bluuebunny/crossref_metadata_2025 huggingface dataset:
A213 REDEFINING MILD-MODERATE ULCERATIVE COLITIS: PATIENTS WITH ENDOSCOPIC MAYO SCORE 1 AND ACTIVE HISTOLOGIC INFLAMMATION HAVE SIMILAR OUTCOMES TO PATIENTS WITH MAYO SCORE 2
Authors: Khan N , Wong E , Narula N
Published: February 2025

Background

Mild-to-moderate ulcerative colitis (UC) is conventionally defined as a total Mayo Clinic score of at least 4, with a Mayo Endoscopic Score (MES) of 2 and a Rectal Bleeding Score (RBS) of at least 1. Historically, endoscopic improvement with treatment has been defined as MES 0 or 1. However, studies have shown differences in prognosis between these two subsets of patients, with those who attain MES 1 reported to have higher rates of relapse. Patients with MES 1 and histologically active disease are currently excluded from contemporary clinical trials based on prevailing inclusion criteria. Consequently, insight into improving therapeutic outcomes for this patient population remains limited.

Aims

This study aims to explore whether UC patients with lower endoscopic burden but active histology have comparable outcomes to those with “conventional” mild-moderate UC.

Methods

This was a post-hoc analysis from the VARSITY study. Patients who completed induction (at week 14) with mild-moderate UC based on the conventional definition were compared to patients with histologically active MES 1 for achieving histo-endoscopic mucosal improvement (HEMI) at week 52, defined as Mayo endoscopic subscore ≤ 1 and Geboes highest grade < 3.2. Secondary outcomes included endoscopic remission (ER) (Mayo endoscopic subscore of 0), histologic improvement (Geboes highest grade < 3.2) and clinical remission (CR) (total Mayo score ≤ 2 and no subscore >1 on any of the four subcomponents). Histologically active disease was defined as Geboes highest grade > 3.2 (>50% of neutrophil crypt involvement in the epithelium).

Results

Week 52 outcomes were comparable among patients with mild-moderate UC compared to those with histologically active disease and MES of 1. At week 52, a similar proportion of patients achieved HEMI [19/79 (24.1%) vs. 28/113 (24.8%), p=0.908], ER [23/79 (29.1%) vs. 35/113 (31.0%), p=0.782], histologic improvement [23/79 (29.1%) vs. 36/113 (31.9%), p=0.685] and CR [38/79 (48.1%) vs. 66/113 (58.4%), p=0.158].

Conclusions

Disease outcomes in patients with MES 1 and a Geboes score > 3.2 were comparable to those with conventional mild-to-moderate UC. These results highlight the need for clinical trialists to revisit and expand the current definition of mild-to-moderate UC. Further validation of these findings in other patient cohorts is recommended.

Funding Agencies

None
A219 SHORT-TERM OUTCOMES OF UPADACITINIB IN PEDIATRIC IBD: A RETROSPECTIVE REVIEW
Authors: Alharbi A , Rozka L , Lawrence S , Jacobson K
Published: February 2025

Background

Pediatric inflammatory bowel disease (IBD) requires innovative treatments to improve symptoms and reduce steroid use. Upadacitinib, a selective JAK-1 inhibitor, has shown efficacy in adults but pediatric data remain limited

Aims

To assess clinical remission at 8 weeks in pediatric IBD patients treated with upadacitinib. Secondary aims include evaluating clinical response, steroid reduction, symptom improvement, biomarker changes, and adverse events

Methods

This retrospective review included pediatric UC and CD patients treated with upadacitinib (45 mg daily for 8-12 weeks). Clinical remission was defined as wPCDAI/PUCAI ≤10 at 8 weeks. Secondary outcomes included clinical response (wPCDAI decrease >17.5 for CD, PUCAI ≥20 for UC), steroid reduction, symptom scores (abdominal pain, urgency, rectal bleeding, stool frequency), biomarkers (CRP, calprotectin), and adverse events. The Naranjo scale assessed adverse event probability

Results

Seven patients (5 CD, 2 UC) with complete 8-week data were analyzed. Median age was 16 years (IQR: 14-17), with a 3:4 male-to-female ratio

Clinical remission

At baseline, 4 patients were on both upadacitinib and steroids, and 3 on upadacitinib alone

At 8 weeks, 3/4 on steroids achieved remission, with 1 fully weaned

All 3 patients on upadacitinib alone achieved steroid-free remission

85.7% (6/7) achieved remission at 8 weeks, p = 0.01

33.3% (2/6) of remissions remained on steroids, and 66.7% (4/6) were steroid-free

Secondary outcomes:

Clinical response

85.7% (6/7) achieved response, with wPCDAI/PUCAI scores improving from 40 (IQR: 30-52.5) to 5 (IQR: 0-15) CD scores improved from 52.5 (IQR: 40-60) to 7.5 (IQR: 0-25), and PUCAI from 32.5 (IQR: 25-40) to 0 (IQR: 0-0), p = 0.01

Steroid reduction

4 patients were on steroids at baseline, with 1/4 fully weaned by 8 weeks

Baseline prednisone: 40 mg (IQR: 30-50) vs. 25 mg (IQR: 10-30) at 8 weeks, p = 0.02

