bluuebunny/crossref_metadata_2025 huggingface dataset:
SHORT NONCODING RNAS AS PREDICTIVE BIOMARKERS FOR THE DEVELOPMENT FROM INFLAMMATORY BOWEL DISEASE UNCLASSIFIED TO CROHN’S DISEASE OR ULCERATIVE COLITIS
Authors: James Jaslin , Riis Lene , Sokilde Rolf , Malham Mikkel , Høgdall Estrid , Langholz Ebbe , Nielsen Boye S
Published: January 2024

BACKGROUND

Numerous pathogenic processes are mediated by short noncoding RNAs (ncRNA). Twenty percent of inflammatory bowel disease (IBD) patients are labelled as IBD unclassified (IBDU) at disease onset. Most IBDU patients are reclassified as Crohn's disease (CD) or ulcerative colitis (UC) within few years. Since the therapeutic methods for CD and UC differ, biomarkers that can forecast the categorization of IBDU into CD or UC are highly desired. Here, we investigated whether short ncRNAs can predict CD or UC among IBDU patients.

METHODS

Of 35 IBDU patients initially diagnosed with IBDU, 12, 15, and eight were reclassified into CD(IBDU-CD), UC(IBDU-UC), or remained as IBDU(IBDU-IBDU) respectively. Eight IBD patients, were included as references. Short ncRNA profiling on RNA from mucosal biopsies were performed using Affymetrix miRNA 4.0 array. Selected probe sets were validated using RT-qPCR.

RESULTS

Among all patients and only adults, 306 and 499 probe sets respectively were differentially expressed between IBDU-CD and IBDU-UC. Six of the probe sets were evaluated by RT-qPCR, of which miR-182-5p, miR-451a and ENSG00000239080 (snoU13) together with age and sex resulted in an AUC of 78.6% (95 % CI: 60 - 97) in discriminating IBDU-CD from IBDU-UC.

CONCLUSIONS

Based on the three-short ncRNAs profile it is possible to predict if IBDU patients within 3 years will be reclassified as CD or UC. We showed that the expression profile of IBDU patients differ from that of definite CD or UC, suggesting that a subgroup of IBDU patients may compose a third unique IBD subtype.
VEDOLIZUMAB DOES NOT ALTER IMMUNOGLOBULIN LEVELS IN BREASTMILK OF MOTHERS WITH IBD
Authors: Urrete Josef , Mitra Taniya , Bertrand Kerri , Chambers Christina , Rivera-Nieves Jesus
Published: January 2024

Diarrheal diseases are a major cause of infant mortality worldwide. Breastfeeding helps prevent such diseases by passive transfer of maternal antibodies against gastrointestinal pathogens previously encountered by the mother. The antibody secreting cells (ASC) that populate the lactating mammary gland (LMG) are educated in gastrointestinal lymphoid tissues, thus they express integrin a4b7. To recruit these ASC, the LMG expresses MAdCAM-1 and CCL28. Vedolizumab (vedo) blocks a combinatorial epitope on integrin a4b7, interfering with lymphocyte recruitment to the gut. Given the shared homing determinants between the gut and LMG, we investigated whether vedo might interfere with ASC trafficking to the LMG, therefore decreasing immunoglobulin (Ig) levels in breast milk.

We measured Ig levels by ELISA in cryopreserved breast milk from mothers enrolled in Mommy’s Milk biorepository at the University of California, San Diego without and with Ulcerative Colitis(UC) or Crohn’s Disease(CD) and lactating mothers with UC and CD treated with vedo for more than 18 months. Milk samples were collected between 1 month and 15.45 months after childbirth.

The levels of secretory IgA (SIgA) in breast milk of mothers without IBD (n=45) was not different from those of mothers with CD not on vedo (n=15) (301 ± 147 ug/mL vs. 322 ± 207 ug/mL). However, milk SIgA from mothers with UC not on vedo (n=7) were lower than non-IBD controls (213 ± 149 ug/mL vs. 301 ± 147ug/mL, p<0.01). We then compared milk SIgA from patients with CD and UC treated with vedo (CD: n= 9; 256 ± 80ug/mL, UC: n=10; 283 ± 87 ug/mL) with those from non-IBD controls (n=45; 301 ± 147ug/mL) and found no differences. Similarly, SIgA levels were not different between CD with or without vedo (256 ± 80 ug/mL vs. 322 ± 207 ug/mL) and as compared with non-IBD controls SIgA in patients with UC with vedo were unexpectedly higher than UC without vedo (283 ±87 ug/mL vs 213 ± 149 ug/mL, p<0.05).

The levels of secretory IgM (SIgM) in milk were not different between mothers with UC or CD treated with vedo compared with non-IBD controls (65 ± 34 ug/mL, 69 ± 32 ug/mL, and 56 ± 37 ug/mL, respectively). Similarly, no significant difference was seen between patients with UC or CD not treated with vedo compared with the non-IBD controls (58±26 ug/mL, and 46 ± 24 ug/mL respectively).

We conclude that vedo does not reduce SIgA nor SIgM levels in lactating mothers with IBD. We speculate that the higher SIgA in patients with UC treated with vedo is due to the small sample size. Vedo does not interfere with passive immunity during the lactation period, thus ASC must be able to use another integrin to arrest on microvessels of the LMG during the final stages of pregnancy.
THE PRACTICE AND PERCEPTION OF LOW RESIDUE DIETS IN ADULT PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Wang Jingzhou , Constant Brad , Morrow Ryan , Funk Sarah , Marden Tyson , Scott Frank
Published: January 2024

BACKGROUND

Low residue diets have been traditionally recommended during disease flares or post-operatively in patients with inflammatory bowel disease (IBD) for the purported benefits of reduced pain or lower risk of bowel obstruction. However, these diets may not be healthy if consumed long-term and can adversely impact quality of life. It remains controversial whether such diets are truly beneficial, and the scale of such dietary practice remains unknown.

