bluuebunny/crossref_metadata_2025 huggingface dataset:
FIBER-DEFICIENT DIET INHIBITS COLITIS THROUGH REGULATION OF THE NICHE AND METABOLISM OF A GUT PATHOBIONT
Authors: Kuffa Peter , Pickard Joseph , Campbell Austin , Schaus Sadie , Adler Jeremy , Martens Eric , Schmidt Tom , Inohara Naohiro , Núñez Gabriel , Caruso Roberta
Published: January 2024

Fiber free exclusive enteral nutrition (EEN) is an effective steroid-sparing treatment used to induce clinical remission in children with Crohn’s disease (CD). However, the mechanism underlying the beneficial effects of EEN remains obscure. We have generated a novel mouse strain that harbors mutations in two CD susceptibility genes (i.e, NOD2 and CYBB) and found that these mice spontaneously develop an early-onset (4 weeks of age), TH1-type gut inflammation, that closely recapitulates the human disease when exposed to a specific murine microbiota. Disease in Nod2/Cybb (DKO) mutants was triggered by a single mucus-dwelling anaerobe, Mucispirillum schaedleri, which markedly accumulates in the intestinal lumen and mucus layer prior to disease development. Given that our mouse model resembles early-onset CD, we have established a novel humanized mouse model of early-onset CD in which germ-free Nod2/Cybb mutants were colonized with microbiotas from early-onset-CD patients and their healthy first-degree relatives. We have found that the early-onset-CD-associated microbiota triggered intestinal inflammation in gnotobiotic DKO mice with all the hallmarks of the human disease. Using the murine and humanized models of early-onset CD we have found that administration of a fiber-free diet prevents the development of colitis and inhibits intestinal inflammation in colitic animals. Furthermore, identification of Mucispirillum as a trigger in our mouse model has allowed us to study the effects of dietary interventions on disease-causing microbes. Remarkably, we have found that a fiber-free diet alters the intestinal localization of Mucispirillum. Mechanistically, the absence of dietary fiber reduces the availability of nutrients and impairs Mucispirillum’s unique metabolic pathway in the intestinal mucus. Thus, appropriate localization of the pathobiont in the mucus layer is critical for the onset of disease, which can be disrupted by fiber exclusion. These results suggest that probing the intestinal niche and metabolism of disease-causing microbes will likely lead to the discovery of novel, more targeted therapies for the treatment of CD.
PREVALENCE OF MALNUTRITION AND MICRONUTRIENT DEFICIENCIES IN OLDER ADULTS WITH ULCERATIVE COLITIS WHO HAVE UNDERGONE BOWEL SURGERY
Authors: Memel Zoe , Thiemann Anna , Dort Cooper , Beck Kendall
Published: January 2024

BACKGROUND

There is little data on the older adult ulcerative colitis (UC) population. We aimed to evaluate the prevalence of malnutrition and micronutrient deficiencies among older adults who have undergone bowel surgery for their UC.

METHODS

This was a single-center, retrospective study of patients 65 years and older with UC. Malnutrition was defined using the European Society for Clinical Nutrition and Metabolism (ESPEN) definition. Eight micronutrient deficiencies and nutrition-related outcomes were measured. The Saskatchewan Inflammatory Bowel Disease–Nutrition Risk Tool was utilized to identify patients at risk for malnutrition. Descriptive statistics were used to summarize data. Characteristics of patients with and without malnutrition were compared using Fisher’s exact tests (analysis of variance for age).

RESULTS

Eighty-eight patients with a mean age of 74.7 years were included. The most common surgery was total proctocolectomy with end ileostomy (n=40,45%). Seven patients (8%) met criteria for malnutrition, 24 patients (31%) were moderate to high risk for malnutrition, and 55 (70%) of patients were low risk. Sixty-six patients (74%) had at least one micronutrient deficiency: 42% with vitamin D deficiency and 32% with iron deficiency. One-third of patients had bone-related disease (27 patients). No statistically significant associations were found among patients with or without malnutrition or among patients with low, moderate, or high risk of malnutrition. Our small study, however, likely lacked sufficient power to detect any differences which may exist.

CONCLUSIONS

The prevalence of malnutrition was low, however, the incidence of at least one micronutrient deficiency was high. Older adults with UC who have undergone bowel surgery should be followed carefully with annual labs to avoid nutrition-related complications.

Table 1 Characteristics of Older Adults with Ulcerative Colitis who have undergone Surgical Resection

Table 2 Rates of Malnutrition and Micronutrient Deficiencies in Older Adult Ulcerative Colitis Population
PATTERNS AND ASSOCIATED FACTORS OF OBJECTIVE INFLAMMATION ASSESSMENT TO TREAT-TO-TARGET: DATA FROM THE IBD QORUS COLLABORATIVE
Authors: Nguyen Thien-Bao , Siegel Corey , Melmed Gil , Singh Siddharth , Harvey Sarah , Oberai Ridhima , Hou Jason , Fudman David
Published: January 2024

BACKGROUND

A Treat-to-Target (T2T) strategy for inflammatory bowel disease (IBD) improves clinical outcomes. The cornerstone of T2T is the routine assessment of objective markers of inflammation to determine treatment efficacy. Despite this, objective testing is often delayed or not performed. This study aims to describe patterns and associated factors of intended assessment of objective markers of inflammation for patients with IBD within the multicenter quality improvement collaborative, IBD Qorus.