Symptom scores

Abdominal pain: 2 (IQR: 1-3) to 0 (IQR: 0-0), p = 0.03

Urgency NRS: 5 (IQR: 3-6) to 0 (IQR: 0-2), p = 0.01

Rectal bleeding: 2 (IQR: 0-3) to 0 (IQR: 0-0), p = 0.04

Stool frequency: 2 (IQR: 1-3) to 0 (IQR: 0-1), p = 0.02

Biomarker response

CRP: 25 mg/L (IQR: 3.1-39) to 10 mg/L (IQR: 2-18), p = 0.03

Calprotectin: 2000 µg/g (IQR: 580-5449) to 800 µg/g (IQR: 74-1378), p = 0.04

Adverse events

71.4% (5/7) experienced acne, 28.6% (2/7) headaches, and 28.6% (2/7) nausea

No serious adverse events were reported. Median Naranjo score: 2

Conclusions

Upadacitinib improved symptoms and reduced steroid use in pediatric IBD, with 85.7% (6/7) achieving remission at 8 weeks. Of these, 66.7% (4/6) achieved steroid-free remission. Clinical response was achieved in 85.7% (6/7), with significant improvements in both UC and CD. Mild adverse events were reported, supporting further exploration of upadacitinib in pediatric IBD. Additional patients will be recruited in the coming months to expand this dataset

Funding Agencies

None
A220 LONG-TERM EFFECTIVENESS AND SAFETY OF USTEKINUMAB DOSE ESCALATION IN PATIENTS WITH REFRACTORY ULCERATIVE COLITIS: A MULTICENTER RETROSPECTIVE COHORT STUDY
Authors: Albino L , van Lierop L , Rosentreter R , Thomas P , Lu C , Siffledeen J , Kroeker K , Ma C , Peerani F , Halloran B , Baumgart D C , Dieleman L , Du L , Hoentjen F , Wong K
Published: February 2025

Background

Ustekinumab dose escalation (DE) may be an effective strategy to recapture clinical response in patients with ulcerative colitis (UC).

Aims

The aim of this study was to assess the real-world long-term effectiveness and safety of ustekinumab DE in patients with refractory UC.

Methods

This multicenter retrospective cohort study included patients with refractory UC who received at least one IV induction ustekinumab dose between January 2016 and November 2021. We compared ustekinumab DE to no DE, examining clinical, biochemical, and endoscopic disease outcomes. The primary endpoint was corticosteroid-free clinical remission (partial Mayo score ≤ 2 without systemic corticosteroids) at the end of follow-up. Cox-proportional hazards regression analysis was performed for factors associated with time to DE and a Kaplan-Meier plot was created for visualizing drug persistence probabilities.

Results

We enrolled 121 patients. Eighty-one patients (67%) underwent DE during a median follow-up of 141 weeks. Corticosteroid-free clinical remission at the end of follow-up was achieved for 53.2% (DE group) and 59.0% (non-DE group). In the DE group, 53% discontinued ustekinumab, mainly due to a lack of effectiveness. At the end of follow-up, 47% of DE patients remained on ustekinumab, compared to 55% in the non-DE group. Ustekinumab persistence probability after 2 years was 40% (DE group) versus 79% (non-DE group). Only 2 patients discontinued ustekinumab for adverse events.

Conclusions

Our results indicate that DE is a common method for optimizing ustekinumab treatment in refractory UC. While DE appears safe, effectiveness and drug persistence of DE beyond 2 years are limited.

Table 1

Proportion of participants in corticosteroid-free clinical, biochemical, combined clinical/biochemical, endoscopic, and combined clinical/biochemical/endoscopic remission at year 1, year 2, and end of follow up for the DE group vs non-DE group. *In the DE group, 8 discontinued ustekinumab before 1 year and an additional 14 before 2 years. **In the non-DE group, 12 discontinued ustekinumab before 1 year and an additional 4 before 2 years. ***Additional patients missing from the denominators had missing values at the presented timepoints.

Kaplan-Meier plot for probabilities of continued ustekinumab usage over the duration of follow-up in years. The green (upper) line represents the non-DE group, the red (middle) line represents the entire cohort, and the blue (bottom) line represents the DE group.

Funding Agencies

None
A227 VEDOLIZUMAB EXPOSURE ASSOCIATED WITH THE RESOLUTION OF OROFACIAL CROHN’S DISEASE: A CASE REPORT
Authors: Alseiari K , Darling M , Mora M , Wilson A
Published: February 2025

Background

Orofacial Crohn’s disease (CD) is a rare and often debilitating manifestation of Crohn’s disease, characterized by deep ulcerations, cobblestone lesions of the buccal mucosa, and hallmark granulomas(1,6). Orofacial Crohn’s disease remains a challenging condition to manage, with limited available data on the use of advanced non-TNF-α therapies (3). Vedolizumab, a gut-selective integrin antagonist, has been shown to be effective for inflammatory bowel disease, but its role in treating orofacial CD has not been fully explored(2,3,5).

Aims

The aim of this case report is to explore the potential efficacy of vedolizumab in treating orofacial Crohn’s disease, a rare and challenging manifestation of Crohn’s disease, by presenting a clinical case where vedolizumab led to significant resolution of both orofacial and gastrointestinal symptoms. This report aims to contribute to the limited data available on the use of non-TNF-α therapies, such as vedolizumab, in managing orofacial Crohn’s disease and to encourage further studies on its therapeutic role in this context.

Methods

This is a case report of a 68-year-old female with a 33-year history of ileo-colonic Crohn’s disease developed severe orofacial CD after infliximab discontinuation due to peri-prosthetic infection. She presented with severe vomiting, oral ulcerations, and diarrhea, along with ileal inflammation and gastric outlet obstruction. Physical examination revealed angular stomatitis and cobblestone ulcers in the buccal mucosa and palate. Histopathology confirmed CD with granulomatous inflammation. Initial treatment with dexamethasone mouthwash and budesonide showed minimal improvement. The patient was transitioned to vedolizumab, receiving three induction doses followed by monthly maintenance.

Results

Within two months of starting vedolizumab, the patient showed significant clinical and endoscopic improvement. By the fourth month, complete healing of the oral ulcerations was achieved, alongside resolution of her gastrointestinal symptoms, including gastric outlet obstruction. Vedolizumab was well-tolerated with no significant adverse effects reported.

