bluuebunny/crossref_metadata_2025 huggingface dataset:
Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease
Authors: Chuang Ling-shiang , Morrison Joshua , Hsu Nai-yun , Labrias Philippe Ronel , Nayar Shikha , Chen Ernie , Villaverde Nicole , Facey Jody Ann , Boschetti Gilles , Giri Mamta , Castillo-Martin Mireia , Thin Tin Htwe , Sharma Yashoda , Chu Jaime , Cho Judy H.
Published: July 2019

Genome-wide association studies have identified over 200 genomic loci associated with inflammatory bowel disease (IBD). High-effect risk alleles define key roles for genes involved in bacterial response and innate defense. More high-throughput in vivo systems are required to rapidly evaluate therapeutic agents. We visualize, in zebrafish, the effects on epithelial barrier function and intestinal autophagy of one-course and repetitive injury. Repetitive injury induces increased mortality, impaired recovery of intestinal barrier function, failure to contain bacteria within the intestine and impaired autophagy. Prostaglandin E2 (PGE2) administration protected against injury by enhancing epithelial barrier function and limiting systemic infection. Effects of IBD therapeutic agents were defined: mesalamine showed protective features during injury, whereas 6-mercaptopurine displayed marked induction of autophagy during recovery. Given the highly conserved nature of innate defense in zebrafish, it represents an ideal model system with which to test established and new IBD therapies targeted to the epithelial barrier.

This article has an associated First Person interview with the first author of the paper.
In silico study of ginsenoside analogues as possible BACE1 inhibitors involved in Alzheimer's disease
Authors: Contreras-Puentes Neyder , Mercado-Camargo Jairo , Alvíz-Amador Antistio
Published: July 2019

Background: Neurodegenerative disorders such as Alzheimer's disease show an alarming prevalence in the population, with around 50 million affected individuals worldwide, and is associated with the development of dementia, mainly affecting the elderly population. Currently, the treatments used are based on slowing the progression of the clinical symptoms of Alzheimer’s; however, no specific treatment has been found that induces reversion of the disease. Natural products may induce a wide range of palliative effects, such as ginseng (Panax ginseng), which produces secondary metabolites called ginsenosides, which have multiple therapeutic applications, including for neurodegenerative diseases such as Alzheimer’s.

Methods: A virtual screening was carried out, using the CHEMBL database to find analogs of ginsenosides based on the ginsenoside Rg1 (CHEMBL501637). Next, the molecules were optimized and their format modified. The structure of BACE1 was downloaded from the Protein Data Bank database (ID: 1FKN) and prepared for the development of molecular docking using the PyRx software. A database of the ligands was created and molecular docking experiments were carried out, obtaining affinity energy values ​​in Kcal/mol.

Results: Of the 27 analogues studied, it was found that the molecules CHEMBL451292, CHEMBL510371 and CHEMBL503302 showed considerable affinity with BACE1 when compared with the reference molecules (verubecestat and donepezil). These affinity energy values for CHEMBL451292, CHEMBL510371 and CHEMBL503302 ​​were -9.6, -8.1 and -7.6 Kcal/mol, respectively. Likewise, the binding site of the ligands to BACE1 were identified, with the main interactions being van der Waals and hydrogen bonding.

Conclusions: Three ginsenoside analogues showed a similar binding energy with BACE1 compared to the reference drugs. The residues involved in the inhibitory activity of BACE1 and the type of predominant interactions were identified, which agreed with previous reports.
bwimage: A package to describe image patterns in natural structures
Authors: Biagolini-Jr. Carlos , Macedo Regina H.
Published: July 2019

