bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality and morbidity after transcatheter aortic valve implantation compared to an age- and sex-matched control population: a population-based study from the SWEDEHEART registry
Authors: Lachonius Maria , Nielsen Susanne J , Giang Kok Wai , Backes Jenny , Bjursten Henrik , Hagström Henrik , James Stefan , Settergren Magnus , Skoglund Kristofer , Jeppsson Anders , Pétursson Pétur 
Published: February 2025

Abstract

Introduction
Data are lacking about the risk for death and major adverse cardiovascular events (MACE) after transcatheter aortic valve implantation (TAVI), compared to the general population. Therefore, we assessed the risk for all-cause death and MACE after TAVI in patients aged 65 years and older, in comparison to an age- and sex-matched control population.

Methods
In total, 5 924 TAVI patients and 10 928 matched controls (mean age 82.1, SD 6.0, and 81.9, SD 6.1, respectively) were included from 2014 to 2020. The SWEDEHEART registry and four mandatory national registers were used to collect data. Cox regression models were used to assess the association with all-cause mortality and MACE risk.

Results
In total, 1 410 (23.8%) of the TAVI patients and 2 115 (19.4%) controls died during the follow-up period. Median follow-up was 1.9 years (IQR 0.9–3.3) respectively. The crude mortality and MACE risks were higher in TAVI patients than in controls (hazard ratios (HR) 1.27 [95% Confidence interval (CI): 1.19–1.36] and HR 1.44 [95% CI: 1.35–1.53], respectively). After adjustment, there was a lower risk for both mortality and MACE in TAVI patients (adjusted hazard ratio (aHR) 0.77 [95% CI: 0.71–0.84] and aHR 0.90 [95% CI: 0.83–0.98], respectively).

Conclusion
After adjustments for comorbidities, the mortality risk was lower in TAVI patients, compared with an age- and sex-matched control population. These findings suggest that the high burden of comorbidities in TAVI patients has a strong impact on the risk for mortality and MACE after TAVI.
A111 EVALUATION OF REFERRAL COMPLETENESS FOR LARGE NON-PEDUNCULATED POLYPS IN LIGHT OF RECENT INTERNATIONAL CONSENSUS: A SINGLE-CENTER STUDY
Authors: Alabdulkarim B , Khalaf K , May G , Mosko J , Teshima C 
Published: February 2025

Abstract

Background
Endoscopic mucosal resection (EMR) is standard-of-care for treating large non-pedunculated colorectal polyps yet often requires referral to expert centers. Hence, inclusion of important information to the therapeutic endoscopist is essential for pre-procedure planning. A recent international consensus statement, comprised of 19 components, aims to improve triage and planning of endoscopic resection for large non-pedunculated colorectal polyps. We sought to determine the current status of inclusion of these reporting elements in referrals to our tertiary center.

Aims
1- Report the rate of complete referrals in light of the international expert consensus statement
2- Investigate the degree of correlation of polyp adjudication between referring endoscopist and local advance therapeutic endoscopiest assessment
3- Explore factors predicting comprehensive reporting

Methods
Single-center review of prospectively collected colorectal polyp referrals for large non-pedunculated polyps from March 2021 to March 2023.

Results
411 referrals for large polyps were received; median size 3 cm; 58% located in ascending colon. 89 % of referrals included the initial assessment date, and only 38% incorporated video or photo documentation, of which 44% were deemed sufficient to demonstrate polyp features. Anatomical location was reported in 96% of referrals, while polyp size was mentioned in only half of the referrals (50%). Polyp morphology was described in 91% as either sessile (n=360) or pedunculated (n=35). Paris classification was reported in 53% of referrals, and LST classification in 90%. 12% of referrals reported four elements of less, while 18% of referrals reported all elements. Correlations with our own endoscopic assessments were diverse, ranging from a robust correlation for anatomical location (r=0.82, 95%CI 0.78-0.86, p &lt; 0.001) to a more modest correlation for Paris classification (r=0.44, 95%CI 0.35-0.52 p &lt; 0.001).

Conclusions
Our study reveals deficiencies in current referral practices and emphasizes the consensus statement’s role in improving the process. Consequences of low-quality referrals may include compromised patient care, leading to delayed diagnoses, inappropriate treatments, and potentially compromised patient outcomes. Thus, we have identified a likely knowledge gap in polyp characterization among referring physicians that will be a focus of a subsequent QI initiative.

