bluuebunny/crossref_metadata_2025 huggingface dataset:
618 The Use of Antibiotics Prophylaxis in Cirrhotic Patients Presenting With Gastrointestinal Portal Hypertensive Bleeding in a Community Teaching Hospital
Authors: Al Yassin Sarmed , Fatakhova Karina , Al-Naqeeb Ghadah , Glazer Emily , Haggerty Gregory , Tofano Michael , Eckardt Sarah
Published: October 2019

INTRODUCTION:

Background: Bacterial infections are common in cirrhotic patients with acute gastrointestinal portal hypertensive bleeding, occurring in 20% within 48 hours. Outcomes including early re-bleeding and failure to control bleeding are strongly associated with bacterial infection. The use of short-term prophylactic antibiotics in patients with cirrhosis and GI hemorrhage with or without ascites has been shown not only to decrease the rate of bacterial infections but also to increase survival. This improved survival is partly related to a decrease in the incidence of early re-bleeding in patients with GI hemorrhage who receive prophylactic antibiotics. Therefore, short-term antibiotic prophylaxis should be considered standard practice in all patients with cirrhosis and acute variceal hemorrhage. The antibiotic of choice in most centers is intravenous Ceftriaxone at a dose of 1 g daily. Duration of antibiotic prophylaxis is short term, for 5-7 days (to be discontinued when hemorrhage resolve and vasoactive drugs discontinued).

METHODS:

300 charts were reviewed in retrospective data analysis for patients presented during 2017 and 2018 with cirrhosis related diagnoses and gastrointestinal bleeding related diagnoses. 43% (171 patients) of the presented patients had active cirrhosis.

RESULTS:

Anatomy and EGJ opening determine outcome in achalasia. Of those 171 patients:

17% (30 of 171) patients that have cirrhosis presented in 2017 and 2018 with gastrointestinal bleeding,

36% (11 out of the 30) patients received empiric antibiotics, whether as prophylaxis or for other indications such as sepsis,

64% (19 out of the 30) patients, antibiotics were not started on admission; therapy started on the second or third day by gastroenterology service, or other service/team.

CONCLUSION:

Our results showed that the majority of patients (64%) with cirrhosis presenting with GI bleed were not started on a proper prophylaxis antibiotic. The ideas and the actions that were proposed and implemented post this study: Increase awareness through nursing and pharmacy staff teaching sessions, as well as residents didactic lectures. Also, through periodic awareness/teaching emails to medical staff. Hospital protocols were reviewed. A questionnaire step, “Warning window,” were integrated into the EMR, that to pop up when a medical provider add “liver cirrhosis” or “variceal hemorrhage” to patient admitting/visit diagnosis list. This intervention was implemented recently. In the next phase, we plan to gather data obtained post intervention, and to be studied and compared.
623 Impact of Hospital Teaching Status on the Outcomes of GI Bleeding Hospitalizations in the U.S.: Insights From the National Database
Authors: Elkafrawy Ahmed A. , Othman Hasan F. , Zafar Yousaf , Hasan Badar , Nehme Fredy , Numan Laith
Published: October 2019

INTRODUCTION:

GI bleeding is a life-threatening GI emergency with a major burden for the health care system in the US. The aim of this study is to evaluate the impact of teaching status of the hospital on the outcomes of hospitalized patients with GI bleeding.

METHODS:

Nationwide Inpatient Sample database (NIS) was queried to identify patients hospitalized between 2006 and 2015 with GI bleeding using (ICD9-CM) codes. Patients were classified into 2 groups according to the teaching status of the admission hospital to either teaching or non-teaching hospitals. Both groups were compared regarding age, gender, race, mortality, undergoing GI endoscopy (EGD, small intestinal endoscopy, flexible sigmoidoscopy or colonoscopy), outcomes and commonly associated comorbidities. Statistical analysis was performed using SPSS V.25.

RESULTS:

We identified 8,211,580 patients admitted with GI bleeding between 2006-2015. Out of them, 3,826,532 patients were admitted to teaching hospitals while 4,385,049 patients were admitted to non-teaching hospitals. Median (IQR) age in patients admitted to teaching hospitals was 67 (53-79) years compared to 71 (56-81) years in non-teaching hospitals. 53.1% of patients admitted to teaching hospitals were males compared to 49.9% in the non-teaching hospitals. GI endoscopy was performed in 46.6% of patients admitted to teaching hospitals compared to 46.1% in non-teaching hospitals (95% CI 1.01, 1.02) (P < 0.001). Patients admitted to teaching hospitals had higher mortality (7.3%) compared to (6.1%) in non-teaching hospitals (95% CI 1.21, 1.22) (P < 0.001). The median length of stay was 4 days in both groups. Shock was present in 7.7% of patients admitted to teaching hospitals compared to 5.3% in patients in non-teaching hospitals (95% CI-1.46-1.48) (P < 0.001). 9.8% of patients with GI bleeding admitted to teaching hospitals were mechanically ventilated compared to 6.5% in non-teaching hospitals (95% CI 1.55-1.57) (P < 0.001). Blood transfusions were administered to 38.5% of patients admitted to teaching hospital compared to 41.9% of patients in non-teaching hospitals (95% CI 0.86-0.87) (P < 0.001).

CONCLUSION:

46% of patients with GI bleeding between 2006-2015 were admitted to teaching hospitals. Admission to a teaching hospital was associated with higher mortality, higher number of endoscopies, higher likelihood of shock and mechanical ventilation but less blood transfusion. Results likely indicate higher level of acuity and complexity of patients admitted to teaching hospitals.
630 Inpatient Capsule Endoscopy Does Not Lead to Increased Hospital Interventions in Stable Small Bowel Bleeding
Authors: Jen Henry , Al Sayah Leona , Sosa Daniel , Taub Erin , Monzur Farah
Published: October 2019

INTRODUCTION:

Wireless capsule endoscopy is an important tool to evaluate for small bowel sources of bleeding when upper and lower endoscopies have been unrevealing. However its use as an inpatient test is controversial with some studies suggesting increased capsule retention, prolonged length of stay, and increased costs. We aimed to assess the yield of inpatient capsule endoscopy when hemoglobin stability or resolution of overt bleeding is achieved prior to capsule deployment.