METHODS

A survey was conducted to better understand the practice and the perception related to low residue diet recommendations among patients with IBD at a large academic medical system in the United States. Adult patients (age ≥18) with an established diagnosis of IBD were identified using ICD-10 codes in the electronic medical record system. The survey contained 23 questions and was disseminated electronically from August 2023 to October 2023.

RESULTS

132 patients (Crohn’s disease: 59, ulcerative colitis: 68, IBD-unclassified: 5) completed the online survey. The median age was 54 years (IQR 41, 67), with a median disease duration of 15 years (IQR 8, 30). Sixty percent of respondents were female. The majority of respondents (57%) reported currently receiving a biologic therapy. 14 (11%) patients reported currently following a low residue diet, and 34 (25%) reported following the diet in the past. Subjects followed the diet for a median duration of 18 months (IQR 6, 72). Among the 48 patients who followed a low residue diet, 33 (69%) reported using the diet to help with disease flare, while 23 (48%) did so to improve IBD symptoms and an additional 9 patients (19%) reported using a low residue diet post-operatively. 32 (67%) were instructed by their healthcare providers to follow this diet; however, only 4 of them were told not to continue this diet indefinitely. Low residue diets were reported to be “very helpful” (n=14, 29%) or “helpful” (n=18, 38%) in improving IBD symptoms. This benefit consisted of reducing pain (65%), bloating (60%), bowel movement frequency (44%), or urgency (38%). However, respondents noted significant adverse impact on quality of life from a low residue diet: 96% reported that the diet at least moderately limited them from eating foods they enjoyed, and 90% reported that it prevented them from eating what they perceived to be a healthy diet.

CONCLUSION

Within this cohort of individuals with IBD, 36% of survey respondents either followed or had followed a low residue diet. While up to 65% of individuals felt that this may improve abdominal pain, bloating, or other symptoms, almost all individuals felt such a diet limited their intake of foods they enjoy and from eating a healthy diet. Further education is required for providers regarding screening for low residue diet use and its appropriate indications to reduce its negative impact on quality of life.
THE RELATIONSHIP OF DIET INTERVENTIONS TO QUALITY OF LIFE IN ADULTS WITH INFLAMMATORY BOWEL DISEASE: A NARRATIVE REVIEW
Authors: Preston Rebekah , Knol Linda , Douglas Joy
Published: January 2024

BACKGROUND

Inflammatory bowel disease (IBD) can negatively impact quality of life (QOL) due to symptoms associated with chronic inflammation within the gastrointestinal (GI) tract. Dietary changes may offer some symptom relief, thus increasing QOL; however, the optimal dietary pattern to improve symptoms in IBD is unknown. The purpose of this review was to investigate the association between various dietary interventions and QOL in adults with IBD.

METHODS

A search strategy was developed using PRISMA guidelines. EBSCOhost was used to simultaneously search eight databases using key terms including ‘inflammatory bowel disease’ or ‘IBD’ or ‘ulcerative colitis’ or ‘Crohn’s disease’ AND ‘dietary interventions’ or ‘dietary advice’ or’ dietary recommendations.’ Relevant publications were hand-searched to identify additional studies. Included studies reported a dietary pattern intervention with QOL as an outcome measure. Studies that did not include adults, a dietary intervention, or a QOL measure were excluded.

RESULTS

After reviewing abstracts of 1,054 studies identified in the initial search, 13 studies met the inclusion criteria. Among these studies, dietary interventions differed and included the low fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAP) diet (n=4), Immunoglobulin G (IgG) diet (n=2), Autoimmune Protocol Diet (AIP) (n=1), Dietary Modified Program (DMP) (n=1), Dietary Modified Framework (DMF) (n=1), Mediterranean diet (n=2), and a high fiber diet (n=2). QOL was measured using various validated questionnaires. Results were inconsistent across studies. Significant improvements in QOL were found using the AIP, DMP, Mediterranean diet, and a high fiber diet. Two of the four low FODMAP studies and one of the two IgG diet studies found significant improvements in QOL, whereas the other three did not. Additionally, the DMF did not significantly improve QOL. It should be noted that the reviewed studies were limited to small sample sizes, a lack of diversity among participants, and short durations. Only one study assessed changes after elimination and reintroduction of suspected trigger foods. A nutrition professional was involved with the dietary intervention in 12 of the 13 studies.

CONCLUSION

Overall, adults with IBD reported improved QOL using a variety of dietary approaches. These approaches aimed to reduce symptoms by reducing foods that may increase inflammation, adding specific foods known to reduce inflammation, or a combination of the two approaches. These dietary approaches are complex and may be difficult to implement. Thus, the Registered Dietitian is needed to tailor dietary approaches to meet the nutrient needs and accommodate the lifestyles of adults with IBD. Additionally, there is a need for additional studies with larger samples sizes, more diverse populations, and additional follow-up periods.
WESTERN DIET DEPLETES SMALL INTESTINAL INTRAEPITHELIAL LYMPHOCYTES VIA FXR-INTERFERON PATHWAY
Authors: Ma Changqing , Trsan Tihana , Mishra Richa , Frein Jennifer , Kern Justin , Jain Umang , Colonna Marco , Stappenbeck Thaddeus , Liu Ta-Chiang
Published: January 2024

BACKGROUND

The prevalence of obesity has continued to increase over the past several decades. Understanding how diet-induced obesity modulates mucosal immunity is of clinical relevance. We previously showed that consumption of a high fat, high sugar “Western” diet (WD) reduces the density and function of small intestinal Paneth cells, a small intestinal epithelial cell type with innate immune function. We hypothesized that obesity could also result in repressed adaptive immunity.

