bluuebunny/crossref_metadata_2025_split huggingface dataset:
7
LACTOBACILLUS REUTERI SUPPRESSES PRO-INFLAMMATORY DRIVEN REACTIVE OXYGEN SPECIES IN VITRO IN HUMAN INTESTINAL EPITHELIAL CELLS AND IN VIVO IN A TNBS COLITIS MOUSE MODEL
Authors: Ruan Wenly , Engevik Melinda , Chang-Graham Alexandra , Hyser Joseph , Versalovic James 
Published: January 2020

Abstract

Background
Reactive oxygen species (ROS) play a role in maintaining intestinal epithelial homeostasis and are normally kept at low levels via antioxidant compounds. Dysregulation of ROS can lead to intestinal inflammation and contribute to inflammatory bowel disease (IBD). Select gut microbes possess the enzymatic machinery to produce antioxidants whereas others can dysregulate levels of ROS. Our model microbe, Lactobacillus reuteri (ATCC PTA 6475), has been demonstrated to reduce intestinal inflammation in mice models. It contains the genes encoding two distinct GshA-like glutamylcysteine ligases. We hypothesize that L. reuteri can secrete γ-glutamylcysteine to suppress ROS, minimize NFκB activation and regulate secretion of e pithelial cytokines.

Methods & Results
Conditioned media from L. reuteri was analyzed via mass spectrometry to confirm the presence of γ-glutamylcysteine. All cysteine containing products including γ-glutamylcysteine were fluorescently tagged in the conditioned media and then incubated with HT29 cell monolayers as well as human jejunal enteroid (HJE) monolayers. γ-glutamylcysteine was demonstrated to enter intestinal epithelial cells based on microscopy. Next, a Thioltracker assay was used to show increased intracellular glutathione levels by L. reuteri secreted γ-glutamylcysteine. HT29 cells and HJEs were then treated with IL-1β or hydrogen peroxide, and L. reuteri metabolites as well as γ-glutamylcysteine significantly suppressed pro-inflammatory cytokine driven ROS and IL-8 production. L. reuteri secreted products also reduced activity of NFκB as determined by a luciferase reporter assay. γ-glutamylcysteine deficient mutants were generated by targeted mutagenesis of GshA genes, and these mutant L. reuteri strains had a diminished ability to suppress IL-8 production and ROS. To further test the role of L. reuteri secreted γ-glutamylcysteine in vivo, a 2,4,6-Trinitrobenzenesulfonic acid (TNBS)- induced mouse colitis model was used. Adolescent mice were orogavaged with PBS, L. reuteri, L. reuteri GshA2 mutant, or γ-glutamylcysteine for a week after which TNBS was rectally administered to induce colitis. We demonstrate that L. reuteri and γ-glutamylcysteine can suppress histologic inflammation compared to PBS control and L. reuteri GshA2 mutant groups.

Conclusions
Together these data indicate that L. reuteri secretes γ-glutamylcysteine which can enter the intestinal epithelial cells and modulate epithelial cytokine production. It acts via suppression of ROS and NFκB which then decreases IL-8 production. We are able to demonstrate this in vitro in both HT 29 cells and HJEs. We now also demonstrate this in vivo in a mouse colitis model. These experiments highlight a prominent role for ROS intermediates in microbiome-mammalian cell signaling processes involved in immune responses and intestinal inflammation.
P117 CONTENT VALIDITY OF THE SUBCUTANEOUS ADMINISTRATION ASSESSMENT QUESTIONNAIRE (SQAAQ) IN ADULT AND ADOLESCENT PATIENTS WITH MODERATE TO SEVERE CROHN’S DISEASE
Authors: Hunter Theresa , Naegeli April , Delbecque Laure , Al-Zubeidi Tamara , Pegram Hannah , Kitchen Helen 
Published: January 2020

Abstract

Background
Subcutaneous (SC) delivery of biologic therapies is typically via a prefilled syringe or an auto-injector designed to offer a more convenient and more consistent administration of drug product. There is currently no gold standard instrument that is used to assess the usability and patient confidence and preference for an injection device in Crohn’s disease (CD). The Subcutaneous Administration Assessment Questionnaire (SQAAQ) was developed to evaluate ease of use and confidence in SC administrations of therapy. The SQAAQ (Figure 1) features 12 items scored on a 7-point Likert scale (1= Strongly Disagree to 7= Strongly Agree). Higher scores indicate better usage experience. The recall period is immediately after patients auto-inject. This study aimed to establish evidence of the content validity of the SQAAQ among patients with moderate to severe CD.

