50 less 10 perecent. A diagnosis of acquired angioedema was made and the patient was started on BERINERT 3000 IU SQ every three days with 1500 IU for break through with significant improvement in the frequency and severity of abdominal pain episodes.

Conclusions
Acquired angioedema is to be considered as a cause of recurrent abdominal pain in a patient with a lymphoproliferative malignancy after common causes and etiologies have been ruled out.

Funding Agencies
None
A114 AMEBIC COLITIS AS A RARE CAUSE OF PSEUDOMEMBRANOUS COLITIS
Authors: Tsoukas S E , Szilagyi A 
Published: February 2020

Abstract

Background
Globally, Entamoeba histolytica results in nearly 40 million cases of amebic colitis and 50 000 deaths annually. The disease is common in Africa, Asia, and Central and South America but infection remains rare in North America, limited to travelers, immigrants, and immunocompromised hosts. The disease ranges from asymptomatic chronic colonization to dysentery and fulminant colitis. Endoscopically, the ulcerations may demonstrate the non-specific pattern of pseudomembranous colitis that is classically seen with Clostridoides difficile infection.

Aims
To discuss an unusual case of pseudomembranous colitis caused by Entamoeba histolytica.

Methods
The patient records were reviewed and a review of the literature was performed.

Results
A 54-year-old male with a remote history of peptic ulcer disease visiting from Guinea presented with a 3-day history of right sided abdominal cramping and intermittent bloody diarrhea. The pain was gradual in onset with moderate severity. He reported &gt;5 episodes of blood intermixed with brown stools. He was incidentally diagnosed with hypertension and started on treatment two weeks prior. He denied recent antibiotic use and family history was unremarkable for inflammatory bowel disease (IBD) or other forms of colitis. There was no abdominal tenderness or bleeding on rectal examination. He had a stable normocytic anemia (Hgb 114), leukocytosis (13.4) with neutrophilia, and elevated C-reactive protein (43.4 mg/L). He was discharged with presumed resolving ischemic colitis. Colonoscopy showed diffuse colonic involvement with areas of patchy yellow plaques and a mix of shallow and deep non-bleeding ulcers suggestive of pseudomembranous colitis. He was discharged with empiric oral vancomycin, later discontinued following negative C. difficile toxin testing. Stool cultures and microscopy detected Entamoeba histolytica. Limited biopsies of the nodular ulcers failed to show any pathologic alterations or trophozoites. The patient was treated for luminal amebiasis with oral metronidazole and paromomycin but was lost to follow up on return to his native country.

Conclusions
Amebic colitis remains a rare entity in the developed world and is limited to travelers or recent immigrants from endemic areas. Diagnosis is typically difficult and may require endoscopy as its clinical course may resemble IBD or infectious colitis. Limited cases exist of fulminant amebic colitis causing pseudomembranous colitis, with even fewer cases of mild dysentery having this appearance. Despite pseudomembranous colitis being commonly associated with C. difficile infection, this pattern of mucosal injury may be seen with other enteric bacterial and protozoan infections, inflammatory conditions, or use of certain medications. In the appropriate clinical context, on exclusion of C. difficile, secondary causes such as active amebiasis should be considered.

Funding Agencies
None
A116 ASSESSING THE EFFECTIVENESS OF THE NURSE NAVIGATOR ROLE IN AN IBD MEDICAL HOME: A RETROSPECTIVE COHORT STUDY
Authors: Gawdat K , Heisler C , Nazer N , Stewart M , Currie B , Phalen-Kelly K , Jones J 
Published: February 2020

Abstract

Background
Patients living with chronic illnesses require long-term and often repeated interactions with the healthcare system. Inflammatory Bowel Disease (IBD) is an incurable, chronic gastrointestinal disease which frequently flares and remits. The nurse navigator (NN) serves as the point of first contact for IBD connecting patients with their multidisciplinary care team in order facilitate and expedite assessment, treatment and navigation through the healthcare system with the goal of improving disease-related outcomes while reducing healthcare system burden.

Aims
The aim of this study was to assess the impact of implementation of an IBD NN role within a multidisciplinary IBD Medical home on access to care, disease related outcomes, patient satisfaction with care, and healthcare resource use.