METHODS

Small intestine samples from non-inflammatory bowel disease (IBD) subjects who underwent resection were used for CD3 immunohistochemistry (IHC), and the CD3+ intraepithelial lymphocytes (IEL) densities were correlated with the patients’ body mass index (BMI). Mice were fed with either standard diet (SD) or WD for various durations, and IELs were isolated for flow cytometry analysis.

RESULTS

In non-IBD subjects, high BMI correlated with reduced IEL density. We recapitulated this in wild type (WT) mice fed with WD. A 4-week WD consumption was able to deplete IEL (including major subsets CD4+, CD8+, CD8α+8β-CD4+, and γδCD8+ T cells) but not splenic lymphocytes, and the effect was reversible after another 4 weeks of SD washout. ob/ob mice that spontaneously developed obesity while fed with SD did not show IEL depletion, suggesting that the quality, not the quantity of the diet is key to this phenotype. Importantly, WD-associated IEL depletion was not dependent on the presence of gut microbiota, as WD-fed germ-free mice also showed IEL depletion. We previously showed that a key molecular pathway activated by WD in the ileum is the FXR pathway. Phagocyte-specific Fxr conditional knockout (cKO) mice were protected from WD-mediated IEL depletion, suggesting that FXR activation in the phagocytes is critical in mediating this phenotype. Activated FXR signaling stimulated phagocytes to secrete type I interferon (IFN), and inhibition of type I IFN signaling within the phagocytes (type I IFN monoclonal antibody treatment and Stat1 cKO mice) prevented WD-mediated IEL loss.

CONCLUSION

WD consumption depletes IEL by a FXR-IFN pathway mediated by gut phagocytes. These findings have significant clinical implications in understanding the pathogenesis of gut inflammatory disorders such as IBD.
CONTINUOUS MONITORING OF CRP, IL-6, AND CALPROTECTIN IN INFLAMMATORY BOWEL DISEASE USING A PERSPIRATION BASED WEARABLE
Authors: Shahub Sarah , Kumar Ruchita Mahesh , Lin Kai-chun , Banga Ivneet Kaur , Choi Natalie , Garcia Nicole , Muthukumar Sriram , Rubin David , Prasad Shalini
Published: January 2024

BACKGROUND

Wearable sensor devices represent a noninvasive technology to continuously track biomarkers linked to inflammatory bowel disease (IBD). We assessed the inflammatory markers associated with IBD in human perspiration.

METHODS

Participants with IBD were monitored for 40-130 minutes with a proprietary wearable sensor device used to measure C-reactive protein (CRP), interleukin-6 (IL-6), and calprotectin. Sensor response using Electrochemical Impedance Spectroscopy (EIS) and serum samples were measured on the same day. Mann Whitney test was used to analyze the relationship between active and remission IBD in serum and perspiration, classified according to endoscopic reports and serum biomarker levels. Asynchronously collected fecal calprotectin from a subset of the population was similarly analyzed.

RESULTS

A total of 33 subjects were enrolled. Expression of CRP in perspiration and serum were comparable between Active and Remission cohorts (p>0.05). Median expression of IL-6 in perspiration was elevated in the Active cohort compared to Remission cohort, and significantly elevated in serum (p<0.05). Expression of calprotectin in perspiration, serum, and stool were significantly elevated in the Active cohort compared to Remission cohort (p<0.05). Temporal data for three ulcerative colitis and Crohn’s disease patients provided insight into the basal levels of the markers across different disease states.

CONCLUSIONS

We demonstrate the clinical utility of perspiration as a noninvasive medium for continuous measurement of inflammatory markers in IBD and find that the measures correlate with serum and stool markers across a range of disease activity.

Positive linear relationship between serum and sweat of all markers.

Serum and sweat levels of both Calprotectin and CRP demonstrate strong linear relationship between mediums.

Serum and sweat levels of IL6 demonstrate moderate linear relationship and high homoscedasticity.
EXPLORING THE RELATIONSHIP BETWEEN PATIENT SYMPTOMS AND PROVIDER GOALS FOR MUCOSAL HEALING IN IBD: INSIGHTS FROM THE IBD QORUS SURVEY DATA
Authors: Troia Angela , Kiparizoska Sara , Harvey Sarah , Weaver Alandra , Oberai Ridhima , Melmed Gil , Siegel Corey , Singh Siddharth , Mattar Mark
Published: January 2024

INTRODUCTION

Patients with inflammatory bowel disease (IBD) often experience symptoms such as abdominal pain, diarrhea, and bloody bowel movements. While these symptoms traditionally guided treatment, their predictive value for disease progression is limited. The latest STRIDE-II guidelines recommend a comprehensive IBD management approach, with an emphasis on short-term symptom relief, intermediate-term biomarker normalization, and long-term achievement of endoscopic remission. This treat-to-target strategy necessitates collaboration between physicians and patients. Our study aims to investigate the relationship between patient-reported outcomes and physician efforts to achieve mucosal healing (MH) using IBD QORUS patient and provider survey data.