METHODS

Patient and provider survey data from IBD Qorus were prospectively collected from 6/2021 to 10/2022 across 35 academic and community practices during routine clinical care visits. Patients with unknown status of mucosal healing were excluded. The primary outcome of "timely assessment" was defined as provider-reported intent to obtain fecal calprotectin (FC), imaging, or endoscopy within 12 months. Factors associated with the primary outcome were assessed using univariate and multivariate logistic regression, adjusting for age, gender, IBD type, and clinical factors.

RESULTS

4,831 encounter-level surveys from the study period were included for analysis. In 73.9% of encounters, providers reported an intent to assess inflammation within the next 6 months. Of these, 77.1% planned to use FC and 57.7% imaging or endoscopy. 89.3% of visits noted an intent to assess inflammation within 12 months. Providers reported in 29.8% of encounters that patients declined FC and in 8.3% that imaging or endoscopy were declined. In the primary univariate analysis, intent for timely assessment was associated with ulcerative colitis (UC), recent emergency department visit or hospitalization, lack of clinical remission, mild Provider Global Assessment, current steroid use, lack of immunomodulator use, lack of steroid-free mucosal healing, care at an academic site, and intent to change therapy. On multivariate analyses, UC (OR 1.38, 95% CI 1.11-1.71), steroid use (OR 2.1, 95% CI 1.1-4.6), and plans to change therapy (OR 1.84, 95% CI 1.2-2.9) remained significantly associated with higher odds of timely assessment. In contrast, steroid-free mucosal healing (OR 0.52, 95% CI 0.41-0.66) and care in community practice (OR 0.63, 95% CI 0.51-0.77) remained significantly associated with lower odds of timely assessment.

CONCLUSION

In IBD Qorus, there is a strong intent to assess objective markers of inflammation. However, lower odds of intended assessment were found among patients with Crohn’s, patients in steroid-free mucosal healing, and those receiving care in community practice, revealing potential care gaps. Interestingly, providers frequently reported that patients declined FC testing, and declined this at higher rates than that for endoscopy or imaging. This study identifies potential areas to improve testing for inflammation under a T2T strategy.
ROUTINELY COLLECTED BLOODWORK REVEALS IMMUNE CELL PATTERNS THAT REFLECT DISEASE ACTIVITY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
Authors: Briand Peyton , Mulder Daniel
Published: January 2024

OBJECTIVE

The standard procedure for evaluation of inflammatory bowel disease (IBD) diagnosis and activity requires endoscopy, but there have been many biomarkers identified that are associated with IBD and are collected much less invasively. White blood cell subsets, also known as “the differential”, is a commonly used test for patients with IBD, but the relationship between the differential and disease activity is unknown. Understanding the connection between the differential and disease activity could provide insight to a patient’s clinical presentation without requiring more invasive testing. The aim of this study was to identify patterns present in the differential of IBD patients and use machine learning to determine how these parameters change with IBD activity.

METHODS

A total of 373 differential counts from 43 patients with IBD were evaluated. All IBD patients with adequate clinical information were included. Disease activity was determined by chart review using the Physician’s Global Activity Score. Binary classification prediction was performed on the training set using multiple supervised machine learning models.

RESULTS

The outcome was balanced, with 56% of the observations experiencing IBD activity at the time of blood collection. A random forest (RF) model performed best with a final fit accuracy of 0.70 and an ROC-AUC score of 0.75. The RF classifier ranked monocytes and neutrophils as having the highest relative importance to the model.

CONCLUSION

The optimal RF model demonstrated an overall correctness in its predictions and as reflected in the ROC-AUC score, can discriminate between active disease state and remission in IBD patients. These results indicate that a pattern is present between the differential and IBD activity and with further exploration, may be used to create a predictive model for IBD diagnosis.
USEFULLNESS OF SERUM LEUCINE-RICH ALPHA2-GLYCOPROTEIN AND FECAL CALPROTECTIN ASSURROGATE MARKERS IN ULCERATIVE COLITIS
Authors: Miyazono Satoshi , Imazu Noriyuki , Umeno Junji , Matsuno Yuichi , Kawatoko Shinichiro , Nagasue Tomohiro , Fujioka Shin , Kawasaki Keisuke , Moriyama Tomohiko , Torisu Takehiro
Published: January 2024

BACKGROUND AND AIM

Serum Leucine-rich alpha-2 glycoprotein (LRG) was identified as a novel biomarker for rheumatoid arthritis and IBD by using a proteomics approach. Several studies have suggested that serum LRG levels and fecal calprotectin (fCal) were correlated with clinical activities in patients with ulcerative colitis (UC). We compared utility of these biomarkers for monitoring disease activity in UC.

METHODS

A single-center observational study was conducted at Kyushu University Hospital. A total of 101 patients who underwent colonoscopy during the period from February to December 2021 were enrolled. The associations between endoscopic and histological activity and biomarkers were investigated. Endoscopic activity was defined as Mayo endoscopic score (MES) of 1 or less for mucosal healing and 0 for complete mucosal healing. For histological activity (n=90), Geboes score of 2 or less was defined as histological remission.

RESULTS

Subjects ranged in age from 16 to 80 years (35 males and 66 females). There were 63 cases of total colitistype, 32 cases of left-sided colitis type, and 6 cases of proctitis type. The MES at enrollment were as follows: MES 0 in 41 cases, MES 1 in 33 cases, MES 2 in 19 cases, and MES 3 in 8 cases. In comparison between the mucosal healing and non-mucosal healing groups, LRG was significantly lower in the mucosal healing group (p<0.0001). The correlation coefficient of LRG with MES was r=0.614 (p<0.0001), which was higher than that of fCal, r=0.414 (p<0.0001). In ROC analysis with mucosal healing as the outcome, the AUC and cut-off value of LRG were 0.781 and 17.9 μg/ml, respectively, and for fCal were 0.850 and 396 μg/g, respectively. In the ROC analysis with complete mucosal healing as the outcome, the AUC for LRG was 0.690, which was lower than the AUC of 0.846 for fCal . When compared by histological remission, LRG was lower in the histological remission group (p<0.001). In the ROC analysis with histological remission as the outcome, the AUC for LRG was 0.722 (cutoff value 14.2 μg/ml) and for fCal was 0.837 (cutoff value 119 μg/g).