Methods
This was a retrospective cohort study comparing an IBD patient population that had access to a 24/7 NN-led helpline to a reference population who did not have access to such a service. Data between August 2017 and October 2019 were extracted from patient charts. Distribution of number of flares and time to clinical assessment between the NN exposed cohort and a non-NN exposed cohort are planned using multivariate analysis. This is a preliminary description of the NN-exposed cohort only.

Results
Preliminary results identified a total of 643 patients in the NN-exposed cohort. The majority of our NN-exposed population were female (64.3%). The mean age was 46.42 ± 16.86 years. Sixty-five percent of patients had CD, 33% UC and 2% IBDU. Of the 729 calls extracted, care coordination (39%) was the most frequent indication for calls followed by flare (25%), and medication education (16%). Patients made the majority (52.8%) of calls compared to NN initiated calls (47.2%). The mean number of calls per patient was 2.64 ± 2.51 (range 1–18) during the study period. Time to clinic assessment post flare call was on average 10.22 ± 8.51 days.

Conclusions
These results are descriptive of the NN-exposed cohort. Data comparing outcomes amongst the NN-exposed cohort to the non-exposed cohort will be presented at CDDW.

Funding Agencies
None
A121 SILENCING ENTERIC SENSORY NEURONS ABOLISHES THE EXCITATORY EFFECT OF SERTRALINE ON VAGAL AFFERENTS
Authors: West C , Stanisz A , Bienenstock J , Kunze W A 
Published: February 2020

Abstract

Background
Two thirds of vagal afferents supplying the small intestine terminate on intrinsic primary afferent neurons (IPANs) of the enteric nervous system via intraganglionic laminar endings (IGLEs) rather than the luminal epithelium (FASEB J, 28, 3064–3074, 2014). The IPAN to IGLE connection forms a functional intramural sensory synapse within the myenteric plexus. We have recently shown (Sci Rep, 9, 14290, 2019) that the antidepressant behavioural effects of selective serotonin reuptake inhibitors (SSRIs) are dependent on the vagus nerve and that intraluminal application of the SSRIs fluoxetine and sertraline increase vagal afferent firing rate in vitro.

Aims
We hypothesize that the vagal afferent response to intraluminal sertraline is mediated by IPAN to IGLE sensory signaling.

Methods
Mesenteric nerve recordings were performed using 2–3 cm jejunal segments and attached mesentery from 6–8 weeks old male Balb/c mice. Jejunal tissue was pinned out and dissected in a petri dish of Krebs to remove excess mesentery to isolate the mesenteric nerve bundle. Multi-unit electrical activity was recorded by patch-clamp electrode using an amplifier and signal converter by sucking onto the mesenteric nerve bundle with a glass micropipette. Baseline firing was recorded for 30 mins during luminal Krebs perfusion. The vagal afferent firing response to sertraline (10 µM) was measured in the absence or presence of 5 µM of the intermediate conductance calcium-dependent (IKCa) channel opener 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazole-2-one (DCEBIO) to the serosa to selectively silence IPANs. Dataview software (J Neuroscience Methods, 185, 151, 2009) was used to isolate single unit firing post-hoc. Vagal fibre action potentials were identified by response to CCK.

Results
Intraluminal sertraline decreased the mean vagal interspike interval (increased vagal firing frequency) by 29% (p = 0.008) compared to Krebs control (N = 15 fibres). In contrast, addition of luminal sertraline in the presence of DCEBIO increased mean vagal interspike interval by 48% (p = 0.0103) compared to Krebs control (N = 12 fibres). Serosal addition of the N-type Ca2+ channel blocker w-Conotoxin GVIA simultaneously with luminal sertraline increased the mean vagal interspike interval by 12% (p = 0.0282) compared to Krebs control (N = 7 fibres).

Conclusions
Silencing of myenteric IPANs to vagus neurotransmission blocked excitatory response of vagal afferent fibres to intraluminal sertraline. Blocking myenteric neurotransmission reduced the vagus excitatory response to sertraline by more than 50%. These results suggest that the therapeutically necessary vagus nerve stimulation by sertraline involves activation of the myenteric intramural sensory synapse.