Funding Agencies
None
A117 EXPECT THE UNEXPECTED. UNUSUAL PATHOLOGY FINDINGS FROM ROUTINE POLYPECTOMY. A REVIEW OF SUBMUCOSAL GI LESIONS
Authors: Adesina O 
Published: February 2025

Abstract

Background
Granular cell tumours (GCTs) are rare benign submucosal neoplasms. They most commonly arise from neural or Schwann cells. While GCTs are frequently encountered in the oral cavity, skin, and breast, gastrointestinal involvement remains a clinical rarity. This case series highlights the incidental detection of GCTs during routine colonoscopy. In this setting, we provide insights into the diagnostic challenges and management approaches for such submucosal lesions.

Aims
To present a case series of two patients with incidentally discovered GCTs during routine colonoscopy, discuss the diagnostic and management strategies for GCTs, and offer a review of current literature with implications for clinical practice.

Methods
We present two cases of GCTs identified during routine colonoscopic polypectomy. The clinical presentations, diagnostic processes, and management strategies were analyzed using the existing literature. Particular focus was given to the challenges of identifying submucosal lesions in the gastrointestinal tract and determining appropriate follow-up care based on histopathological findings.

Results
The first case is a 75-year-old man who underwent a colonoscopy after a positive fecal immunochemical test (FIT), with normal physical and laboratory findings. Multiple polyps were identified, and histopathology confirmed a GCT in the cecum. The patient was asymptomatic, and a surveillance colonoscopy was scheduled.
The second case is a 74-year-old woman who was referred to gastroenterology after a positive FIT. She was asymptomatic, with normal physical and laboratory findings. Initial colonoscopy revealed two resected polyps. A follow-up colonoscopy a year later identified three additional polyps, one of which was a GCT. Surveillance colonoscopy was advised in four years.
GCTs of the gastrointestinal tract are rare, most commonly found in the distal esophagus (about 60%). Typically submucosal, they rarely invade the mucosa or muscularis propria. Other notable subepithelial lesions include gastrointestinal stromal tumours (GISTs), leiomyomas, lipomas, ectopic pancreatic tissue, and neuroendocrine tumours. Unlike GCTs, GISTs and leiomyosarcomas are more often malignant. Endoscopic, radiologic, and endosonographic assessments assist in the risk stratification of subepithelial lesions, with one study demonstrating these features having a 92.9% specificity for detecting GISTs. Histology remains crucial for confirmation of diagnosis. Management of benign GCTs may involve endoscopic resection or surveillance, whereas malignant cases may require more extensive treatment, including adjuvant chemotherapy or radiotherapy.

Conclusions
GCTs are rare findings in gastrointestinal pathology. Treatment involves resection or close surveillance. Further research is needed to refine optimal diagnostic and therapeutic approaches for these uncommon neoplasms.

Funding Agencies
None
A118 DE NOVO CROHN’S DISEASE FOLLOWING ORTHOTOPIC LIVER TRANSPLANTATION IN A PATIENT WITH PRIMARY SCLEROSING CHOLANGITIS: A CASE REPORT
Authors: Bello A , Samad N 
Published: February 2025

Abstract

Background
Primary sclerosing cholangitis (PSC) is strongly associated with inflammatory bowel disease (IBD), most commonly ulcerative colitis, with up to 80% of PSC patients developing IBD during their lifetime. However, the development of de novo Crohn’s disease following orthotopic liver transplantation (OLT) is rare, complicating both immunosuppressive management and long-term patient outcomes.

Aims
The aim of this study is to report a rare case of de novo Crohn’s disease post-OLT in a PSC patient, exploring their presentation, the role of tacrolimus in its development and highlighting successful management with vedolizumab.

Methods
We conducted a retrospective case analysis of a 44-year-old female patient who underwent OLT in 2021 for PSC-related decompensated cirrhosis. Prior to the transplant, the patient had no history of IBD, and a screening colonoscopy revealed normal colonic mucosa, although histological analysis indicated proctitis. Approximately two years post-OLT, while on the immunosuppresive agent tacrolimus, the patient developed new gastrointestinal symptoms, including abdominal pain, diarrhea, tenesmus, and nocturnal bowel movements. Diagnostic evaluation included endoscopic assessment and histopathological analysis of biopsy samples.