CONCLUSION

Both LRG and fCal are valuable biomarkers reflecting disease activity in UC.
ASSOCIATION OF HIDRADENITIS SUPPURATIVA AND INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Polpichai Natchaya , Trongtorsak Angkawipa , Sereeaphinan Chudapa , Danpanichkul Pojsakorn , Wattanachayakul Phuuwadith , Wetwittayakhlang Panu
Published: January 2024

INTRODUCTION

Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic inflammatory skin condition that affects apocrine gland-bearing areas. Previous studies have demonstrated that HS is potentially associated with various autoimmune diseases. However, the relationship between HS and inflammatory bowel disease (IBD) has been unclear.

METHODS

A comprehensive literature search was conducted in electronic databases, PubMed and Embase, from inception to October 2023. We included published studies that provided estimated effects with a 95% confidence interval (CI) or raw data. The quality of the selected studies was evaluated using the Newcastle-Ottawa Scale. Crohn's disease and ulcerative colitis were analyzed separately. Data from each study were combined using the random-effects model and the generic inverse variance method to calculate the pooled odds ratio (OR) with a 95% confidence interval (CI) and I2 statistics.

RESULTS

Ten case-control studies involving 26,496,569 individuals (110,648 with HS and 26,385,921 without HS) were included in this meta-analysis. HS was associated with significantly higher risk in the IBD group (Pooled OR 2.18; 95% CI 1.42-3.32; P = 0.0003; I2 = 97%). Additionally, our analysis demonstrated a significant association between HS and ulcerative colitis (Pooled OR 1.49; 95% CI 1.26-1.78; P < 0.00001, I2 = 63%) and between HS and Crohn's disease (Pooled OR 1.79; 95% CI 1.33-2.40; P = 0.0001; I2 = 88%).

CONCLUSION

Our meta-analysis demonstrated that HS is significantly associated with IBD and IBD subtypes (Crohn's disease and ulcerative colitis). This finding emphasizes the need for awareness when patients with HS present with symptoms associated with IBD. Further studies should be conducted to understand the mechanism of the gut-skin axis in shared immune and inflammatory processes.
HERMANSKY-PUDLAK SYNDROME-ASSOCIATED INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW ON CLINICAL MANIFESTATIONS AND INVESTIGATIONS INTO OPTIMAL MANAGEMENT
Authors: Miranda Clive , Javaheri Nariman , Carlson Alexander , Aijaz Ali , Nallapeta Naren
Published: January 2024

Hermansky-Pudlak Syndrome (HPS) is a rare autosomal condition resulting from a mutation in 1 of at least 7 different genes leading to the triad of tyrosine-positive oculocutaneous albinism, platelet dysfunction leading to prolonged bleeding time, and ceroid lipofuscin within the reticuloendothelial system. The latter of these can result in systemic derangements including renal failure, pulmonary fibrosis, cardiomyopathy, and a disabling granulomatous colitis. This colitis is a unique type of inflammatory bowel disease (IBD) with complications such as intestinal fistulization, ileitis, enterocolitis and perianal disease. There is data to suggest that HPS colitis is due to the development of classical IBD. However, optimal management remains undetermined. Our systematic review aims to analyze the clinical presentation behind HPS colitis, endoscopic versus histopathological findings, and ultimate treatment plans required for optimal management of this disease among HPS genotypes.

A comprehensive literature review was conducted on patients with HPS and its associated colitis manifestations from inception to August 2023. Analyses on patient demographics, clinical presentation, HPS genotype, endoscopic versus histopathological findings, medical versus surgical interventions were thoroughly performed.

Six cohort studies on HPS patients with coexisting colitis were identified. A total of 84 patients comprised these studies with mean age 32 +/- 9.65. Racial breakdowns were 68% Puerto Rican, 23% white, 4% Indian, 2% Mexican, 1% Honduran, and 1% African American. 59 patients had the HPS-1 genotype, 8 with HPS-3, 3 with HPS-4, and 1 with HPS-6. The most common presenting symptoms were hematochezia (37%), diarrhea (23%), abdominal pain (16%), and constipation (10%). Endoscopic evaluation showed normal gross findings in 65% of cases and abnormalities in only 35%. However, IBD-associated histopathological positivity was more prevalent with the most common findings being granulomas (33%), macrophages without colitis (19%), macrophages with colitis (15%), and lymphoid aggregates (10%). Medical therapy was initiated in 48 cases with the most common medications being steroids (46%), followed by anti-TNFa agents (40%), and immunomodulators (35%). 28 cases required surgical intervention with the most common operation performed being a (subtotal) colectomy and ileostomy. There were scattered cases of laparoscopic loop ileostomies, total colectomies, and proctocolectomies too. Interestingly, 10 patients received no intervention whatsoever.

