bluuebunny/crossref_metadata_2025 huggingface dataset:
A159 SERUM IGG RESPONSE TO THE D0-D1 HINGE PEPTIDE OF COMMENSAL FLAGELLIN PREDICTS THE FUTURE ONSET OF CROHN’S DISEASE IN HEALTHY FIRST-DEGREE RELATIVES
Authors: Wu R Y , Xue M , Zhao Q , Jeong S , Griffiths A , Dieleman L , Steinhart A , Aumais G , Bressler B , Panaccione R , Deslandres C , Mack D , Bernstein C N , Marshall J , Turner D , Xu W , Duck L W , Elson C , Turpin W , Lee S , Croitoru K
Published: February 2025

Background

Elevated antimicrobial antibody levels have been reported up to 6 years before diagnosis of Crohn’s disease (CD), but the specific antibody response is poorly defined.

Aims

Here, we characterized the nature of the antimicrobial antibody responses before the diagnosis of CD in healthy first-degree relatives (FDR) of CD patients.

Methods

The CCC-GEM Project nested case-control cohort consisted of FDRs who later developed CD (n=77), matched 1:4 by age, sex, follow-up duration, and geographical location with FDRs who remained healthy (n=304). Sera at enrollment were probed for antimicrobial reactivity using a microbiota antigen microarray and a flagellin peptide cytometric bead array. Conditional logistic regression was used to assess association with CD onset and partial Spearman was used to correlate the serologic responses with gut permeability (fractional urinary excretion of lactulose-to-mannitol ratio (LMR)) and fecal calprotectin (FCP).

Results

19 (out of 49) IgG antimicrobial antibody responses were significantly associated with the risk of CD; these antibodies were reactive to Lachnospiraceae family, particularly Roseburia-derived flagellins (q<0.02); 5 antibodies positively correlated with FCP (q<0.046), whereas 3 antibodies positively correlated with LMR (q<0.049). These IgG-seroreactive flagellins shared significant amino acid sequence homology, characterized by a conserved “hinge peptide” within D0-D1 domains of the amino-terminus. Elevated IgG seroreactivity to this hinge peptide (determined by cytometric bead array) was associated with multi-flagellin reactivity and future risk of CD.

Conclusions

Increased antibody response in healthy asymptomatic FDRs towards Lachnospiraceae flagellins is associated with future risk of CD, and markers of gut inflammation and altered intestinal permeability. Importantly, pre-CD participants shared seroreactivity towards a conserved bacterial flagellin epitope, suggesting a possible role in the early immunopathogenesis of CD.

Funding Agencies

CCC, CIHRThe Leona M. and Harry B. Helmsley Charitable Trust
A160 PATIENT SATISFACTION WITH NUTRITIONAL COUNSELLING IN MULTIDISCIPLINARY CARE FOR INFLAMMATORY BOWEL DISEASE
Authors: Majdzadeh Z , Pulver C , Rosenfeld G
Published: February 2025

Background

The exact role of diet in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), remains uncertain with no definitive dietary guidelines established. Nutritional interventions in IBD aim to address nutrient deficiencies, alleviate symptoms, and promote long-term remission. Despite the increasing recognition of nutrition in IBD management, evidence on the impact of nutritional counselling in multidisciplinary IBD care centres on patient-reported outcomes remains limited.

Aims

The primary objective of this study is to determine patient satisfaction with nutrition counselling as an adjunct therapy for IBD and explore its potential to improve patient-reported outcomes.

Methods

The IBD Centre of British Columbia (IBDC) is a multi-disciplinary, tertiary care centre in Vancouver, British Columbia that offers nutritional counselling by a registered dietician with experience in managing IBD. Adult patients of the IBDC, who completed at least 3 nutrition counselling sessions for IBD management, were invited to complete an online survey using a 5-point Likert scale that focused on 4 themes: whether the sessions provided new personalized information to patients, their effectiveness in improving patients’ dietary needs, impact on IBD symptoms, and overall patient satisfaction.1 Patients who had previously consented to research were invited to participate; ethics was obtained from the Providence Health research ethics board.

Results

A total of 69 patients (44 females, 25 males) completed the survey, with a mean age of 43.440 (+/- 15.48) years, and mean disease duration of 12.6 (+/- 11.23) years. Among these, 41 (59.4%) had CD, and 28 (40.6%) had UC. For the purposes of analysis, responses were categorized as positive, negative or neutral. A significant portion of patients (88.4%) reported that the dietitian sessions successfully managed their IBD related nutritional needs. Additionally, 78.3% incorporated the dietary recommendations into their daily dietary routines. Notably, more than 68% of participants reported that nutritional counselling sessions were effective in improving their symptoms. Overall, patient satisfaction with the dietitian sessions was high, at 76.8%.

Conclusions

High patient satisfaction and symptom relief were reported by patients when surveyed about nutritional counselling as an adjunct therapy in their multidisciplinary IBD care. These findings underscore the importance of integrating personalized dietary interventions into standard IBD care and support the growing recognition that nutrition improves patient-reported outcomes. Future research should explore the impact of nutrition counselling on IBD disease outcomes.

References

1. Craven, Meredith et al. Inflammatory Bowel Disease Patient Experiences with Psychotherapy in the Community. J Clin Psychol Med Settings. 2019;26(2):183-193.