METHODS

This was a multi-center prospective study that used patient and provider matched survey data from the Crohn’s & Colitis Foundation IBD QORUS program. Surveys completed between June 2021-October 2022 were analyzed. Univariate and multivariate analyses were performed to determine the relationship between severity of patient reported symptoms and frequency of MH assessment with modalities including endoscopy and fecal calprotectin, as well as to determine how symptoms and MH status influence treatment.

RESULTS

In total 5,460 paired patient and provider surveys (Crohn’s disease (CD), n=3,276; ulcerative colitis (UC), n=2,184) were included in the analysis. Demographic information including age, sex and steroid-free MH, as well as severity of patient-reported symptoms were similar between CD and UC patients (Table 1). Abdominal pain severity reported by both IBD populations significantly impacted plans for future endoscopy (CD, p=0.000019; UC, p=0.000055) but not for fecal calprotectin testing. Reported stool frequency in both IBD populations significantly impacted future endoscopy plans (CD, p=0.000001; UC, p=0.000001) and future fecal calprotectin testing (CD, p=0.000304; UC, p=0.000001). Reported blood in stool had no effect on MH assessment in CD patients whereas it significantly affected plans for endoscopy (p=0.000001) and fecal calprotectin testing (p=0.000001) in UC patients. Provider discussions regarding MH occurred with 82.4% of CD patients and 85.3% of UC patients, and treatment plans in those without steroid free MH were influenced by severity of symptoms (p=0.000001).

DISCUSSION

Patient reported symptoms influenced fecal calprotectin and endoscopy plans in both IBD groups. Similarly, severity of symptoms in those without steroid-free MH significantly affected treatment management. These findings suggest that target-based treatment for IBD is feasible in the clinical setting and holds the potential to enhance patient outcomes.
FREE AIR FROM WHERE? SPONTANEOUS PNEUMOMEDIASTINUM AND SUBCUTANEOUS EMPHYSEMA IN A PATIENT WITH ULCERATIVE COLITIS IN THE ABSENCE OF COLONIC OR ESOPHAGEAL PERFORATION
Authors: Tai Lorraine Chong , Makarevich Edwin , Alvarez Andrea , Rubenstein Ivana , Singh Satya
Published: January 2024

INTRODUCTION

The development of Spontaneous Pneumomediastinum and Subcutaneous Emphysema in patients with Inflammatory Bowel Disease (IBD) has often been associated with perforation related to toxic megacolon or prior endoscopic procedures. We describe a case of Ulcerative Colitis complicated by Clostridium difficile (C diff) colitis in which Spontaneous Pneumomediastinum and Subcutaneous Emphysema developed without any evidence of perforation.

CASE REPORT

A 20-year-old male with a past medical history of recently diagnosed Ulcerative Colitis presented for evaluation of rectal pain, dysphagia, hematochezia, fecal incontinence, and urinary hesitancy. He endorsed dysphagia with the inability to tolerate solids or liquids for 4 days. He was diagnosed with Ulcerative Colitis 5 months prior to presentation and had unintentionally lost 90 lbs over the past 2 months. His home medication regimen included infliximab started 2 weeks prior, mesalamine PO tablets and suppositories, and a prednisone taper initiated at 10 mg TID. Laboratory tests confirmed anemia, leukocytosis, thrombocytosis, and elevated ESR and CRP levels. Chest X-ray and CT scans of the neck and chest showed moderate pneumomediastinum and subcutaneous emphysema. Given the symptoms of dysphagia along with the imaging findings of pneumomediastinum and subcutaneous emphysema, there was concern for esophageal perforation. However, an Esophagram and Upper GI series were both unremarkable. Abdominal CT revealed colitis of the descending and sigmoid colon without any evidence of free air or free fluid. Fecal Occult Blood Test and C diff antigen and toxin assays were positive. He was treated with oral vancomycin, IV fluids, IV methylprednisolone, and total parenteral nutrition (TPN). His symptoms significantly improved with a decrease in stool frequency and bloody stools. TPN was weaned and he was able to tolerate an oral diet. A repeat CT scan of the chest showed a complete resolution of the pneumomediastinum.

CONCLUSION

There are only a few reported cases in the literature of spontaneous pneumomediastinum and subcutaneous emphysema in patients with IBD in the absence of colonic or esophageal perforation. The spontaneous isolated presentation of air leaking from a chronically diseased hollow organ remains rare. In our patient there was no evidence of perforation, therefore the pneumomediastinum and subcutaneous emphysema likely resulted from the release of free air from colonic micro-perforations caused by the severe inflammation related to his Ulcerative Colitis flare and C. diff infection.

CT Chest demonstrating pneumomediastinum and subcutaneous emphysema of the neck

CT Neck demonstrating subcutaneous emphysema
INDOLENT SYSTEMIC MASTOCYTOSIS MASQUERADING AS CHRONIC ANEMIA IN ULCERATIVE COLITIS: A CASE STUDY
Authors: Hassan Syed Adeel , Flomenhoft Deborah
Published: January 2024

BACKGROUND

Anemia is a frequent systemic/extra-intestinal manifestation of inflammatory bowel disease (IBD). It has a complex multifactorial etiology which suppresses erythropoiesis due to pro-inflammatory mediators, myelosuppression, iron and micronutrient deficiency. It significantly impacts quality of life (QoL) and increases hospitalizations, length of hospital stays and mortality rates. It Is commonly thought to arise as a consequence of IBD or it’s related therapy. Current strategies are aimed at correction of anemia with low priority towards identifying a specific cause. Here, we represent a case of UC with chronic anemia secondary to systemic mastocytosis (SM).