Currently R is the most popular software for data analyses among biologists. Here, we present bwimage, a package designed to describe patterns from black and white images. The package can be used for a wide range of applications. We implemented functions previously described in the literature to calculate parameters designed originally, but not exclusively, for vegetation structures. Additionally, we propose a new parameter: the aggregation index. We demonstrate applications for field work, providing examples that range from calculation of canopy openness, description of patterns in vertical vegetation structure, to patterns in bird nest structure. We provide advice and illustrated examples of how to produce high quality images for analyses.
An experimental evaluation tool for the Public Innovation Lab of the Uruguayan government
Authors: Zurbriggen Cristina , Lago Mariana González
Published: July 2019

In many parts of the world, governments are building new platforms, methods, and innovative experimental spaces to better respond to current complex problems. Laboratories in the public sector have emerged as experimental spaces that incorporate co-creation approaches to promote public innovation and social transformation. Although there is abundant literature about public innovation and reports on innovative practices, little progress has been made on how to evaluate these. In this paper, we describe the process that led to the development of an experimental evaluation tool for public innovation as part of an action-research process in a laboratory within the Uruguayan Government. The pilot prototype, the ‘Roadmap’ as we named it, seeks to provide a timely and purposeful means to learn from the co-creation processes and be accountable to public authorities and society. Aiming to build a learning system within the organisation to communicate results, we designed the Roadmap based on the confluence of various approaches, namely, development evaluation, organisational learning and reflexive monitoring. Other relevant approaches to public innovation and evaluation were also considered, such as public design evaluative thinking, social innovation evaluation, and systemic evaluation of learning.
THE CONVERSATION: Feedback Structures, Ways of Knowing, and Neurodivergence
Authors: Holt Allison Leigh
Published: July 2019

This paper discusses communication as a community of feedback systems. Arguing that meaningful communication between human and non-human species is contingent upon first reconsidering human understandings of human consciousness and cognition, the author identifies axes of communication
as perceiving-sensing, adjusting-processing, and responding-exchanging, beyond language. Drawing upon theories of enactivism and her work teaching media to neurodivergent students, the author proposes experimental time-based media as a useful model for communication between humans and the
not-quite-fixed world of all things that exist, with or without categorization, and between those things themselves.
“Inter Alia: Aliens and AI”
Authors: Raley Rita , Samolsky Russell
Published: July 2019

Contemporary anxiety concerning our efforts to communicate with aliens might be understood in terms of the exponential advances in neural network research (so-termed “Artificial Intelligence”) and the probability that the aliens we encounter are more likely to be alien AIs
than organic beings. The premise of our paper is that the disquieting sense that AI possesses, or is possessed of, an external intelligence, one that operates autonomously, unpredictably, and, in our deepest fears, mutinously, is projectively displaced onto extra-planetary aliens. Our paper
offers an analysis of Trevor Paglen’s satellite work, The Last Pictures, as well as Eduardo Kac’s Inner Telescope and Lagoogleglyph series. We conclude with a speculative imagining of an AI-archaeologist encountering in the distant future the orbital ring of dead satellites, one
of which contains Paglen’s curated image archive.
Fermenting Communications: Fermentation Praxis as Interspecies Communication
Authors: Hey Maya
Published: July 2019

Microbes are in, on, and around us at all times, yet we cannot easily communicate with them. How do we (continue to) live with microbial life in ways that allow for our mutual thriving? Using a performative lens, this paper analyzes the material practices of fermentation as a way of
connecting with different scales of life. It attempts to challenge conventional understandings of communications (e.g. encoding/decoding models put forth by Stuart Hall) by examining the layered manner in which fermentation engages with matter and meaning. The material practices of fermentation
require embodied knowledge to work with microbial life, and the discursive considerations of fermentation challenge anthropocentric thought. Thus, materially and discursively, fermentation functions as a continual form of engagement. Thought of as a form of communication, fermentation helps
us to consider some of the invisible relations we have with microbes and connect with micro-species we often take for granted.
On Talking to Bees
Authors: Cartiere Cameron
Published: July 2019