METHODS:

We performed a retrospective study of 161 patients with suspected small bowel bleeding over a 3 year period. Primary outcome was inpatient endoscopic interventions in patients with positive capsule findings but stable precapsule hemoglobin or resolved overt bleeding. Other outcomes included length of stay, success of intervention, outpatient follow-up, rehospitalization, and capsule complications.

RESULTS:

A total of 119 of the 161 patients (79.9%) had positive capsule findings. Only 70 patients underwent subsequent endoscopic intervention prior to discharge. Even in patients with active bleeding seen, 15% were discharged without endoscopic intervention. Hemoglobin stability and resolution of overt bleeding prior to capsule deployment were found to be significant predictors of whether patients underwent intervention. Those who had a stable hemoglobin for 8, 24, and up to 48 hours prior to capsule deployment had significantly less endoscopic interventions prior to discharge (P = 0.0026). Additionally, patients with a stable precapsule hemoglobin had a significantly decreased chance of having an identified lesion with successful treatment on enteroscopy (P = 0.0097). Those who had resolution of overt bleeding prior to capsule deployment also had significantly less endoscopic interventions prior to discharge (P = 0.0036). However, those with a stable hemoglobin with positive capsule findings had higher rehospitalization rates with only 14% having follow-up outpatient enteroscopies. Overall capsule retention rate was 19%. Capsules extended length of stay by an average of 1.7 days with 45% of patients discharged within 48 hours of capsule read.

CONCLUSION:

Inpatient capsule endoscopy extends length of stay with high retention rates without changing in-hospital endoscopic management of patients with small bowel bleeding who have achieved hemoglobin stability and resolution of overt bleeding prior to capsule deployment. These patients however tend to have higher rehospitalization rates and require close outpatient follow-up.
636 Hyperbaric Oxygen Therapy Is Effective in the Treatment of Inflammatory Disorders of the Ileal Pouch
Authors: Fahad Hamna , Shen Bo , Kochhar Gursimran
Published: October 2019

INTRODUCTION:

Inflammatory disorders of ileal pouch-anal anastomosis (IPAA) including chronic pouchitis, Crohn's Disease (CD) of the pouch and cuffitis are common and their management can be challenging. Hyperbaric oxygen (HBO) has been used for the treatment of ulcerative colitis (UC) and CD; however, its use in pouchitis has not been systemically evaluated. The aim of our study was to assess the response to HBO therapy in patients with inflammatory diseases of the pouch.

METHODS:

In this retrospective case series, we included all patients above the age of 18, with history of IPAA and medically refractory pouchitis. HBO was executed with standard protocol with 2.4 to 3.0 PSI with a total of 30 sessions over 2 months. A modified Pouchitis Disease Activity Index (mPDAI) was used to quantify symptom and endoscopy sub-scores. The Wilcoxon Signed Rank test was used to compare the results. A P value of < 0.05 was taken to be significant.

RESULTS:

A total of 21 patients were included in the study, 52.4% (n = 11) of these were males. The mean age of our sample was 40.4 ± 12.3 years. The indications of HBO were pouchitis (n = 18), fistulae (n = 9), surgical site/anastomotic ulcers (n = 7), active cuffitis (n = 6), ischemic ulcers (n = 4); most patients had more than one indication (Table 1). Thirteen patients (61.9%), reported subjective symptomatic improvement in stool frequency, bleeding, urgency and fevers. Of these, six patients (28.5%) reported complete remission of symptoms (Figure 1). Seventeen patients (80.9%) had endoscopic improvement. Among these 2 (10%) showed endoscopic remission (Figures 1 and 2). Of the 9 patients who had fistulae, 7 (77.8%) showed healing of the fistula tract. Overall, 19 (90.5%) patients had improvement in their mPDAI. Mean mPDAI of our cohort prior to therapy was 8.71. Of those who showed response, the mPDAI improved by a median of 3 (IQR 2-3) points. No side effects were seen in our cohort. The mean mPDAI was significantly better after HBO therapy (P < 0.05).

CONCLUSION:

Hyperbaric oxygen therapy led to symptomatic and endoscopic improvement, as noted by the mPDAI, in majority of patients. Most patients with fistulae had significant endoscopic improvement.
646 Molecular Response to Ustekinumab in Moderate-to-Severe Ulcerative Colitis by Serum Protein and Colon Transcriptomic Analysis: Results From the UNIFI Phase 3 Maintenance Study
Authors: Li Katherine , Yang Feifei , Hayden Karen , Strawn David , Wadman Eric , Bhagat Sunita , Marano Colleen , Friedman Joshua R.
Published: October 2019

INTRODUCTION:

The cytokines IL-12 and IL-23 are elevated in ulcerative colitis (UC), and genetic association suggests they play causative roles in the disease. Ustekinumab (UST), an anti-IL-12p40 monoclonal antibody that binds both cytokines, is an effective therapy for moderate-to-severe UC. We previously observed a partial normalization of UC disease signatures in colonic biopsy gene expression and serum protein levels following UST induction therapy. However, the molecular effects of maintenance UST therapy in UC pts are unknown.