Funding Agencies

None
A175 MACHINE LEARNING MODELLING OF MULTIMORBIDITY PATTERNS AND PREMATURE MORTALITY IN INFLAMMATORY BOWEL DISEASE
Authors: Tennakoon G , Postill G , Harish V , Itanyi I , Tang F , Buajitti E , Kuenzig E , Rosella L , Benchimol E
Published: February 2025

Background

Multimorbidity is the co-occurrence of two or more chronic conditions in one individual. It is associated with reduced quality of life, poorer disease outcomes, increased hospitalizations, and polypharmacy. Although linked to premature mortality in general populations, the relationship between multimorbidity and premature mortality in inflammatory bowel disease (IBD) is unknown.

Aims

(1) characterize multimorbidity patterns across the life course within the context of IBD; (2) identify how the sequence of condition accumulation contributes to premature death.

Methods

We conducted a population-based retrospective matched cohort study using health administrative data from Ontario, Canada, including decedents with IBD between 2010 and 2020. Consensus K-Means Clustering was employed to characterize multimorbidity patterns, allowing us to identify potential groups of patients with similar condition profiles. Recurrent Neural Network (RNN) and Long Short-Term Memory (LSTM) models were trained to analyze the impact of the sequence of condition accumulation on premature mortality, considering either early-onset (diagnosed before 60 years of age) or all life conditions. These models were chosen for their ability to process sequential data, which is crucial for understanding how the order and timing of condition onset in multimorbidity progression impacts premature mortality.

Results

Among 9,278 IBD decedents (49% female), we identified three multimorbidity clusters: (α) mood disorders and/or osteo- and other arthritis, (β) cancer with low multimorbidity, and (γ) cardiovascular comorbidities (Figure 1). Premature deaths accounted for 47.2% (n=4,380) of all deaths. All models performed well, with Area Under the Curve (AUC) values ranging from 0.84 to 0.88. The LSTM model achieved the best performance (AUC 0.88) in predicting premature mortality, using data from early-onset conditions. Key predictors of premature mortality were young ages of diagnosis for mood disorder, osteoarthritis, other mental health disorders, hypertension, and male sex.

Conclusions

This study provides novel insights into multimorbidity patterns in IBD. Our findings reveal three specific multimorbidity clusters in the IBD population and we identified conditions important for predicting premature mortality. These results highlight the importance of providing multidisciplinary care for patients with IBD throughout their lives.

Figure 1. IBD patient multimorbidity clusters. (A) Consensus matrix showing three patient clusters based on comorbidities. Darker blue indicates more consistent patient pairing. (B) Heatmap showing chronic condition prevalence in the three clusters (α, β, γ). Darker blue indicates higher prevalence.

Funding Agencies

None
A177 RESILIENCE AND EMPOWERMENT OF INDIGENOUS PERSONS LIVING WITH INFLAMMATORY BOWEL DISEASE: A PHOTOVOICE STUDY FROM CANADA
Authors: Teucher U , Jennings D , Gannon A , Andkhoie M , Brass C , Fowler S , Johnson-Jennings M , Osei J , Porter L , Porter R , Sanderson R , Souza Lira A P , Peña-Sánchez J
Published: February 2025

Background

There is limited evidence about inflammatory bowel disease (IBD) among Indigenous peoples (Inuit, Métis, and First Nations [FN]). Healthcare utilization inequities between FN and non-FN individuals with IBD have been documented.

Aims

We aimed to explore the perceptions of FN persons living with IBD, including identifying barriers and facilitators to access healthcare and understanding their expectations of healthcare for IBD.

Methods

Six FN community members shared their experiences and perspectives about IBD. Four were individuals living with IBD and two were parents of FN persons living with IBD. Participants were asked to make photos in response to: “What is IBD for you?”, “What does it mean to be healthy and unhealthy when living with the diagnosis of IBD?”, “What do you expect when looking for healthcare at a clinic or a hospital?”, and “What are your challenges when accessing care?”. Then, they participated in semi-structured group reflections about their photo selections. Reflexive thematic analysis was utilized to analyze photographs, questionnaires, and reflections.

Results

The analysis revealed five themes: 1. Diagnosing IBD; 2. Living with IBD; 3. The Health-Sickness Dichotomy; 4. Healthcare Enablers and Barriers; and 5. Advocacy. The 1st theme encapsulates participants’ experiences regarding delays in diagnosis, the tendency of healthcare practitioners to focus on symptoms rather than the underlying disease, and the emotional responses to receiving an IBD diagnosis. The 2nd theme traces participants’ experiences as they navigate a changed reality, confront issues of bodily betrayal, dignity, and resilience. The 3rd theme highlights the contrasts between health and illness as experienced through physical symptoms, dietary choices, and social interactions. The 4th theme captures participants’ experiences within the healthcare system, including their expectations, positive encounters, and challenges such as inadequate knowledge among some healthcare providers, negative interactions, finding adequate language and use of metaphors to speak about a stigmatizing illness, and the use of humor as a coping mechanism and a barrier. The 5th theme reflects participants’ experiences advocating for themselves or relying on supportive networks to advocate on their behalf. Participants recognized the value of patients and advocates as experts in navigating their health journeys.

Conclusions

Drawing on participants’ lived experiences, this study highlights the gaps in the healthcare system faced by Indigenous patients living with IBD, while revealing potential solutions to enhance their healthcare experiences and outcomes.

Funding Agencies

SHRF-SCPOR
A184 DISCOVERY OF POTENTIAL LGR5 LIGANDS
Authors: Gendron F , Arguin G , Acosta Montalvo J , Boudreau P
Published: February 2025

Background

LGR5, an intestinal stem cell marker, is crucial in mediating R-spondin (RSPO) signaling, supporting canonical WNT signaling for tissue development and renewal. This pathway is pivotal in gastrointestinal (GI) disease, assisting wound healing and playing a role in cancer progression and chemoresistance. While modulating the WNT pathway holds therapeutic potential, directly targeting it risks disrupting cell differentiation and organ function. LGR5, whose activity complements but does not fully overlap with the WNT pathway, represents a safer target for therapeutic intervention.

