bluuebunny/crossref_metadata_2025 huggingface dataset:
RACIAL AND GENDER DISPARITIES IN THE DEVELOPMENT OF CROHN’S DISEASE COMPLICATIONS: A RETROSPECTIVE ANALYSIS
Authors: Iqbal Humzah , Haddadin Rakahn , Haidary Hasib , Zhang Patrick , Prajapati Devang
Published: January 2024

BACKGROUND

Crohn’s disease (CD) is a chronic systemic inflammatory disease that most commonly affects the gastrointestinal tract (GI) and is characterized by transmural inflammation. Complications of CD include fistulization, abscess formation, and GI bleed. CD predominantly affects patients with European ancestry, however Black and Hispanic patients have been noted to have phenotypic differences in disease presentation. Gender may also play a role in CD, with some studies suggesting that men develop more severe disease.

METHODS

Patients with a diagnosis of CD were identified using the 2020 Nationwide Inpatient Sample (NIS). Patients were stratified based on the presence of CD complications which included fistula, abscess, and bleed. Patients with complications were further stratified based on the specific complication. Data were collected regarding age, gender, race, primary insurance, median income, hospital region, hospital bed size, and comorbidities. The relationship between gender, race, and the development of fistula, abscess, or bleed among patients hospitalized with CD was analyzed using multivariate regression analysis.

RESULTS

A total of 178,279 patients with a diagnosis of CD were included in the study. Of these, 23,889 (13.4%) developed a complication of CD including fistula, abscess, or bleed. Female patients with CD had a statistically significant lower odds of developing a CD complication (aOR 0.79, P < 0.001). Higher odds of developing a complication of CD were seen in Black patients (aOR 1.47, P < 0.001) and Hispanic patients (aOR 1.29, P < 0.001). Black patients with CD had increased odds of developing fistula (aOR 1.35, P < 0.001), abscess (aOR 1.26, P = 0.004), and bleed (aOR 1.60, P < 0.001). Hispanic patients with CD had higher odds of developing a bleed (1.46, P < 0.001).

CONCLUSION

CD is a complex inflammatory process that is influenced by both genetic and environmental factors. Complications of CD such as fistulization, abscesses, and GI bleed are commonly seen. Our study found that women are at lower risk of developing these complications compared to men. Despite CD being primarily seen in White patients, our study found that Black and Hispanic patients are more likely to develop complications of CD. Further studies are needed to elucidate the socioeconomic and genetic factors that are responsible for these findings.

Inclusion process for the study.
IDENTIFYING THE ROLE OF ACINETOBACTER CALCOACETICUS IN DRIVING INTESTINAL INFLAMMATION
Authors: Glover Janiece , Sullivan Kaitlan , Browning Brittney , Ticer Taylor , Gutierrez Alyssa , Dooley Sarah , Engevik Amy , Hartman Jessica , Engevik Melinda
Published: January 2024

BACKGROUND

Inflammatory bowel disease (IBD) is a life-long condition characterized by chronic inflammation of the gastrointestinal tract. Among the potential causes of IBD, the gut microbiota has been implicated in perpetuating inflammation. Analysis of the IBD Transcriptome and Metatranscriptome Meta-Analysis (IBD TaMMA) database revealed that Acinetobacter calcoaceticus is one of the top 10 highest elevated bacteria in Crohn’s’ disease patients. Acinetobacter are well-characterized for their antibiotic resistance, but little is known about their interaction with the gut. We hypothesize that A. calcoaceticus colonizes the gut and promotes intestinal inflammation.

MATERIALS & RESULTS

We grew commercially available and clinical isolates of A. calcoaceticus in vitro with stressors found in the gut. All strains grew in a range of pHs (4-7), osmolarity (0.1-1 M NaCl), ethanol (1- 5%) and hydrogen peroxide (0.05-0.1%); indicating that A. calcoaceticus is well-adapted to withstand the harsher conditions of the gastrointestinal tract. To further investigate the ability of A. calcoaceticus to colonize the gut, we utilized Caenorhabditis elegans as a model. All A. calcoaceticus strains colonized the nematode's gut. We likewise found that all A. calcoaceticus strains colonized human stool-based bioreactors; suggesting that A. calcoaceticus can colonize the gastrointestinal tract. To identify whether A. calocaceticus stimulated inflammation, we incubated intestinal organoids and macrophages with live A. calcoaceticus or LPS derived from our A. calcaoceticus strains and found that both conditions stimulated pro-inflammatory cytokines. In order to confirm our in vitro findings, we oral gavaged adult BalbC mice with A. calcoaceticus and examined fecal levels using selective agar and qPCR. Acinetobacter was observed at low levels in the vehicle control mice and at high levels in our mice gavaged with A. calcoaceticus (average 9.9x 107 CFU); suggesting that A. calcoaceticus colonized the murine gut. To examine the ability of A. calcoaceticus to enhance inflammation, we oral gavaged mice with either a vehicle control (PBS) or A. calcoaceticus and the following day we administered 2,4,6-trinitrobenzene sulfonic acid (TNBS) to induce colitis. Mice treated with A. calcoaceticus and TNBS lost more weight and had worse histological scores than mice treated with vehicle control and TNBS; indicating A. calcoaceticus worsens intestinal inflammation. Finally, to expand the niche of Acinetobacter, we pre-treated mice with antibiotics and then subsequently administered bacteria and TNBS. In this model, A. calcoaceticus exacerbated inflammation above that of non-antibiotic treated mice.