METHODS:

We evaluated the molecular effects of UST in the UNIFI Phase 3 maintenance study of moderate-to-severe UC (n = 961). Pts in response to UST 8 wks after intravenous induction were randomized to maintenance treatment with subcutaneous placebo or UST 90 mg q12w or q8w. Colonic biopsy mRNA and serum samples from the first ∼60% of pts treated in the UNIFI phase 3 induction study were analyzed, with equal representation of pts with or without a history of biologic therapy failure (Table 1). Biopsy and serum samples from healthy pts were analyzed as controls.

RESULTS:

At Wk44 after the start of maintenance therapy, expression of colonic genes dysregulated in UC was altered towards normal levels in all treatment groups, with the greatest improvements among those receiving UST and those in clinical remission (P < 0.05 for Wk 44 versus start of maintenance). No dose effect was observed between q8w and q12w UST doses, and no significant improvements in disease signature occurred in non-responders to placebo or UST. UST maintenance therapy magnified the normalization of serum proteins following UST induction; among pts receiving q8w UST who were in remission at Wk44, the proteins IFNγ, IL-17A, MMP3, and SAA reached concentrations comparable to those seen in healthy controls. Similar trends occurred in pts in remission following q12w UST and to a lesser degree among UST-treated pts not in remission at Wk44. Among pts receiving placebo maintenance therapy who were in remission at Wk 44, the disease-associated serum proteins that decreased following UST induction were not further reduced during maintenance. As previously observed in the induction studies, UST maintenance did not reduce serum TNF levels.

CONCLUSION:

UST maintenance therapy suppressed IL-12 and IL-23-related serum proteins and promoted normalization of the UC disease transcriptomic profile. These results provide insight into the molecular mechanisms associated with the efficacy of UST maintenance therapy.
650 The Effects of HIV Status on Complications and Outcomes in Patients With Inflammatory Bowel Disease: An Analysis Using the Nationwide Inpatient Sample Database
Authors: Shaikh Amjad , Patel Preet , Huynh James , Patel Pavan , Ahlawat Sushil
Published: October 2019

INTRODUCTION:

The effects of HIV status on inflammatory bowel disease (IBD) has been described in the literature but has been limited in cohort size. Here, we examine data from patients with IBD and HIV in the Nationwide Inpatient Sample database over a 7-year period.

METHODS:

Data between 2008 and 2014 from the Nationwide Inpatient Sample database was extracted. Inclusion criteria for both groups included patients with a primary diagnosis of either Crohn's disease or Ulcerative colitis using International Classification of Diseases, 9th Revision codes. Exclusion criteria included all patients less than 18 years of age. Test group consisted of patients with a primary diagnosis of Crohn's disease or Ulcerative colitis and a concurrent diagnosis of HIV. In hospital mortality and complications including anemia, malabsorption, malnutrition, stenosis, obstruction, fistulas, abscesses, ulcers, perforations, and hemorrhage were compared between the two groups. Univariate and multivariate analyses were used to generate odds ratios. Multivariate analysis included age, gender, race, and calculated Elixhauser scores. Elixhauser Comorbidity scores predicting mortality and readmission were calculated based on weighted scores from 29 different comorbidities. Scores were compared between the two groups using univariate analysis.

RESULTS:

There were a total of 121835 patients with IBD and no HIV and 475 patients with IBD and HIV for hospitals in the United States between 2008 and 2014. There was no significant difference in hospital mortality between the two groups on univariate analysis (OR 0.5161, P = 0.5092). Of the complications studied, there was a significant difference for obstruction (OR 0.3447, P < 0.0001), ulceration (OR 1.97, p = 0.0063), and hemorrhage (OR 1.75, P = 0.0001) on univariate analysis. For the multivariate analysis, HIV status has a significant effect on anemia (OR 0.291, P = <0.001), malnutrition (OR 0.3, P = <0.001), obstruction (OR 0.411, P = <0.001), and hemorrhage (OR 1.47, P = <0.001).

CONCLUSION:

HIV status does not seem to have a significant effect on mortality, but appears to be protective against obstruction, anemia, and malnutrition. We suspect the immunocompromised status of HIV patients may lead to fewer bouts of acute inflammation, reducing the rates of complications. It may also be of interest to compare rates of procedures and interventions between the two groups to further explore potential differences.
659 Epidemiology of Major Depressive Disorder, Anxiety Disorder, and Bipolar Disorder in Crohn's Disease in the United States Between 2014 and 2019: A Population-Based National Study
Authors: Chouhan Vijit , Mansoor Emad , Saleh Mohannad Abou , Katz Jeffry , Regueiro Miguel , Cooper Gregory S.
Published: October 2019

INTRODUCTION:

Studies have shown that patients with Crohn's disease (CD) are at an increased risk for developing various psychiatric illnesses including depression, anxiety, and bipolar disorder. However, these studies have been limited by a small sample size. We aimed to describe the epidemiology of psychiatric illness in CD through utilization of a large sample population.

METHODS:

We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of electronic health record data from 26 major integrated US healthcare systems. We identified an aggregated patient cohort of eligible patients with a diagnosis of CD and depression, anxiety, and bipolar disorder between 2013 and 2018 based on the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT). We also identified patients with a diagnosis of depression, anxiety, or bipolar disorder without CD. We calculated the overall prevalence of depression, anxiety, and bipolar disorder in CD amongst various patient groups. We also performed univariate analyses to identify risk factors for psychiatric illness in CD.

RESULTS:

Of the total number of patients in the database with CD, 28,640 had depression, 38,640 had anxiety, and 11,410 had bipolar disorder, with prevalences of 19%, 25%, and 8%, respectively. Depression, anxiety, and bipolar disorder in CD were more prevalent than in individuals without CD. Within CD, psychiatric illness was more prevalent in elderly (age >65 years old), females, and Caucasians. Compared to patients with psychiatric illness without CD, patients with psychiatric illness and CD were more likely to have a history of alcohol abuse, tobacco use, substance use, personality disorder, and corticosteroid use.