Results
Endoscopic examination revealed inflammation characterized by ileitis and left-sided colitis. Histopathology confirmed a diagnosis of de novo Crohn’s disease. The patient’s clinical course was complicated by the need to balance her immunosuppressive therapy with treatment for Crohn’s disease. Vedolizumab, a gut-selective biologic agent targeting the α4β7 integrin, was initiated alongside her existing immunosuppressive regimen. Over the course of treatment, the patient demonstrated significant clinical improvement, with a marked reduction in abdominal pain and diarrhea, as well as an overall improvement in quality of life.

Conclusions
The development of de novo Crohn’s disease in patients with PSC following OLT, though rare, presents a complex clinical challenge. Immunosuppressive agents, particularly tacrolimus, may play a contributory role in the pathogenesis of de novo IBD, though the precise mechanisms remain unclear. Early diagnosis and intervention with targeted therapies, such as vedolizumab, are critical in managing IBD in this population, as they allow for effective control of gastrointestinal inflammation while maintaining necessary immunosuppression. This case underscores the importance of vigilant surveillance in post-OLT patients to ensure timely intervention. Further research is warranted to elucidate the underlying risk factors and optimize therapeutic strategies for de novo IBD in the post-transplant setting, particularly in PSC patients who may be at increased risk.

Funding Agencies
None
A122 CHARACTERIZATION OF COLORECTAL NEOPLASIA IN PEOPLE WITH LYNCH SYNDROME
Authors: Al-Bayati K , Brar K , Rothenmund H , Chordiker B , Stone J , Kim C , Singh H 
Published: February 2025

Abstract

Background
Lynch syndrome (LS) is an autosomal dominant condition that is associated with germline variants in the MLH1, MSH2, MSH6, or PMS2 genes or a deletion in the EpCAM gene which inactivates MSH2. LS is the most common cause of hereditary colorectal cancer (CRC), accounting for 3% of all new diagnoses. In 2017, Manitoba implemented an initiative where all CRC biopsy and surgical specimens for patients ≤ 70 years of age are screened for LS through mismatch repair immunochemistry. If confirmed to have LS, cascade testing is offered, and systematic evidence-based screening is recommended. Recent hypotheses suggest alternative pathways of development of CRC in LS, with variation by affected gene. Guidelines recommend delaying onset of screening colonoscopy to age 30-35 for those with MSH6 and PMS2 mutations. However, there are limited contemporary data on pre-CRC lesions in LS, including any differences according to impacted gene. Lower rate of CRC in young persons with MSH6/PMS2 may be related to removal of pre-CRC lesions

Aims
The objective of this study is to characterize colorectal lesions among a population-based cohort of LS individuals

Methods
The database of individuals with pathogenic/likely pathogenic (P/LP) LS gene variants in Manitoba is augmented with colonoscopy data and pathological findings. We report descriptive statistics to describe the neoplastic lesions (pre-CRC lesions and CRC) in those with LS with data stratified by gene type. Prevalence estimates among individuals with LS without CRC amongst those with advanced CRC precursor lesions was reported. Advanced CRC precursor lesions are defined as either ≥1 cm in size, villous/tubulovillous histology, high grade dysplasia, or serrated polyps with dysplasia

Results
A total of 482 people with LS were analysed (33.9% males). 198 individuals with LS had documented CRC, of which 28.3% were in the cecum. Prevalence of advanced CRC precursors was 9/81 in people with MSH6 mutation, 18/102 with MLH1 mutation, 16/112 with PMS2 mutation, and 30/136 with MSH2 mutation. Median age at diagnosis of advanced CRC precursors was 56-years with average polyp size of 16.5 mm. 1/8 individuals under the age of 35 years old at the time of the colonoscopy in the MSH6 group had advanced CRC precursors, compared to 1/25 of individuals in the PMS2 mutation group. There were no CRC diagnosed below the age of 35 in the PMS2 and MSH6 groups