Methods
A semi-structured interview guide was used to conduct face-to-face qualitative interviews with adult (18+ years) and adolescent (12–17 years) patients from the US with a clinician confirmed diagnosis of CD. Cognitive debriefing interviews were structured into sections that explored patients’ opinions, interpretation, and acceptance of the SQAAQ. Data were coded using Atlas.ti using a framework approach where pre-defined codes were applied to quotes that demonstrated patients’ understanding/interpretation, acceptance, and usage of the instructions, items, response scale/options, and recall period.

Results
Twenty-four patients (adults, n=16; adolescents, n=8) participated in the interviews. Thirteen adults and 3 adolescents experienced moderate disease severity (reported by clinicians). Adult and adolescent groups contained an equal proportion (50%) of male and female participants. Adults had a mean age 50.3 years (range 27.0–75.0), adolescents with mean age 15.6 years (range 14.0–17.0). Overall, two-thirds (n=16, 67%) of patients were white, and the mean duration for CD diagnosis was 8.0 years (range 1.0–23.7). Ten (42%) patients had been on SC treatment for a mean 4.5 years (range 0.2–16.9), all self-administered. Seven (29%) patients had been receiving intravenous treatment for a mean 2.1 years (range 0.2–5.4). The SQAAQ was found to be conceptually relevant, understandable and usable by adults and adolescents with CD. Notably the measurement concepts were confirmed as relevant by patients who currently used SC treatment devices. The patients with no SC experience (n=7, 29%), understood the item wording, response scales, and recall period and had few difficulties completing the measure.

Conclusion
Content validity of the SQAAQ was established in this sample of adolescent and adult patients with CD. The SQAAQ is appropriate for inclusion in CD clinical trials for SC treatment devices with adult and adolescent patients.
P123 THIRTY DAY READMISSIONS AMONG PATIENTS WITH COMPLICATED INFLAMMATORY BOWEL DISEASE AND EFFECTS ON OUTCOMES: RESULTS OF ANALYSIS OF 2016 NATIONWIDE READMISSION DATABASE
Authors: Sharma Sachit , Khan Zubair , Aziz Muhammad , Vohra Ishaan , Acharya Ashu 
Published: January 2020

Abstract

Objective
To determine the rate of hospital readmissions within 30 days of discharge in patients with complicated Inflammatory Bowel Disease (IBD) and its impact on mortality, morbidity, and health care cost in the United States.

Methods
We performed a retrospective study using the Nationwide Readmission Database(NRD) for the year 2016 (Data on 35.6 million discharges). We collected data on hospital readmissions of 29,356 adults who were hospitalized for complicated Inflammatory Bowel Disease(Crohn’s disease and Ulcerative Colitis) and discharged. Complications were defined using ICD 10 codes. Patients with age less than 18, elective admission and admission during December month were excluded. The primary outcome was rate of all-cause readmission within 30 days of discharge. Secondary outcomes were reasons for readmission, readmission mortality rate, morbidity and resource use. Multivariate regression analysis was used to determine the independent predictors of 30-day readmission.

Results
Among patients admitted to US hospitals with complicated IBD, the total time at risk was 407,983 days, with the first readmission occurring at day 1 and the last readmission at day 30. The 30-day rate of readmission was 17.6%, with the most common cause of readmission being Crohn’s disease of small intestine with intestinal obstruction (9%). The mortality rate among patients readmitted to the hospital (0.6%), was higher than that for index admissions (0.3%) (P &lt; .01). Mean length of stay was 5.5 days for index admission and 5.9 days for readmission (p=0.01). Mean total charge for index admission was $44,768 compared to $48,766 for readmission (p&lt;0.01). Mean total cost for index admission was $11,491 compared to $12,704 for readmission (p&lt;0.01). A total of 30,943 hospital days were associated with readmission, and the total health care in-hospital economic burden was $65 million (in costs) and $251 million (in charges). Independent predictors of readmission were age, insurance status, higher Charlson comorbidity score, lower income, teaching status of hospital and longer stays in the hospital. Older age, private insurance, median income more than $48,000 were associated with lower odds for readmission, whereas higher comorbidities and admission to teaching hospital were associated with increased odds for readmission.