CONCLUSIONS

These data show that A. calcoaceticus can promote intestinal inflammation and may be a contributing factor to the inflammation experienced by IBD patients.
MICROBIAL DRIVERS OF REGION-SPECIFIC SUSCEPTIBILITY TO CHRONIC, TNF-INDUCED INTESTINAL INFLAMMATION
Authors: Vega Paige , Wang Jiawei , Simmons Alan , Xu Yanwen , Yang Yilin , Ro James , Banerjee Amrita , Harned Mariah , Roland Joseph , Washington Mary , Liu Qi , Lau Ken
Published: January 2024

BACKGROUND

The majority of Crohn’s disease patients present with ileitis or ileocolitis, however, the factors that drive the development of inflammation in these different sites remain elusive. The TnfΔARE mouse model recapitulates many features of Crohn’s disease and is driven by systemic overexpression of TNF.

AIMS

To-date, the TnfΔARE model is published as a spontaneous intestinal inflammation model that is specific to the ileum, however, we observe severe colonic inflammation that is dependent on the murine housing facility. We aimed to use experimental approaches to investigate the epithelial and microbial factors that drive ileal and colonic inflammation in the TnfΔARE model of Crohn’s disease.

METHODS

Tnf ΔARE mice were housed in two murine housing facilities, termed “restrictive” and “permissive”. Pathological scoring was used to assess intestinal inflammation in TnfΔARE mice. Murine co-housing methods were used to expose non-colitic mice to those with colitis. Shotgun metagenomics was performed to determine differences in the intestinal microbiota between the two murine housing facilities. Doxycycline treatment was used to treat Chlamydia muridarum (CM) infection in mice. Various in vivo and in vitro perturbations were performed to test the role of intestinal epithelial cell expression of indoleamine 2,3-dioxygenase (IDO1) in ileal and colonic inflammation. Human single-cell RNA-sequencing (scRNA-seq) data, along with tissue samples, were analyzed to determine whether epithelial cell signaling pathways and microbiota were conserved in Crohn’s disease patients.

RESULTS

Tnf ΔARE mice from the restrictive murine housing facility developed the expected phenotype of ileitis, while TnfΔARE mice from the permissive murine housing facility developed ileocolitis. Upon co-housing, restrictive facility TnfΔARE mice develop ileocolitis. Permissive facility mice, but not restrictive facility mice, harbored the obligate intracellular bacterium CM in proximal colonic epithelia. Doxycycline treatment effectively cleared CM colonization and was associated with a reduction in colonic inflammation. IDO1 expression was upregulated in intestinal epithelial secretory cells in CM-infected mice and perturbation of this pathway resulted in a reduction of intestinal inflammation. Analysis of patient scRNA-seq and tissue samples revealed IDO1-expressing epithelial cells in the ascending colon and the presence of epithelia-associated microbiota.

CONCLUSION

Here, we associate CM infection with the development of ileocolitis the TnfΔARE mouse model of Crohn’s disease. We reveal the role of IDO1-expressing intestinal secretory cells in TnfΔARE mice with and without colonic involvement. Finally, we demonstrate conservation of these pathways and microbiota in human Crohn’s disease samples.
INFLAMED INTESTINAL ENDOTHELIAL CELLS ESTABLISH SELF-REGULATORY NICHES VIA IL16 DEPENDENT RECRUITMENT OF CD4 EXPRESSING VESSEL-ASSOCIATED MACROPHAGES
Authors: Ren Xingsheng , Manzanares Laura , Sumagin Ronen
Published: January 2024

Macrophages, play important roles in initiation and resolution of inflammation. Notably, a subset of tissue macrophages strategically localizes to the blood vessels, exerting essential regulatory functions at the blood-tissue interface, including regulation of vascular permeability and neutrophil (PMN) transendothelial migration (TEM). Although the number of vessel-associated macrophages (VAMs) is increased in inflamed tissue, the underlying mechanisms of VAMs recruitment are unknown.

Our current study uncovers a novel mechanism whereby inflamed intestinal vascular endothelial cells (ECs) release IL-16 to selectively recruit CD4+ tissue macrophages to become VAMs.

Whole-mount confocal microscopy studies in CX3CR1-EGFP macrophages reporter mice confirmed significant increases in VAMs numbers in several murine models of intestinal inflammation. Surprisingly, the majority of VAMs were found to express a classical T cell marker, CD4 and to be of an inflammatory phenotype, enriched for ICAM-1 and TNFα expression. VAMs-derived TNFα was previously found to prime ECs to form PMN TEM hot spots.

Whole genome mRNA sequencing, and flow cytometry protein expression analyses revealed heightened expression of the CD4 ligand, IL-16 by inflamed intestinal lamina propria ECs.

In vitro, using transwell assays, recombinant IL-16 and supernatants derived from murine (bEnds.3) endothelial cells induced robust migration of murine, LPS/IFNγ-stimulated bone marrow-derived macrophages. Whereas antibody-mediated IL-16 or CD4 neutralization in cultures and in vivo reduced VAMs recruitment.

Collectively, our findings establish CD4 as a novel marker of VAMs and identify the regulatory role of ECs IL-16 and macrophages CD4+ axis in VAMs recruitment in inflamed mucosal tissues.
VEDOLIZUMAB RESPONSE AND NON-RESPONSE IN ULCERATIVE COLITIS: INSIGHTS FROM SPATIAL TRANSCRIPTOMICS
Authors: Mennillo Elvira , Lee Gyehyun , Lotstein Madison , Tsui Jessica , Mahadevan Uma , Fragiadakis Gabriela , Combes Alexis , Kattah Michael
Published: January 2024

BACKGROUND

Vedolizumab (VDZ) is an anti-a4b7 integrin monoclonal antibody effective for treating ulcerative colitis (UC). The cellular and genetic factors that mediate VDZ response and non-response remain unclear. Our previous data employing different multi-omics revealed an impact of VDZ on myeloid dendritic cells (mDCs) and mononuclear phagocytes (MNPs), in addition to lymphocytes, influencing stromal and epithelial compartments.