HPS-associated colitis is a debilitating condition that remarkably resembles IBD. There is no consensus on optimal therapy and many patients ultimately require operative intervention. The HPS-1 gene appears to be highly prevalent in this condition and younger patients are more affected, however more research is needed.
INFLAMMATORY BOWEL DISEASE AND RHEUMATOID ARTHRITIS
Authors: Martinez Evelyn Calderon , Vilchez Esmeralda , Ng Wern Lynn , Gautam Seema Sharma , Gavilanes Diana , Joseph Maria , Zevallos-Delgado Christian
Published: January 2024

Inflammatory bowel disease has been associated with arthritis since the late 20th century, but it was not until a few decades ago that IBD-associated arthritis was recognized as a distinct pathology independent from rheumatoid arthritis (RA). There is evidence that RA and other autoimmune conditions exist in higher rates in patients with IBD compared to the general population. This is an important distinction because of the different pathophysiology, clinical manifestations, management, complications, and prognosis of both diseases.

METHODS: This study was reviewed and approved by the University of Pittsburgh Medical Center of Central Pennsylvania Review Board. Using Epic’s SlicerDicer function, patients with Inflammatory Bowel disease were identified using ICD-10 codes (K50 and K51). Those with incomplete information or duplicated were excluded obtaining a total of 3613 patients. Data collected included basic demographic information, surgical history, and the presence of Rheumatoid arthritis. We reported continuous variables as mean (range) and categorical variables as number (percent). We used Student’s t-test to analyze between group differences for the continuous variables. When it was determined that variances for the comparisons of continuous data were unequal, Welch-Satterthwaite t test statistics were used. We used chi-square test to analyze between group differences for the categorical variables. The Fisher exact test was employed when any of the expected frequencies was five or less. All tests were 2-sided with criterion for statistical significance at a p-value less than 0.05. All the analyses were done by SAS 9.4 (SAS Institute, Cary NC).

RESULTS: Of the approximately 2.7 million adults in SlicerDicer, there were 3613 patients (0.13%) identified with Inflammatory Bowel disease. Patients with Ulcerative Colitis accounted for 37% of the total group (n= 1343) and 2270 patients (62.8%) had Crohn’s Disease. From the total, 2084 were women (57.68%) and 1529 (42.32%) were men. The mean age was 53.3 +- 18.5. 848 (23.47%) had documented Rheumatoid arthritis. Mortality was higher in patients with IBD and RA than those with IBD alone (7.31% vs 3.98%, p value= <0.0001). More than 90% of the patients were white (n=3321).

CONCLUSION: IBD patients with RA have higher mortality than patients with IBD alone.
THE ROLE OF ALCOHOL USE 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 type of inflammatory bowel disease (IBD) characterized by transmural inflammation that can occur anywhere along the gastrointestinal (GI) tract. Complications of CD include fistulization, abscess formation, and GI bleed. Many social and environmental factors have been associated with CD. The role of alcohol use remains unclear, with some studies suggesting that it may increase the risk of CD and worsen symptoms, and others showing no relationship between alcohol and CD. We aimed to assess the association between alcohol use and the development of CD complications using a large nationwide database.

METHODS

Patients with a diagnosis of CD were identified using the 2020 Nationwide Inpatient Sample (NIS). Patients were stratified based on whether they had a history of alcohol use. Outcomes included development of fistula, abscess, or bleed. Data were also collected regarding age, gender, race, primary insurance, median income, hospital region, hospital bed size, and comorbidities. The relationship between alcohol use 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, 7,131 (4.0%) had a history of alcohol use. Patients in the alcohol group had lower odds of developing fistula (aOR 0.51, P < 0.001) and abscess (aOR 0.42, P < 0.001). There was no difference in the development of bleed in CD patients with alcohol use compared to without. Patients in the alcohol group had overall lower odds of developing any complication of CD (aOR 0.60, P < 0.001).

CONCLUSION

CD is a chronic and complex inflammatory disease that can lead to a variety of GI complications including fistula formation, abscess, and bleeding. Many genetic, environmental, social, and immune factors play a role in the disease course. Our study found that alcohol use is associated with a decreased risk of developing CD-related fistula or abscess. Patients with a history of alcohol use have been shown to exhibit earlier and more severe GI symptoms in CD, possibly leading to earlier presentation. Additionally, alcohol use has been found to suppress the immune response, potentially explaining our findings. Further studies are needed to assess the role of alcohol in the pathogenesis and disease course of CD.

Inclusion process for the study.
DECIPHERING THE BURDEN OF INFLAMMATORY BOWEL DISEASE LANDSCAPE (1990-2019) IN HIGH INCOME NORTH AMERICA: PROJECTIONS, TEMPORAL SHIFTS, AND A GLIMPSE BEYOND TO 2040
Authors: Patel Rahul , Roy Vivek , Bollu Sashank Sai , Anne Sai Nitya Tejaswi , Naradasu Pranathi Royal , Patel Sneh , Desai Hardik Dineshbhai
Published: January 2024

BACKGROUND

In High-Income North America, IBD ranks as the 6th leading cause of disability and the 9th primary cause of mortality among all digestive diseases. The increasing prevalence in this region underscores the urgent need to address both the clinical and socio-economic challenges of managing this chronic condition in a developed setting.

METHOD

Utilizing Global Burden of DIsease tool, we estimated IBD prevalence, incidence, mortality, and Disability Adjusted Life Years (DALYs) of IBD in High-Income North America. Standardized statistical techniques facilitated comparisons by age, sex, year within this specific region. The DisMod-MR 2.1 tool was employed to estimate incidence and prevalence, while mortality rates were discerned using the Cause of Death Ensemble Model (CODEm). Additionally, we projected the deaths and Years of Life Lost (YLLs) up to 2040 using regression analysis.