Conclusions

This case demonstrates the potential efficacy of vedolizumab in treating orofacial Crohn’s disease, a rare and challenging presentation of Crohn’s disease. Nonetheless, vedolizumab binds to the α4β7 integrin, blocking its interaction with MAdCAM-1 on the surface of gastrointestinal endothelial cells (5). Since MAdCAM-1 is also expressed in the oral mucosa (4), we believe that vedolizumab may offer a promising alternative for patients with orofacial Crohn’s disease who do not respond to traditional therapies. Further studies are needed to establish its role in managing this condition

Funding Agencies

None
A229 THE ASSOCIATION OF MENTAL HEALTH DISORDERS WITH FATIGUE AND PHYSICAL ACTIVITY IN PERSONS WITH IBD
Authors: Dolovich C L , Chochinov S , Ly G , Oketola A , Narvey S , Larance S , Raman M , Webber S , Bernstein C N
Published: February 2025

Background

Fatigue is one of the most common symptoms among persons with inflammatory bowel disease (IBD) that impairs their quality of life. Fatigue acts as one of the greatest barriers of physical activity (PA) participation in adults with chronic disease, while PA is a strong contributor to improving fatigue symptoms.

Aims

The aim of this study was to assess the relationship between fatigue and PA in patients with IBD. A secondary aim was to assess the impact of mental health and disease activity on both PA and fatigue outcomes.

Methods

Participants from the University of Manitoba IBD Research Registry (n=2740) were invited to complete a cross-sectional survey to understand how persons with IBD experience PA and exercise. The international Physical Activity questionnaire (IPAQ) was used to define low vs. moderate/high levels of PA. The Modified Fatigue Impact Scale (MFIS) was used to define participants as Fatigued (MFIS ≥38) vs. non-fatigued (MFIS<38). Mental health and disease activity were defined based on Generalized Anxiety Disorders-7 (GAD), Patient Health Questionnaire (PHQ-9) and Inflammatory Bowel Disease Symptom Inventory (IBDSI). Descriptive statistics, bivariate and logistic regression analysis were used to assess the relationships defined in the aims.

Results

Among 1257 (46%) who completed the survey, there was 1075 (86%) and 1119 (89%) completed data for fatigue and PA, respectively. 93/706 (13%) of persons participated in low PA and were fatigued. Older patients were both less fatigued & less active than younger patients (median IQR: 62 (53-70) vs 60 (50-68), p=0.045). Nonactive to low physically active and high fatigued patients were more likely to have an education of high school degree or less (39% vs 25%, p<0.01), an income less than $50,000 (32% vs 14%, p<0.0001), not in a relationship (27% vs 17%, p<0.01), have an ostomy bag (14% vs 7%, p=0.02), and ever smoked (19% vs 6%, p<0.0001) compared to moderate/high physically active non-fatigued patients. The odds of low PA and high fatigue were greater for persons with anxiety [aOR 95%CI; 3.0 (1.2-7.2)], depression [23.5 (10.8-53.6)], and active disease [3.97 (1.9-8.3)].

Conclusions

Patients with IBD are more likely to be participating in low levels of PA & be fatigued when they have a lower education & income, not in a relationship, have an ostomy bag and are a current or previous smoker. The odds of low PA and fatigue are up to 23 times greater for persons with a mental health disorder. New insights on PA and fatigue provide an impetus for PA intervention as it may help alleviate fatigue symptoms and enhance quality of life among persons with IBD.

Funding Agencies

CAGn/a
A230 DEATH, MITOCHONDRIA, AND INFLAMMATION IN E. COLI-LF82 INFECTION
Authors: Mohan A , Wang A , McKay D , Shutt T E
Published: February 2025

Background

The Crohn’s disease-associated adherent invasive E. coli (AIEC) (strain LF82) decreases mitochondrial membrane potential and fragments the epithelial mitochondrial network. Other groups have also reported activation of NF-κB-mediated inflammation and generation of reactive oxygen species in AIEC-LF82 infected epithelia. It remains unclear how these findings integrate over the course of AIEC-LF82 infection and how they influence each other over the course of infection.

Aims

To characterize the sequence of events following AIEC-LF82 infection in a non-cancer derived epithelial cell model focusing on mitochondrial disruption, cell death, mtDNA release, and inflammatory gene expression.

Methods

The fetal derived human colon epithelial cell line (FHC) were infected with E. coli-LF82 or the commensal E. coli-HB101 at multiplicity of infection (MOI) of 100 or uninfected over the course of various experiments. FHCs were stained with SYTOX green and imaged on a CellCyte X system for 24h to measure cell death or stained with MitoTracker Deep Red and imaged on a spinning disc-confocal microscope for 16h to assess mitochondrial morphology. Also, in fixed-cell preparations mitochondrial networks were imaged by staining with anti-TOMM20 antibodies. Imaging of cytosolic DNA was performed via immunofluorescent staining of mtDNA and the mitochondrial network. As markers of inflammation, CXCL10 and IL-6 mRNA were assessed via qRT-PCR.

Results

Epithelia infected with E. coli-LF82 but not E. coli-HB101 displayed dramatic fragmentation of their mitochondrial network at 6h (p < 0.0001) (n=6), while SYTOX green imaging revealed significant cell death beginning at 9h (p < 0.001) (n=3). Furthermore, our preliminary data indicates that transcription of inflammatory cytokines including CXCL10, and IL-6 occurs at 8h while cytosolic escape of mtDNA occurs at 6h, after mitochondrial network disruption, but prior to cell death.

Conclusions

The data begins to unravel the sequence of events in a non-cancer derived epithelium after infection with E. coli-LF82, integrating mitochondrial function, inflammatory gene expression, and cell viability and providing a more fulsome understanding of the course of E. coli-LF82 infection. Together, these data advance understanding of relationship between mitochondrial fragmentation and cell death in the context of a Crohn’s disease-relevant pathobiont, AIEC-LF82.

