bluuebunny/crossref_metadata_2025_split huggingface dataset:
A17 EVIDENCE OF PROTEASE-MEDIATED PRO-NOCICEPTIVE EFFECTS OF FECAL SUPERNATANTS FROM CROHN'S DISEASE PATIENTS
Authors: Wood H , Alward T , Abu Omar A , Guzman-Rodriguez M , Vanner S , Reed D , Lomax A 
Published: March 2023

Abstract

Background
Abdominal pain is a debilitating symptom of Crohn’s disease (CD). Despite the current treatment options for this disease, abdominal pain is an unresolved problem that commonly persists in the absence of active inflammation. This suggests that something other than inflammation is driving the pain during the quiescent phase. We have previously reported that microbial proteases can directly modulate the excitability of dorsal root ganglia (DRG) neurons, many of which are pain-sensing. We hypothesize that luminal proteases of CD patients are contributing to their abdominal pain.

Purpose
Determine whether luminal mediators in CD fecal samples induce changes in pain signalling.

Method
The effects of patient (active CD [n = 3] and healthy volunteer (HV) [n = 3]) fecal supernatant (FS) samples on pain-sensing neurons were assessed using ex-vivo single unit afferent nerve recordings from mouse colons. Each sample was tested in colonic preparations from a least 5 mice. To further examine cellular mechanisms, DRG neurons were isolated and incubated overnight in media containing CD FS or HV FS media. Changes in neuronal excitability were recorded by determining the rheobase (lower rheobase=increased excitability) using patch clamp recordings (n ≥ 9 DRG neurons/group). Protease inhibitors were applied in both bioassays to determine whether these inhibited the excitatory effect of FS. Lastly, total proteolytic activity in the CD and HV fecal samples was calculated using a casein colorimetric protease detection assay.

Result(s)
FS from HV had no effect on afferent nerve excitability (p = 0.8920). FS from active CD patients increased action potential discharge from colonic afferent nerves by 85% (p&lt;0.0001) and selectively increased the activation of high-threshold units, which are putative nociceptors, by 44% (p=0.0074). A protease inhibitor cocktail (1:1000) and protease-activated receptor (PAR)-2 antagonist GB83 (10µM) both blocked the excitatory effects of CD FS (p&lt;0.05). Overnight incubation with CD FS also had an excitatory effect on DRG neurons compared to HV FS (rheobase decreased by 46%, p&lt;0.05). The effect of CD FS was blocked by GB83 (10µM) (p&lt;0.001) and a serine protease inhibitor (FUT175; 100µM) (p&lt;0.05) independently, but the activity was not blocked by E64 (30nM) a cysteine protease inhibitor. A 200-fold increase (p&lt;0.0001) in total proteolytic activity was found in CD FS compared to HV FS.

Conclusion(s)
Luminal serine proteases, but not cysteine proteases, appear to be driving nociceptive signalling in CD patients. This provides insight into the generation of pain in CD patients and may be a potential target to mitigate this action. Further research is required to elucidate whether these pro-nociceptive proteases are of bacterial or host origin and their effects in the quiescent phase.

Disclosure of Interest
None Declared
A23 INTESTINAL STEM CELL REGULATION BY THE BACTERIAL METABOLITE ADP-HEPTOSE VIA ACTIVATION OF THE ALPK1-TIFA SIGNALLING PATHWAY
Authors: Goyal S , Gray-Owen S , Girardin S 
Published: March 2023

Abstract
NOT PUBLISHED AT AUTHOR’S REQUEST

Please acknowledge all funding agencies by checking the applicable boxes below
CCC, CIHR

Disclosure of Interest
None Declared
A43 SEX DIFFERENCES IN THE ASSOCIATION OF HIV WITH METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE (MAFLD)
Authors: Kablawi D , Tadjo T F , Milic J , Elgretli W , Gioè C , Lebouché B , Cascio A , Guraldo G , Mazzola G , Sebastiani G 
Published: March 2023

Abstract

Background
People with HIV (PWH) are at high risk for metabolic dysfunction-associated fatty liver disease (MAFLD). In the general population, sex differences seem to exist in frequency and severity of MAFLD, with higher prevalence of MAFLD in men, but higher incidence of liver fibrosis in women. Less is known about sex differences in MAFLD and liver fibrosis in the setting of HIV infection.

Purpose
The aim of this study is to investigate the sex differences in the prevalence of MAFLD in PWH and the severity of liver fibrosis among this population.