RESULTS

From 1990 to 2019, the overall IBD prevalence in High-Income North America showed a decline from 1,100,006 (95%UI: 961,427-1,248,969) to 920,749 (859,032-982,587). However, deaths rose sharply from 2,442 (2,189-2,963) in 1990 to 6,313 (5,075-6,885) in 2019, marking an Annual Percentage Change (APC) surge of 159% (84-182). Meanwhile, DALYs grew by 17% (2-33). Age-Standardized Rates (ASR) indicate a reduction in incidence and DALYs rates by 30% and 22%, respectively, while mortality rates climbed by 42% (1-54). Country-specific trends show Canada and Greenland with incidence APC increases of 28% and 37%, respectively, while the U.S. saw a 12% decline. For mortality, the U.S. led with a 172% APC rise, followed by Greenland at 1,485% and Canada at 49%. In age-specific trends, children under five witnessed a 20% APC surge in incidence per 100,000 population, whereas the under-20 age bracket saw a 13% rise. Notably, those aged under 70 experienced an 89% jump in deaths from 1990-2019.

CONCLUSION

The marked shift in IBD prevalence and mortality in High-Income North America over three decades underscores the escalating challenge this disease presents to the healthcare landscape. The substantial increase in deaths, especially in countries like the U.S. and Greenland, combined with the age-specific trends, emphasizes the pressing need for targeted interventions and robust healthcare policies. Notably, in 2019, IBD was responsible for 4.43% of all deaths linked to digestive diseases and contributed to 6.13% of the total disabilities arising from digestive conditions. This data accentuates the profound and growing impact of IBD in the region and demands immediate, evidence-based action.
EVOLVING LANDSCAPE OF INFLAMMATORY BOWEL DISEASE IN G20 NATIONS (1990-2019): A COMPREHENSIVE GLOBAL ASSESSMENT
Authors: Patel Rahul , Sajeev Krishna , Sojitra Vani , Patel Krina Manojbhai , Naradasu Pranathi Royal , Patel Sneh , Desai Hardik Dineshbhai
Published: January 2024

BACKGROUND

As pivotal players in the global economy, the G20 countries not only lead in economic dynamics but also in health challenges. Recent data reveals an escalating burden of Inflammatory Bowel Disease (IBD) in these nations. Understanding this trend is crucial to frame healthcare strategies and ensure the well-being of a significant portion of the global population.

METHOD

We employed data on IBD prevalence, incidence, mortality, and DALYs for G20 countries from the Global Burden of Disease (GBD) 2019 study. Using standardized statistical techniques, we analyzed by age, sex, year and location across G20 countries, estimating incidence and prevalence with the DisMod-MR 2.1 tool and mortality through the Cause of Death Ensemble Model (CODEm).

RESULTS

From 1990 to 2019, IBD prevalence figures in the G20 nations escalated from 2,999,730 (95%UI: 2,625,581-3,416,963) to 4,254,467 (3,809,445-4,751,041), marking a 42% (38-46) surge in the Annual Percentage Change (APC). Meanwhile, the incidence rose by 30% (26-35), mortality by 72% (49-97), and DALYs by 27% (15-43). Among these nations, China witnessed a striking 314% increase in incidence, closely followed by South Korea at 288%. Death rates were most pronounced in European Union members, with Portugal at the helm (441%), trailed by Italy (433%) and Germany (418%). Germany also led in DALYs growth with a 289% APC. Examining Age-standardized mortality rates, Germany again topped the list with a 244% increase, shadowed by Italy (186%) and the United States (147%). Over the past three decades, older populations demonstrated a rising IBD burden. In gender comparisons, males experienced a more significant incidence increase (32% vs. females at 28%) and DALYs (30% vs. females at 24%). Conversely, females had a steeper death rate growth, 77% as opposed to males at 67%.

CONCLUSION

In 2019, IBD was responsible for 2.02% of digestive disease-related deaths and 2.30% of associated disabilities in the G20 nations. The stark rise in IBD prevalence, especially in countries like China, South Korea, and European Union members, emphasizes a pressing need for targeted clinical approaches and proactive health policies to mitigate this escalating burden.

Age-standardized rate (per 100,000 person years) of Inflammatory Bowel Disease in G20 Countries, 2019. A: ASIR, B: ASMR, C:ASDALR.
PATIENTS WITH ULCERATIVE COLITIS AFFECTED BY NON-ALCOHOLIC FATTY LIVER DISEASE HAVE A GREATER RISK OF MORTALITY AND WORSE CLINICAL OUTCOMES
Authors: Rahima Kenan , Khokhlov Leonid , Albuni Mhd Kutaiba , Hijazi Mohamad , Ikpeze Tochukwu , Muddana Venkata
Published: January 2024

Ulcerative colitis (UC) affects millions of patients worldwide and keeps trending upward. 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 UC. We sought to investigate this population.

METHODS: We queried NIS 2017-2020 for adults hospitalized with UC & 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 489870 hospitalizations with UC and 21695 (4.4%) had NAFLD. NAFLD & non-NAFLD cohorts had a mean age of 57 vs. 57.2 yrs; males 55.1% vs 46%; Caucasians 73% vs 75.8%; Heart failure 15% vs 12%; Pulmonary Hypertension (PH) 3.9% vs 2.5%; Acute Kidney Injury (AKI) 35% vs 17%; obesity 13% vs 13.4%; Dyslipidemia 24 % vs 30.6%; anemia 26.8% vs 22.6%; Acute Coronary Syndrome (ACS) 5.3% vs 3.6%; stroke 1% vs 1.4%, respectively.