A reflection on the evolution of group and swarm communications in a multi-city, international collaborative SSHRC-funded research project in support of native pollinators, considering the communications of the bees to their keepers as well as to each other, and how the land as their
artistic collaborator communicates to the human partners (the university, the city, the artists), along with human and organizational signals.
Control social e imaginarios en las teleseries actuales
Authors: Bonete-Vizcaíno Fernando
Published: July 2019

Control social e imaginarios en las teleseries actuales estudia la relación entre las series de televisión y la construcción de la identidad en la era del show business. La obra reúne, en dieciocho capítulos organizados en tres bloques, el análisis de cerca de una veintena de grandes series actuales. La vigilancia del estado moderno, los mecanismos ideológicos y tecnológicos utilizados para orientar la conducta, la perpetuación de nuevos modelos familiares y éticos, la hipersexualidad o el estado de la política son algunos de los elementos estudiados en esta obra que arroja luz sobre un fenómeno de éxito indiscutible de nuestros días: las series de televisión.
P024 Treatment patterns of biologic therapies used to treat ulcerative colitis: A retrospective database analysis in the United States
Authors: Erin Comerford , Marco DiBonaventura , Timothy Smith , Anthony Louder , David Gruben , Leonardo Salese , Daniel Quirk
Published: July 2019

BACKGROUNDs:

Treatment goals for ulcerative colitis (UC) focus on inducing a response and maintaining long-term disease remission. The current study sought to document the real-world treatment patterns during the first year of biologic therapy in the United States.

METHODS:

This retrospective analysis used the PharMetrics Plus claims data from January 1, 2013 to October 1, 2017. Biologic-naïve patients aged ≥18 years with UC (ICD9:556.* or ICD10 K51.*) who newly initiated biologic therapy (adalimumab [ADA], infliximab [IFX], vedolizumab [VEDO], golimumab [GOL]) were included. Patients had to have 12 months of continuous enrollment prior to (pre-index) and after (post-index) their first biologic drug claim (index). Patients with Crohn's disease or a history of biologic therapy in the pre-index period were excluded. Treatment patterns were reported descriptively, including combination therapy (frequency of an IM with a biologic), persistence (frequency of patients using their index therapy at the end of the 12-month post-index period without a 60-day gap), and adherence (calculated based on the proportion of days covered).

RESULTS:

A total of N = 3,595 patients with UC were included (51.7% male; age = 42.4 years [SD = 13.6]; disease duration = 1.3 years [SD = 1.0]) with the following treatments at index: N = 2,055 on ADA, N = 1,218 on IFX, N = 152 on GOL, and N = 170 on VEDO. Use of a concomitant IM therapy at index occurred as follows: ADA = 30.75%, IFX = 32.10%, GOL = 29.61%, and VEDO = 25.29%. A total of 59.2% of patients who initiated a biologic therapy remained persistent (i.e., continued on therapy) throughout the 12-month post-index observation period. This varied by therapy: ADA = 56.2%, IFX = 64.9%, GOL = 44.1%, and VEDO = 69.4%. Non-persistent patients predominantly discontinued without switching to another medication or restarting their original medication (discontinuation rates ranged from 42.3% to 52.7% among ADA, GOL, and IFX patients). However, non-persistent VEDO patients predominantly restarted the same therapy after a ≥60 day discontinuation period (36.5%). Switching therapies immediately (i.e., less than 60 days) was also common across each treatment (ADA = 27.1%, IFX = 31.2%, GOL = 31.0%, VEDO = 28.9%). Adherence to biologic therapy, measured by the proportion of days covered, were as follows: ADA = 0.72, IFX = 0.81, GOL = 0.69, VEDO = 0.84.