Method
This was a multicenter cohort study including consecutive PWH who underwent screening for MAFLD and liver fibrosis by liver stiffness measurement (LSM) with associated controlled attenuation parameter (CAP). MAFLD was defined as the presence of hepatic steatosis, diagnosed as CAP&gt;270 dB/m, plus any among type 2 diabetes, overweight (BMI&gt;25 Kg/m2) or two other metabolic abnormalities. Significant liver fibrosis was diagnosed as LSM&gt;8 kPa. Incidence of MAFLD and significant liver fibrosis was assessed through survival analysis.

Result(s)
1359 PWH (25% females, 30% HCV coinfected) were included. Prevalence of MAFLD at baseline was lower in women than in men with HIV (17.7% vs. 24.3%, p=0.013). Conversely, there was no difference in prevalence of liver fibrosis (10.7% vs. 13.4%). Women with MAFLD were more frequently of black ethnicity (48% vs. 14%, p&lt;0.001), had lower ALT (26.4+20.4 vs. 33.4+22.5; p=0.035), higher HDL cholesterol (1.46+0.57 vs. 1.11+0.33; p&lt;0.001), lower triglycerides (1.69+0.96 vs. 2.47+2.63; p=0.035) compared to men with MAFLD. 485 of these PWH were followed for a median of 3.5 years. Incidence of MAFLD was similar between women and men with HIV. However, incidence of liver fibrosis was higher in women compared to men with HIV (7.0 per 100 person-years [PY] vs. 5.9 per 100 PY; p=0.035) (Figure 1). The higher incidence of significant liver fibrosis occurred particularly after the age of 50 years. On multivariable Cox regression analysis and after adjusting for age, presence of MAFLD (adjusted hazard ratio [aHR] 3.3, 95% CI 2.0-5.6) and female sex (aHR 2.2, 95% CI 1.3-3.5) were independent predictors of developing significant liver fibrosis while CD4 cell count was protective (aHR 0.99, 95% CI 0.99-0.99).

Image

Conclusion(s)
MAFLD seems a sexual dimorphic disease in PWH. Despite having lower rates of MAFLD, women with HIV have higher incidence of significant liver fibrosis compared to men, especially after 50 years of age. Future studies should target adequate consideration of sex differences in clinical investigation of MAFLD to fill current gaps and implement precision medicine for PWH.

Please acknowledge all funding agencies by checking the applicable boxes below
None

Disclosure of Interest
None Declared
A127 TIMING OF CHOLECYSTECTOMY AFTER ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN A TERTIARY CENTRE: EVALUATION OF OUTCOMES
Authors: Liu C S , Kao D , Mohamed M , Bigam D , Zepeda-Gomez S 
Published: March 2023

Abstract

Background
Endoscopic retrograde cholangiopancreatography (ERCP) is the treatment of choice for patients with choledocholithiasis. Early cholecystectomy (within 24 to 72 hours) is recommended after the initial ERCP to reduce the risk of subsequent biliary events.

Purpose
To investigate the timing of cholecystectomy after ERCP in patients with choledocholithiasis and its associated outcomes in a single tertiary care centre.

Method
This is a retrospective analysis of adult patients who underwent cholecystectomy after ERCP from August 2021 to April 2022 at the University of Alberta Hospital. Outcomes data were stratified according to the length of time between ERCP and cholecystectomy, within 72 hours (early) or after 72 hours (delayed).

Result(s)
During the study period, 55 subjects were examined. Indications for ERCP included gallstone pancreatitis (24/55, 44%), choledocholithiasis (19/55, 34%), and acute cholangitis (12/55, 21%).
In total, 30 (55%) subjects received cholecystectomy within 72 hours, while 25 (45%) subjects received cholecystectomy after 72 hours. The two groups were comparable in age, sex ratios, and comorbidities. Out of the patients who received cholecystectomy after 72 hours, 8 (32%) subjects received their cholecystectomy on a subsequent admission. Of these, 2 subjects developed recurrent biliary events before their cholecystectomy, and 1 subject required a conversion to open cholecystectomy. There were no recurrent biliary events amongst the individuals with early cholecystectomy.
Subjects who received early cholecystectomy had a shorter total hospital stay compared to those with delayed cholecystectomy (4.5 days vs 7.3 days, p=0.0002). There was no significant difference between early and late cholecystectomy in conversion rate (3% vs 8%, p=0.58), average operating time (86min vs 83min, p=0.79), intraoperative complications including adhesions (13% vs 12%, p&gt;0.05) and empyema (27% vs 28%, p&gt;0.05), as well as histological rate of chronic cholecystitis (88% vs 92%, p=0.68).
Reasons associated with significantly delayed (&gt;7 days) cholecystectomy after ERCP (n=12) include requiring coordination/consultation with other services prior to operation (3 subjects), prolonged course of gallstone pancreatitis (3 subjects), poor candidate for operation due to comorbidities (2 subjects), surgical cancellation/delays (2 subjects), post-ERCP pancreatitis (1 subject), and patient preference (1 subject).