CONCLUSION:

This is one of the largest studies to date to describe the epidemiology of psychiatric illness in CD. Individuals with CD were more likely to suffer from depression, anxiety, and bipolar disorder compared to their non-CD counterparts. Prevalence of psychiatric illness in CD was more common in elderly, females, and Caucasians. Psychiatric illness should be actively screened for and treated accordingly in CD.
663 Onset of Response With Infliximab vs. Vedolizumab in the Treatment of Bio-Naïve Inflammatory Bowel Disease
Authors: Fourment Chris , Ritter Timothy E. , Kuten Samantha A. , Hardin Thomas C. , Van Anglen Lucinda J.
Published: October 2019

INTRODUCTION:

Both infliximab (IFX) and vedolizumab (VDZ) are approved for the treatment of inflammatory bowel disease (IBD) in adults. Compared to IFX, VDZ is thought to have a slower onset of response. The purpose of this study was to characterize the incidence and timing of clinical remission between IFX and VDZ.

METHODS:

We performed a retrospective cohort study of bio-naïve adult patients (pts) treated with IFX or VDZ for ulcerative colitis (UC) or Crohn's disease (CD) at a large multicenter gastroenterology private practice. Pts were case-matched 1:1 based on age, gender, diagnosis, and baseline disease severity using the partial Mayo (pMayo) for UC and the modified Harvey-Bradshaw Index (mHBI) for CD. Primary endpoints were clinical remission rates at 6 months (mos), defined as pMayo less than 2 or mHBI less than 5, and time to remission represented by a Kaplan Meier curve. Pts in remission at baseline and those discontinuing therapy <6 mos were excluded from analyses.

RESULTS:

A total of 77 IFX (58 UC, 19 CD) and 77 VDZ (58 UC, 19 CD) case-matched pairs were generated. Baseline demographics were similar between IFX and VDZ groups: mean age 45 ± 16.9 vs 46 ± 16.2, male gender 60% vs 61%. Thirty-three pts were excluded from efficacy analyses: 8 in remission at baseline, 25 discontinuing therapy < 6 mos (16 IFX, 11 VDZ). Data are presented for the remaining 121 pts: IFX 60 (47 UC, 13 CD) and VDZ 61 (48 UC, 13 CD). Disease severity scores over 6 mos are depicted in Figure 1, with both IFX and VDZ demonstrating a rapid response by 2 weeks of treatment. Remission rates were similar among IFX and VDZ-treated UC patients (78.7% vs 64.6%, P = 0.13), and significantly higher for IFX-treated CD patients (84.6% vs 46.2%, P = 0.04). There was no difference in time to remission (Figure 2).

CONCLUSION:

We observed rapid onset of response and high remission rates among bio-naïve pts treated with both IFX and VDZ. While IFX-treated CD patients experienced significantly higher remission rates, our numbers were small. Importantly, time to remission did not differ between IFX and VDZ-treated pts. These data need to be verified in a larger cohort.
664 Relapse Rate From Deep Remission After Withdrawal of Anti-TNFa in Inflammatory Bowel Disease: A Meta-Analysis
Authors: Gulati Alakh , Alipour Omeed , Shao Ling , Zhang Bing
Published: October 2019

INTRODUCTION:

Clinical remission has traditionally been the therapeutic target in the treatment of inflammatory bowel disease (IBD). However, emerging paradigms suggest deep remission (DR), often defined as clinical remission and mucosal healing with or without additional criteria, as a goal of therapy. Literature suggests longer intervals to relapse after withdrawing anti-TNFα therapy in DR, compared to clinical remission, in patients with IBD. This meta-analysis aims to determine the rates of relapse following anti-TNFa withdrawal in patients with DR.

METHODS:

Using search terms (“inflammatory bowel diseases” OR “IBD” OR “crohn*” OR “ulcerative colitis” OR “UC” OR “colitis”) AND (“mucosal healing” OR “deep remission” OR “complete remission” OR “full remission” OR “endoscopic remission”), 7,514 studies were identified from Pubmed and EMBASE on Oct 1, 2018. Inclusion criteria were adult IBD patients achieving DR with anti-TNFα treatment, defined as clinical remission and mucosal healing, who were followed to assess for relapse, defined as clinical or endoscopic disease activity. Studies with pediatric patients, patients maintained on steroids, and non-English publications were excluded. Publications were reviewed for inclusion independently by two authors; a third served as tie-breaker. Statistics was performed with OpenMetaAnalyst.

RESULTS:

Four manuscripts and one abstract with 234 cases at 1-year and 104 cases at 2-years were included. Anti-TNFα agents used were infliximab or adalimumab in all studies. All patients were withdrawn from anti-TNFα after achieving DR, some were continued on salicylate or immunomodulators. Within one year of withdrawal, 28.3% (67/234; I2 = 54.64%, P = 0.066) of patients demonstrated relapse from DR. Within two years, 47% (49/104; I2 = 0%, P = 0.721)) relapsed. No predictors of relapse from DR were reported.

CONCLUSION:

Literature describes the 1-year and 2-year relapse rate after anti-TNFα withdrawal from patients who achieved clinical remission to be approximately 40% and 60%, respectively. We found 1-year and 2-year relapse from DR after anti-TNFα withdrawal to be 28.3% and 47%. While the rates of relapse from DR are greatly reduced compared to relapse from clinical remission, nearly half of patients still experience relapse within two years after stopping anti-TNFα. This highlights the need for patient-physician discussion on significant relapse risk prior to stopping anti-TNFα therapy despite achievement of deep remission.
666 Outcomes Following Therapeutic Drug Monitoring of Vedolizumab
Authors: Graziano Elliot J. , Gheysens Katherine , Cross Raymond K. , Campbell James , Vaughn Byron
Published: October 2019

INTRODUCTION:

Therapeutic drug monitoring (TDM) of biologic therapies is increasingly used in the management of inflammatory bowel disease (IBD). It is established that for anti-tumor necrosis factor medications, a dose escalation will have a positive clinical response in up to 86% of those with low serum drug concentrations. However, it is unknown if trough concentration predicts response to VDZ dose escalation. The objective of this study was to evaluate the impact of TDM on clinical outcomes in patients with IBD treated with VDZ.