Funding Agencies

TRIANGLE
A231 SINGLE GUIDEWIRE MAIN PANCREATIC DUCT CANNULATION AS A RISK FACTOR FOR POST-ERCP PANCREATITIS: FINDINGS FROM A MULTI-CENTER PROSPECTIVE ENDOSCOPY REGISTRY
Authors: Gupta M , Chau M , Howarth M , Cartwright S , Ficaccio S , Elmunzer B J , Forbes N
Published: February 2025

Background

Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) remains a relatively common adverse event. Though multiple cannulations of the main pancreatic duct (PD) are a known risk factor for PEP, the impact of a single cannulation of the main PD remains controversial.

Aims

Given the importance of identifying those at risk for PEP, especially in light of the growing evidence for preventative interventions such as PD stenting, we aimed to identify if single PD cannulation is a risk factor for PEP.

Methods

We analyzed data from a multi-center, prospective registry collected from 2018-2024 with associated protocolized 30-day follow-up for patients undergoing ERCP for any biliary indication. PEP was defined as recurrent admission or prolongation of existing admission due to the development of characteristic abdominal pain occurring after ERCP with pancreatic enzyme elevation >3 times the upper limit of normal at least 1-day post ERCP and/or imaging findings characteristic of pancreatitis. The association of single PD cannulation and PEP was evaluated with multivariable logistic regression utilizing known risk factors and preventive interventions as covariates. Results were reported as odds ratios (OR) with associated 95% confidence intervals.

Results

PEP complicated 287 (3.8%) of the 7,479 ERCPs studied. Single main PD cannulation (OR 2.14, 1.45-3.12), and multiple main PD cannulation (OR 2.58,1.76-3.76), were independent risk factors for PEP in all comers. This trend was also maintained in those with native papilla for single PD (OR 2.20, 1.43-3.24) and multiple PD (OR 2.50, 1.65-3.77) cannulations. Single main PD cannulation to both the pancreatic head (OR 1.89, 1.02-3.30) and the pancreatic body (OR 2.61, 1.44-4.57) were associated with PEP compared to no main PD cannulation. Further, a trend towards increased risk with any number of side PD cannulations (OR 1.15, 0.63-2.00) was seen, though these analyses were likely underpowered.

Conclusions

Single main PD duct canulation, to the pancreatic head or body, represents an independent risk factor for PEP in this analysis. Additionally, there appears to be additive risk associated with multiple main PD cannulations and deeper main PD cannulations. These results highlight the risk of any degree of PD cannulation, supporting the potential utility of routine preventative interventions, such as PD stenting in these cases.

Funding Agencies

None
A236 BOTH METABOLIC UNHEALTHINESS AND OBESITY ARE REQUIRED TO INCREASE GALLSTONE DISEASE RISK: A LARGE-SCALE CROSS-SECTIONAL STUDY
Authors: Baeg M , Ko S
Published: February 2025

Background

Obesity and metabolic unhealthiness are well-known risk factors of gallstones. However, as obesity and metabolic health are closely related, it is difficult to differentiate its effects.

Aims

The aim of our study was to investigate the relationship between metabolic health status, obesity, and gallstone disease.

Methods

We performed a retrospective cross-sectional study of subjects undergoing health screening at a university hospital. Subjects with abdominal ultrasonography and fasting insulin results were included. Subjects were classified into 4 groups based on metabolic and obesity criteria: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUNO), and metabolically unhealthy obese (MUO). Gallstone disease was defined as those with gallstones on ultrasonography or a history of cholecystectomy. Multivariable analysis was used to identify gallstone disease risk factors with MHNO subjects as reference.

Results

We included 12,052 subjects (6,014 MHNO, 1,662 MHO, 2,211 MUNO, 2,165 MUO). There were 568 subjects with gallstones and 241 with prior cholecystectomy history. The prevalence of gallstone disease was 5.5% in MHNO, 7.1% in MHO, 7.2% in MUNO, and 9.2% in MUO. Gallstone disease risk was significantly increased in the MUO group (OR 1.449, 95% CI 1.198-1.752, P<0.001). but showed only a tendency in the MHO group (OR, 1.219, 95% CI, 0.976–1.522, P=0.080) and was insignificant in the MUNO group (OR, 0.989, 95% CI, 0.808–1.211, P=0.917). Older age significantly increased gallstone disease risk, but alcohol consumption was protective. When metabolic unhealthiness and obesity were analyzed separately, obesity significantly increased gallstone disease risk while metabolic unhealthiness did not.

Conclusions

We demonstrated that gallstone disease risk was significantly increased only in those with both metabolic unhealthiness and obesity.

Funding Agencies

None
A239 PERFORMANCE OF CLINICAL RISK PREDICTION MODELS FOR POST-ERCP PANCREATITIS: A SYSTEMATIC REVIEW
Authors: Sabrie N , Minahs G , Vaska M , Meng Z W , Brenner D , Forbes N
Published: February 2025

Background

Pancreatitis is common following endoscopic retrograde cholangiopancreatography (ERCP). Despite increased vigilance of post-ERCP pancreatitis (PEP), both its incidence and associated mortality are rising. Risk prediction models may provide more accurate stratification of patient risk and proactive mitigation of PEP incidence and/or severe associated outcomes.

Aims

We aimed to systematically review and summarize the available literature on PEP risk prediction models and their respective peformance.

Methods

We conducted an electronic search of MEDLINE, PubMEd, Cochrane, and CINAHL from inception through April 9, 2024 for studies evaluating the details and performances of available PEP prediction models. Studies were eligible if they used statistical measures to quantify their model’s predictive ability. Risk of bias was determined using the PROBAST tool.