Image

Conclusion(s)
Early cholecystectomy is associated with a shorter length of hospital stay and absence of recurrent biliary events. Other post-cholecystectomy outcomes were comparable. Early laparoscopic cholecystectomy should continue to be encouraged through an interdisciplinary approach.

Please acknowledge all funding agencies by checking the applicable boxes below
None

Disclosure of Interest
None Declared
A177 RISK OF VENOUS THROMBOEMBOLISM IN COVID-19 PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED MATCHED COHORT STUDY
Authors: Khan R , Kuenzig E , Tang A , Im J , Widdifield J , McCurdy J , Kaplan G , Benchimol E 
Published: March 2023

Abstract

Background
Venous thromboembolism (VTE), is associated with significant morbidity and mortality. Inflammation increases the risk of VTE, and it is a well-recognised complication of both inflammatory bowel disease (IBD) and COVID-19.

Purpose
To compare the risk of VTE among individuals with and without IBD following a positive COVID-19 test.

Method
Using health administrative data from Ontario, Canada we conducted a retrospective matched cohort study.All Ontario residents with a positive SARS-CoV-2 PCR test between January 1,2020 and December 30,2021 who had been diagnosed with IBD prior to their COVID-19 infection (identified using a validated algorithm) were matched to 5 individuals without IBD based on year of birth, sex, mean neighbourhood income quintile, date of positive COVID-19 test, and rural/urban residence. Individuals with a cancer diagnosis in the 5 years prior to their first COVID-19 positive test were excluded. Individuals were followed from positive COVID-19 PCR test until VTE event, death, migration out of Ontario or March 31, 2022.VTEs were identified from emergency department or hospitalization data using ICD-10 codes. Incidence rate of VTEs among individuals with IBD were assessed at 1, 6 and 12 months. Proportional cause-specific hazards models compared the risk of VTEs in people with and without IBD, treating death as a competing risk and controlling for vaccination status (2nd dose ≥14 days prior to positive COVID-19 test) and a history of VTE (VTE in the 5 years prior to infection).

Result(s)
There were 4293 people with IBD (44% Crohn’s disease, mean age ±SD 46.1±17.2 y) matched to 20,207 with out IBD (mean age 45.3±16.8 y) with a positive SARS-CoV-2 PCR test. Within 1 month of a positive COVID-19 test, the crude incidence rate of VTE in individuals with IBD was 4.77(95%CI, 4.75-4.80) per 100,000 person-days compared to 8.25(95%CI, 8.20-8.30) per 100,000 among people without IBD.Within 6 months, these rates were 1.86(95%CI, 1.86-1.87) and 2.12(95%CI, 2.11-2.12) per 100,000 person-days among people with and without IBD, respectivley. Within 12 months, these rates were 1.59(95% CI, 1.58-1.59) and 1.42(95% CI, 1.42-1.42) per 100,000 person-days among people with and without IBD, respectively.After adjusting for vaccination status and history of VTE there was no difference in the risk of VTE for people with and without IBD (HR 1.08, 95%CI, 0.64 to 1.83).

Conclusion(s)
IBD patients with COVID-19 were not more likely to experience a VTE infection compared with the general popluation. The risk of VTE was highest soon after COVID-19 and declined thereafter.

Please acknowledge all funding agencies by checking the applicable boxes below
None

Disclosure of Interest
None Declared
A188 INFORMING IMMUNOCOMPROMISED POPULATIONS: AN EFFECTIVE AND EFFICIENT COVID-19 KNOWLEDGE TRANSLATION STRATEGY
Authors: Windsor J W , Coward S , Lee K , Specic A , Ghandeharian S , Benchimol E I , Kaplan G G 
Published: March 2023

Abstract

Background
Throughout the COVID-19 pandemic, one of the major challenges was conveying expert health information, which was evolving rapidly, to confer population-level advice; this was especially relevant to at risk groups, such as those who are immunocompromised due to conditions like inflammatory bowel disease (IBD) or medications to manage disease.

Purpose
To provide sufficient information to those with IBD (&gt;0.75% of the Canadian population or roughly 300,000 individuals) and their carers to allow self assessment of personal risks related to COVID-19.