Conclusions
This population-based study is characterizing neoplastic lesions in individuals with LS highlighting the distribution of these lesions according to gene variants. The data analysis thus far raises concerns on the recent guidelines recommendations to increase the age of onset of colonoscopy surveillance to 35 years old in those with PMS2/MSH6 mutation; those recommendations did not consider the effect of removal of CRC precursors on CRC occurrence

Funding Agencies
None
A140 DUPILUMAB IMPROVED HISTOLOGY, CLINICAL SYMPTOMS, AND ENDOSCOPIC FEATURES IN ADULTS AND ADOLESCENTS WITH EOSINOPHILIC ESOPHAGITIS THROUGH 52 WEEKS REGARDLESS OF BASELINE DISEASE DURATION: POST-HOC SUBGROUP ANALYSIS OF THE PHASE 3 LIBERTY EOE TREET STUDY
Authors: Gonsalves N , Schlag C , Santander C , Peterson K , Alkhouri R , Xia C , Raphael B P , Radwan A 
Published: February 2025

Abstract

Background
Limited literature is available on EoE disease duration and response to therapy. Dupilumab is approved for EoE in patients aged ≥12 years, weighing ≥40 kg, in the EU, and in patients aged ≥1 year, weighing ≥15 kg, in the USA and Canada.

Aims
To assess the long-term efficacy of dupilumab in patients with EoE stratified by baseline disease duration.

Methods
In Part B of LIBERTY EoE TREET (NCT03633617), patients received 24 weeks of dupilumab 300 mg or placebo weekly (qw). Eligible patients who completed Part B received dupilumab through 52 weeks (Part C). Co-primary endpoints were the proportion achieving peak esophageal intraepithelial eosinophil count (PEC) ≤6 eosinophils/high-power field (eos/hpf) and absolute change in Dysphagia Symptom Questionnaire (DSQ) total score. Secondary endpoints included proportion achieving PEC &lt;15 eos/hpf, percent change in PEC, and mean change in Endoscopic Reference Score (EREFS) total score and Histologic Scoring System (HSS) grade/stage scores. Data were stratified by baseline disease duration defined as time since diagnosis (≤5 years, &gt;5-≤10 years, &gt;10 years).

Results
At Part B baseline in the dupilumab and placebo groups, respectively, 43 and 48 patients had EoE for ≤5 years, 22 and 13 patients had EoE for &gt;5-≤10 years, and 15 and 18 patients had EoE for &gt;10 years. At Week 24, PEC ≤6 eos/hpf and DSQ total score favored dupilumab over placebo, regardless of disease duration. Dupilumab also improved percent change in PEC and change in EREFS and HSS grade/stage scores across all disease duration subgroups vs placebo (Table). At Week 52, improvements were maintained in patients who received continued dupilumab; patients who switched from placebo to dupilumab at Week 24 also showed improvement in all outcomes. Overall safety was consistent with the known dupilumab safety profile.

Conclusions
These results show that dupilumab 300 mg qw is an effective long-term treatment for patients with EoE, including a subset of patients with longstanding disease potentially inadequately addressed by alternative therapies.

Funding Agencies
Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
A143 PREDICTIVE SCORES AND CLINICAL FAILURE AFTER PER-ORAL ENDOSCOPIC MYOTOMY
Authors: Parvizian M K , Rai M , Bechara R 
Published: February 2025

Abstract

Background
Achalasia is a rare esophageal motility disorder characterized by incomplete lower esophageal sphincter relaxation and absent peristalsis. Increasingly, per-oral endoscopic myotomy (POEM) has been used as a first-line therapy for achalasia. However, a small proportion of patients will experience clinical failure after POEM (Eckhardt Score&gt;3). Several small studies have attempted to predict which patients will experience failure after POEM; however, none have been validated outside their original centers.

Aims
To compare the performance of the Zhongshan, JAMS, and Urakami scores to predict key outcomes post-POEM.

Methods
A single centre retrospective cohort study from March 2016 to January 2024 including all adult patients undergoing POEM for achalasia with at least 3 months of follow-up was conducted. The performance of the different scores in predicting clinical failure and the presence of minimal symptoms (Ekhardt Score &lt;=1) was analyzed. Scores were calculated and patients categorized as high-risk for failure (&gt;=5% risk) or low risk based on score cutoffs from the original validation studies.