Results

Nineteen studies met eligibility criteria and were included. Logistic regression models were used in 15 studies, with machine learning models representing the second most commonly employed approach. Ten studies reported the performance of their risk prediction models using derivation data, with areas under the receiver operating curve (AUC) ranging from 0.68 to 0.86. Fifteen studies reported the performance of their risk prediction models on internally validated data, with AUCs ranging from 0.66 to 0.97. Eight studies reported on the performance of their risk prediction models on external validation data, with AUCs ranging from 0.67 to 0.98.

Conclusions

Numerous PEP clinical prediction models exist with variable performances. The use of PEP prediction tools can support the management of patients following ERCP. Implementation studies assessing the optimal usability of these tools, followed by prospective evaluations, are needed to evaluate their potential impacts on reducing PEP in real-world practice.

Table 2. Summary of methods used to inform post-ERCP pancreatitis prediction models.

Funding Agencies

None
A241 AMOXICILLIN-CLAVULANATE INDUCED LIVER INJURY WITH CONCOMITANT AMPULLARY STENOSIS: A CASE REPORT AND LITERATURE REVIEW
Authors: Kecskemeti K , Gibbings N , Fung S
Published: February 2025

Background

Amoxicillin-clavulanate drug-induced liver injury (DILI) has been reported at a rate of 1 in 2,400 prescriptions1. Patients tend to present with a cholestatic pattern of liver enzyme elevation while hepatocellular enzyme elevation is more commonly reported in younger patients. In mild cases, once amoxicillin-clavulanate is discontinued the patient’s recovery tends to be rapid.

Aims

We present a patient case and a literature review regarding concomitant ampullary stenosis and amoxicillin-clavulanate induced liver injury.

Methods

We present a case report outlining a patient’s course and management in hospital. We then conducted a literature review on Pub-Med using the following terms: “ampulla stenosis” and “drug-induced liver injury”.

Results

A 56-year-old female with a remote history of a cholecystectomy was prescribed amoxicillin-clavulanate for suspected diverticulitis. She completed a 5-day course and then represented with worsening abdominal pain. She was found to have significant transaminitis with a mixed cholestatic-hepatocellular pattern (ALT 726, AST 351, ALP 289). She underwent an MRCP which showed extensive extrahepatic and intrahepatic biliary duct dilations which was disproportionate to expected post-cholecystectomy changes and suggestive of ampullary stenosis. Amoxicillin-clavulanate was discontinued on admission and her liver enzymes normalized as an out-patient three weeks after admission (ALT 34, ALP 125). She was referred for outpatient endoscopic ultrasound for assessment and treatment of her ampullary stenosis.

The literature review on PubMed yielded a single case report (n = 1) of a patient with atorvastatin induced liver injury and underlying ampullary stenosis2. In that case, the patient improved when the medication was discontinued and then underwent a sphincterotomy.

Conclusions

Although seldomly reported in the medical literature there is one other case report of concomitant drug-induced liver injury in a patient with ampullary stenosis. To our knowledge, this is the first case report of amoxicillin-clavulanate induced liver injury in a patient with ampullary stenosis. Potential mechanisms may include ampullary stenosis related biliary stasis which may exacerbate the toxic effects of medications on the liver.

Patient’s Biochemical Investigations in Hospital

Note: AST was not measured on July 30th. INR was not recorded during the patient’s hospitalization

Funding Agencies

NoneN/A
A242 SCLEROSING MESENTERITIS OF THE PORTA HEPATIS PRESENTING AS CHOLANGIOCARCINOMA WITH RECURRENT CHYLOUS ASCITES AND GASTRIC OUTLET OBSTRUCTION
Authors: Hoang T T , Karavelic A , Sunil A , Murray T , Telford J , Clement E , Gador A
Published: February 2025

Background

Sclerosing mesenteritis (SM) is characterized by chronic fibroinflammatory infiltration of the abdominal mesentery. While commonly affecting the small bowel, we present the first reported case of SM mimicking hilar cholangiocarcinoma by involving the porta hepatis, resulting in chylous ascites, gastric outlet obstruction, and duodenal perforation.

Aims

To broaden recognition of this rare disease and expand literature on treatment options

Methods

Case report and literature review

Results

A 59-year-old man with previous alcoholic pancreatitis presented with one month of progressive abdominal pain and distension. He was found to have large volume chylous ascites and a hilar mass on computed tomography scan. Magnetic resonance cholangiopancreatography confirmed a soft tissue density at the porta hepatis with intra- and extrahepatic duct dilation. Endoscopic ultrasound (EUS) revealed a soft tissue mass and biopsies showed a chronic lymphohistiocytic infiltrate but no malignancy. Positron emission tomography, liver biopsy, and bidirectional endoscopy were unrevealing. Serial large-volume paracenteses were performed for comfort, though portal hypertension was ruled out via transjugular measurements. One month into hospitalization, he developed gastric outlet obstruction from extrinsic mass and required nasojejunal feeding. This was complicated by a contained duodenal perforation managed non-operatively. Palliative dexamethasone was started for presumed cholangiocarcinoma which entirely resolved his symptoms. He was discharged after three months but represented off steroids with recurrent ascites and gastric outlet obstruction. Diagnostic laparoscopy was negative. EUS-guided biopsy again showed the same chronic inflammatory infiltrate. He was diagnosed with SM and started on oral prednisone which resolved his symptoms. He remains in remission as an outpatient on colchicine, tamoxifen, and low-dose prednisone.

Conclusions

SM is a rare disease characterized by chronic mesenteric inflammation, fibrosis, and fat necrosis. While 10% of cases are incidental findings, complications occur in 24% of patients and include recurrent chylous ascites, small bowel obstruction, and intestinal perforation. Diagnosis is challenging given non-specific findings but can be made on histology and radiology. This benign disease is often mistaken for malignancy, resulting in unnecessary diagnostic tests. To our knowledge, this is only the second reported case of hilar SM, and the first to present with the aforementioned complications. Treatment includes prednisone and tamoxifen, with colchicine, azathioprine, or thalidomide used as steroid-sparing agents. Increased recognition of this entity will help avoid unnecessary diagnostic interventions and inform options for medical therapy.