METHODS:

This was a retrospective study of patients with IBD treated at two institutions (University of Minnesota, University of Maryland) with VDZ who had a VDZ trough concentration post induction between November 2016 and October 2018. A positive response was defined as improvement in the factor that was the etiology of dose escalation and categorized as clinical response, biomarker (i.e., CRP) response, or endoscopic response. An a priori VDZ trough concentration of 10 ug/ml was chosen as the cut off for a low level. Data was collected including demographics, disease characteristics, management changes and outcomes. VDZ concentration was performed using a commercial test (Inform Diagnostics, Irving, TX). Student's t-test and Fisher's exact test were used for continuous and categorical variables respectively in JMP Pro 14.0.0.

RESULTS:

48 trough concentrations were obtained in 43 patients. 51.2% had Crohn's disease while 48.8% had ulcerative colitis/indeterminate colitis. Following TDM, 62.5% (30/48) of patients underwent a dose change: 23 dose escalations, 5 stoppages and 2 dose de-escalations. 65% (13/20) of dose escalations (3 had inadequate follow-up) had a positive response to dose adjustment: 8 symptomatic response, 1 biologic response and 4 endoscopic response. Among those with a low VDZ trough <10 ug/ml, 75% (9/12) improved following dose escalations versus 50% (4/8) of those with VDZ trough ≥10 ug/ml (P = 0.356). The mean CRP prior to dose escalation was 7.0 mg/L (SD = 10.2) compared to 6.4 mg/L post dose escalation (SD = 12.3) (P = 0.863).

CONCLUSION:

TDM in VDZ results in frequent clinical management changes. While there was a greater percentage of patients that demonstrated clinical improvement following dose escalation with low drug levels, the difference was not statistically significant. Larger cohorts are needed to evaluate the impact of TDM with VDZ as our study was underpowered to identify small to moderate differences based on the pre-determined low VDZ level.
669 Increased Prevalence of Sinusitis Among Patients With Inflammatory Bowel Disease
Authors: Rai Victoria , Rubin David T.
Published: October 2019

INTRODUCTION:

Sinusitis is characterized by inflammation of sinus tissue by infectious or noninfectious agents. The pathophysiology of sinusitis involves a combination of an inflammatory response by the nasal mucosa and, in some cases, excess bacteria growth. Though it is thought that similar dysfunction of the epithelial barrier in the gut with inflammatory bowel disease (IBD) occurs in the nasal passage with sinusitis, there has not yet been an established association between the two, and there are limited data describing the relationship between IBD and acute or chronic maxillofacial sinus inflammation or infection.

METHODS:

This is a retrospective study at our tertiary IBD center. We used our institution's anonymized electronic medical record data warehouse to identify patients with diagnostic codes for both sinusitis (J32) and IBD (K50.90 and K51.90), and recorded directionality of diagnoses and medication exposures. Patients with a confirmed diagnosis of IBD between January 2000 and May 2019 and age ≥18 years were included. Demographic and disease related information were collected. Categorical variables were analyzed using Fisher's exact test and continuous variables were analyzed using Wilcoxon rank sum test.

RESULTS:

The data warehouse includes 2.4 million patients in the time period defined, of which 14379 have IBD. There were 13446 non-IBD patients with a diagnostic code for sinusitis (0.56%), and 387 IBD patients with a code for sinusitis (2.69%; OR 4.8, 95% CI 4.3-5.3). We did not identify directionality in sinusitis diagnosis in IBD. Univariate analysis is reported in Table 1. Among the IBD patients, multivariate analysis adjusting for age of IBD diagnosis, sex, and race identified female gender (OR 1.47, 95% CI 1.19-1.83), black/African-American race (OR 3.75, 95% CI 1.55-12.34), history of bowel obstruction (OR 1.68, 95% CI 1.28-2.18), and past or current use of steroids (OR 2.51, 95% CI 1.99-3.19) as risk factors for having sinusitis in IBD. No significant differences were observed in average age at IBD diagnosis, smoking status, other immune medications or IBD type (Crohn's disease or ulcerative colitis).

CONCLUSION:

In our tertiary center, IBD patients had nearly 5-fold greater odds of sinusitis than non-IBD patients. Female gender, black/African-American race, bowel obstruction, and steroid use was associated with a diagnosis of sinusitis associated with IBD. Additional evaluation of these risk factors and potential screening and prevention strategies are warranted.
670 Development of a Novel Web-Based Yoga, Breathing, and Meditation Site for Patients With Inflammatory Bowel Disease
Authors: Rai Victoria , Lanson Biana G. , Rubin David T.
Published: October 2019

INTRODUCTION:

Multiple studies have demonstrated that patients practicing yoga-based interventions/techniques have decreased anxiety and depression, increased self-efficacy and improved quality of life. This has included prior work with inflammatory bowel disease (IBD) patients. We developed novel videos and an educational website about yoga and breathing techniques which allows patients to perform these exercises on their own.

METHODS:

We worked with a certified yoga instructor and professional film crew to develop an online set of yoga, breathing and meditation exercises for those with digestive illnesses (IBDyoga.com) (Figure 1). The exercises are embedded in a non-profit foundation website and also available YouTube since Sept 2017. The website was promoted directly to patients in clinic, through group educational seminars and via social media. The site also features a voluntary survey regarding yoga and IBD. We report the outcome of these efforts.