CASE

A 41 y/o female with UC presents to the outpatient clinic with complaints of fatigue. Further questioning revealed a baseline of 1-2 formed bowel movements per day. She did not report any hematochezia or weight loss. She was managed on 300 mg of vedolizumab every 4 weeks. Prior failure to medications includes anti-tumor necrosis factor inhibitors and tofacitinib. Labs were consistent with albumin 4.5 mg/dL and CRP < 1 mg/dL. Iron studies revealed low iron, TIBC and ferritin levels. Fecal calprotectin measurements were not available due to patient non-compliance. Patient (Pt) was thought to have experienced a UC flare and colonoscopy was recommended. Colonoscopy was unrevealing with no sign of active disease on examination (Mayo Endo 0). Pt was referred to hematology where she underwent a bone marrow biopsy revealing multifocal dense infiltrates of mast cells (≥15 mast cells in aggregates) expressing CD2+ and CD 25+ with 25% showing atypical morphology in bone marrow biopsies. KIT D816V mutation was also positive. The serum tryptase level in this pt was 47.1ug/L. She was then placed on anti-histamines, proton pump inhibitors and steroid therapy.

CONCLUSION

SM is a clonal disorder of MC that infiltrates one or more organs. It almost always involves the bone marrow. Gastrointestinal (GI) symptoms are present in up to 80% patients. These symptoms are secondary to systemic effects of MC mediators. Incidence of SM in UC has never been established. SM has been shown to mimic Crohn’s disease and is difficult to differentiate based on clinical and endoscopic features. Furthermore, little is known regarding histopathological features of GI involvement in SM. The presence of chronic anemia despite adequate therapy in a clinically/endoscopically inactive UC patient should raise suspicion of other pathologic causes of anemia. Our case highlights the importance of diagnosing the specific cause of anemia in IBD as it may lead to inaccurate clinical judgements of disease flares leading to undue alteration in therapy.
INFECTIOUS COMPLICATIONS IN PATIENTS WITH PRIMARY SCLEROSING CHOLANGITIS AND INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Natt Navneet , May Tyrel , Malhi Gurpreet , Dumond Jennifer , Tandon Parul
Published: January 2024

BACKGROUND

Primary sclerosing cholangitis (PSC) is a cholestatic immune-mediated liver disease that can be associated with inflammatory bowel disease (IBD) in up to 80% of patients. Those with concurrent PSC-IBD exhibit a distinct disease phenotype with increased risk of complications such as malignancy and pouchitis; however, the risk of infections is not yet clearly defined in this population.

AIMS

The aims of this systematic review and meta-analysis are (1) to determine the incidence of infections in patients with PSC-IBD and (2) to identify risk factors for infections in this population.

METHODS

MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception to March 24, 2022 for primary studies that reported incidence or risk factors for infection in adult and pediatric patients with PSC and IBD. Case reports and case series with less than five patients were excluded, as were any studies where infection rates in PSC-IBD patients could not be separated from those with PSC or IBD alone. The primary outcome of this study was incidence of all-cause infections including bacterial, viral, or fungal infections, and sepsis. The secondary outcomes included incidence of site-specific infections and mortality due to infection. A random-effects model was used to calculate pooled odds ratios (OR) with 95% confidence intervals (CI) comparing incidence of all-cause infections in PSC-IBD to those with PSC alone or IBD alone.

RESULTS

Seventy-one studies were included. The pooled incidence of all-cause infections in patients with PSC-IBD was 21.8% (95% CI 0.17-0.26, I2=95.9%), 31.1% (95% CI 0.16-0.46, I2=93.4%) in those with PSC alone, and 4.4% (95% CI -0.01-0.10, I2=99.2%) in those with IBD alone. Patients with PSC-IBD had an over three-fold increased odds of all-cause infection compared to those with isolated IBD (OR 3.67, 95% CI 2.07-6.50). Patients with PSC-IBD were more likely to develop sepsis (OR 3.35, 95% CI 2.29-4.90) and have infections resulting in mortality (OR 11.25, 95% CI 2.03-62.37) compared to those with IBD. The most common infections in the PSC-IBD group were sepsis followed by clostridioides difficile infection. There was no significant difference in the odds of infection between patients with PSC-IBD and those with PSC alone (OR 1.21, 95% CI 0.68-2.18). However, on sub-group analysis, patients with PSC-IBD undergoing liver transplantation (LT) were more likely to develop infection post-LT compared to those with PSC alone (OR 4.86, 95% CI, 2.32-10.17), with cytomegalovirus (CMV) being the most commonly reported infection.

CONCLUSION

Compared to those with IBD, patients with PSC-IBD appear to be at a higher risk of infection and resultant complications such as sepsis and death. Future studies are needed to elucidate specific risk factors such as immunosuppressive therapy and disease activity.
ASSOCIATION OF INFLAMMATORY BOWEL DISEASE AND AUTOIMMUNE PRIMARY ADRENAL INSUFFICIENCY
Authors: Haider Salman , Ramai Daryl , Shah Saira , Rahman Asad Ur , Hussain Moazzam , Al-Bustami Iyad , Bandaru Praneeth , Etienne Denzil
Published: January 2024

AIMS

To assess the prevalence and association of inflammatory bowel disease (IBD) with autoimmune primary adrenal insufficiency (APAI).

BACKGROUND

Patients with inflammatory bowel disease are at risk for developing other immune mediated diseases (IMD). There is a paucity of data on the association of IBD with autoimmune primary adrenal insufficiency/ autoimmune adrenalitis. To date, only small series have been published in the literature and well-designed population-based studies have not yet examined this association.