Aims

This study seeks to identify novel ligands for LGR5, focusing on bioactive molecules in the gut lumen and secreted soluble factors from epithelial cells. In addition, RSPO-derived peptidomimetics were designed and assessed as potential LGR5 ligands.

Methods

Luminal lavages from mice intestines were subjected to size-exclusion chromatography, and their activity was tested using impedance assays in HEK293 cells expressing human LGR5 (HEK293/LGR5). Active fractions were further analyzed using pull-down assays and LC-MS/MS to identify LGR5 interacting proteins. Media from cultured IECs were also processed and evaluated for potential LGR5 ligands using LC-MS/MS. Protein-protein interactions (PPIs) were confirmed via immunoprecipitation (IP). Finally, RSPO peptidomimetics based on the FU2 domain, known to bind LGR5, were tested for their ability to modulate β-catenin activity through luciferase reporter assays.

Results

An isoform of Urotensin II (iUTS2) from the cell culture media and three proteins from intestinal luminal extracts were identified as potential LGR5 ligands. The interaction between iUTS2 and LGR5 was confirmed through IP. As a proof of concept, six RSPO peptidomimetics were designed and tested. Although none of the peptides fully replicated RSPO1 activity, three were found to enhance the effect of RSPO1 on WNT3a-induced β-catenin activity, indicating their potential as modulators of LGR5.

Conclusions

This study presents the first identification of potential endogenous and peptidomimetic LGR5 ligands. Although in the preliminary stages, these findings represent a significant step toward developing selective LGR5 ligands, offering insight into LGR5 receptor functions. Such discoveries hold promise for future LGR5-targeted therapies, which could restore tissue homeostasis in conditions like inflammatory bowel disease or impede cancer progression by preventing cell adaptation and dissemination.

This work was funded by a CCC-GIA research grant (2022-2025) and NSERC (RGPIN-2019-05294).

Funding Agencies

CCCNSERC
A186 BALLOON-ASSISTED ENDOSCOPY IN THE MANAGEMENT OF SMALL BOWEL CROHN’S DISEASE – AN OVERALL EXPERIENCE FROM A CANADIAN TERTIARY CARE HOSPITAL
Authors: Fazal M , Bowron J C , Reeson M , Zepeda-Gomez S , Halloran B
Published: February 2025

Background

Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract with a wide spectrum of gastrointestinal symptoms and disease complications including strictures, fistulae, malabsorption etc. Balloon-Assisted Endoscopy (BAE) at our institution plays a vital role in managing small bowel Crohn’s disease, to which conventional endoscopy has limited access. It allows better diagnostic and therapeutic abilities through better visualization, biopsies, and endoscopic balloon dilations of strictures.

Aims

Our aim is to evaluate the efficacy and safety of Balloon-Assisted Endoscopy, including Single-Balloon Endoscopy (SBE) and Double-Balloon Endoscopy (DBE), in patients with Small Bowel Crohn’s disease by analyzing the demographics, indications, complications, and endoscopic therapies performed.

Methods

Retrospective analysis of 231 patients who underwent a total of 532 BAE procedures between April 2012 – January 2024 at the University of Alberta Hospital (a tertiary care referral centre). The cohort included both DBE (344) and SBE (188) procedures and clinical findings and outcomes were analyzed.

Results

A total of 532 BAE procedures (344 DBE, 188 SBE) were performed on 231 patients during April 2012 – January 2024. Out of 231 patients, 126 (54.5%) were males and the mean age of the cohort was 52.96 years. The mean duration of disease was 17.55 years and 109 patients (47.18%) had history of surgical resection before their first DBE. 94 patients (40.6%) underwent diagnostic DBE out of which 56 patients had single and 38 patients had multiple endoscopies. Whereas, 137 patients (59.3%) underwent therapeutic DBE with 60 patients undergoing single and 77 patients requiring multiple therapeutic procedures. Obstructive symptoms were reported before 96 procedures (18%). We were able to diagnose Adenocarcinoma (3 patients), Meckel’s Diverticulum (2 patients), retrieve Video-Capsule (1 patient) and achieve hemostasis via hemoclips in 4 patients. A total of 398 strictures were encountered out of which 16 (4.02%) were non-traversable and 3 (0.75%) were failed dilations. We had a > 95% successful dilation rate. Adverse events included aspiration leading to termination of procedure (n=3, 0.56%), mucosal/submucosal tears (n=4, 0.75%), bleeding requiring clips (n=3, 0.56%) and perforation requiring emergent surgery (n=1, 0.18%).

Conclusions

We are reporting on one of the largest single center cohorts of BAE done in IBD patients in the literature. Overall, BAE has a strong safety profile in retrospective analysis of our cohort with a high success rate in both assessing disease and dilating the majority of strictures encountered. 40.6 % of our patients benefited from BAE as an ongoing diagnostic modality: assessing disease status and response to therapy.

Funding Agencies

None
A197 ASSOCIATION BETWEEN ANTIMICROBIAL SEROLOGIES AND IBD LOCATION AND BEHAVIOUR: DATA FROM THE CIDSCANN INCEPTION COHORT
Authors: Fanous Vukas E , Muise A , Jacobson K , Huynh H , Otley A , deBruyn J , Mack D , Deslandres C , El-Matary W , Walters T , Griffiths A , Ricciuto A
Published: February 2025

Background

Antimicrobial serologies have been associated with Inflammatory Bowel Disease (IBD) type and Crohn’s disease (CD) progression. However, prospective pediatric data examining these associations while considering disease location are sparse.