Method
On March 17, 2020, Crohn’s and Colitis Canada (CCC) convened the COVID-19 & IBD Taskforce comprised of adult and pediatric gastroenterologists, IBD nurses, infectious disease experts, scientists, public health officials, communication and government relations experts, and patient advisors. The taskforce met weekly (later monthly) to synthesize rapidly evolving information on COVID-19 and personal risk assessment. Expert reviews of population-level recommendations were tailored to the IBD community and communicated through website FAQs and infographics; a public-oriented burden report with foci on additional special populations (e.g., pregnant people, pediatrics, seniors), IBD medications, and mental health and access to care during the pandemic; and through a moderated, online webinar series. The 1- to 2-hour webinar recordings were then curated into 3- to 5-minute video clips to answer specific questions and uploaded to CCC’s YouTube page. YouTube and website metrics show the continued efficacy of this strategy.

Result(s)
More than 24,778 households registered for the first 23 webinars, with more than one third registering for more than one webinar. As of April 1, 2021 (just after the 23rd webinar), there have been 54,136 views of the archived full (1- to 2-hour) webinars and a further 78,862 views of individual webinar segments (3- to 5-minute curated clips), for a total of 126,187 views. Additionally, traffic to the CCC website increased exponentially with 484,755 unique views to the COVID-19 web pages, viewed for up to 28.29 minutes. Since April 2021, after an additional seven webinars, these numbers have continued to swell to 33,243 (registrants), 81,370 (webinar views), 92,862 (segment views), and 810,156 (unique website views); this is demonstrative of the continued impact of the electronic knowledge translation strategy.

Image

Conclusion(s)
While many within the IBD community were secluded during the early portions of the pandemic due to lockdown restrictions and public health advice not tailored to immunocompromised individuals, advice tailored to this community and presented through electronic methods proved to be an effective and efficient knowledge translation strategy.

Please acknowledge all funding agencies by checking the applicable boxes below
CCC

Disclosure of Interest
None Declared
A201 EFFECT OF MIRIKIZUMAB ON BOWEL URGENCY CLINICALLY MEANINGFUL IMPROVEMENT AND REMISSION: RESULTS FROM THE PHASE 3 LUCENT INDUCTION AND MAINTENANCE STUDIES
Authors: Travis S , Hibi T , Hisamatsu T , Fisher D , Shan M , Gibble T H , Rubin D , Jones J 
Published: March 2023

Abstract

Background
Bowel urgency (BU) was assessed in mirikizumab (miri) Phase 3 LUCENT studies in moderately-to-severely active UC using the validated Urgency Numeric Rating Scale (UNRS). UNRS measures BU severity in the past 24 hours from 0 (no urgency) to 10 (worst possible urgency). Psychometric evaluation of the UNRS showed Clinically Meaningful Improvement (CMI) is &gt;3 point change; Remission is a score of 0 or 1.

Purpose
This analysis evaluated the proportions of patients in LUCENT studies achieving BU CMI and BU remission.

Method
The modified intent-to-treat (mITT) population (patients receiving ≥1 dose of miri or placebo (PBO); N= 1281) was randomized at induction study baseline in a 3:1 ratio to IV doses of 300mg miri or PBO every 4 weeks (Q4W) during induction (W0, 4, and 8). Patients achieving Clinical Response, measured by Modified Mayo Score (MMS), to miri during induction were re-randomized at W0 of the maintenance study in a 2:1 ratio to subcutaneous (SC) 200mg miri or PBO Q4W through W40 (52 weeks of treatment). Patients recorded their UNRS score daily in an e-diary. Mean weekly UNRS scores were calculated from diary data if ≥4 days of data were available. Rates of BU CMI and BU remission in the miri v PBO groups were compared at W12 (induction) in the mITT population with a baseline UNRS score ≥3, and W52 (maintenance) among miri clinical responders at W12 with a baseline UNRS score ≥3. Cochran-Mantel-Haenszel tests with non-responder imputation for missing values were used for all treatment comparisons.

Result(s)
Patient population: mean age 43 years, 60% male, disease duration 7 years; 63.0% left-sided colitis; 36.3% pancolitis; 46.7% moderate disease (MMS 4-6); 53.2% severe disease (MMS 7-9). Significantly higher proportions of miri versus PBO patients achieved BU CMI (48.7% v 32.2%) and BU remission (22.1% v 12.3%) at W12 (both p&lt;0.001; Table) in the induction study. Similarly, at W40 of maintenance, significantly greater proportion of miri patients achieved BU CMI (65.2% v 41.9%) and BU remission (42.9% v 25.0%) compared to PBO among miri induction responders (both p&lt;0.001; Table).