Funding Agencies

None
A247 ACTIVATION OF VISCERAL AFFERENT NEURONS INVOLVED IN NOCICEPTION BY A BACTERIUM ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE
Authors: Nakhle R , Wood H M , Baker C C , Reed D E , Lomax A E
Published: February 2025

Background

Inflammatory bowel disease (IBD) is characterized by chronic relapsing inflammation of the gastrointestinal tract. Severe abdominal pain is a common symptom of IBD, yet effective pain treatments are limited. Proteolytic activity is elevated in IBD compared to healthy individuals. Recently, protease production by the gut bacterium Bacteroides vulgatus has been correlated with the severity of IBD.

Aims

Since proteases acting on protease-activated receptor 2 (PAR-2) can activate visceral pain pathways, we test the hypothesis that mediators from B. vulgatus activate visceral pain pathways and can directly activate dorsal root ganglia (DRG) neurons, altering pain signalling.

Methods

The effects of B. vulgatus ATCC 8482 supernatant or brain heart infusion (BHI) growth media on nociceptive neurons were assessed using ex-vivo single-unit afferent nerve recordings from C57bl/6 mouse colons. To further examine cellular mechanisms, Ca2+ imaging was performed on dissociated DRG neurons following the superfusion of B. vulgatus culture supernatant. As TRPV1 is an ion channel expressed mainly on nociceptive neurons, the effect of B vulgatus culture supernatant on Ca2+ influx in response to the TRPV1 agonist capsaicin was also quantified. “N” represents mice, while “n” represents single afferent units or DRG neurons.

Results

Perfusion of B. vulgatus supernatant (1:20) through the lumen of murine colons significantly increased basal firing frequency by 50% (p < 0.001, N = 8, n = 38) and mechanosensitivity of colonic afferent axons by 48% (p < 0.05, N = 8). Interestingly, only the putative nociceptor high-threshold units were activated upon perfusion of this bacterial supernatant (p < 0.01, N = 8, n = 13), while the wide-dynamic range units were unaffected (p > 0.05, N = 8, n = 30). The BHI growth media did not alter basal activity (p > 0.05, N = 6, n = 23) or afferent nerve mechanosensitivity (p > 0.05, N = 6). Superfusion of B. vulgatus supernatant (1:100) increased intracellular [Ca2+] by 16% (p < 0.0001, N= 7, n = 51). Furthermore, exposure to the B. vulgatus supernatant significantly elevated Ca2+ influx in response to the TRPV1 agonist capsaicin (100 nM; p < 0.0001, n = 77, N = 7), while the BHI media did not alter intracellular [Ca2+] in response to capsaicin (p > 0.05, n = 66, N = 7).

Conclusions

Mediators released by Bacteroides vulgatus can activate visceral afferent nerves involved in nociception. Additionally, B. vulgatus can directly modulate DRG neuronal Ca2+ homeostasis and sensitize TRPV1 in these neurons. Future studies will explore whether proteases are responsible.

Funding Agencies

CIHR
A249 PROTON PUMP INHIBITOR USE AND RISK OF DEMENTIA: AN UMBRELLA REVIEW OF SYSTEMATIC REVIEWS AND META-ANALYSES
Authors: Abu-Mallouh B E , Al-Naamani K , Martel M , Barkun A
Published: February 2025

Background

Clinical studies about the association between long term PPI use and dementia have been inconsistent, with systematic reviews and meta-analyses (SR/MA) reaching disparate conclusions.

Aims

This umbrella review of SR/MA attempts to clarify the current understanding of any possible association linking PPI use to dementia.

Methods

We searched Embase, Medline, CENTRAL and ISI Web of Science for fully published SR/MA in English up to June 2024 using controlled vocabulary and text words ((1) proton pump and (2) dementia (dementia and mild cognitive impairment, Alzheimer disease)). SR/MA methodological quality was scored using the AMSTAR-2 tool.

Results

Eleven SR/MA published (May 2016 - February 2023) described 21 studies (one randomized trial). Only one high-quality SR/MA significantly associated PPI use with dementia. None of six SR/MA investigating PPI use and Alzheimer’s disease showed a significant association. Significant associations with dementia in subgroup analyses were found in one SR/MA each for older patients (age > 65 years) (HR=1.39 (1.17;1.65)), long term PPI use (> 5 years) (HR=1.28 (1.12; 1.46)), short term PPI use (< 5 years) (RR=1.62 (1.40–1.86)), when only considering higher quality studies (RR=1.54 (1.12; 2.13)), and amongst European populations (HR=1.46 (1.23–1.73)). Two SR/MA found an association when only assessing prospective cohort studies (RR=1.36 (1.19; 1.55)), (RR=1.44 (1.36; 1.52)).

Conclusions

Most SR/MA suggest no link between PPI use and dementia. Only properly designed, adequately powered randomized trials can rule out a small but significant association possibly linking PPI use to dementia.

N = study number in SR/MA, HR = hazards ratio, RR = relative risk, OR = odds ratio, NA = Not applicable

Funding Agencies

None
A251 EOSINOPHILIC ESOPHAGITIS IN AN END-STAGE ACHALASIA PATIENT
Authors: Pan S , Woodman K
Published: February 2025

Background

Achalasia is a rare motility disorder involving abnormal esophageal motility and impaired lower esophageal sphincter relaxation. A growing number of reports have identified esophageal eosinophilia levels consistent with eosinophilic esophagitis (EoE) in achalasia patients, suggesting a possible pathophysiological association between both conditions that may yield clinical significance for diagnosis and treatment.