Aims

1) Describe rates of serology positivity by disease location; 2) Assess the ability of serologies to predict CD progression to stricturing (B2) /penetrating (B3) behaviour, while accounting for IBD location.

Methods

Children with CD enrolled in the prospective multicentre Canadian Children IBD Network (CIDsCaNN) were included. ASCA IgA and IgG, CBir1, OmpC and ANCA positivity were measured centrally at Cedars-Sinai. We assessed variables at diagnosis and last follow up. We used Pearson’s Chi-Squared test to compare proportions and Mann-Whitney U test to compare medians between groups. We used multivariable Cox regression to determine the association between serologies and progression to B2/B3 amongst CD patients with B1 at diagnosis, while accounting for L1 location. We calculated area under the ROC curve (AUC) to quantify predictive ability.

Results

There were 512 CD patients included: median age 13 y (IQR 10.8-14.9), follow up 3.3 y (IQR 1.9-5.0). There were 50/452 (11%) B1 CD patients who progressed (L1: 16/77 (21%); L2: 7/112 (6%); L3: 27/241 (11%)). ASCA+ was more frequent among patients with L1/L3 compared to L2 CD (28% vs 13%, p=0.009), while CBir1+ and OmpC+ rates did not differ by CD location (55% vs 48%, p=0.19 and 9% vs 9%, p=0.85). ANCA+ rate was higher among L2 CD compared to L1/L3 CD (30% vs 10%, p<0.001). In univariate survival analysis, CBir1+, ASCA+ and L1 were associated with progression to B2/B3 (Table 1). In multivariable analysis, only positivity for CBir1+ and L1 were associated with progression. CBir1 titre had only moderate ability to predict progression (AUC 0.65 (95%CI 0.57-0.72)).

Conclusions

While ASCA and CBir1 are associated with complicated CD in univariate analysis, this appears to be mediated by small bowel location for ASCA. While CBir1 was independently associated with B2/B3 disease, its predictive ability alone was limited.

Table 1. Unadjusted and Adjusted Hazard Ratios for Progression to B2 or B3 Complications

Funding Agencies

CIHRCh.I.L.D Foundation
A207 INFLIXIMAB IN VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE (VEO-IBD), DOSING AND OUTCOME: A RETROSPECTIVE CROSS-SECTIONAL STUDY
Authors: Sethuraman A , Kishore S B , Binomar H , Jacobson K
Published: February 2025

Background

VEO-IBD patients defined as children with IBD diagnosed before 6rys of age, account for approximately 10% of pediatric IBD patients. They are uniquely at risk of inadequate infliximab (IFX) exposure. We report the dosing patterns, efficacy and safety of IFX use in a cohort of patients with VEO-IBD.

Aims

To study the response rate and outcome of IFX in VEOIBD patients with active therapeutic drug monitoring. Our primary aim was to study the rate of clinical remission and outcome of patients with VEOIBD on IFX. Our secondary aim was to study the IFX failure rate in VEOIBD children and also to study the association of body weight (BW) and body surface area (BSA) dosing.

Methods

A retrospective chart review was conducted for all children with VEOIBD diagnosed between 1st January 2013 to 31st December 2022 with a minimum follow up of one year at a single centre. The patients were identified from the British Columbia paediatric IBD database. Clinical data, including IBD medication use and response were collected from the medical record. REB approval was obtained for this study.

Results

A total of 77 patients were identified and reviewed in our study with 28 (34.1%) exposed to infliximab, with a mean follow up of 65.6 months (±31.7mo). The mean age at diagnosis was 45.9 months (SD±18.5m). Among them, 14 (50%) were diagnosed with Crohn’s disease and 11 (39%) and 3 (11%) with ulcerative colitis and IBD-U respectively. 19/28 (67.8%) patients were started on IFX below 6yrs of age. The median time from diagnosis to IFX commencement was 11.9 months (IQR 3.9-11.9mo). The median pre dose 3 and pre dose 4 infliximab trough levels were 4.35 μg/mL and 5.2 μg /mL respectively with a mean IFX induction dose of 6.7 mg/kg (SD ±2.14mg/kg) and 160.6 mg/m2 body surface area. 18/28 (64.3%) patients needed a dose change after induction with the rest needing dose optimization at follow up. 12/28 (42.8%) were on concomitant therapy with methotrexate or azathioprine. 17/28 (60.7%) continued on IFX as their therapy, with a mean IFX dose of 300mg/m2 and 10.25 mg/kg to achieve clinical remission at last follow. The median drug level for these patients was 7.15 μg/mL.

Clinical remission at last follow up on IFX was achieved in all 17/28 patients with 7/17 in biochemical remission, defined at fecal calprotectin <250μg/g. Infliximab failure occurred in 11/28 (39.3%) of patients with 10/11 due to secondary loss of response. Among those 11, 7 were exposed to a 2nd biologic and 4 to a 3rd biologic with response in 7. Three patients required a colectomy and 1 underwent a bone marrow transplant.

Conclusions

Infliximab trough levels pre dose 3 and 4 are often low in VEO-IBD patients and dose optimization is very common.

Funding Agencies

None
A225 UPTAKE AND OUTCOMES OF MENTAL HEALTH AND NUTRITION COUNSELLING FOR RECENTLY DIAGNOSED IBD PATIENTS.
Authors: Narous M , Ly G , vagianos K , Kredentser M , Graff L , Shaffer S , Singh H , Bernstein C N
Published: February 2025

Background

Inflammatory bowel disease (IBD) significantly impacts both physical and mental health, with patients experiencing elevated levels of anxiety and depression. Nutritional management is also crucial, as dietary choices can influence physical symptoms. Despite the importance of integrated mental health and nutrition services, numerous barriers, such as limited awareness and access, contribute to suboptimal engagement among patients with IBD.