Funding Agencies
NSERC, OGS
A126 RETROGRADE LABELLING OF NODOSE GANGLIA IN VIVO BY FLUORESCENT TRACERS
Authors: Tashtush A A , Lomax A E 
Published: February 2020

Abstract

Background
The gut-brain axis is a bidirectional connection between the gastrointestinal tract (GI)and the central nervous system. The vagus nerve has been recognized as a principal component of this axis. Vagus nerve plays important role in maintaining homeostasis and normal GI functions, its afferent fibers can detect microbiota metabolites also. Many studies have demonstrated that the upper GI tract receives dense vagal innervation, which decreases distally throughout the tract. However, the distal colon sensory innervation of the vagus nerve remains controversial.

Aims
To illuminate the extent to which the vagus nerve innervates the colon, to determine whether anatomical evidence exists for double-labeled vagal afferents supplying the proximal and distal colon in the nodose ganglia.

Methods
C57Bl/6 mice (n=8) were injected in the proximal and distal colon with alternating solutions of retrograde tracers 1.7% Fast blue (FB) and 5% of lipophilic tracer DiI. Animals were left to recover for 10–13 days then underwent cardiac perfusion. Nodose ganglia were collected and fixed in 4% paraformaldehyde. 12 um tissue sections were then analyzed under a fluorescent microscope at 350nm and 555nm wavelength.

Results
In total, 27% of nodose cell bodies were labeled from the entire colon. Following proximal DiI injections, the percentage of labeled cell bodies in the nodose ganglia were 24.3± 3.9%. However, we observed a lower percentage of labeled neurons from the distal colon, with 9.3± 1.4% after DiI injections. FB labelling from the distal colon was three times less than that observed for DiI. Within the nodose ganglia, 40% of all distally labelled neurons were labelled with both tracers.

Conclusions
These findings indicate that in mice, both distal and proximal colon receives visceral sensory innervation from the vagus nerve. Thus, providing evidence for a sensory anatomical connection of the vagus nerve between these two parts of the colon.

Funding Agencies
CCC, CIHR
A130 RETROGRADE TRACING ANALYSIS OF THE SENSORY INNERVATION OF THE MOUSE COLON
Authors: Osman S , Lomax A E 
Published: February 2020

Abstract

Background
Visceral pain is a primary symptom of many gastrointestinal diseases. One feature of visceral pain is its vague localization. We hypothesized that overlap in the receptive fields of spinal primary afferent neurons that innervate the gut may contribute to this vague localization. Many studies have confirmed that the proximal and distal colon are mainly innervated by spinal afferent neurons with cell bodies in thoraco-lumbar and lumbo-sacral dorsal root ganglia (DRG), respectively. However, no murine studies have examined whether individual DRG neurons simultaneously innervate both proximal and distal colon.

Aims
To determine the extent of overlap in receptive fields of colon-projecting DRG neurons.

Methods
C57BL/6 mice (n=8) were anesthetized, and two retrograde neuronal tracers with distinct fluorescence emission spectra (Fast blue and DiI) were injected separately into the smooth muscle layers of proximal and distal colon. Mice were left for 10–13 days for dye transport, before being euthanized. Thoraco, lumbar and lumbo-sacral DRGs (T8-13, L1-4, L5-S2) were dissected and fixed in 4% paraformaldehyde overnight. 12μm cryostat sections were obtained and analyzed using a fluorescent microscope equipped with filter cubes that detect Fast blue and DiI.

Results
When DiI was injected into the proximal colon, we observed labelling to be highest in T8-13 DRG with 12.6 +/- 4.5% of cell bodies labelled, followed by L1-4 was (8.2 +/- 1.4%) and in L5-S2 (6.5 +/- 0.8%). DiI injections into the distal colon resulted in labelling of similar numbers of neurons labelled in T8-13 and L1-4 ganglia, whereas half as many neurons were labelled in L5-S2 ganglia. This data shows that the majority of spinal afferent innervation of the colon originates in thoracolumbar DRG. Most importantly, 26.4% and 17.6% of thoracolumbar and lumbo-sacral DRG neurons labelled by Fast blue injection into the proximal colon were also double-labelled by DiI injected into the distal colon. Similarly, 16.6% and 13.8% of neurons in thoracolumbar and lumbosacral DRG labelled by Fast blue injection into the distal colon were double-labelled by DiI injected into the proximal colon.

Conclusions
These data reveal a surprisingly large number of DRG neurons that innervate the colon have receptive fields that cover both the proximal and distal colon, which may contribute to the poor spatial localization of pain emanating from the colon.

Funding Agencies
CCC, CIHR