METHODS

We performed a mass cytometry (CyTOF) experiment on peripheral blood and colon biopsies in healthy controls (HC, n=6), patients with UC on anti-TNF or 5-ASA (UC, n=5/6) and patients with UC on VDZ (UC-VDZ, n=5). Subsequently, we carried out a retrospective longitudinal spatial analysis using 1000-plex RNA and 62-plex protein CosMx on archived formalin-fixed paraffin-embedded (FFPE) biopsies before and after treatment in VDZ responders (VDZ-R) and non-responders (VDZ-NR) (Fig.1). Lastly, gene set enrichment analysis (GSEA) using VDZ response and non-response signatures obtained from our longitudinal spatial transcriptomic data were validated in an external publicly available dataset.

RESULTS

CyTOF results confirmed that VDZ is associated with a shift of a4b7+ cells from tissue to blood across multiple subsets. Spatial data showed elevated activated MNPs in UC compared to HC and UC-VDZ. Following treatment, these levels decreased in VDZ-R but increased in VDZ-NR. Neighborhood enrichment analysis revealed a trend toward increased proximity of activated fibroblasts and activated MNPs in UC, which was reduced following treatment. Furthermore, to explore differences pre-treatment, we performed pseudobulk differentially expressed (DE) gene analysis comparing VDZ-NR versus VDZ-R. Stromal and MNP-expressed genes including MMP1, MMP2, and THBS1 were among the top DE genes in VDZ-NR, while genes associated with the IEC crypt base including REG1A, OLFM4, AGR2, SPINK1, and LYZ were related to VDZ-R. GSEA confirmed significant enrichment of the identified VDZ-NR and VDZ-R gene signatures in patients pre-VDZ, aligning with their outcome. The VDZ-R signature was specific to VDZ and was not associated with anti-TNF response. The VDZ-NR signature was also associated with anti-TNF non-response.

CONCLUSION

Longitudinal spatial transcriptomics of archived FFPE specimens highlighted potential pathways associated with VDZ responsiveness, identifying epithelial-, MNP-, and fibroblast-enriched genes. Validation in an external dataset emphasized the specificity of the VDZ-associated response signature.

Fig1. a, Schematic of retrospective, longitudinal analysis of archived FFPE specimens using 1000-plex CosMx spatial transcriptomics of 126,368 cells. b, Dot plot representation of a subset of genes from pseudobulk DE gene analysis for the indicated subsets.
INFLAMMATORY BOWEL DISEASE IN YOUTH UNDER 20 FROM 1990-2019: A GLOBAL PERSPECTIVE ON REGIONAL AND NATIONAL VARIATIONS FROM THE GBD 2019 ANALYSIS
Authors: Patel Rahul , Mohammed Yassmeen Sharafeldin , Akula Sai Bhavani , Aramin Mohammed A S , Naradasu Pranathi Royal , Patel Sneh , Desai Hardik Dineshbhai
Published: January 2024

BACKGROUND

Inflammatory Bowel Disease (IBD) ranks as the 9th primary cause of mortality and the 10th main source of disability worldwide among individuals aged under 20. Grasping the worldwide implications for this age bracket is pivotal for shaping health care approaches and optimizing patient care.

METHOD

Leveraging the Global Burden of Disease instrument, we discerned the incidence, prevalence, mortality, and Disability Adjusted Life Years (DALYs) of IBD by age, gender, and year across 204 nations and territories spanning 1990-2019. The DisMod-MR 2.1 tool shed light on non-fatal health metrics like incidence and prevalence, whereas the Cause of Death Ensemble Model (CODEm) framework illuminated fatal health outcomes.

RESULTS

From 1990 to 2019, the overall prevalence of IBD escalated from 74,975 (95%UI: 60,678-92,219) to 88,828 (72,606-108,301), marking an Annual Percentage Change (APC) of 18% (16-22). Incidence exhibited an APC surge of 23% (20-26). Conversely, deaths and DALYs plummeted by 56% and 53% respectively during the same period. Delving into global regions, Sub-Saharan Africa noted a 6% death upswing, trailed by the African Union at 65% and Low SDI nations at 1%. Southeast Asia, East Asia, and Oceania recorded the steepest APC in age-standardized incidence rates at 67%, followed by High-SDI regions at 35%, OECD nations at 31%, and affluent countries at 30%. The 15-19 age bracket registered the most pronounced incidence rise by 24%. Males witnessed a steeper APC in incidence (24% vs. females at 21%) and prevalence (21% vs. females at 16%) from 1990-2019.

CONCLUSION

In 2019, IBD was responsible for 1.61% of all mortality linked to digestive diseases and contributed to 1.50% of the total digestive disease-induced disabilities. For pediatric clinicians, these findings underline the necessity for early intervention, tailored care strategies, and rigorous research into pediatric IBD. From a policy-making perspective, there is an urgent demand for resource allocation, enhanced public health campaigns, and international collaboration to mitigate the growing threat of IBD among the youth.