Aims

We sought to assess the uptake of integrated psychologist and dietician services in a clinical setting, and to further understand the mental health and nutrition needs of individuals with IBD.

Methods

In a pilot study initiated in May 2022, recruiting from an IBD clinic at Manitoba’s provincial tertiary hospital, consecutive individuals ages 16+ with IBD diagnosed within 3 years were invited to enrol. Participants completed baseline screening tools including the DASS-21, PHQ8, GAD7, PROMIS, and SaskIBD (nutrition risk) and were offered appointments with an IBD psychologist, dietitian or both, when flagged through the screening tools. Descriptive data were collected regarding clinical screening, psychological diagnoses and interventions, as well as dietary needs and nutrition counselling provided.

Results

Of 226 eligible, 101 were enrolled (42% Crohn’s disease), and 64 accepted referral to clinical psychology. Of those, >50% and 36-49% met screening criteria for moderate to severe depression and anxiety, respectively. Median scores (± std dev) for DASS-21 were 14 ±9.6 (depression), 8 ±6.6 (anxiety), and 16 ±7.9 (stress); PHQ8 10 ±5.2; and GAD7 8 ±4.7. At an initial semi-structured diagnostic interview, approximately 50% of patients were confirmed to have a psychological diagnosis, most commonly depression (20.6%), anxiety (31.7%) and insomnia/sleep disorder (15.9%). Median number of psychologist visits was 1 ±4.13 (range 0-19); 44.4% of patients returned for follow-up. Of the 37 patients who were not flagged/declined to proceed with the psychologist, only 4 screened positive (1 moderate depression; 3 moderate-severe anxiety). Almost all participants (n=84) were flagged to see the dietitian, with the main needs relating to types of food to avoid and strategies for weight gain or loss. Of those, 52% screened positive for moderate to severe risk of malnutrition, with a median SaskIBD score of 3 ±2.1.

Conclusions

In a prospective cohort of recently diagnosed IBD patients, there is a demonstrable need for integrated mental health and dietitian expertise with excellent uptake of these services when easily accessible in an outpatient gastroenterology clinic. Ongoing data are being collected to characterize outcomes of this comprehensive model of care for IBD patients.

Funding Agencies

CCC
A244 EVIDENCE THAT IMPAIRED VAGAL SATIETY SENSING IN OBESITY IS DRIVEN BY LUMINAL MEDIATORS
Authors: Chakraborty A , Sachdev S , Reed D E , Lomax A E
Published: February 2025

Background

Obesity occurs when energy intake exceeds energy expenditure. The physiological changes causing excess energy intake are unclear. Satiety is conveyed from the gut to the brain by vagal afferent neurons (VANs) that have cell bodies in the nodose (NG) and axons that connect the gut and brain stem. There is evidence of diminished satiety sensation in obesity. In the current study, we characterised VAN activity in the jejunum of obese mice and investigated whether mediators secreted into the lumen contribute to this effect. We hypothesized that obese mice would have diminished VAN activity and secrete luminal mediators that inhibit VAN signalling.

Aims

Characterise changes in VAN satiety sensing in obese mice and determine if luminal mediators can induce these changes.

Methods

Genetically leptin-deficient male [N = 6] and female obese (Ob) [N = 8] mice were used, with heterozygous littermates (Het) [male N = 7, female N = 7] serving as controls. Ex-vivo afferent nerve recordings were conducted on VAN axons attached to the mouse jejunum. Changes in firing frequency were assessed in response to meal-related hormonal and mechanical stimuli, namely 100 nM cholecystokinin (CCK) and distension to 60 mmHg. Additionally, naïve NG neurons were incubated in luminal contents collected from the small intestine of Ob and Het mice to determine the potential role of luminal mediators. Patch clamp recordings were carried out on these cells and changes in excitability were assessed using rheobase (higher rheobase indicates decreased excitability).

Results

Ob mice had rates of basal jejunal afferent discharge 70% lower than Het mice (p <0.01) and showed 60% less activation in response to 100 nM CCK (p <0.05). Ob mice also showed a 40% attenuation in distension response compared to Het mice (p <0.01). In patch clamp experiments, NG cells from Ob mice (n = 23 cells from N = 8 mice) had a 33% higher rheobase than Het (n = 18 cells from N = 8 mice; p <0.01). Overnight incubation of NG neurons from naïve mice with luminal contents collected from the jejunum of Ob mice increased the rheobase to over double the rheobase of cells incubated with samples from Het control mice (Ob n = 12, het n = 12, p <0.05). These changes to rheobase were blocked by pre-incubation of NG neurons with the orexin-1 receptor agonist SB-334867 (p <0.01).

Conclusions

Our findings suggest that during obesity, mediators are produced that can attenuate vagal satiety signaling. The ability to inhibit these changes using the orexin-1 receptor antagonist implicate orexin receptors in impaired vagal satiety signaling during obesity.

Funding Agencies

None
Appropriateness and Consistency of an Online Artificial Intelligence System’s Response to Common Questions Regarding Cervical Fusion
Authors: Miller Mark , DiCiurcio William T. , Meade Matthew , Buchan Levi , Gleimer Jeffrey , Woods Barrett , Kepler Christopher
Published: February 2025

Study Design:

Prospective survey study.

Objective:

To address a gap that exists concerning ChatGPT’s ability to respond to various types of questions regarding cervical surgery.