Results
156 patients were included in our study. The median age of participants was 57.5 (IQR 36-68), and 70 were female (44.9%). 6 patients experienced clinical failure (3.8%) and 115 had minimal symptoms post-POEM (73.7%). The Urakami score demonstrated the highest sensitivity for predicting clinical failure (1.00; 95% CI 0.54-1.00) and presence of more than minimal symptoms (1.00; 95% CI 0.91-1.00), while the Zhongshan score exhibited the highest specificity for clinical failure (0.82; 95% CI 0.74-0.88) and more than minimal symptoms (0.84; 95% CI 0.76-0.90). (Table 1)

Conclusions
This study reports the first validation of predictive scores in POEM patients outside of their centres of origin. The Urakami score may play a role in identifying patients at low risk of clinical failure, while the Zhongshan score may help identify patients at high risk of clinical failure. Using these scores can aid in counseling patients pre-POEM about their expected outcomes.
Test characteristics of various scores to predict outcomes after POEM

Funding Agencies
None
A151 STRATEGIES TO ENHANCE THE CLINICAL APPLICATIONS OF A NOVEL PH SENSITIVE ANALGESIC IN A PRECLINICAL MODEL OF COLITIS
Authors: Parkar N , Jimenez Vargas N , Blazevic L , Stein C , Vanner S J 
Published: February 2025

Abstract

Background
Improved pain management is an identified top five priority for the treatment of patients suffering from inflammatory bowel disease. Although conventional opioids and NSAIDs can provide pain relief, their side effects pose serious health risks. We developed a unique pH-sensitive analgesic, NFEPP, that is only active at sites of injury/inflammation without affecting healthy tissues, e.g. brain and gut. Preclinical studies using parenteral routes(s.c. or i.v.) demonstrate that NFEPP exhibits potency comparable to fentanyl, but without the risks of addiction or severe side effects like respiratory depression. The duration of action of NFEPP is ~2 hrs, which would require continuous infusion or frequent applications to treat a painful disorder. To broaden the potential clinical applications, strategies are needed to increase its half-life and to understand its efficacy compared to conventional treatments.

Aims
To examine the therapeutic index(TI) of NFEPP and determine if a high index could be exploited to extend its duration of action, and to compare the analgesic efficacy of NFEPP with a standard NSAID, diclofenac.

Methods
Acute colitis was induced in C57BL/6 mice by administering 2.5% dextran sulfate sodium(DSS) in drinking water for five days. Following s.c. injections of vehicle, NFEPP, fentanyl or diclofenac, visceromotor responses (VMRs) to colorectal distension were measured using telemetric transmitters inserted in the abdominal wall muscles. To assess cardiorespiratory side effects, mice were monitored via pulse oximetry.

Results
NFEPP(0.4 mg s.c.) and fentanyl(0.4 mg s.c.) exhibited similar analgesic effects on VMR but fentanyl markedly inhibited O2 saturation (~10%; p&lt;0.05), causing hypoxia. NFEPP at 50X’s this analgesic dose(20 mg/kg s.c.) had no effect on O2 saturation, suggesting a very high TI. We therefore examined whether the duration of action of NFEPP could be extended into the range of other oral analgesics by increasing the dose (doubling the dose increases T1/2 by ~&lt;1, 1st order kinetics). NFEPP 0.4 mg/kg s.c. was tested at 2 hrs and 1.6 mg/kg s.c. at 6 hrs. NFEPP (1.6 mg/kg s.c.) caused a 37.8% (p&lt;0.05) reduction in VMR responses after 6 hrs, similar to the effect of NFEPP 0.4 mg/kg at 2 hrs (36.8% reduction in VMR; p&lt;0.01). Comparator studies of the efficacy of NFEPP(0.4 mg/kg s.c.; ~EC75 dose) and diclofenac(30 mg/kg s.c., ~EC100 dose) demonstrated a 54.2% (p&lt;0.001) and 49.7% (p&lt;0.01) reduction in VMR, respectively.

Conclusions
NFEPP has a very high TI compared to fentanyl, and this property could potentially be exploited to increase its half-life in oral and/or patch formulations by increasing the dose without risk of respiratory depression. NFEPP has similar or greater analgesic efficacy compared to NSAIDs and could potentially be an alternative for some clinical indications.

Funding Agencies
CIHR