Source: Global Burden of Disease 2019, IHME
INSURANCE DENIALS AND DELAYS IN CARE FOR PEDIATRIC PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Behbahani-Nejad Pareenaz , Finkler Michael , Momotaz Hasina , Perry Sharon , Young Denise , Sferra Thomas , Moses Jonathan
Published: January 2024

INTRODUCTION

Biologics are effective medications used for induction and maintenance of remission in pediatric patients with inflammatory bowel disease (IBD). Insurance companies often require clinicians to obtain prior authorization (PA) prior to administration of biologics. Recent data determined that PA was associated with delays in care in pediatric IBD patients and an increased risk of subsequent healthcare utilization. Our study aim was to assess the effect of the PA process and its impact on care delivery for pediatric patients with IBD.

METHODS

A retrospective chart review of pediatric patients with IBD was conducted, including those with the diagnosis of ulcerative colitis or Crohn’s disease prescribed a biologic medication. Data obtained from medical records included demographics, IBD characteristics, insurance PAs, and clinical outcomes from 2015 to 2023. Outcome measures included time from initial PA submission to completion of the PA process, time from initial PA submission to first outpatient dose, frequency of insurance mandated medication changes, and number of hospitalizations for an inpatient dose. Analyses examined differences between those with PAs that were approved versus those who were initially denied.

RESULTS

We analyzed 134 patients who received a new biologic during our study period, of which 100 were newly diagnosed patients. Of the total sample, mean age was 12.5 years, 53.7% were male, with 96.2% non-Hispanic, 77.6% white, and 69.4% patients had Crohn’s disease. The most common medication prescribed was infliximab (81.3%). Of the patients in the approved group, 72.9% of patients had commercial insurance compared to 52.1% in the denied group (p=0.0152). Median time from initial PA submission to completion of PA process was 13 days for those denied vs. 3 days for those approved (p<0.0001). Of the patients denied, median time from initial PA submission to denial was 4 days (0-27) and median time from denial to subsequent approval was 7 days (0-75). Median time from initial PA submission to first outpatient dose was 30 days in the denied group vs. 13 days for the approved group (p<0.0001). 51% of patients in the denied group required hospitalization for their first biologic dose after PA initiation compared to 20% in the approved group (p=0.0002).

CONCLUSION

We found a significant delay in care for patients who received a prior authorization denial from insurance. Time from initial authorization submission to first dose was significantly different between the approved and denied groups. Prior authorization denials were also associated with significantly higher rate of hospitalizations for an infusion, potentially driving up overall cost of care.
IDENTIFYING FACTORS THAT WORSEN IN-HOSPITAL OUTCOMES IN PATIENTS WITH VENTRICULAR TACHYCARDIA (VT) AND INFLAMMATORY BOWEL DISEASE (IBD)
Authors: John Jason , Kapoor Akshay , Dasu Neethi , Khalid Yaser , Blair Brian , Joo Lucy
Published: January 2024

BACKGROUND

IBD is a proinflammatory state that can have numerous complications involving all systems of the body. There is a known association with cardiovascular disease. However, there are limited studies that have examined the impact of cardiac arrhythmias such as VT on patients with IBD (Crohn’s Disease and Ulcerative Colitis). The aim of this study was to evaluate the economic burden and various hospital outcomes associated with patients with IBD with and without VT.

METHODS

Patients aged 18 years with IBD and VT versus IBD alone were identified from the US Nationwide Inpatient Sample (NIS), from the years 2010-2019. ICD 9 and 10 codes were utilized and multivariate regression analysis utilizing propensity matching (Kernel method) was used to estimate the odds ratios of in-hospital mortality, the average length of hospital stay (LOS), and hospital charges (TOTHC), after adjusting for age, gender, race, primary insurance payer status, hospital type and size (number of beds), hospital region, hospital teaching status, and other demographic characteristics. Weighted analysis utilizing Stata 17 MP was performed.

RESULTS

For patients with Crohn’s disease and depression, mean age at readmission was 51.6 years and there was a high readmission rate and mortality at 30 days (readmission rate 5.2%, p<0.01 and mortality rate 2.8%, p<0.01) which increased significantly at 90 days (readmission rate 8.4%, p<0.01). Hospital LOS and TOCHG remained relatively the same compared to the index admission for both 30 day and 90 day readmissions (Table 1). A very similar trend was seen for UC and depression as well: mean age at readmission was 51.4 years and there was a high readmission rate and mortality at 30 days (readmission rate 5.0%, p<0.01 and mortality rate 2.6%, p<0.01) which increased significantly at 90 days (readmission rate 8.4%, p<0.01 and mortality rate 2.9%, p<0.01). The top 10 causes of readmission at 30 days and 90 days for both UC and Crohn’s are summarized in Table 1.

CONCLUSION

Our study revealed that patients with IBD and VT had increased mortality, LOS, and TOTHC were increased compared to patients with IBD only. Further studies are required to further evaluate this patient population.
DEPRESSION MAY BE A STRONGER UNIQUE PREDICTOR OF FATIGUE THAN SELF-REPORTED IBD DISEASE ACTIVITY
Authors: Duarte Brooke , Salwen-Deremer Jessica
Published: January 2024

Fatigue is a frequent and debilitating symptom of inflammatory bowel disease (IBD) and can include mental and physical exhaustion, tiredness, or weakness. Modifiable psychosocial factors, such as depression and anxiety, are associated with fatigue in IBD, and provide insight into potential treatment targets. However, little is known about distinct ways in which psychosocial factors relate to subtypes of fatigue. The current study examined associations between psychosocial factors and 5 fatigue subtypes: general, physical, mental, reduced motivation, and reduced activity.