RESULTS:

From Sept 2017 to June 2019, the Yoga Active Practice, Yoga Restorative Practice, and Breathing Exercises videos posted to YouTube received 4957, 1298, and 614 views respectively with mean view duration 9:25 min, 5:26 min, and 1:37 min, respectively. IBDyoga.com received 1900 unique pageviews with 692 returning users and a mean time on page of 2 min. 26 visitors completed our survey, 30% of whom were in self-described clinical remission from IBD and 70% with active IBD symptoms. 27% reported that they were new to yoga/meditation, 27% reported that they tried yoga/meditation techniques in the past, and 46% were experienced in these techniques. 81% of new to yoga/breathing/meditation reported as IBD symptomatic. 59% of total responders reported more energy, 77% reported better mood, and 67% reported less anxiety, while in symptomatic responders, 71% reported more energy and better mood, and 69% reported less anxiety. There were not significant differences between symptomatic and non-symptomatic visitors to IBDyoga.com with IBD.

CONCLUSION:

These novel yoga, meditation and breathing videos and resources for patients with chronic illness have attracted over 8900 views in the past 20 months. At IBDyoga.com, most of the users reported active IBD symptoms, and of those who completed the exercises, most reported having more energy, better mood and less anxiety. Additional work to promote this resource and study its potential benefits is ongoing.
674 Faster Sedation Times for Inflammatory Bowel Disease (IBD) Patients Undergoing Elective Endoscopic Procedures Can Be Safely Achieved With a Higher Propofol Induction Dosage Compared to Non-IBD Patients
Authors: Zhang Daniel S. , Stana Roman , Abraham Bincy
Published: October 2019

INTRODUCTION:

Patients with inflammatory bowel disease (IBD) frequently undergo endoscopic procedures for diagnosis and management of disease activity. We have shown in a prior study that our IBD patient population have higher sedation requirements, which is consistent with other studies.1–3 However, there is limited data on induction dosing requirements comparing the IBD patient population to the non-IBD population. Here we conducted a retrospective study comparing the induction propofol dose and sedation time required for IBD patients compared to non IBD patients.

METHODS:

Patients 18 years or older undergoing elective outpatient endoscopy with an American Society of Anesthesiologists (ASA) score of 2 or less using total intravenous anesthesia (TIVA) from one designated anesthesiologist was included in the study. Adverse events were recorded. Age, body mass index (BMI), relevant comorbidities, medications, and endoscopic disease activity scores were recorded. The primary outcome was induction dose, which was defined as the amount of propofol per kilogram required to adequately and safely anesthetize a patient for the procedure as determined by the anesthesiologist. The secondary endpoint was the time to sedation. We used one anesthesiologist to reduce any variations in delivering anesthesia. The sample size needed for the primary outcome with 80% power and an alpha 0.05 was 88 total patients based on a mean difference of 0.5 mg/kg propofol induction dose.

RESULTS:

A total of 152 patients undergoing elective outpatient endoscopies met inclusion criteria, with 108 patients in the IBD arm and 44 patients in the non-IBD arm. Baseline characteristics were similar except for lower BMI 25.7 in the IBD group vs 29.1 kg/m2 in non-IBD group (Table 1). Baseline characteristics of the IBD group are shown in Table 2. Propofol induction dose was greater in the IBD group 3.42 ± 0.39 mg/kg compared to the non-IBD group 1.79 ± 0.17 seconds (P < 0.05) (Table 3). Sedation time was lower in the IBD group 38.9 ± 2.1 seconds when compared to the non-IBD group 88.5 ± 8.8 seconds (P < 0.05). No adverse events were reported in either group.

CONCLUSION:

Induction propofol dosage was significantly greater and sedation times were significantly faster in the IBD group compared to the non IBD group. Further studies are needed to understand the mechanism of propofol in contributing to anesthesia in the setting of inflammatory diseases compared to the general population.
682 Investigating the Pathogenesis of Ulcerative Colitis Through Meta-Analysis of Gene Expression Omnibus Data
Authors: Khorfan Kamal , Aljabban Jihad , Gurakar Merve , Khan Hajra , Aljabban Nabeal , Mukhtar Mohamad , Hadley Dexter
Published: October 2019

INTRODUCTION:

Ulcerative colitis (UC) is an inflammatory bowel disease that causes inflammation of the colon and rectum, alongside extra-colonic manifestations. The etiology is unclear but is thought to include such factors as genetic predisposition, immune regulation, microbiome, and environmental triggers. Though strides have been made in treatment, the failure of anti-IL13 drugs demonstrates our limited knowledge of UC pathology. Here we use meta-analysis to dissect UC pathogenesis.

METHODS:

We employed our STARGEO platform to search Gene Expression Omnibus and performed meta-analysis on 465 colon samples from active UC patients, using 326 healthy colon samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis.

RESULTS:

Our analysis identified granulocyte adhesion and diapedesis, TREM1 signaling, and communication between innate and adaptive immune cells as top canonical pathways. TNF, IFNγ, and IL1 were top upstream regulators with predicted activation. We noted upregulation of the DUOX/DUOXA2 enzyme system, responsible for generating reactive oxygen species. We also found upregulation of calprotectin S100A8, which defines UC severity, and downregulation of the E3 ubiquitin ligase RNF5 responsible for controlling S100A8 expression. Impaired epithelial integrity was suggested by upregulation of matrix metalloproteinases MMP1 and MMP3 and down regulation of claudin 8. Furthermore, downregulation of aquaporin 8 and guanylin suggests loss of absorption. Upregulation of the amino acid transporter SLC6A14 and aldolase B may represent a compensation for loss of absorptive function. We also found metabolic dysfunction through downregulation of phosphoenolpyruvate carboxykinase 1, and UDP-glucuronosyltransferases UGT1A7/A5/A3. Lastly, we found downregulation of several miRNAs including mir-188, 192, 200a/b, 215, and 320.