METHODS

We identified patients from the Healthcare Cost and Utilization Project - National Inpatient Sample between the years 2016 to 2020. Our cohort included IBD patients of all ages, and our control group consisted of non-IBD patients. The study's primary outcome was to evaluate the association of APAI in the study group compared to the control group. Secondary outcomes included demographics of IBD patients with APAI. ICD-10 diagnostic codes were used to identify patients.

RESULTS

During the study period, a total of 1,652,070 IBD patients were identified. Of these, 3,699 had a concurrent diagnosis of APAI, yielding an overall prevalence rate of 0.22%. In the non-IBD cohort, the total number of patients were 173,000,000 and the prevalence of APAI was 0.06%. Patients with IBD who had APAI were 70% females, and 90% were of white ethnic background. Among IBD patients, Crohn’s disease had a higher prevalence of APAI than Ulcerative Colitis, 0.27% vs. 0.14 %, respectively (p<0.001). Patients with IBD-APAI also had other coexisting IMDs, with asthma having the highest prevalence (13.11%), followed by rheumatoid arthritis (10.41%) and type-1 diabetes mellitus (2.57%). On multivariable logistic regression analysis, patients with IBD had 3.04 times higher odds of having a concurrent APAI diagnosis than patients without IBD (OR 3.046, CI: 2.796- 3.318, P<0.001). Women were 1.59 times more likely to have APAI than men (OR 1.590, CI: 1.539 - 1.643, p<0.001). On subgroup analysis, patients with CD had 1.9 times higher odds of having APAI than UC (OR: 1.901 CI: 1.579 - 2.290, p<0.001).

CONCLUSIONS

Patients with IBD, especially women of white ethnic background, have a higher association of APAI than non-IBD patients. CD patients are more likely to develop APAI than UC. Further studies are needed to understand the association and overlapping pathologic mechanisms between IMDs which may help further understand IBD-related comorbidities.

Figure

Table
PATIENTS WITH CROHN'S DISEASE AFFECTED BY NON-ALCOHOLIC FATTY LIVER DISEASE HAVE A GREATER RISK OF MORTALITY AND WORSE CLINICAL OUTCOMES
Authors: Rahima Kenan , Albuni Mhd Kutaiba , Hijazi Mohamad , Ikpeze Tochukwu , Bitar Bassel , Muddana Venkata
Published: January 2024

Crohn's disease (CD) has a high prevalence rate and it affects millions of patients worldwide. Non-Alcoholic Fatty Liver Disease (NAFLD) is an emerging disease predisposing to adverse outcomes. There is limited evidence of clinical outcomes of NAFLD in patients with CD. We sought to investigate this population.

METHODS: We queried NIS 2017-2020 for adults hospitalized with CD & NAFLD. The primary outcome was inpatient mortality. Secondary outcomes were cardiogenic shock, cardiac arrest, GIB, intubation, LOS & total hospital charge. Multivariable logistic regression analysis was used to estimate clinical outcomes.

RESULTS: There were 792409 hospitalizations with CD and 26229 (3.3%) had NAFLD. NAFLD & non-NAFLD cohorts had a mean age of 57.8 vs. 52.5 yrs (P<0.05); males 46.17 % vs 42.1% (P<0.05); Caucasians 82.42 % vs 77.1% (P<0.05); Heart failure 16.47% vs 10% (P<0.05); Pulmonary Hypertension (PH) 4% vs 2%; Acute Kidney Injury (AKI) 33.6% vs 16.1 (P<0.05)%; obesity 14.7% vs 12.8 % (P<0.05); Dyslipidemia 22.2% vs 22.2% (P=0.89); anemia 23.8% vs 20.1 (P<0.05)%; Acute Coronary Syndrome (ACS) 4.5 % vs 2.6% (P<0.05); stroke 1.2% vs 1.1 (P=0.49)%, respectively.

CONCLUSION: The CD with NAFLD cohort showed significantly higher mortality, worse clinical outcomes & resource utilization (Table 1). They were older, had more males, and Caucasians, and had higher rates of obesity, HF, PH, AKI, anemia, and ACS. NAFLD is associated with greater risk for MACE, GIB, & ICU care. NALFD is an important risk factor among patients with CD that predicts adverse outcomes.
HUMAN β-DEFENSIN 2 ISOFORMS EXPRESSION ON PEDIATRIC IBD
Authors: Martinez Evelyn Calderon , Ng Wern Lynn , Joseph Maria , Guzman Adalberto , Chávez Luis Márquez , Htoo Moe , Zevallos-Delgado Christian
Published: January 2024

Inflammatory bowel disease (IBD), which includes Ulcerative Colitis (UC) and Chron’s disease, affects a million people around the world. IBD is developed during the different stages of human life and has mostly been studied in adults. However, this disease has been observed in childhood.