Aims

The aim of the present report is to highlight this association, through the case of a Type 1 Achalasia patient whose mid-esophageal biopsies were significant for concurrent EoE.

Methods

The case and its associated figures were compiled from the patient’s medical records following informed consent.

Results

A 38-year-old gentleman was referred to our motility service for manometric assessment. The patient suffered from a 4-5 year history of persistent, progressively worsening dysphagia, recurrent regurgitation and weight loss. Endoscopic assessment prior to assessment by our service was significant for EoE. Manometry patterns were consistent with Type 1 achalasia, though it was unclear whether this had developed prior to or after the patient’s EoE. The patient’s symptoms continued to progress in the months after his achalasia diagnosis, despite proton pump inhibitor therapy, steroid therapy and an elimination diet. He was ultimately referred to the General Surgery service in Hamilton, Ontario for completion of a Heller Myotomy. The post-operative course was uncomplicated, and he was able to return to an oral diet shortly afterwards, with some lingering dyspepsia but no further dysphagia or regurgitative symptoms.

Conclusions

The present case supports pre-existing reports in the literature that achasia and EoE can happen concurrently, and that a pathophysiological correlation may be involved, notably regarding the inflammatory processes in EoE and how they might contribute to esophageal neuronal damage. Continued research is needed to better understand this relationship.

Esophageal pressure topography plots taken from high-resolution manometry performed on April 18, 2023, representing the average pressure patterns of successful swallows during the endoscopic procedure. Highlighted is the relaxation of the upper esophageal sphincter during initiation of the swallow (A), along with the absence of peristaltic pressures along the length of the esophagus (B) in the setting of incomplete deglutitive relaxation of the lower esophageal sphincter (C), consistent with type 1 achalasia.

Funding Agencies

None
Mechanisms and Manifestations of Group B Streptococcus Meningitis in Newborns
Authors: Alexander Natalie G , Cutts William D , Hooven Thomas A , Kim Brandon J
Published: February 2025

Group B Streptococcus (GBS; Streptococcus agalactiae) is a gram-positive colonizer of the healthy intestinal and genitourinary microbiota. During and shortly after birth, neonates and infants can be opportunistically infected leading to sepsis, pneumonia, or meningitis among other illnesses. GBS is the leading cause of neonatal meningitis globally, and while prophylactic treatments have been successful for reducing early-onset disease, no decrease in the incidence of late-onset disease has occurred and no vaccine is currently available. In this review, we describe GBS both from a clinical and molecular standpoint. We first describe the history of GBS perinatal disease and its clinical presentation and treatment, as well as patient outcomes. We then present recently discovered GBS interactions at the blood–brain barrier that contribute to disease and inflammatory responses, and efforts to develop a broadly effective GBS vaccine.
Configuration of single giant planet systems generating ‘Oumuamua-like interstellar asteroids
Authors: Zheng Xi-Ling , Zhou Ji-Lin
Published: February 2025

The first discovered interstellar small object, ‘Oumuamua (1I/2017 U1), presents unique physical properties of extremely elongated geometric shape and dual characteristics of an asteroid and a comet. These properties suggest a possible origin through tidal fragmentation, which posits that ‘Oumuamua was produced through intensive tidal fragmentation during a close encounter with a star or a white dwarf, resulting in its shape and ejection from its natal system. According to this mechanism, a high initial orbit eccentricity and a small pericentre of the parent body are necessary to produce ‘Oumuamua-like objects. To verify whether this mechanism can occur in single giant planet systems, we conduct long-term numerical simulations of systems with a low-mass ($0.5\,M_\odot$) host star and a giant planet in this study. We determine that an eccentric orbit ($e_\text{p}\sim 0.2$) and a Jupiter-mass ($M_\text{p}\sim M_\text{J}$) of the planet appears to be optimal to generate sufficient perturbations for the production of ‘Oumuamua-like objects. When the planetary semi-major axis $a_\text{p}$ increases, the proportion of planetesimals ejected beyond the system $P(\text{ej})$ increases accordingly, while the possibilities of ejected planetesimals undergoing stellar tidal fragmentation $P(\text{tidal}|\text{ej})$ remains relatively constant at $\sim 0.6~{{\ \rm per\ cent}}$. Focusing on stellar tidal fragmentation alone, the ratio of extremely elongated interstellar objects to all interstellar objects is $P_\text{e}\sim 3~{{\ \rm per\ cent}}$.
On the origin of metal species in the human brain: a perspective on key physicochemical properties
Authors: Brooks Jake , Everett James , Sadler Peter J , Telling Neil , Collingwood Joanna F
Published: February 2025

Normal functioning of the human brain is dependent on adequate regulation of essential metal nutrients. However, it is also highly sensitive to metal-mediated toxicity, linked to various neurodegenerative disorders. Exposure to environmental metal sources (especially to particulate air pollution) can stimulate toxicity and neuropathologic effects, which is particularly evident in populations chronically exposed to high levels of air pollution. Identifying the sources of metal-rich deposits in the human brain is important in not only distinguishing the effects of environmentally-acquired metals from endogenous metal dysregulation, but also for tracing pollutant sources which may be subject to exposure control. This perspective reviews evidence for key physicochemical properties (size/morphology, chemical composition, oxidation state, magnetic properties and isotopic composition) concerning their capacity to distinguish sources of metals in the brain. The scope for combining analytical techniques to study properties in tandem is also discussed.
Plant PI-PLC signaling in stress and development
Authors: Laxalt Ana M , van Hooren Max , Munnik Teun
Published: February 2025