Summary of Background Data:

Artificial Intelligence (AI) and machine learning have been creating great change in the landscape of scientific research. Chat Generative Pre-trained Transformer(ChatGPT), an online AI language model, has emerged as a powerful tool in clinical medicine and surgery. Previous studies have demonstrated appropriate and reliable responses from ChatGPT concerning patient questions regarding total joint arthroplasty, distal radius fractures, and lumbar laminectomy. However, there is a gap that exists in examining how accurate and reliable ChatGPT responses are to common questions related to cervical surgery.

Materials and Methods:

Twenty questions regarding cervical surgery were presented to the online ChatGPT-3.5 web application 3 separate times, creating 60 responses. Responses were then analyzed by 3 fellowship-trained spine surgeons across 2 institutions using a modified Global Quality Scale (1–5 rating) to evaluate accuracy and utility. Descriptive statistics were reported based on responses, and intraclass correlation coefficients were then calculated to assess the consistency of response quality.

Results:

Out of all questions proposed to the AI platform, the average score was 3.17 (95% CI, 2.92, 3.42), with 66.7% of responses being recorded to be of at least “moderate” quality by 1 reviewer. Nine (45%) questions yielded responses that were graded at least “moderate” quality by all 3 reviewers. The test-retest reliability was poor with the intraclass correlation coefficient (ICC) calculated as 0.0941 (−0.222, 0.135).

Conclusion:

This study demonstrated that ChatGPT can answer common patient questions concerning cervical surgery with moderate quality during the majority of responses. Further research within AI is necessary to increase response.
FSP1 expression as a predictor of platinum resistance and recurrence in epithelial ovarian cancer
Authors: Xing Hang , Bi Hai-Ning , Yin Qi , Zhang Ji , Zhang Xue , Li Yao-Jiao , Gong Xue-Mei , Shi Ji-Fang
Published: February 2025

The objective of this study is to assess the differential expression of ferroptosis suppressor protein 1 (FSP1) in relation to clinical features, platinum resistance, and recurrence in epithelial ovarian cancer (EOC). In addition, the potential significance of FSP1 in EOC as a predictor of platinum resistance and recurrence in EOC was explored. Patients with pathologically confirmed EOC who underwent surgical treatment were included in this analysis. Immunohistochemistry was employed to evaluate FSP1 expression in ovarian tissues, with quantitative analysis performed on the samples. Clinical data were collected during follow-up, and patients were categorized according to platinum resistance and recurrence criteria. Statistical analysis was conducted using SPSS version 27.0. A total of 40 tissue samples from patients with EOC were analyzed, along with 21 samples from benign ovarian tumors and 20 samples from normal ovarian tissues. The expression of FSP1 was significantly higher in the EOC group compared to both benign and normal tissue groups. Meanwhile, the expressions of FSP1 were higher in groups with clinically advanced stages, high-grade carcinoma, presence of cancerous ascites, lymph node metastasis, and in the clear cell EOC group, compared to those with clinically early stages, low-grade carcinoma, absence of cancerous ascites, no lymph node metastasis, and other pathological subtypes. A positive linear correlation was identified between FSP1 expression in EOC tissues and serum levels of CA125 and human epididymis protein 4 at the time of diagnosis. The elevated expression of FSP1 is positively correlated with serum CA125 and human epididymis protein 4 levels at the time of diagnosis, which is a risk factor for EOC drug resistance and recurrence. These findings suggest that FSP1 may serve as a valuable biomarker for predicting platinum resistance and recurrence in patients with EOC.
Hemorrhagic Descemet Membrane Detachment after Gonioscopy-Assisted Transluminal Trabeculotomy
Authors: Mirza Gunsu Deniz , Mirza Enver
Published: February 2025

Purpose:

To report a rare case of hemorrhagic Descemet membrane detachment (DMD) after Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) and to discuss its management.

Methods:

A 71-year-old male patient with advanced pseudoexfoliation glaucoma and dense cataract was planned to perform combined GATT and cataract extraction. DMD was noticed after blood reflux from Schlemm’s canal during GATT. Circumferential ab-interno trabeculotomy was completed and DMD was reattached with air tamponade. Cataract extraction was postponed to prevent progression of DMD.

Results:

Hemorrhagic DMD was monitored during a 3-month follow-up. Spontaneous resorption was not observed. A side port incision was made at the site of hemorrhagic DMD during cataract extraction. The space upon DM was washed out with a balanced salt solution to allow drainage of the hemorrhage and an air bubble was left in the anterior chamber. On the first postoperative day after cataract extraction, DM was observed to be attached and the hemorrhage had disappeared completely.

Conclusions:

Hemorrhagic DMD is an unusual complication after GATT and it may be challenging to manage. Surgeons who perform GATT should be aware of this rare corneal complication.
A Survey of Program Directors on Procedural Competence and Volume in the US Pulmonary and Critical Care Fellowships
Authors: Josan Enambir , Pastis Nicholas , Peng Jing , Ma Jianing , Mahmood Kamran , Danckers Mauricio , Ghattas Christian , Revelo Alberto , Pannu Jasleen
Published: February 2025

Background:

In the United States, Pulmonary and Critical Care Medicine (PCCM) fellowship training traditionally requires performing a minimum number of bronchoscopy and pleural procedures to be deemed competent. However, expert panel recommendations favor assessments based on skill and knowledge. PCCM trainees have a variable exposure to the advanced procedures in the presence of interventional pulmonary (IP) fellowships, so we surveyed the PCCM program directors (PD) across the United States to assess the procedural volume and competency of their fellows.