CONCLUSION(S):

For UC patients initiating biologic therapy, at least 25% initiated concomitant IM therapy. A significant number (40%) of patients discontinued their biologic therapy within the first 12 months. These findings suggest a number of patients experience suboptimal levels of disease control within the first year of biologic therapy.
P039 Efficacy and safety of ustekinumab in patients with refractory Crohn's disease: data from a real world study in Brazil
Authors: Rogerio Parra , Julio Chebli , Liliana Chebli , Erika Bertges , Antonio José Alves Júnior , Orlando Ambrogini Junior , Tárcia Gomes , Marley Feitosa , Omar Féres , Joaquim Rocha José
Published: July 2019

BACKGROUND:

Ustekinumab (UST) is a fully human monoclonal antibody against IL-12/23. UST induced a clinical response and maintained a higher rate of response than placebo in patients with Crohn's disease (CD). UST was approved in Brazil in November 2017. Real world data regarding efficacy and safety to UST in CD is lacking in our country. We report our experience of UST use in patients with CD refractory to anti-TNF therapy.

METHODS:

An open-label prospective not controlled study was performed including patients from 4 academic medical centers with severely active, refractory CD starting on UST (IV infusions followed by scheduled subcutaneous [SC] injections) between November 2017 and August 2018. We evaluated clinical response and remission (based on Harvey-Bradshaw index [HBI]), C-reactive protein (CRP) and faecal calproprotectin (FC) levels. Clinical response and clinical remission were defined by HBI decrease ≥3 and HBI ≤3, respectively. Patients were evaluated by HBI from baseline until week 32. CRP and FC were evaluated from baseline and at week 16.

RESULTS:

Thirty-seven patients were treated with UST during the study period. The mean age was 37.5 years (IQR: 22–68), disease duration 10.7 years (IQR: 1–29), 75.6% had previous surgeries, 54% had perianal disease, 68.5% had anaemia. Mean HBI at baseline was 10.5 (IQR: 5–19). At baseline mean CRP was 25.9 mg/L and mean FC was 1,134.6 mg/kg (IQR: 150–3,157). At week 8, 81.1% achieved clinical response and 40.5% achieved clinical remission. At second SC injection (week 16 or 20), 63.3% of individuals achieved clinical remission (19/30). After the third SC injection (week 24 or 32), 66.7% of patients presented clinical remission (14/21). CRP decreased to 15.9 mg/L at week 8 and to 10.8 mg/L at week 16. Mean FC at week 16 was 996.2 mg/Kg (IQR: 5–2,362), exhibiting a decrease of 138.4 mg/Kg from baseline. One patient stopped UST due to non-response. No new safety signals were observed.

CONCLUSION(S):

UST therapy was successful for inducing clinical remission and improving laboratory biomarkers of disease activity in patients with refractory CD. Both UST induction and maintenance regimens until week 32 were well tolerated. This result support a favorable safety profile.
P042 Inflammatory bowel disease is no longer a contraindication for radiation therapy: A systematic review of outcomes with modern RT techniques
Authors: Gaurav Bahl
Published: July 2019

BACKGROUND:

Inflammatory bowel disease (IBD) continues to be considered a contraindication to the use of Radiation Therapy (RT). Oncologists are often unwilling to deliver RT, due to a perceived risk of severe bowel toxicity, or IBD exacerbation. Modern precision RT techniques allow significant reduction in dose to normal organs, and several studies have reported low toxicity rates. We performed a systematic review of recent studies to summarize the current evidence regarding RT toxicity in cancer patients with IBD.

METHODS:

MEDLINE and EMBASE databases were searched, using combinations of key terms, for relevant studies published over the past 10 years (2008–2018). Reference lists of eligible articles were also hand-searched. A total of 278 articles were screened, and 9 studies met our search criteria to be included in this review.