Conclusions
In a retrospective study of patients hospitalized for complicated IBD in 2016, 17.6% were readmitted to the hospital within 30 days of discharge. Readmission was associated with higher mortality, morbidity, and resource use. Age, insurance status, higher comorbidity score, lower income and admission to teaching hospital were independent predictors of readmission.
P016 IMPROVING TUBERCULOSIS RE SCREENING IN INFLAMMATORY BOWEL DISEASE PATIENTS RECEIVING BIOLOGIC THERAPY: A SINGLE CENTER QUALITY IMPROVEMENT INITIATIVE.
Authors: Drevno David , Hickok Sherry , Ali Sabina 
Published: January 2020

Abstract

Background
Biological agents have revolutionized the management of inflammatory bowel disease (IBD). There is a known increased risk of tuberculosis (TB) reactivation with biologic therapy (1). ACG guidelines recommend screening for active and latent TB infection (LTBI) prior to starting certain biologic agents (2). However, there are no consensus guideline on the utility of yearly screening testing in IBD patients without TB risk factors. With a number of patients now receiving the biologic therapy outside their primary care centers it has become increasingly difficult to effectively provide ongoing TB screening. With this quality improvement exercise, we aim to improve TB re-screening in patients receiving biologics by completing a yearly phone screening for exposure history.

Method
An interdisciplinary team from GI and ID developed a TB risk factor screening questionairre, adapting the California Department of Public Health’s Pediatric TB Risk Assessment tool (3). A list of patients receiving biologics was sorted by month of birth in the EMR. When the current calendar month aligned with the patient’s birth month, a GI RN reviewed the TB questionnaire with the patient (≥18 yo) and/or legal guardian by phone. If one or more TB risk factors were identified, the GI RN would notify the provider and a QuantiFERON-TB Gold (QFT) was ordered to be completed.

Results
60 patients were found on biologic therapy (median age 17 yo) (38 males, 22 females) (68% CD, 28% UC, 3.3% IBD-U)(75% IFX, 12% ADA, and 3% other) to be to eligible TB screening between January - July 2019, 48 patients completed the phone screening. All 61 patients had completed TB screening prior to starting biologic therapy, which was reported to be negative. 13 patients were unable to be reached. 6/48 were identified as having at least 1 risk factor for TB. 5/6 patients with a positive screen had a negative QFT. 1 patient was away at college and a request to his adult GI managing his biologic was sent.

Conclusion
Screening for LTBI is required prior to starting a biologic therapy, though there are no guidelines for routine TB screening following initiation of the biologic. We propose performing an annual phone screening for TB exposure history for IBD patients on biologic therapy. QTF testing remains appropriate in patients with potential risk factors, such as being a health care worker or travel to/living in high endemic TB regions.

References
P028 URGENT MEDICAL ACCESS FOR PATIENTS WITH INFLAMMATORY BOWEL DISEASE AT A PRIVATE COMMUNITY GASTROENTEROLOGY PRACTICE
Authors: Kwon Michelle , Tse Chung Sang , Danielewicz Michael , van Deen Welmoed , Shah Samir 
Published: January 2020

Abstract

Background
Patients with inflammatory bowel disease (IBD) have chronic, life-long diseases with relapsing-remitting pattern that often require frequent utilization of healthcare services.[1] Urgent access to specialty care can help identify patients with acute medical needs so they can receive appropriate care in a timely manner. This can avoid unnecessary high-cost medical interventions, such as visits to the emergency department (ED), which often lead to excess use of steroids, narcotics, and radiographic imaging, all important measures of quality of IBD care.[2] We sought to introduce an access/quality improvement program at a private gastroenterology practice with the goal of triaging and returning urgent calls from IBD patients in a timely manner and mitigate avoidable visits to the ED.

Methods
Gastroenterologists, nurses, and support staff at our private practice developed four criteria for “urgent” IBD calls: new, severe abdominal pain; new, severe anal pain; fever greater than 101 Fahrenheit; and refractory emesis. Patient calls that met any of these criteria were highlighted with a red flag and labelled as “IBD URGENT” by support staff in the electronic medical system. The primary gastroenterologist (or covering provider) then responded to these calls as soon as possible with a goal of responding within 4 hours. Subsequently, patients were advised to go to the ED for further emergent evaluation, given same/next day clinic visits, and/or given advice, such as medication changes, by the gastroenterologists.