Phosphoinositide-specific phospholipase C (PI-PLC) signaling is involved in various plant stress and developmental responses. Though several aspects of this lipid signaling pathway are conserved within animals and plants, clear differences have also emerged. While animal PLC signaling is characterized by the hydrolysis of PIP2 and production of IP3 and DAG as second messengers to activate Ca2+ and PKC signaling, plant PI-PLCs seem to predominantly use PIP as substrate and convert IP2 and DAG into inositolpolyphosphates and phosphatidic acid (PA) as plant second messengers. Sequencing of multiple plant genomes confirmed that plant PLC signaling evolved differently from animals, lacking homologs of the IP3 gated-Ca2+ channel, PKC and TRP channels, and with PLC enzymes resembling the PLCζ subfamily, which lacks the conserved PH domain that binds PIP2. With emerging tools in plant molecular biology, data analyses, and advanced imaging, plant PLC signaling is ready to gain momentum.
Ceramide-1-phosphate enhances defense responses against Sclerotinia sclerotiorum in Brassica napus
Authors: Ouyang Zhewen , Tan Zengdong , Ali Usman , Zhang Ying , Li Bo , Yao Xuan , Yang Bao , Guo Liang
Published: February 2025

Sclerotinia stem rot caused by Sclerotinia sclerotiorum is one of the most severe diseases affecting the growth and production of Brassica napus. Sphingolipid metabolism plays a crucial role in plant response to pathogens. In this study, we show that ceramide kinase (CERK) is significantly induced during S. sclerotiorum infection to produce higher levels of ceramide-1-phosphate (C1P) in B. napus. The balance between ceramide (Cer) and C1P affects plant resistance to S. sclerotiorum, with CERK mutant lines exhibiting greater susceptibility to S. sclerotiorum and CERK overexpression lines showing enhanced resistance to this pathogen. Moreover, we identified candidate C1P-binding proteins by proteomic analysis and determined that C1P binds to and promotes the activity of a Gly–Asp–Ser–Leu lipase protein involved in B. napus resistance to S. sclerotiorum infection. In conclusion, our results indicate that C1P plays a key role in S. sclerotiorum resistance through metabolic regulation and signal transduction in B. napus.
Three Xanthomonas Cell Wall Degrading Enzymes and Sorghum Brown midrib 12 Contribute to Virulence and Resistance in the Bacterial Leaf Streak Pathosystem
Authors: Wang Qi , Veley Kira , Johnson Joshua M. B. , Sumner Josh , van Erven Gijs , Kabel Mirjam A. , Dhungana Singha , Berry Jeffrey , Boyher Adam , Braun David M. , Vermerris Wilfred , Bart Rebecca S.
Published: February 2025

With an increasing demand for renewable fuels, bioenergy crops are being developed with high sugar content and altered cell walls to improve processing efficiency. These traits may have unintended consequences for plant disease resistance. Xanthomonas vasicola pv. holcicola (Xvh), the causal agent of sorghum bacterial leaf streak, is a wide-spread bacterial pathogen. Here, we show that Xvh expresses several bacterial cell wall degrading enzymes (CWDEs) during sorghum infection, and these are required for full virulence. In tolerant sorghum, Xvh infection results in induction of a key enzyme in monolignol biosynthesis, Brown midrib 12 (Bmr12), but this did not affect lignin content nor composition. Mutation of Bmr12 rendered the tolerant genotype susceptible. Bmr12 encodes caffeic acid O-methyltransferase (COMT), an enzyme that generates sinapaldehyde as its major product. Growth inhibition of Xvh in the presence of sinapaldehyde was observed in vitro. We conclude that mutations that alter the components of the sorghum cell wall can reduce sorghum resistance to Xvh and that Xvh CWDEs contribute to bacterial virulence. Given the enhanced bioprocessing characteristics of bmr12 sorghum, these results provide a cautionary tale for current and future efforts aimed at developing dedicated bioenergy crops.
Development and Validation of a Machine Learning Prediction Model for Textbook Outcome in Liver Surgery: Results From a Multicenter, International Cohort
Authors: Wang Jane , Ashraf Ganjouei Amir , Hibi Taizo , Lluis Nuria , Gomes Camilla , Romero-Hernandez Fernanda , Yin Han , Calthorpe Lucia , Okamura Yukiyasu , Abe Yuta , Tanaka Shogo , Tanabe Minoru , Morise Zeniche , Asbun Horacio , Geller David , Abu Hilal Mohammed , Adam Mohamed , Alseidi Adnan ,   International Hepatectomy Study Group
Published: February 2025

Objective:

This study aimed to (1) develop a machine learning (ML) model that predicts the textbook outcome in liver surgery (TOLS) using preoperative variables and (2) validate the TOLS criteria by determining whether TOLS is associated with long-term survival after hepatectomy.

Background:

Textbook outcome is a composite measure that combines several favorable outcomes into a single metric and represents the optimal postoperative course. Recently, an expert panel of surgeons proposed a Delphi consensus-based definition of TOLS.

Methods:

Adult patients who underwent hepatectomies were identified from a multicenter, international cohort (2010–2022). After data preprocessing and train-test splitting (80:20), 4 models for predicting TOLS were trained and tested. Following model optimization, the performance of the models was evaluated using receiver operating characteristic curves, and a web-based calculator was developed. In addition, a multivariable Cox proportional hazards analysis was conducted to determine the association between TOLS and overall survival (OS).

Results:

A total of 2059 patients were included, with 62.8% meeting the criteria for TOLS. The XGBoost model, which had the best performance with an area under the curve of 0.73, was chosen for the web-based calculator. The most predictive variables for having TOLS were a minimally invasive approach, fewer lesions, lower Charlson Comorbidity Index, lower preoperative creatinine levels, and smaller lesions. In the multivariable analysis, having TOLS was associated with improved OS (hazard ratio = 0.82, P = 0.015).

Conclusions:

Our ML model can predict TOLS with acceptable discrimination. We validated the TOLS criteria by demonstrating a significant association with improved OS, thus supporting their use in informing patient care.