Patients 18 and above from Dartmouth-Hitchcock’s IBD Center with Crohn’s disease or ulcerative colitis were invited to participate in a survey via an electronic medical record system message. Measures included the Patient Reported Outcomes-3, Multidimensional Fatigue Inventory, Pain Catastrophizing Scale, Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, Insomnia Severity Index, and Brief Pain Inventory. Five forward linear regressions were performed with step 1 including disease activity, step 2 including covariates (age, gender, IBD diagnosis) and step 3 allowing for the inclusion of insomnia, pain severity, depression, anxiety, and pain catastrophizing.

Participants were 312 individuals above the age of 18 (M=48.62, SD=16.10). Participants were 66.3% women and 96.5% White. 60.9% were diagnosed with Crohn’s disease and 39.1% with ulcerative colitis. 54.8% were categorized as having active disease based on self-reported symptoms. For all five subtypes of fatigue, depression emerged as the most influential psychosocial predictor. Depression accounted for 21% of the variance in general fatigue, 14% in physical fatigue, 18% in activity avoidance, 19% in reduced motivation, and 29% in mental fatigue. Regarding differences among subtypes, insomnia was only significant in the model predicting general fatigue, accounting for an additional 2% of the variance, and anxiety was only significant in the model predicting activity avoidance, accounting for an additional 3% of the variance. In comparison, self-reported disease activity accounted for 23% of the variance in general fatigue, 7% in physical fatigue, 8% in activity avoidance, 12% in reduced motivation, and 10% in mental fatigue.

Depression is a notable factor associated with all subtypes of fatigue in IBD, especially mental fatigue. There are differences in how psychosocial factors relate to fatigue subtypes such that anxiety is uniquely associated with activity avoidance and severity of insomnia is uniquely associated with general fatigue. Results suggest that assessment of fatigue in IBD should also include assessment of depression as standard of care. Additionally, helping patients engage in behavioral interventions to reduce depression, anxiety, and insomnia may be critical for managing fatigue.

Results of forward regressions predicting fatigue subtypes
INFLAMMATORY BOWEL DISEASE (IBD) COMMUNITY PREFERENCES FOR PSYCHOSOCIAL SUPPORT: THE ROLE AND SCOPE OF PEER SUPPORT FOR YOUTH WITH IBD
Authors: Bugwadia Amy , Dunn Ashley , Bensen Rachel , Wren Anava
Published: January 2024

INTRODUCTION

Youth with inflammatory bowel diseases (IBD) experience psychosocial challenges which can negatively impact their body image, self-efficacy, IBD symptoms, and risk of disease recurrence. Peer support programs have high desirability amongst IBD patients and can improve disease management skills, self-efficacy, and mental health generally. Existing peer support programs vary, ranging from one-on-one peer coaching to professionally-led support groups to IBD summer camps. However, there is limited research identifying best practices for peer support in IBD. Community-based participatory research (CBPR) is a framework that centers patient voices in all phases of research, providing an opportunity to equitably represent patient preferences in the development of peer support programs.

METHODS

Our mixed-methods community survey was disseminated across the US to adults eighteen or older with IBD via patient organizations. This survey assessed patient preferences for a peer support program, including structure (e.g., support group, 1:1 mentor, group activities) and program topics (e.g., body image, social life, medical care). Participants ranked these on a 5-point Likert scale (from “Not at all important” to “Extremely important”) and also had an open-ended opportunity to provide other topic suggestions. Given our CBPR approach, we recruited a Patient Advisory Board (PAB), composed of adults diagnosed with IBD in childhood, and conducted one-on-one interviews to assess patient perspectives of the survey results.

RESULTS

Our sample included 77 participants (mean age 29, 39.5% with ulcerative colitis, 60.5% with Crohn’s disease). Participants ranked doing non-IBD activities (e.g., games, meals) as quite a bit important, while IBD activities (e.g., IBD comic book) were ranked moderately important. PAB members emphasized that the strength of a patient-led support program is the shared experience and “normalcy” of having IBD, and that limiting a program to IBD activities wouldn’t allow for spontaneous conversation and trust-building. The average ranking of all topics surveyed fell between “extremely important” to “quite a bit important.” In order of importance, topics included navigating social life and mental health, increasing independence while growing older, planning for the future, communicating with the healthcare team, disclosure to friends, navigating school, body image, medical management, and nutrition. Themes suggested by participants included sexual intimacy, fertility, and advocacy. PAB members emphasized the role of peer support interventions as complementary to medical care, and specifically, how peer mentorship can allow for ‘real world’ examples of navigating life with IBD, outside traditional topics discussed in medical appointments. We will use this mixed-methods data to inform our design of a novel IBD peer support program.
THE COLONIC MUCOSAL MICROBIOME IN IBD-ASSOCIATED ARTHRITIS IS MORE VARIABLE THAN IN IBD ALONE
Authors: Alizadeh Madeline , Wong Uni , Siaton Bernadette , Patil Seema , George Lauren , Raufman Jean-Pierre , Scott William , von Rosenvinge Erik , Ravel Jacques , Cross Raymond
Published: January 2024

BACKGROUND

Inflammatory bowel disease (IBD)-associated arthritis affects over 25% of those with IBD and is associated with several risk factors including disease location. The intestinal microbiome varies throughout the intestinal tract and is thought to play a role in the development of IBD, although the precise mechanism remains unexplored. To better characterize its relationship with IBD-associated arthritis, we analyzed the intestinal microbiome from a subset of subjects in the LOCATION-IBD cohort.

METHODS

Microbiome analysis was performed on 16S rRNA V3V4 amplicon sequencing data generated from mucosal biopsies from the terminal ileum (TI), hepatic flexure (HF), and the distal descending colon (DDC) of participants in the LOCATION-IBD cohort. Alpha diversity was assessed using the Shannon index, while beta diversity between samples from the same participant were assessed using Jenson-Shannon Divergence (JSD). ZicoSeq was used to assess differential abundances in composition between those with vs without IBD-associated arthritis.