Results
Over a 15-month period from June 2018 to August 2019, we received a total of 167 “IBD URGENT” calls (average 11 calls per month); of these, 92% (153 calls) received a response from a gastroenterologist within 4 hours. Abdominal pain, diarrhea, blood in the stools, and vomiting were the most common reasons for urgent calls. Only 10% (16 calls) of calls were patients with worrisome symptoms in which they were advised to go to the ED, 37% of calls led to same/next day clinic visits (62 calls), and 58% resulted in advice/orders from the gastroenterologist such as laboratory testing, medication continuation/changes (97 calls); 12% (20 calls) resulted in both urgent clinic visits and advice (e.g., obtain laboratory testing and then present for office visit).

Conclusion
We piloted an urgent care hotline for IBD patients to receive rapid medical access at a private community gastroenterology practice. The majority of patients were successfully managed with outpatient medical care, including same/next-day office visits and advice for laboratory testing/medication changes. Only a minority (10%) of calls resulted in ED visits. We plan to continue this project with the aim to return more than 90% of the urgent calls within 4 hours.

References
P049 RESPONSIVENESS OF THE PATIENT-REPORTED OUTCOME MEASUREMENT INFORMATION SYSTEM (PROMIS) TO CHANGES IN DISEASE STATUS AND QUALITY OF LIFE AMONG PEDIATRIC PATIENTS WITH CROHN’S DISEASE
Authors: Brenner Erica , Long Millie , Mann Courtney , Chen Wenli , Reyes Camila , Lin Li , Reeve Bryce , Kappelman Michael 
Published: January 2020

Abstract

Background
Patient Reported Outcome Measurement Information System (PROMIS) provides valid, self-reported measures of physical, emotional, and social health that can inform research and clinical care in children with chronic conditions. Prior research in pediatric Crohn’s disease (CD) has demonstrated robust correlations between PROMIS and disease activity. However, responsiveness, defined as sensitivity to clinical change, has not been yet been thoroughly evaluated.

Aims
We sought to evaluate the responsiveness of the PROMIS Pediatric measures relative to changes in 1) disease activity and 2) disease-specific health-related quality of life (HRQOL).

Methods
IBD Partners Kids & Teens is an internet-based cohort of children with IBD. Participants age 9 to 17 report symptoms related to disease activity [Short Crohn’s Disease Activity Index (SCDAI)], the IMPACT III HRQOL measure, and PROMIS domains of Anxiety, Depression, Pain Interference, Fatigue, and Peer Relationships. We conducted longitudinal analyses using mixed linear models to examine the extent to which PROMIS measures were responsive to changes in SCDAI and IMPACT III, adjusting for time and taking into account the clustering of individual participants. A change threshold of 70 points in SCDAI was used as a minimally important difference (MID). We also graphically depicted changes in PROMIS domains corresponding to improved, stable, or worsened disease activity and evaluated changes in PROMIS versus changes in IMPACT III using Pearson’s correlation.

Results
Our study sample included 544 participants with CD (mean age 13 years, 44% female) from 44 states. All PROMIS domains were responsive to changes in SCDAI, indicating improved physical, emotional, and social health corresponding to improved disease activity (Table 1, p&lt; 0.001). Observed effect estimates ranged from 1.9 for Peer Relationships to 6.9 for Fatigue, in line with estimates of MID in both adult IBD and other pediatric chronic conditions. Of 246 participants with 2 or more completed reports (689 pairs of consecutive reports), disease activity was stable in 527, worse in 72, and improved in 67. Figure 1 demonstrates changes in PROMIS scores as a function of change in disease activity. Changes in PROMIS scores were also strongly associated with changes in IMPACT 35 scores (R=-0.5 for Anxiety, R=-0.5 for Depression, R=-0.6 for Pain Interference, R= -0.7 for Fatigue, and R=0.35 for Peer Relationships).