RESULTS:

From the 9 relevant studies, 198 patients with IBD, treated using radiation therapy, and with outcome data available, were included. The reported median follow-up was 55.2 months. The majority of patients (n = 148, 75%) were male; 113 (57%) had Ulcerative Colitis, 81 (41%) had Crohn's Disease, and 4 patients had IBD NOS. Nineteen patients (9.5%) were reported to have active IBD within 6 -12 months prior to starting RT. Colo-rectal carcinoma was the most common malignancy (n = 91, 46%), followed by prostate cancer (n = 83, 42%), anal-canal (n = 10, 5%), and gynecological malignancies (n = 6, 3%). External beam RT was used as part of treatment for 173 patients (87%), while 25 received brachytherapy alone. About 28% (n = 55) also received concurrent chemotherapy. From studies that reported the RT technique used, about 43% of patients were treated with Intensity Modulated RT (IMRT). RT dose ranged from 25 Gy/5 for pre-op rectal cancers to over 70 Gy for prostate cancers. Median BED (a/b = 3, rectum) was calculated to be 83.3 Gy. Acute toxicity data was available for 190 patients: clinically significant acute toxicity, ≥Grade 3, was reported in 29 patients (15.3%). Late RT toxicity data was available for 115 patients: ≥Grade 2 GI toxicity was reported in 21 (10.5%), and ≥Grade 3 in 7 (3.5%) of patients.

CONCLUSION(S):

With the use of modern RT techniques, GI toxicity is relatively low for patients with IBD, and is not numerically different from that reported for patients without IBD. Patient selection and meticulous RT planning is important, however, evidence does not suggest that IBD in itself is a contraindication for RT.
P053 Comparison of accuracy between fecal immunochemical test and fecal calprotectin for predicting mucosal healing in quiescent ulcerative colitis patients
Authors: Young Kim Eun , Soo Kim Eun , Seok Lee Hyun , Ik Jang Byung , Ok Kim Kyeong , Jin Lee Yoo
Published: July 2019

BACKGROUND:

Non-invasive stool tests including fecal immunochemical test (FIT) and fecal calprotectin (FC) are known to be a reliable biomarker for mucosal healing (MH) in ulcerative colitis (UC). However, direct comparison of these fecal tests for predicting MH in inactive UC patients has yet to be evaluated. We aimed to compare the accuracy of FIT and FC for predicting MH in UC patients in clinical remission.

METHODS:

This was a prospective, multicenter study conducted in 3 tertiary hospitals between February 2016 and January 2018. UC patients in clinical remission for at least 3 months or more underwent colonoscopy and MH was evaluated using Mayo endoscopic subscore (MES). Fecal samples were collected for FIT and FC 24 hours before colonoscopy. Receiver operating characteristic (ROC) curve and cut-off value of the best accuracy for predicting MH was assessed in each test. Independent predictive factors for MH were identified by logistic regression analysis.

RESULTS:

Among 127 patients (male 86, median age of diagnosis 44 [range 14–77]) of UC in clinical remission, only 65 (51.2%) showed complete MH (MES = 0). Area under curve (AUC) of FC was significantly higher than FIT (AUC 0.858 vs 0.707, P < 0.001) whereas this difference disappeared when MH was defined as MES 0 or 1 (AUC 0.820 vs 0.813, P = 0.891). When cut-off value was set as 70 μg/g for FC and 10 mg/mL for FIT, sensitivity, specificity, positive predictive value and negative predictive value were 89.2, 71, 76.3, and 86.3 and 92.3, 50, 65.9, and 86.1, respectively. Multivariate logistic regression analysis showed that age of diagnosis >45, hematocrit >44, FC <70 μg/g, and FIT <10 mg/mL were identified as independent predictive factors for MH (MES = 0).

CONCLUSION(S):

Our study demonstrated that FC is more sensitive than FIT for predicting complete MH in quiescent UC patients. The best cut-off value of FC and FIT for MH in these patients is found as 70 μg/g and 10 mg/mL, respectively. Age of diagnosis and hematocrit are additional predictors for MH.
P056 Autoimmunity against type I collagen in ulcerative colitis
Authors: Dilyara Mukhametova , Diana Abdulganieva , Oleg Zinkevich , Nellya Saphina , Marina Koporulina , Alfiya Odintsova
Published: July 2019

BACKGROUND:

Immunological disorders play an important role in the pathogenesis of ulcerative colitis (UC). Collagen is the main component of the intercellular matrix of connective tissue. It can be assumed that the immune disorders leading to the production of autoantibodies to collagen play a role in the pathogenesis of UC. Aim: to study the level of IgM and IgG to type I collagen (COL1) in UC.