CONCLUSION: The UC with NAFLD cohort showed significantly higher mortality, worse clinical outcomes & resource utilization (Table 1). They were older and had more of 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 UC that predicts adverse outcomes.
PROTEIN ARGININE METHYLTRANSFERASE 1 REGULATES ADULT INTESTINAL CELL PROLIFERATION AND ENTEROENDOCRINE CELLS DIFFERENTIATION
Authors: Peng Zhaoyi , Bao Lingyu , Shi Yun-Bo
Published: January 2024

The adult intestinal epithelium is a complex, self-renewing tissue composed of specialized cell types with diverse functions. Intestinal stem cells (ISCs) at the base of crypts divide and differentiate into absorptive and secretory cells. Enteroendocrine cells (EEC), one type of secretory cells, are the most abundant hormone-producing cells in mammals and involved in the control of energy homeostasis. Many studies investigated the mechanisms that control cell fate determination; however, regulation of EEC development and function are still unclear or controversial. Here, we found that Protein arginine methyltransferase 1(PRMT1), a major arginine methyltransferase, is highly expressed in the proliferating transit-amplifying (TA) cells and ISCs of adult mouse intestinal crypts. By using tamoxifen-induced intestinal epithelial cell-specific deletion of PRMT1 in adult mice, we observed the number of EEC dramatically increased. Transcription analyses showed the expression levels of Enteroendocrine-specific hormone and transcription factors are upregulated in PRMT1-deficient small intestine. In addition, the top enriched upregulated pathways were all associated with EEC functions. Concomitantly, Neurogenin 3-expressing progenitor cells accumulate in the mutant small intestine, and its target genes such as Neuod1, pax4, insm1 are upregulated of mutant crypts by RT-PCR. Furthermore, intestinal epithelium of the mutant mice showed elongated crypts in the small intestine, while increased cell proliferation in TA cells. Additionally, inducible PRMT1 deletion led to increased cell death, which compensated for increased cell proliferation in the crypts to maintain overall intestinal morphology and intestinal homeostasis. Together, our results revealed that the loss of PRMT1 in the adult intestinal epithelium altered TA cell proliferation and EEC differentiation, which was probably via Neurogenin 3-mediated pathway. Thus, our results may provide potential roles of PRMT1 as an essential transcriptional regulator of EECs specification and strategy for metabolic disorder.
COST-DRIVERS OF HEALTHCARE EXPENDITURES IN INFLAMMATORY BOWEL DISEASE
Authors: Berinstein Jeffrey , Melmed Gil , Allen John , Berry Sameer
Published: January 2024

INTRODUCTION

Inflammatory bowel diseases (IBD) are gastrointestinal (GI) conditions associated with significant costs. Effective management of IBD should focus on improving patient symptoms and outcomes while containing healthcare costs. To develop high-value treatment strategies and influence policy on high-value care, we must first have a better understanding of the primary drivers of cost in this population.

METHODS

We conducted a real-world descriptive cohort study using data from IBM Watson, which is a nationwide insurance claims database covering millions of commercially insured individuals across the US. We identified adult patients aged 18 to 65 years with encounters associated with a diagnosis of IBD in the primary or secondary position from January 2019 to January 2020 based on ICD-10-CM codes for Crohn's disease (555.x) and ulcerative colitis (556.x). Analysis of IBD prevalence, costs, and service utilization was based on ICD, CPT, and NDC codes related to IBD conditions and services. All other codes without an associated GI diagnosis in the primary or secondary position were attributed to all-cause costs. Measures of cost and utilization were calculated as a per member per year (PMPY).

RESULTS

105,496 patients with IBD were identified (Table 1). The mean PMPY total costs were $40,842 of which $31,051 (76%) were directly related to GI-related costs. Mean PMPY total costs in this population ranged from $1,178 to $144,945, with 15% of members experiencing costs > $76,346 PMPY. The main drives of GI-related costs can be divided into the following three categories: Inpatient costs ($8,206 [26%]), outpatient medical service costs ($11,306 [36%]), and drug costs ($11,539 [37%]) (Table 2). Per member utilization includes: 0.22 inpatient admissions, 0.10 surgeries, 1.02 GI visits, 2.87 non-gastroenterologist GI visit (which could include a visit to a primary medical doctor, rheumatologist, dietician, etc), 4.57 GI-testing, 0.48 GI imaging, 0.61 GI endoscopy, and 1.07 biologic medication prescriptions.

CONCLUSIONS

IBD care carries a significant financial burden on the US healthcare system. Unplanned emergency service and medication utilization continue to make up the majority of costs of IBD care and need to be the focus of value-based interventions. While appropriate high-cost pharmaceutical utilization should not be reduced, innovative strategies leveraging more cost-effective medication delivery may provide an important opportunity to curb costs. Furthermore, the high rate of non-gastroenterologist GI visits suggests that there is a potential for optimizing care pathways, by incorporating multidisciplinary care including, PCPs, mid-level providers, and other ancillary services into the IBD care model.
INFLIXIMAB MARKET SHARE AND ASSOCIATED COST SAVINGS FOLLOWING BIOSIMILAR MARKET ENTRY
Authors: Paglinco Samantha , Abdel-Rasoul Mahmoud , McNicol Megan , Boyle Brendan , Dotson Jennifer , Michel Hilary , Maltz Ross
Published: January 2024

BACKGROUND

Biologic medications have transformed treatment for autoimmune conditions, including inflammatory bowel disease (IBD), but have also contributed to rising healthcare expenditures in the United States (US). Biosimilars, which are highly similar in safety and efficacy to the originator biologic, were introduced to create competition and reduce cost. Limited studies exist evaluating the impact biosimilars have had on biologic market share and cost savings. The objective of this study was to evaluate the impact infliximab biosimilars have had on the cost and market share of the infliximab originator product.