CONCLUSION:

UC pathogenesis represents a multifactorial disease process that remains elusive. Here we suggest several mechanisms that may underpin UC development and susceptibility. In a recent study, inverse expression of RNF5 and S100A8 was found to coincide with UC severity and our results give credence to this correlation. Our results also demonstrate the parts that DUOX/DUOXA2 system and loss of epithelial and metabolic integrity have in UC. Lastly, miRNAs have an emerging role in UC and mimic therapy of the downregulated miRNAs we identified may prove efficacious. These results provide novel insights into UC pathophysiology and potential therapeutic avenues.
683 Audit of Introducing Fecal Bile Acid Diagnostic Test in Evaluation of Diarrhea in Patients With Inflammatory Bowel Disease in a Tertiary Care Center
Authors: Chedid Victor , Vijayvargiya Priya , Donato Leslie , Calderon Gerardo , Raffals Laura E. , Camilleri Michael
Published: October 2019

INTRODUCTION:

Patients with inflammatory bowel disease (IBD), whether Crohn's disease (CD) or ulcerative colitis (UC), have known alterations in the enterohepatic circulation of bile acids (BA) that may contribute to chronic diarrhea, but the fecal BA patterns are not well defined. We aimed to audit all patients with IBD who had fecal BA measurements as part of evaluation of chronic diarrhea at a tertiary care center.

METHODS:

Methods: 65 patients with IBD (18 with UC and 47 with CD) were evaluated at a single center and underwent measurements of fecal total and individual BAs based on a 48-hour collection performed at the end of a 4-day, 100-gram fat diet. The electronic medical records were interrogated to obtain type of IBD, disease activity, location of disease, prior surgery, IBD related therapies, presenting symptoms, and response to treatment with BA sequestrants. Bile acid diarrhea (BAD) diagnosis was based on >10% primary BAs, >4% primary BAs + >1,000 µmol/48 h, or total fecal BAs >2,337 µmol/48 h. IBD disease activity was based on radiologic, endoscopic and histologic parameters. Data are reported as mean ± standard error of the mean (SEM).

RESULTS:

Table 1 summarizes the patterns of BAD in our cohort with IBD. Figure 1 demonstrates the mean ± SEM of total fecal BAs and % primary BAs in each group of IBD patients. Among patients with UC, 10 had poorly controlled disease and 8 had well controlled disease, and both cohorts had elevated primary BAs (mean 28.9% ± 12.5%; 34.6% ± 21%, respectively). All patients with an ileal pouch anal anastomosis (IPAA) had elevated total fecal BAs (BADt) compared to those with an intact colon. In patients with CD, those with ileal resections had elevated BADt and % primary BAs (6263 µmol/48 h ± 1012 µmol/48 h; 79% ± 5.9%, respectively). Patients with an intact ileum, had elevated % primary BAs regardless of disease activity: controlled CD 34.7% ± 9.3%; poorly controlled CD 57.8% ± 9.5%; 15 out of 47 patients with CD were started on BA sequestrants with a positive response in 10/15.

CONCLUSION:

Discussion: BAs may play a role in the pathophysiology of chronic diarrhea in patients with IBD, regardless of inflammatory disease activity. Future studies are required to assess the impact of fecal bile acid testing and treatment with BA sequestrants on inflammation and chronic diarrhea in patients with IBD.
706 Impact of Baseline Corticosteroid Therapy on Tofacitinib Induction Efficacy and Infection Risk in Patients With Ulcerative Colitis: Data From Global Clinical Trials
Authors: Lichtenstein Gary R. , Cohen Benjamin L. , Salese Leonardo , Soonasra Arif , Modesto Irene , Wang Wenjin , Woodworth Deborah A. , Chan Gary , Quirk Daniel , Su Chinyu , Peyrin-Biroulet Laurent
Published: October 2019

INTRODUCTION:

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis (UC). Oral corticosteroids (CS) can be used as induction therapy, but side effects are a concern.
1

METHODS:

We evaluated efficacy and infection risk with tofacitinib 10 mg twice daily (BID) based on baseline CS use in UC induction studies. Remission (total Mayo score ≤2, no individual subscore >1, rectal bleeding subscore 0), mucosal healing (Mayo endoscopic subscore ≤1) and clinical response (decrease from baseline total Mayo score of ≥3 points and ≥30%, and decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of 0 or 1) were evaluated in the 8-week, Phase 3 tofacitinib OCTAVE Induction 1 & 2 studies (NCT01465763 & NCT01458951; pooled data). Induction studies allowed stably dosed CS (25 mg/day maximum). Efficacy and safety data were summarized by oral CS use at induction baseline (BLC-Yes/No). Infections of interest included herpes zoster (HZ), serious infections (SIs), and adjudicated opportunistic infections (OIs).

RESULTS:

Of 1139 patients (pts) (placebo [PBO]: n = 234; 10 mg BID: n = 905) in OCTAVE Induction 1 & 2, 525 (46.1%) were on CS at baseline (<15 mg daily dose: 32.8%; ≥15 mg daily dose: 67.2%). A statistically significant treatment effect of tofacitinib 10 mg BID vs PBO was observed for remission, mucosal healing, and clinical response at Week 8, for both subgroups of pts with and without baseline oral CS use (Table 1). Differences vs PBO were numerically greater for pts not receiving oral CS at baseline. In OCTAVE Induction 1 & 2, infections of interest occurred with similar frequency among both subgroups of pts: the proportion of PBO-treated pts with HZ was 0.8% for BLC-No vs 0.0% for BLC-Yes; and 0.2% for BLC-No vs 1.0% for BLC-Yes with 10 mg BID. The proportion of PBO-treated pts with SIs was 0.0% for BLC-No vs 0.0% for BLC-Yes; and 1.0% for BLC-No vs 0.2% for BLC-Yes with 10 mg BID. The proportion of PBO-treated pts with OIs was 0.0% for BLC-No vs 0.0% for BLC-Yes; and 0.2% for BLC-No vs 0.5% for BLC-Yes with 10 mg BID.