Image

Conclusion(s)
Miri had a highly significant and clinically meaningful benefit on reducing bowel urgency, one of the most disruptive UC symptoms. The Urgency Numeric Rating Scale usefully quantified the baseline level and change in bowel urgency after treatment across a spectrum of severity.

Please acknowledge all funding agencies by checking the applicable boxes below
Other

Please indicate your source of funding;
Eli Lilly and Company

Disclosure of Interest
None Declared
A285 CHANGE IN ALT DURING MODIFIED OPTIFAST WEIGHT LOSS PROGRAM IN INDIVIDUALS AT RISK FOR NON-ALCOHOLIC FATTY LIVER DISEASE
Authors: Meddings Maybury L , Kelly E , Dent R , Bielawska B 
Published: March 2023

Abstract

Background
Obesity is linked to various health complications, including diabetes, metabolic syndrome, cardiovascular disease, and non-alcoholic fatty liver disease (NAFLD). NAFLD is the most frequent cause of abnormally high alanine aminotransferase (ALT) levels. ALT is released at higher levels during hepatocellular injury and represents a simple, low cost and non-invasive method of assessing liver damage. There are conflicting data on ALT response to weight loss between men and women, with some evidence of transient increase in ALT levels in women.

Purpose
The aim of this study was to assess the impact of a dietary weight loss intervention with Optifast on ALT in patients with obesity who have baseline elevated ALT levels.

Method
This was a retrospective cohort study of Ontario adults who participated in a 26 week weight loss program, including 6 or 12 weeks of low-calorie liquid diet meal replacement with Optifast 900® (Nestlé, Canada), between 1992 and 2015. We included patients with elevated baseline ALT levels, defined by &gt; 40 U/L, who had at least one follow-up ALT between week 15 and 26. We excluded patients with nonadherence to dietary intervention, established liver disease or using hepatotoxic drugs, excessive alcohol intake (&gt;11U/wk for females and &gt;14U/wk for males), and insufficient data to calculate FIB-4. The primary outcome was change in ALT levels, measured by normalization (post-intervention ALT &lt; 40 U/L), percentage decrease and absolute decrease. Multiple linear regressions were obtained for the relationship between ALT changes and age, sex, body mass index (BMI) and FIB-4. All analyses were conducted in SPSS. P value of ≤0.05 was considered statistically significant.

Result(s)
444 patients met study criteria. Mean age was 47.1 years +/- 10.9, 49 % of patients were female, and mean BMI was 43.5 kg/m2 +/- 7.9. All patients lost weight, with mean weight loss 27.3 kg +/- 11.5 and a mean 20.7% decrease from baseline weight. Mean ALT at baseline was 58.9 U/L +/- 25.4 and mean ALT post intervention was 32.3 U/L +/- 28.1 (p &lt;0.01). 85.1% of patients had normalization of ALT. Mean % decrease in ALT was 41.9% and mean absolute decrease in ALT was 26.6 U/L +/- 25.4. Younger age and higher baseline FIB-4 were significantly associated with a larger decrease in ALT levels, while sex and initial BMI were not significantly associated with changes in ALT.

Conclusion(s)
In patients with obesity and baseline elevated ALT, dietary weight loss intervention with Optifast leads to ALT normalization in most patients, regardless of sex. Younger age at baseline and higher baseline FIB-4 are significantly associated with greater decrease in ALT.

Please acknowledge all funding agencies by checking the applicable boxes below
None

Disclosure of Interest
None Declared
How Sensory Language Shapes Influencer’s Impact
Authors: Cascio Rizzo Giovanni Luca , Berger Jonah , De Angelis Matteo , Pozharliev Rumen 
Published: March 2023

Abstract
Influencer marketing has become big business. But while influencers have the potential to spread marketing messages and drive purchase, some posts get lots of engagement and boost sales, while others do not. What makes some posts more impactful? This work examines how sensory language (e.g., words like “crumble” and “juicy” that engage the senses) shapes consumer responses to influencer-sponsored content. A multimethod investigation, combining controlled experiments with automated text, image, and video analysis of thousands of sponsored social media posts, demonstrates that sensory language increases engagement and willingness to buy the sponsored product. Furthermore, the studies illustrate that these effects are driven by perceived authenticity. Sensory language leads consumers to infer that influencers actually use the product they are endorsing, which increases perceived authenticity, and thus engagement and purchase. These findings shed light on how language shapes responses to influencer-sponsored content, deepen understanding of the drivers of authenticity, and suggest how to develop more impactful social media campaigns.