METHODS

Infliximab claims were reviewed and analyzed using the Merative MarketScan Commercial Claims and Encounters Database. Using only outpatient claims, both the infliximab originator and biosimilars were identified using Current Procedural Terminology codes from January 1, 2015, to December 31, 2021. Patients with commercial insurance, ages 0 to 64 years, and receiving infliximab for any indication were included. The Medical Care Consumer Price Index was used to adjust for inflation to December 2021 dollars. Outcomes of interest included market share of all infliximab products, cost per infliximab infusion, and cost per vial (one vial=100 mg) of the medication.

RESULTS

There were 471,748 claims for infliximab infusions that met our inclusion criteria, with 42,100 unique patients, 55% female, and a median age of 40 (inter-quartile range (IQR) 26 – 52) years old at the time of medication initiation. Indications for infliximab products included IBD (67%), rheumatoid arthrtiis (18%), psoriasis (9%), ankylosing spondylitis (5%), other (4%), with some patients receiving infliximab for multiple indications.

Utilization of infliximab biosimilars increased over time, reaching the highest utilization in December 2021, accounting for 24% of the market share. The median cost of the infliximab originator peaked at $1,491 per vial in December 2017, 13 months after market entry of the first biosimilar (infliximab-dyyb). The cost of the infliximab originator then decreased by 45% over time, reaching a low of $821 per vial in December 2021. Had infliximab biosimilars not been introduced to the market, the projected cost of the infliximab originator in December 2021 would have increased by 20% to $1793 per vial. Thus, infliximab biosimilars contributed to a theoretical decrease of 55% in the cost of infliximab originator during the time period studied.

CONCLUSIONS

The market share of infliximab biosimilars in the US has steadily increased since their introduction in 2016. The competition of infliximab biosimilars has contributed to the decrease in cost of both the infliximab originator and biosimilar products. Future studies are needed to determine if patients are seeing an out-of-pocket savings because of biosimilar introduction.
THE IMPACT OF TREATMENT SWITCH AMONG PATIENTS WITH ULCERATIVE COLITIS NEWLY TREATED WITH A BIOLOGIC – A JAPAN RETROSPECTIVE CLAIMS DATABASE STUDY
Authors: Garcia Ana Dubon , Sanon Myrlene , Tan Jin Yu , Miyazaki Celine , Yu DaeYoung , Jing Zhao
Published: January 2024

INTRODUCTION

Biologics have largely expanded treatment options for ulcerative colitis (UC) patients. Despite advanced treatments, up to 50% of patients treated with any biologic also suffer loss of response or intolerance. This study assessed the healthcare resource utilization (HCRU) associated with treatment switch as an indicator of suboptimal treatment of UC in patients newly treated with a biologic in a real-world setting in Japan.

METHODS

A retrospective cohort analysis was performed using the Japan Medical Data Center (JMDC) claims database for the period from 01/01/2016 through 09/30/2022. Adult patients with at least two UC diagnoses and newly treated with a biologic on or after the UC diagnosis were included. The index date was defined as the date of the first observed biologic prescription fill or injection after the UC diagnosis. Patients with a record of pregnancy one year before or one year after the index date and patients with at least two CD diagnosis were excluded. Patients were classified as switchers if they discontinued their index biologic treatment and switched to another biologic or 5-aminosalicylic acid or immunomodulator during a 12-month study period after the index date. All-cause HCRU during the study period were described and compared (unadjusted) between the 2 cohorts (switchers vs non-switchers).

RESULTS

Among 47,572 patients diagnosed with UC, 1,214 met criteria for inclusion, of which 261 (21.5%) were in the switchers cohort and 953 (78.5%) in the non-switchers cohort. Overall, the mean age (SD) was 41.3 (12.4) years old and 31% (n=376) were female. In the switchers group, 85.8% (n=224) discontinued index treatment and switched to another biologic, 5.0% (n=13) to a 5-ASA and 11.1% (n=29) to an immunomodulator. Among switchers, 59.0% (n=154) of switching occurred during the first 6 months after index treatment.

During the 12-months follow-up period, the mean number of outpatient visits were similar between cohorts (15.5 visits vs 14.3 visits, p = 0.01). However, a greater proportion of the switchers cohort experienced inpatient hospitalization compared to non-switchers (43.7% [n=114] vs 19.6% [n=187], p<0.001). In addition, the inpatient hospitalizations had a longer mean length of stay in the switchers group vs non-switchers (12.9 days vs 4.5 days, p<0.001).

CONCLUSION

This real-world analysis using the JMDC database showed that roughly one out of five patients newly treated with a biologic switched to another treatment within 12 months of the treatment initiation. Those who experience treatment switch were also more likely to be hospitalized and had a longer length of stay versus patients who did not switch treatment. These findings highlight the continued burden of non-remission associated with treatment switch and the need for more efficacious and safe treatment interventions early in disease management.
UNCOVERING UNIQUE NEEDS AND BARRIERS TO CARE AMONG LGBTQ+ PATIENTS WITH IBD: INSIGHTS FROM A COMMUNITY SURVEY TO INFORM INCLUSIVE PRACTICES
Authors: Chedid Victor , Aiello Alicia , Chadha Chelsie Anderson , Carter Jeffrey , Simone Laura , Balmer Jennifer
Published: January 2024