In the case of pediatric IBD, the causes are mostly related to genetic disorders. Human β-defensin 2 isoforms (DEFB4A and DEFB4B) are one of the families strongly related to the development of multiple diseases such as asthma and colorectal cancer. The main purpose of this study was to determine the factors that can affect the progression of pediatric IBD. Using gene expression data from 190 pediatric patients (Control= 55 samples, CD = 92 samples, and UC= 43 samples) available at the Gene Expression Omnibus (Accession code = GSE117993), the differential gene expression was determined using GEO2R tool (significant level cut-ff = 0.05 and Log 2-fold threshold= 2). The results showed that DEFB4A/B were upregulated when comparing UC and CD with Control. On the other hand, DEFB4A/B was downregulated compared to CD with UC. Human β-defensin 2 isoforms have been strongly related to the development of multiple diseases, including IBD in adult patients. In the case of pediatric patients, these isoforms could represent a potential maker to assess the progression of IBD.
EPISODE OF CARE MODEL PROVIDES A MORE ACCURATE ESTIMATE OF COSTS FOR PATIENTS WITH IBD COMPARED TO THE TRADITIONAL CALENDAR YEAR MODEL
Authors: Berinstein Jeffrey , Melmed Gil , Allen John , Berry Sameer
Published: January 2024

INTRODUCTION

Inflammatory bowel diseases (IBD) are gastrointestinal (GI) conditions characterized by chronic inflammation of the digestive tract, which are associated with significant costs. Traditionally, research has focused on the overall costs of a disease per calendar year, however examining the cost of a specific illness-related index event and the surrounding episode of care may provide a more representative estimate of the costs of care and identify opportunities for targeted value-based interventions.

METHODS

We conducted a cohort study using data from IBM Watson, a claims-based database covering millions of commercially insured individuals. We identified adult patients aged 18 to 65 years with encounters associated with a primary or secondary diagnosis of IBD from 01/01/2018 to 12/31/2019 based on ICD-10 codes. We defined an episode of care as 360 days of continuous care (90 days prior to the index event to 270 days after such event) around an emergency room (ER) visit, gastroenterologist visit, and non-gastroenterologist GI visit (which could include a visit to a PCP, rheumatologist, dietician, and other services attributable to IBD symptoms). Measures of cost and utilization were calculated as a per member mean over 360 days.

RESULTS

105,496 IBD patients with 1 year of continuous enrollment between 01/01/2019 to 12/31/2019 (calendar year cohort) and 81,774 patients with 2 years of continuous enrollment between 1/1/2018-12/31/2019 (episode of care cohort) were identified. Among IBD patients identified in the episode of care cohort, 13,164 (16.1%) patients had an IBD-related ER visit, 42,001 (51.4%) patients had a gastroenterologist visit, and 28,699 (35.1%) patients had a non-gastroenterologist GI visit. The mean per member calendar year total cost and GI-related costs were $40,842 and $31,051 respectively, compared to $68,0565 and $54,060 for an ER episode, $42,915 and $34,870 for gastroenterologist visit episode, and $48,556 and $38,120 for a non-gastroenterologist GI visit episode. Per member GI inpatient admissions (0.84), GI ER visits (1.98), GI-tests (5.90), and GI-imaging (0.91) were highest in the ER episode of care. Per member gastroenterologist visits (2.20), GI-related medication administration services (1.22) and biologic medication (1.41) were highest in the gastroenterologist episode of care. Per member non-gastroenterologist GI visits (4.50), and non-biologic GI medications (8.26) were highest in the non-gastroenterologist GI visits episode of care (Table 1 and 2).

CONCLUSION

This study found large variations in costs and utilization when looking at IBD- specific episodes of care. This episode-centered approach provides insights for developing targeted strategies to identify and intervene at the critical moments when patients seek advanced care, which may lead to patient-centered and cost-efficient healthcare delivery.
INCREASING ACCESS TO INTERDISCIPLINARY IBD CARE FOR NEWLY DIAGNOSED IBD PATIENTS USING TELEMEDICINE: AN EXTENSION OF THE COMPASS-IBD PROGRAM
Authors: Lewis Ayanna , Khan Mahnoor , Lanka Chandana , Manning Laura , Matos Kristina , Hyne Amanda , Tse Stacy , Botterman Evan , Dubinsky Marla , Keefer Laurie , Ungaro Ryan
Published: January 2024

INTRODUCTION

Interdisciplinary care is increasingly being recognized as important in the care of inflammatory bowel disease (IBD) patients. However, access to additional resources to do this are frequently only available in tertiary-care IBD centers. We piloted a telemedicine version of an interdisciplinary care program for recently diagnosed IBD patients.

METHODS

The Mount Sinai Health system has a well-established IBD center, located at the Mount Sinai Hospital in New York. Patients who were diagnosed with IBD in the last 18 months were identified by a primary gastroenterologist working at a community site within the Mount Sinai health system. Once identified, patients were referred electronically and enrolled in the Comprehensive Care for the Recently Diagnosed IBD Patient (COMPASS-IBD) program. This existing program provides interdisciplinary care to newly diagnosed IBD patients. IBD patients have access to a physician who works at the IBD Center, a nutritionist specializing in IBD diets, an experienced IBD clinical pharmacist and a licensed clinical social worker dedicated to the mental and social needs of patients with IBD. After an initial assessment, these patients were then provided access as needed to the program experts. All appointments were done virtually using telemedicine. After completing intake, recommendations were consolidated and provided to the patient and the patient’s primary gastroenterologist electronically. The patient then followed up with his/her primary gastroenterologist.

RESULTS

For this pilot study, twelve newly diagnosed inflammatory bowel disease patients were identified at community sites within the Mount Sinai health system. Enrolled patients met with all members of the COMPASS- IBD program team for their initial intake. The referring gastroenterologist received summary recommendations for all patients who completed the intake. Participating patients were overall satisfied with the intervention and use of telemedicine as a primary modality. No major barriers to virtual program implementation were identified.