CONCLUSION:

Tofacitinib demonstrated significant induction efficacy vs PBO for both subgroups of pts with and without baseline CS use. Proportions of HZ, SIs, and OIs in OCTAVE Induction 1 & 2 were generally similar for both subgroups of pts. The relatively small number of events and short duration of follow-up (8 weeks) are limitations.
713 A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study of a Targeted Release Oral Cyclosporine Formulation in the Treatment of Mild to Moderate Ulcerative Colitis: Influence of Immunosuppressants at Baseline
Authors: Bloom Stuart , Iqbal Tariq , Nwokolo Chuka , Jairath Vipul , Hall Jesse , Dzyngel Bruce , Gardzinski Peter
Published: October 2019

INTRODUCTION:

Patients (pts) with ulcerative colitis (UC) who have failed immunosuppressants (IM) and biologics have demonstrated poorer response to subsequent therapies.
1
Cyclosporine (CsA) could be an alternative option since it has similar efficacy and safety to infliximab for severe UC,
2
but its use is limited due to concerns regarding systemic toxicity. ST-0529 is a novel oral formulation of CsA that delivers the drug directly to the colon, allowing for precise targeting of the diseased tissue while potentially limiting the risk of systemic toxicity.

METHODS:

A phase IIa study was conducted in a total of 118 subjects with baseline Disease Activity Index (DAI) < 6 (mild UC) or ≥6 (moderate UC), randomized 1:1 to receive 75 mg ST-0529 once daily (n = 53) or placebo (n = 65) for 4 weeks. The primary endpoint was the induction of clinical remission (DAI score ≤2, with no individual score >1 and rectal bleeding subscore of 0 or 1). The secondary endpoints were safety and tolerability, mucosal healing, clinical response, and histological healing.
3,4
Post-hoc subgroup analysis was conducted in 93 subjects with moderate UC, of whom 75 received at baseline 5-ASA alone or in combination (n = 51, with/without steroids; n = 24, with/without IM) to evaluate the impact of them on clinical improvement (DAI reduction ≥3) and composite subscores (rectal bleeding and stool frequency with or without mucosal appearance evaluation).

RESULTS:

Table 1 shows the influence of baseline medications on the improvement of DAI scores in subjects with moderate UC, and Tables 2 and 3, the impact of IM on the analyzed parameters. Safety was balanced for the overall population.

CONCLUSION:

This analysis showed that clinical improvement and composite subscores were influenced by baseline medication in pts with moderate UC. The poorer response in the IM treated group was potentially a function of severity or refractory disease and/or concomitant use of UC medication (prednisone < 10 mg/day, 5-ASAs or purine analogues) at baseline. Concomitant UC medications were not restricted at study entry as long as pts maintained stable dosing regimens throughout. These preliminary data support further investigation of ST-0529 usage as a twice daily treatment for the induction and maintenance of remission in UC pts with moderate disease, which will be the focus of the phase IIb trial.
738 Current Treatment Patterns Among Patients With IBD in the U.S. Initiating Biologic Therapy
Authors: Bornheimer Rebecca , Hass Steve , Nag Arpita , Oster Gerry
Published: October 2019

INTRODUCTION:

Treatment options for inflammatory bowel disease (IBD: Crohn's disease [CD] and ulcerative colitis [UC]) now include targeted therapies such as tumor necrosis factor (TNF) inhibitors and integrin receptor antagonists. With increasing therapeutic options, it is crucial to understand clinical use of these agents. This study reports on the current pattern and duration of biologic use in patients with IBD.

METHODS:

Adults (≥18 years) with CD or UC who initiated treatment with biologics between January 1, 2012 and December 31, 2016 were identified using the IQVIATM Real-World Data Adjudicated Claims Database – US. Treatment episode duration was defined as time from first (index date) to final receipt, identified based on a ≥90-day gap in therapy, surgery for IBD, or therapy switching, whichever came first. In patients with CD or UC who had ≥2 claims for biologics, we examined length of treatment episodes by product as well as for biologics overall. Kaplan–Meier (KM) methods were used.

RESULTS:

We identified a total of 18,140 and 11,474 patients with CD and UC, respectively, who began treatment with a biologic for IBD during the study period and had not received a biologic prior to January 1, 2012. Over an average follow-up of 22.9 months, the mean duration of biologic treatment was 13.5 months (CD: 13.7; UC: 13.1). After 12 and 24 months of treatment, 7.0% (CD: 7.2%; UC: 6.8%) and 11.0% (CD: 11.2%; UC: 10.6%) of patients beginning biologic therapy had undergone surgery for IBD, respectively. The number of patients beginning treatment with individual biologics is presented in Figure 1. Among patients starting treatment with adalimumab or infliximab, ∼10% had previously received another biologic during the 6-month period prior to index date for that biologic, compared with ∼30–40% of patients starting treatment with other biologics. The mean duration of treatment with adalimumab or infliximab was 12.2 months. Treatment episodes were shorter for other biologics (shortest duration: 4.8 months for patients with CD beginning ustekinumab). By month 6 of treatment, KM estimates of the percentage of patients with CD starting another IBD biologic ranged from 4.1% (ustekinumab) to 8.1% (certolizumab); for UC, the range was 3.6% (vedolizumab) to 15.9% (golimumab).

CONCLUSION:

Most patients starting biologic therapy have no evidence of prior receipt of IBD-related biologics. Duration of biologic treatment for IBD averages approximately 1 year for adalimumab and infliximab but is shorter for other agents.