bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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&lt;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&lt;0.001). Women were 1.59 times more likely to have APAI than men (OR 1.590, CI: 1.539 - 1.643, p&lt;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&lt;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.

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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

Abstract
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&lt;0.05); males 46.17 % vs 42.1% (P&lt;0.05); Caucasians 82.42 % vs 77.1% (P&lt;0.05); Heart failure 16.47% vs 10% (P&lt;0.05); Pulmonary Hypertension (PH) 4% vs 2%; Acute Kidney Injury (AKI) 33.6% vs 16.1 (P&lt;0.05)%; obesity 14.7% vs 12.8 % (P&lt;0.05); Dyslipidemia 22.2% vs 22.2% (P=0.89); anemia 23.8% vs 20.1 (P&lt;0.05)%; Acute Coronary Syndrome (ACS) 4.5 % vs 2.6% (P&lt;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

Abstract
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

Abstract

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

Abstract

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

Abstract

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

Abstract
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.