DISCUSSION

We demonstrated the feasibility of providing interdisciplinary care via telemedicine for recently diagnosed IBD patients. This supports a “hub and spoke” model for IBD care. We believe our pilot study shows a simple way for health systems to increase access to interdisciplinary IBD care for patients with limited access to tertiary-care IBD Centers. This approach may also help in achieving health equity for underserved IBD patient populations.
INSURER-MANDATED MEDICATION UTILIZATION BARRIERS ARE ASSOCIATED WITH DECREASED INSURANCE SATISFACTION AND ADVERSE CLINICAL OUTCOMES: AN IBD PARTNERS SURVEY
Authors: Constant Brad , Long Millie , Scott Frank , Higgins Peter
Published: January 2024

BACKGROUND & AIMS

Insurer-mandated barriers to timely initiation of advanced therapies used to treat inflammatory bowel disease (IBD) have been shown to worsen clinical outcomes and increase healthcare utilization, yet rarely alter the medication ultimately prescribed. Using the IBD Partners research network, we analyzed patient-reported impacts of these barriers on insurance satisfaction and clinical outcomes.

METHODS

We analyzed 2018-2019 IBD Partners insurance survey data to evaluate the frequency and impacts of medication utilization barriers on insurance satisfaction and clinical outcomes. Barriers included medication denials, prior authorizations, step therapy requirements, insurer-forced medication switches, and gaps in care. Stratified analyses measuring the frequency of these barriers were conducted among private versus public health plans. Variables associated with insurance satisfaction, measured on a 1-7 Likert scale, were identified. The association between insurance-related barriers and clinical outcomes (surgery, corticosteroid requirement, and disease activity) within one year of the initial survey were evaluated.

RESULTS

2017 patients (Age 46 [IQR 34, 58], 73% female) were included. Sixty-four percent had Crohn’s Disease, 34% had ulcerative colitis, and 3% had IBD-Unclassified. Seventy percent had received a biologic, and 86% were corticosteroid-exposed. The median disease duration was 15 years (IQR 9, 25). Regarding insurance characteristics, 86% had private insurance (81% via their employer, 5% via Affordable Care Act) and 12% had public insurance (11% Medicare, 2% Medicaid). Insurer-mandated barriers to care were experienced by 72%, including prior authorizations (51%), medication denials (15%), step therapy requirements (11%), and insurer-forced medication switch (7%). These barriers were generally more common among those with public insurance (Figure 1).

Sixty-two percent were at least somewhat satisfied with their insurer. Medication denials, prior authorization-related delays, gaps in therapy, and high-deductible health plan coverage were each uniquely associated with insurance dissatisfaction.

Insurance barriers, medication denials, insurer-forced medication switches, and prior authorizations were each associated with negative clinical outcomes in the year following survey administration. Notably, medication denial was associated with a 9-fold increased likelihood of IBD-related surgery, and an insurer-forced medication switch was associated with a 2.5-fold increased likelihood of corticosteroid rescue.

CONCLUSIONS

Patients with IBD frequently experience insurer-mandated barriers to care which are associated with decreased insurance satisfaction and negative downstream clinical outcomes. Together, these data illustrate the negative impacts of insurer-mandated medication barriers on patients with IBD.
ULCERATIVE COLITIS-DERIVED INTESTINAL EPITHELIAL CELLS ARE PROTECTED FROM CELL DEATH BY THE IMMUNE MEDIATORS RELEASED FROM RESTING AND ACTIVATED SYSTEMIC T CELLS
Authors: Malhotra Riya , Cruz Michelle , Lyons Renae , Levine Alan
Published: January 2024

Immune dysregulation is a major driver in the pathogenesis of ulcerative colitis (UC), but the specific mechanisms of disease initiated by the adaptive immune system remain unknown. While many studies have focused on the contribution of individual T cell subsets, disrupted communication between the epithelium and T cells in the underlying lamina propria is not fully understood in UC. This study examines the impact of T cells isolated from healthy participants on primary cultures of epithelial cells derived from UC donors. Blood derived human CD4+ and CD8+ T cells were isolated by immunomagnetic negative selection and activated by anti-CD3/CD28 cross-linking. Activated and resting T cells were then co-cultured with UC-derived colonic epithelial spheroids, consisting predominantly of stem cells, suspended in Matrigel. Spheroid damage and epithelial cell death were measured by histological scoring of brightfield microscopic images and zombie violet positive staining, detected using flow cytometry, respectively.

Our earlier studies showed that activated CD4+ T cells co-cultured with spheroids from healthy donors stimulated significant spheroid damage and epithelial cell death in a dose- and time-dependent manner. In addition, we reported that the addition of conditioned media (CM) from activated CD4+ T cells to healthy spheroids also induces spheroid damage and epithelial cell death. Neither resting CD4+ nor CD8+ T cells nor activated CD8+ T cells stimulate the same response (Panel A). Our preliminary results indicate that UC-derived epithelial cells, isolated from spheroids, exhibit a higher base line of spontaneous lethal sectoring (42%), when compared to spheroids isolated from healthy colons (10%). In stark contrast to healthy spheroids, addition of CM from resting and activated CD4+ or CD8+ T cells protect the ulcerative colitis-derived spheroids from damage and isolated UC epithelial cells from spontaneous death. We have not yet identified which T cell subset are protecting UC-derived epithelial cells from damage and death. Thus, our results distinguish the healthy epithelial spheroid response to T cell CM from UC spheroids in three distinct ways: [1] CM is protective in UC, [2] Both CD4 and CD8 cells mediate this response in UC, and [3] CM from resting and activated T cells secrete the responsible immune mediators. Overall, these results signify that the biological response of UC-derived epithelial cells to immune mediators is different from that seen with healthy epithelial cells, indicating a metabolic and genetic difference in the epithelium from the UC patient.