INTRODUCTION

Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ+) individuals face a myriad of disparities and unique challenges that impact their clinical care and outcomes, however, less is known regarding the specific needs of sexual and gender minorities with inflammatory bowel disease (IBD). Methods: The aim of this study was to better understand the unmet needs and potential barriers to care that LGBTQ+ persons with IBD experience. A survey was disseminated in March 2023 via email distribution by Girls with Guts and the AIDS Institute to individuals with IBD who identify as LGBTQ+. The data was analyzed with descriptive analysis with frequencies and percentages (%). Results: A total of 217 people completed the survey, including 165 cisgender, 34 transgender, and 18 gender nonbinary individuals with IBD. The majority of respondents identified as lesbian or gay (56%) or bisexual (27%), and most reported an IBD diagnosis of Crohn’s Disease (61%). Most indicated their IBD care team was aware of their gender identity (76%) and sexual orientation (75%), either through direct discussions or being asked on medical forms, however nearly half report that they sometimes to very frequently delay seeking IBD care (49%) or refrain from sharing information with their IBD care team (63%) because of worry or fear of mistreatment or judgement (Figure 1). Only 37% of individuals agreed their IBD care team meets their unique needs as an LGBTQ+ person, and respondents reported most commonly turning to online sources of health information (55%) and other members of the LGBTQ+ community (42%) rather than their IBD care team (26%) for information on IBD as it relates to their gender, sexual orientation, and/or sexual practices. Overall, respondents most frequently cited worry about judgement or mistreatment (40%) as a barrier to discussing sexual orientation and gender identify (SOGI) with their IBD care team, however, this concern was more frequently reported by transgender (65%) and gender nonbinary (72%) individuals than cisgender persons (33%) (Figure 2). Nearly half (46%) agreed the clinic where they receive their IBD care could be described as LGBTQ+ safe and inclusive, however, this percentage varied by location, with individuals living in small towns or rural areas expressing more disagreement. Overall, respondents identified their IBD care teams could most improve by becoming more knowledgeable in LGBTQ+ concerns related to IBD (46%), initiating conversations related to SOGI and sexual practices (30%), and displaying visible signs of LGBTQ+ acceptance (29%).

CONCLUSION

Collectively, these data provide insight into the unique challenges and needs of LGBTQ+ individuals with IBD and may be used to inform strategies that support equitable IBD care. Future studies should focus on the impact of such strategies on IBD-related outcomes.
ENHANCED MITOCHONDRIAL BIOGENESIS INCREASES ANTI-OXIDANT ENZYMES AND IMPROVES TISSUE INFLAMMATION IN HUMAN IBD TISSUE
Authors: Bhogoju Sarayu , Kapur Neeraj , Vekaria Hemendra , Goretsky Tatiana , Hassan Syed Adeel , Kim Jong Hyun , Awuah Samuel , Sullivan Patrick , Chaiswing Luksana , Barrett Terrence
Published: January 2024

BACKGROUND

In patients with inflammatory bowel disease (IBD), there exists a connection between mitochondrial dysfunction and two key issues: increased oxidative stress and attenuated ATP production. Previously we presented at this meeting the effect of a novel gold-based compound (AuPhos) on enhancing mitochondrial function in attenuating mice colitis (). In the present study we interrogate the effect of AuPhos on mitochondrial biogenesis in biopsies from control and active ulcerative colitis (UC) (Mayo 1-2) patients and normal human colonic epithelial cells (NCM460). We postulate that AuPhos-induced mitochondrial function enhances biogenesis and anti-oxidant levels and improves tissue inflammation in human IBD tissue.

METHODS

Effects of AuPhos on mitochondrial and anti-oxidant proteins were evaluated in NCM460 cells by western blot (WB) +/- low-dose TNF(1ng/ml). Human colonic biopsy samples (n=3) were collected and treated ex-vivo with vehicle or AuPhos (3h, 4oC), and processed for protein and mRNA analysis by WB and RT-qPCR, respectively. Flow cytometry of mitotracker green quantified mitochondrial mass in NCM460 and intestinal epithelial cells (IECs) from human control and UC tissues (n=3, Mayo 1-2).

RESULTS

AuPhos increased mitochondrial mass (mitotracker, Fig.1A,1B) and biogenesis protein levels PGC1α, NRF2 and TFAM (Fig.1C) in human intestinal epithelial cells (IECs), biopsies, and in NCM460 cells. Protein analysis in NCM460 cells show that AuPhos increases downstream antioxidant markers such as manganese superoxide dismutase (MnSOD), glutathione peroxidase 4 (GPX4), thioredoxin reductase2 (Trx2), and catalase expression when compared to the TNF or control samples. AuPhos substantially upregulates levels of mitochondria complex (mtCO1, mtCO2 Cox6A1, ATP5A1) and anti-oxidant enzyme (MnSOD, GPX, PRDX-2, -4, and -6) mRNA and protein levels in human colonic biopsies compared to vehicle and TNF treated samples (Fig. 1D). Furthermore, AuPhos reduces tissue cytokine and chemokine mRNA levels (IL1β, MCP1, RankL, and TNFα) in human UC tissues (Fig. 1E).

CONCLUSIONS

The current study reveals that AuPhos increases mitochondrial biogenesis, mitochondrial complex, and antioxidant enzyme levels in human IBD tissue. THE REDUCTION IN TISSUE CYTOKINES AND CHEMOKINES SUGGESTS THAT ENHANCED MITOCHONDRIAL FUNCTION IMPROVES TISSUE INFLAMMATION. This suggests the potential of AuPhos in treating IBD through the restoration of mitochondrial biogenesis.