Methods:

Survey invitations were emailed between April 2022 and May 2022, and responses were collected from PCCM fellowship programs. The PD assessed the competency and volume of procedures performed by PCCM fellows at the end of training. The primary objective was to determine the effect of IP fellowship or IP faculty on fellows’ procedural competency. The secondary objective was to assess the same impact on procedural volume.

Results:

The survey response rate was 41.9% (n=109/260) with an average of 4.23 fellows/program (95% CI: 3.9-4.6). 74.5% (73/98) programs reported having access to IP faculty, while 26.5% (26/98) had an AABIP-accredited IP fellowship. No significant difference was noted for procedural competency or volume in programs with or without an IP fellowship or IP faculty during training. Most programs reported that PCCM fellows do not perform advanced bronchoscopy procedures.

Conclusion:

An IP fellowship or IP faculty at a PCCM training institution did not appear to influence the PD-assessed volume or competency of common bronchoscopy and pleural procedures performed by fellows.
Building a cancer risk and survival prediction model based on social determinants of health combined with machine learning: A NHANES 1999 to 2018 retrospective cohort study
Authors: Zhang Shiqi , Jin Jianan , Zheng Qi , Wang Zhenyu
Published: February 2025

The occurrence and progression of cancer is a significant focus of research worldwide, often accompanied by a prolonged disease course. Concurrently, researchers have identified that social determinants of health (SDOH) (employment status, family income and poverty ratio, food security, education level, access to healthcare services, health insurance, housing conditions, and marital status) are associated with the progression of many chronic diseases. However, there is a paucity of research examining the influence of SDOH on cancer incidence risk and the survival of cancer survivors. The aim of this study was to utilize SDOH as a primary predictive factor, integrated with machine learning models, to forecast both cancer risk and prognostic survival. This research is grounded in the SDOH data derived from the National Health and Nutrition Examination Survey dataset spanning 1999 to 2018. It employs methodologies including adaptive boosting, gradient boosting machine (GradientBoosting), random forest (RF), extreme gradient boosting, light gradient boosting machine, support vector machine, and logistic regression to develop models for predicting cancer risk and prognostic survival. The hyperparameters of these models—specifically, the number of estimators (100–200), maximum tree depth (10), learning rate (0.01–0.2), and regularization parameters—were optimized through grid search and cross-validation, followed by performance evaluation. Shapley Additive exPlanations plots were generated to visualize the influence of each feature. RF was the best model for predicting cancer risk (area under the curve: 0.92, accuracy: 0.84). Age, non-Hispanic White, sex, and housing status were the 4 most important characteristics of the RF model. Age, gender, employment status, and household income/poverty ratio were the 4 most important features in the gradient boosting machine model. The predictive models developed in this study exhibited strong performance in estimating cancer incidence risk and survival time, identifying several factors that significantly influence both cancer incidence risk and survival, thereby providing new evidence for cancer management. Despite the promising findings, this study acknowledges certain limitations, including the omission of risk factors in the cancer survivor survival model and potential biases inherent in the National Health and Nutrition Examination Survey dataset. Future research is warranted to further validate the model using external datasets.
Rheumatoid arthritis and risk of hearing impairment: A genetic correlation and bidirectional Mendelian randomization study
Authors: Liu Zhongxing , Xiang Guohong , Wang Lichen , Duan Lincheng , Guo Peng
Published: February 2025

Prior research has indicated a connection between rheumatoid arthritis (RA) and hearing impairment (HI), although there is disagreement among researchers. An extensive assessment of the causal relationship between RA and HI was the aim of this Mendelian randomization (MR) study. We examined summary-level data from RA and HL genome-wide association studies using inverse variance weighted (IVW) analysis. We further supplemented the results with weighted median (WM), MR-Egger, MR-RAPS, and maximum likelihood techniques. We used sensitivity analyses to check the accuracy of the MR analysis results. Genetically, higher RA substantially increases the likelihood of HI (IVW: P = 8.78 × 10−03, odds ratio (OR) = 1.014, 95% confidence interval (CI): 1.003–1.024). Sensitivity analysis reveals a consistent direction of the association using the following methods: Bayesian MR (P = 8.72 × 10−03, OR = 1.014, 95% CI: 1.004–1.025), MR robust adjustment profile score (P = 2.31 × 10−02, OR = 1.013, 95% CI: 1.002–1.024), maximum likelihood method (P = 2.70 × 10−02, OR = 1.014, 95% CI: 0.996–1.026), WM (P = 1.35 × 10−01, OR = 1.012, 95% CI: 0.996–1.029), and MR-Egger (P = 1.41 × 10−01, OR = 1.011, 95% CI: 0.996–1.027). Despite not achieving statistical significance, the WM and MR-Egger approaches offered reliable guidance. Moreover, we replicated our results on other datasets and obtained similar results (IVW: P = 8.71 × 10−03, OR = 1.016, 95% CI: 1.004–1.028), indicating the validity of our results. Our study provides evidence linking RA to a higher risk of HI. In order to gain more insight into treatments that change the disease or prevent hearing loss, audiological testing is necessary for the diagnosis and follow-up of individuals with RA.
Advances in controlled release drug delivery systems based on nanomaterials in lung cancer therapy: A review
Authors: Fu Jiang , Yu Li , Wang Zixu , Chen Haoyu , Zhang Song , Zhou Haining
Published: February 2025