RESULTS

In this analysis, we included a subset of samples from participants in the LOCATION-IBD cohort with (n= 68 from 25 participants) and without (n = 86 from 29 participants) joint EIMs and with joint pain of unclear etiology (n= 14 from 5 participants). Overall, samples clustered predominantly based on participant, and similar genera were present across TI, HF, and DDC mucosal samples. Shannon diversity was similar across samples, regardless of the associated arthritis category, though diversity was lower in those with CD compared to those with UC (p-value = 0.0007, Tukey post-hoc p-value = 0.0004) and trended to be higher in sites of inflammation (p-value = 0.0645). JSDs between samples for an individual participant were higher for those with compared to those without IBD-associated arthritis (p-value = 0.038). In those with joint EIMs, Flavonifractor and Fusicatenibacter were significantly lower without accounting for sampling location, whereas other species including Lachnoclostridium (increased) and Fusobacterium (decreased) were noted in the proximal colon.

CONCLUSIONS

To our knowledge, this represents the first assessment of the mucosal microbiome across several intestinal sites in individuals with and without IBD-associated arthritis. Our finding that similar bacteria are found across the terminal ileum, proximal colon, and distal colon, but that less site-to-site concordance is seen in those with IBD-associated arthritis, aligns with previous findings that the involvement of specific colonic segments is associated with IBD-associated arthritis. Further, our finding that the abundances of specific bacteria are altered, frequently in a site-specific manner, identifies potential opportunities for future studies.
CLINICAL OUTCOMES OF INFLAMMATORY BOWEL DISEASE AFTER ORTHOTOPIC HEART TRANSPLANT
Authors: Kurdi Ahmed , Pardi Darrell , Loftus Edward , Kaur Manreet , Farraye Francis , Hashash Jana Al
Published: January 2024

BACKGROUND

Limited data are available on outcomes of patients with pre-existing inflammatory bowel disease (IBD) who undergo orthotopic heart transplantation (OHT) or develop de novo IBD post-OHT. We aimed to assess the incidence and disease outcomes of pre-existing and de novo IBD in OHT patients while evaluating the effect of IBD on OHT outcomes.

METHODS

A retrospective review of records was performed from a tri-site tertiary care system between July 2000 and July 2022. A total of 83 OHT receipients were concomitantly diagnosed with colitis of infectious or inflammatory etiology. Only patients with a diagnosis of IBD were included. Sub-analyses of the outcomes and immunosuppressive regimens of OHT recepients were done relative to those with pre-existing or de novo IBD.

RESULTS

A total of 8 OHT patients with concomitant IBD were identified. The median patient age (IQR) was 54 (23) with OHT and IBD onset at 50 (21.2) and 32.5 (15.7), respectively. Six patients were diagnosed with ulcerative colitis (UC) and 2 were diagnosed with Crohn’s disease. Five of the patients were female. All patients developed IBD within 11.5 (8) years within OHT. Only 1 patient developed de novo IBD 15 years after the first OHT and 7 years prior to a second OHT. OHT immunosuppressive regimens included a combination of tacrolimus (TAC) and prednisone (n=2), TAC and mycophenolate mofetil (MMF) (n=2), TAC, MMF, and sirolimus (n=2), TAC and sirolimus (n=1), and MMF with sirolimus (n=1). Therapy for pre-existing IBD included maintenance of 5-aminosalicylic (5-ASA) (n=3), escalation to vedolizumab (VD) (n=2), and discontinuation of IBD therapy (5-ASA and azathioprine) (n=3). De novo IBD consistent with UC (15 years post-OHT) was managed with 5-ASA (n=1). Six patients (including de novo IBD case) maintained clinical and endoscopic remission of IBD with no flares post-OHT while 2 patients (1 UC and 1 CD) with active disease flares responded clinically and endoscopically to VD escalation from 5-ASA and azathioprine. Among two UC patients with ileal J-pouch pre-OHT, 1 developed refractory pouchitis requiring diverting ileostomy (while on TAC and prednisone) with no pouchitis in the other (maintained on TAC and MMF). Good graft tolerance limited to mild acute cellular rejection episodes was noted in 6 patients, while multiple or no rejection episodes were noted in the remaining two. None of the patients developed CMV or MMF-induced colitis. One patient died due to progressive functional decline unrelated to graft failure or IBD.

DISCUSSION

The clinical course and treatment of IBD preceding OHT or de novo (though rare) is not significantly worsened or altered post-OHT. The majority of patients achieve clinical and endoscopic remission while on heart transplant-related immunosuppression. Biologic therapy escalation to VD resulted in clinical remission with no effect on graft tolerance.

Table 1 Clinical outcomes of OHT patients with concomitant IBD
FROM RESISTANCE TO RESPONSE: 52 WEEKS OF SUBCUTANEOUS INFLIXIMAB IN REFRACTORY CROHN'S DISEASE PATIENTS AFTER THE MULTIPLE TREATMENT FAILURES
Authors: Lukas Milan , Cerna Karin , Duricova Dana , Lukas Martin
Published: January 2024

BACKGROUND

Infliximab (IFX), an anti-TNFα monoclonal antibody, has been utilized since the late 1990s as an effective therapeutic agent for the treatment of Crohn's disease (CD). Since 2020, subcutaneous IFX (IFX-SC) has been available for treating CD. This study aimed to conduct a 52-week observation of IFX-SC treatment in refractory CD patients who had failed on at least two previous lines of biologic therapy patients.