Conclusion
This study provides evidence for the longitudinal responsiveness of the PROMIS Pediatric measures to change in disease status and HRQOL in pediatric CD patients. The results support use of the PROMIS Pediatric measures in clinical outcomes research.
26 USTEKINUMAB DOSE ESCALATION EFFECTIVE IN REAL-WORLD USE FOR LUMINAL AND PERIANAL CROHN’S DISEASE
Authors: Glass Jason , Alsamman Yasser , Chittajallu Punya , Ahmed Tasneem , Fudman David 
Published: January 2020

Abstract

Introduction
Ustekinumab (UST) is effective for induction and maintenance of remission in Crohn’s disease (CD) as demonstrated in the UNITI trials. There is paucity of data in real world experience for dose escalation with UST, particularly for perianal disease. This study examines the effectiveness and safety of dose escalation in both luminal and perianal CD at a tertiary IBD referral center.

Methods
A retrospective, single center cohort study was conducted at the University of Texas Southwestern Medical Center examining outcomes of UST dose escalation in CD. Dose escalation was defined as increasing frequency to every four or six weeks. The primary outcomes were improvement in perianal disease as documented by the treating clinician and a composite outcome reflecting disease response. Patients who met the composite outcome had at least one of the following: steroid-free clinical response, objective improvement in disease activity on follow up CT, MRI or endoscopy, or normalization of CRP. Secondary outcomes included IBD-related surgery and adverse events. Patients were followed up to 6 months after dose intensification.

Results
38 patients underwent dose intensification. 28 patients (74%) were escalated to every 4 week dosing and 10 patients (26%) were escalated to every 6 weeks. Baseline characteristics were recorded (see Table 1). 18/38 (48%) were escalated for primary non-response. Median time from UST induction to dose escalation was 10 months (IQR 2–24 months). Following escalation, patients were followed for a medianof 4.5 months (range 1–6 months). Nearly all (92%) patients had prior exposure to anti-TNF therapies and 74% had prior exposure to an anti-integrin therapy. Pre-escalation inflammatory markers included median CRP of 9.55 mg/Land median fecal calprotectin of 340 μg/mg. Median UST trough prior to escalation was 1.3 μg/mL(IQR 0.8–2.1).
Overall, half (19/38) of patients who underwent dose escalation met the primary composite outcome of disease response and 50% (12/24) of patients with active perianal disease showed evidence of improvement after escalation. 60% (6/10) of the patients on steroids at time of escalation achieved steroid-free response. 72% (8/11) of those who underwent follow-up endoscopy showed endoscopic improvement. 50% (6/12) of patients who had radiographic follow-up showed signs of improvement. 27% (9/33) had normalization of CRP after dose escalation. 8% (3/38) patients required an IBD-related surgery after dose escalation. Two patients had adverse events recorded (see table 3).

Conclusion
Patients who underwent UST dose escalation demonstrated improvement in perianal disease as well as steroid-free clinical, endoscopic, radiographic, and biochemical response. No increase in serious adverse events was seen in this cohort. Dose escalation is an effective option for non-responders to every 8-week dosing.
Human Papillomavirus Genotype Replacement: Still Too Early to Tell?
Authors: Man Irene , Vänskä Simopekka , Lehtinen Matti , Bogaards Johannes A 
Published: January 2020

Abstract

Background
Although human papillomavirus (HPV) vaccines are highly efficacious in protecting against HPV infections and related diseases, vaccination may trigger replacement by nontargeted genotypes if these compete with the vaccine-targeted types. HPV genotype replacement has been deemed unlikely, based on the lack of systematic increases in the prevalence of nonvaccine-type (NVT) infection in the first decade after vaccination, and on the presence of cross-protection for some NVTs.

Methods
To investigate whether type replacement can be inferred from early postvaccination surveillance, we constructed a transmission model in which a vaccine type and an NVT compete through infection-induced cross-immunity. We simulated scenarios of different levels of cross-immunity and vaccine-induced cross-protection to the NVT. We validated whether commonly used measures correctly indicate type replacement in the long run.

Results
Type replacement is a trade-off between cross-immunity and cross-protection; cross-immunity leads to type replacement unless cross-protection is strong enough. With weak cross-protection, NVT prevalence may initially decrease before rebounding into type replacement, exhibiting a honeymoon period. Importantly, vaccine effectiveness for NVTs is inadequate for indicating type replacement.

Conclusions
Although postvaccination surveillance thus far is reassuring, it is still too early to preclude type replacement. Monitoring of NVTs remains pivotal in gauging population-level impacts of HPV vaccination.