Lung cancer is one of the most common malignant tumors, with the highest morbidity and mortality rates. Currently, significant progress has been made in the treatment of lung cancer, which has effectively improved the overall prognosis of patients, but there are still many problems, such as tumor recurrence, drug resistance, and serious complications. With the rapid development of nanotechnology in the field of medicine, it breaks through the inherent limitations of traditional cancer treatments and shows great potential in tumor treatment. To address the drawbacks of traditional therapeutic means, nanodrug delivery systems can release drugs under specific conditions, thus realizing tumor-targeted drug delivery, which improves the antitumor effect of drugs. In this paper, we review the current treatments for lung cancer and further discuss the advantages and common carriers of nanodrug delivery systems. We also summarize the latest research progress of nanotargeted drug delivery systems in the field of lung cancer therapy, discuss the problems faced in their clinical translation, and look forward to future development opportunities and directions.
Association between obstructive sleep apnea and chronic kidney disease: A cross-sectional and Mendelian randomization study
Authors: Wang Shaokang , Cheng Yupei , Zhang Zhe , Liu Wei , Ou Mi , Yin Tianlong , Meng Yalu , Ban Haipeng , Gu Wenlong , Meng Xianggang , Zhang Lili , Du Yuzheng
Published: February 2025

Previous observational studies have shown that obstructive sleep apnea (OSA) was associated with chronic kidney disease(CKD). Early diagnosis of OSA usually helps better prevent the occurrence of CKD. This cross-sectional investigation was conducted using data from the National Health and Nutrition Examination Survey, which was carried out between 2007 to 2008 and 2015 to 2016. Logistic regression model was employed to assess the impact of OSA on CKD. We did a mediation analysis to assess how much of the effect of OSA on CKD was mediated through mediators. Additionally, Mendelian randomization (MR) analysis assessed the causal link between OSA and various measures of renal impairment and possible mediators: obesity, hypertension and type 2 diabetes mellitus. In the cross-sectional study, the results of unadjusted model showed that participants with OSA had a higher risk of CKD compared to non-OSA (OR = 1.14, 95% confidence intervals [CI]: 1.01–1.28, P < .05). In mediation analysis, the proportion of hypertension and obesity mediating the effect of OSA on CKD was 41.83% and 30.74%, respectively. Univariate MR analysis results showed that: genetically predicted OSA was associated with decreased estimated glomerular filtration ratecystatin c (eGFRcystatin c) level (OR = 0.997, 95% CI: 0.995–0.999, P < .05), increased blood urea nitrogen (BUN) levels (OR = 1.023, 95% CI: 1.008–1.038, P < .05), increased serum creatinine levels (OR = 1.010, 95% CI: 1.002–1.018, P < .05), increased serum cystatin C levels (OR = 1.015, 95% CI: 1.005–1.026, P < .05). Multivariable MR results showed that obesity mediated the causal effect of OSA on eGFRcystatin c, BUN levels and serum cystatin C levels. The cross-sectional study revealed a positive relationship between OSA and CKD, which was mediated by hypertension and obesity. The MR analysis suggest that OSA was associated with several measures of renal impairment, which was mediated by obesity. These findings may inform prevention and intervention strategies against CKD.
Physical activity associated with age at menopause: A Mendelian randomization study
Authors: Sun Xiqiao
Published: February 2025

In previous observational studies, physical activity may have an impact on the age at menopause (ANM), potentially delaying or advancing the onset of menopause. However, the causal relationship between physical activity and age at menopause remains unclear. Therefore, we designed a 2-sample Mendelian randomization (MR) and mediation MR study to explore the causal relationship between physical activity and ANM and to identify potential mediating factors such as BMI, insomnia, hypertension and hyperglycemia. We investigated the causal link between physical activity and age at menopause using 2-sample Mendelian randomization (MR) and tested for potential mediators using 2-step MR. Our approach includes IVW and other MR methods and uses a variety of sensitivity tests to verify the robustness of the results. In 2-sample MR analysis, moderate physical activity was associated with delayed age at menopause (β = 0.64, 95% CI = [0.02–1.26], P = .04), but there was no evidence of a causal relationship between vigorous physical activity and age at menopause (P = .68).In contrast, a 2-step MR method showed that body mass index (BMI) mediated the effects of physical activity and delayed age at menopause (proportion mediated, 4.9%, 95% CI = 0.8 to 8%; P = .02), whereas the mediating effects of insomnia, hypertension and hyperglycemia were not significant. Our study shows that moderate physical activity can delay the age of menopause and is informative for the prevention of ovarian failure and the maintenance of women’s reproductive health.
The Use of External Anchors When Examining Differences in Scale Performance in Patient Experience Surveys
Authors: Abel Gary A. , Hays Ron D. , Campbell John L. , Elliott Marc N.
Published: February 2025

Objectives:

To present an example of using vignettes as an external anchor to assess measurement equivalence for patient experience measures.

Background:

Evaluating measurement equivalence and differences in scale use is helpful for identifying disparities in patient experience based on patient surveys. External anchors, often in the form of scored vignettes, provide an attractive approach to examining differences in scale use but are not commonly used.

Methods:

We analyzed a UK dataset based on the General Practice Patient Survey and a U.S. dataset based on the Consumer Assessment of Healthcare Providers and Systems Clinician and Group survey. A total of 560 White British and 560 Pakistani adults were recruited from various locations across England; 575 Asian American and 505 non-Hispanic White patients were recruited from an internet panel in the United States. Patient encounters and rated the quality of communication using 5 General Practice Patient Survey questions and 3 Consumer Assessment of Healthcare Providers and Systems Clinician and Group questions.

Results:

Using an external anchor in both United States and UK data produced substantial evidence of differential item functioning (DIF). However, an “internal” DIF analysis (without an external anchor) produced little evidence of DIF.

Conclusions:

Using an external anchor does not require the assumption made by internal methods that some items do not display between-group DIF. These assumptions may not hold for patient experience items if a single factor, such as extreme or negative response tendency, governs all items equally.