MATERIALS AND METHODS

The study included 32 patients diagnosed with CD who had failed on 2 to 7 previous lines of biological therapy. Observed cohort was monitored at weeks W0, W4, W14, W30, and W52, recording Harvey-Bradshaw Index (HBI) , C-reactive protein (CRP) and fecal calprotectin (FC) concentrations, trough infliximab (TL-IFX) and anti-infliximab (anti-IFX) serum levels. Endoscopic, ultrasonographic and magnetic resonance disease scores (SES-CD, IUS and MaRIA) were determined at baseline and W52.

RESULTS

52-week persistence on IFX-SC treatment was recorded in 18 out of 32 patients (56.3%). A significant decrease of HBI (P <0 .0001), CRP (P =0 .0035), FC (P =0.0012), SES-CD (P =0.013), IUS (P =0.0034) and MaRIA (P =0.0261) was observed. TL IFX increased significantly (.0073), and median TL-IFX levels reached 19.75 μg/mL at W52. During the therapy, 8 out of 16 initially anti-IFX positive individuals seroconverted to negative anti-IFX (50 %); no new sensitization to IFX was recorded in the cohort. None of the patients treated with IFX-SC in W52 needed concomitant immune-modifying treatment. Baseline clinical, laboratory, and imaging markers did not demonstrate any predictive value for IFX-SC treatment failure, except for baseline high levels of anti-IFX (P = <0.0001).

CONCLUSION

In the cohort of refractory CD patients, over half achieved one-year treatment persistence on IFX-SC, displaying a highly favorable trend in all disease activity markers. The IFX-SC treatment appears to be effective and safe; however, further research is needed to identify potential predictors of therapeutic responsiveness.

Acknowledgement: This work was supported by the IBD-COMFORT Foundation
PATIENT PERCEPTIONS OF ENDOSCOPIC TESTING IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE
Authors: Duncan Eric , Sanon Myrlene , Griffo Cindy , Amatelli Doreen , Barthelmes Jennifer , Wirth Daniel , Kachroo Sumesh , Lee Rebecca , Hoops Timothy , Naessens Dominik
Published: January 2024

BACKGROUND

Inflammatory bowel disease (IBD) is associated with significant patient and societal burden. Treatments for IBD have traditionally focused on symptom management. However, clinical guidelines (Selecting Therapeutic Targets in Inflammatory Bowel Disease [STRIDE] II) now recommend treat-to-target approaches. Mucosal healing on endoscopy is becoming a key prognostic parameter in the management of IBD. In light of new guidelines, we aimed to qualitatively assess patient understanding of, and perspectives on, endoscopic measures in the context of disease monitoring and assessing treatment impact.

METHODS

Twenty patients diagnosed with IBD across the United States, United Kingdom, Spain, Italy, and France participated in TeleWebs (web-enabled phone interviews; United Kingdom, Spain, Italy, France) or a 5-day online bulletin board exchange (United States) discussing their condition and experiences. Specific information regarding disease history, conversations with physicians, experiences with endoscopy, and reactions to information shared on endoscopy were captured over a 5-day period. All respondents were recruited from double opt-in volunteer consumer market research panels.

RESULTS

Patients generally link disease remission to the absence of symptoms. Knowledge and perceptions of endoscopic measurements are largely driven by their physician perspectives and explanation to patients. Some patients are aware of healthy mucosa as a key part of remission, while others have no concept of the term. Patients report they find it psychologically reassuring to know that they are “healthy inside”. Due to its value, most patients are willing (5.7 on a 1 to 7 Likert Scale) to undergo endoscopy annually, but would be reluctant to do so more frequently. Table 1 outlines barriers and drivers reported by patients on the adoption of endoscopy.

CONCLUSION

The insight from this study provides understanding of patient perceptions of endoscopy and its place in treating their IBD. This study demonstrates that despite the barriers to the use of endoscopy, patients recognize its clinical relevance for disease management and are willing to periodically undergo a procedure.
RISANKIZUMAB DOSE ESCALATION IN PATIENTS WITH CROHN'S DISEASE
Authors: Nichols Patrick , Kozlicki Miranda , Fann Jessica , Zuckerman Autumn , Dalal Robin
Published: January 2024

BACKGROUND

Patients (pts) who do not achieve optimal response at standard dosing of biologic therapies or lose response over time often benefit from escalated doses of biologic therapies to manage moderate to severe Crohn’s disease (CD). Currently, no data exists on dose escalating risankizumab, an interleukin-23 inhibitor recently approved for the treatment of moderate to severe CD. This cohort study aimed to describe pt characteristics, insurance access, and response to therapy in pts prescribed risankizumab more frequently than the FDA-approved maintenance dosing of 180mg or 360mg every 8 weeks (wks).

METHODS

We conducted a retrospective single-center cohort study of pts with CD who were initiated on an escalated dose of risankizumab between June 2022 and July 2023. Pts must have received at least one escalated dose during the defined time frame for inclusion. Pt and disease characteristics, steps required to secure insurance access, and early treatment outcomes were collected from the electronic health record and reported descriptively.

RESULTS

A total of 211 pts completed three standard risankizumab intravenous induction infusions during the study period. Twelve pts were initiated on an escalated maintenance dosing frequency. All 12 pts received the 360mg dose. Seven pts were escalated to a frequency of every 6 wks (58%) and 5 pts were escalated to every 4 wks (42%). Pts were mostly female (67%) with a median age of 42 years (interquartile range [IQR] 30-52). The median number of previous biologic/small molecule drug failures was 4 (IQR 2-5). Eleven (92%) pts previously required a dose escalated biologic, the median years since diagnosis was 15 (IQR 10-17), and median body mass index was 25 kg/m2 (IQR 22-27). Six pts (50%) previously required surgical intervention. Pts received a median of 3 (IQR 2-3) risankizumab injections on standard dosing before a decision to escalate was made. Reasons for escalated dosing included colonoscopy/imaging/pathology results showing inflammation (n=7) or persistent symptoms (n=5). Five (42%) pts were able to access the escalated dose without an additional authorization, 5 (42%) required a prior authorization that was approved, and 2 (17%) required at least one level of appeal or peer to peer review. Through 10/03/2023, 6 pts had a documented improved response to the escalated dosing (50%), 3 remained stable (25%) and 3 had no change (25%) at a median of 88 days (IQR 72-103) from escalation.

CONCLUSION

This study demonstrated the need for heavily treatment-experienced pts with severe CD to dose escalate risankizumab, often requiring an additional insurance authorization. Most pts improved or remained stable on the escalated dosing, showing promise for risankizumab dose escalation outcomes. More research is needed to assess risankizumab dose escalation long-term outcomes and the role of trough levels.
The effects of torula yeast as a protein source on apparent total tract digestibility, inflammatory markers, and fecal microbiota dysbiosis index in Labrador Retrievers with chronically poor stool quality
Authors: Timlin Claire L , Dickerson Sarah M , Fowler Jason W , Mccracken Fiona B , Skaggs Patrick M , Ekmay Ricardo , Coon Craig N
Published: January 2024

This study examined the effects of varying protein sources on apparent total tract digestibility, inflammatory markers, and fecal microbiota in Labrador Retrievers with historically poor stool quality. Thirty dogs (15 male, 15 female; aged 0.93 to 11.7 yr) with stool quality scores ≤2.5 on a 5-point scale (1 representing liquid stool and 5 representing firm stool) were randomly assigned to 1 of 3 nutritionally complete diets with differing protein sources and similar macronutrient profiles: 1) chicken meal (n = 10); 2) 10% brewer’s yeast (n = 10); or 3) 10% torula yeast (n = 10). Another 10 dogs (five male, five female) with normal stool quality (scores ranging from 3 to 4) received diet 1 and served as negative control (NC). All dogs were fed diet 1 for 7 days, then provided their assigned treatment diets from days 7 to 37. Daily stool scores and weekly body weights were recorded. On days 7, 21, and 36, blood serum was analyzed for c-reactive protein (CRP), and feces for calgranulin C (S100A12), α1-proteinase inhibitor (α1-PI), calprotectin, and microbiota dysbiosis index. Apparent total tract digestibility was assessed using the indicator method with 2 g titanium dioxide administered via oral capsules. Stool scores were greater in NC (P < 0.01) as designed but not affected by treatment × time interaction (P = 0.64). Body weight was greater (P = 0.01) and CRP lower (P < 0.01) in NC dogs. Dry matter and nitrogen-free extract digestibility did not differ among groups (P ≥ 0.14). Negative controls had greater fat digestibility compared to BY (94.64 ± 1.33% vs. 91.65 ± 1.25%; P = 0.02). The overall effect of treatment was significant for protein digestibility (P = 0.03), but there were no differences in individual post hoc comparisons (P ≥ 0.07). Treatment did not affect S100A12 or α1-PI (P ≥ 0.44). Calprotectin decreased at a greater rate over time in TY (P < 0.01). The dysbiosis index score for BY and TY fluctuated less over time (P = 0.01). Blautia (P = 0.03) and Clostridium hiranonis (P = 0.05) abundances were reduced in BY and TY. Dogs with chronically poor stool quality experienced reduced body weights and increased serum CRP, but TY numerically increased protein digestibility, altered the microbiome, and reduced fecal calprotectin. Torula yeast is a suitable alternative protein source in extruded canine diets, but further research is needed to understand the long-term potential for improving the plane of nutrition and modulating gut health.
Sexual Role Functioning, Sexual Satisfaction, and Intimacy After Surviving Burn Injuries: A Scoping Review of Associated Factors, Screening Tools, and Burn Care Staff Preparedness
Authors: Bayuo Jonathan , Wong Arkers Kwan Ching , Wong Frances Kam Yuet , Baffour Prince Kyei , Kuug Anthony Kolsabilik
Published: January 2024

Although concerns regarding intimacy abound among burn survivors, these are often not captured during rehabilitation. Considering that sexuality remains a part of humans suggests a critical need to pay attention to this aspect. To guide further work, this review sought to examine existing studies to ascertain what is known about factors associated with sexual role functioning, sexual satisfaction, and intimacy, the scree ning tools employed, and the preparedness of burn care staff in initiating discussions about these. We employed a scoping review approach with extensive searches in 4 peer-reviewed databases for studies reporting on the phenomenon, published in English from 2010 to date. A total of 17 studies comprising of 13 studies reporting on the burn survivors and 4 reporting on burn care staff were retained. Though we identified both sociodemographic and clinical factors associated with postburn sexual role functioning, sexual satisfaction, and intimacy, the existing evidence appear limited which made it rather difficult to draw definitive conclusions. The sexuality subscale of the Burn-Specific Health Scale-Brief emerged as the commonly used screening/assessment tool. The evidence suggest that burn care staff are generally unprepared to initiate discussions regarding sexual role functioning, sexual satisfaction, and intimacy and often, there is no personnel assigned to this task. There is a great need for studies to strengthen the evidence base regarding the factors associated with postburn sexual role functioning, sexual satisfaction, and intimacy. In addition, it is imperative to build capacity of burn care practitioners with the requisite know-how needed to navigate through sexual issues.