METHODS:

We prospectively included 61 patients with UC and 30 healthy controls. Mean age in UC was 37 ± 1.5 years and in control group—30 ± 1.5. Severity of UC was assessed by Mayo score: remission—5, mild—25, moderate—26, severe—5. Extraintestinal manifestations of UC were in 24 patients (39%). Level of serum IgM and IgG to COL1 was assessed by enzyme immunoassay.

RESULTS:

In active UC levels of IgM to COL1 was increased (0.17 [0.10; 0.20] mkg/mL) compared with healthy (0.09 [0.07; 0.12] mkg/mL; P < 0.01). The difference between remission (0.1 [0.09; 0.19] mkg/mL) and exacerbation, remission and control group was not detected (P > 0.05). In patients with severe UC IgM to COL1 was 0.19 [0.18; 0.25] mkg/mL, which was higher than in moderate UC—0.12 [0.08; 0.17] mkg/mL (P < 0.05) and mild—0.18 [0.11; 0.20] mkg/mL (P > 0.05). There was a tendency to increase of IgM to COL1 in patients with extraintestinal manifestations (0.17 [0.10; 0.22] mkg/mL) than without them (0.12 [0.09; 0.18] mkg/mL). The level of IgG to COL1 in active UC (24.69 [16.36; 99.12] mkg/ml) was higher than in the control group 11.36 [6.93; 19.83] (P < 0.05) and remission—13.15 [8.88; 26.21] (P > 0.05). There was not revealed the difference of IgG levels depending on the severity of disease. There was a tendency to increase of IgG to COL1 in patients with extraintestinal manifestations (16.18 [9.46; 26.21] mkg/mL), than without them (12.78 [8.81; 28.31] mkg/mL). There was increasing of ESR (r = 0.36; P < 0.05) and leukocytosis (r = 0.32; P < 0.05) with increase of IgM level to COL1.

CONCLUSION(S):

In active UC the level of serum antibodies of class IgM and IgG to COL1 increased compared with healthy. The maximum increase was found in the group of patients with severe relapse and in the presence of extraintestinal manifestations.
P061 Ulcerative colitis: Risk factors for relapse in clinical remission patients
Authors: Cátia Arieira , Henrique Guimarães , de Castro Francisca Dias , João Moreira Maria , José Cotter
Published: July 2019

BACKGROUND:

Ulcerative colitis (UC) is a chronic inflammatory bowel disease, characterized by periods of remission and relapse. The aim of this study was to identify factors associated with a higher risk of relapse in patients in clinical remission.

METHODS:

retrospective study, including UC patients in clinical remission with minimum follow up of 2 years. Clinical relapse was defined as a need for therapeutic escalation and UC-related hospitalization or surgery. Statistical analysis was carried out by means of t-test and chi-square (univariate analysis) and logistic regression (multivariate analysis). A P value < 0.05 was considered statistically significant.

RESULTS:

169 patients were included, 51.5% female. Clinical relapse was observed in 30,2% of the patients. In the univariate analysis, relapse was more frequent in patients with higher number of previous relapses (2.7 vs 1.0; P < 0,.001), younger age at diagnosis (36.6 vs 41.2 years; P = 0.045) and with therapeutic non-adherence (82.4% vs 17.6%; P < 0.001). Patients who presented at clinical remission with a Mayo Endoscopic Score (MES) of 0 had a recurrence rate of 5.6%, significantly lower than the rate of 43.2% presented by the group with mild endoscopic disease activity (MES 1) and also lower than the rate of relapse of 73.3% presented by the group with moderate endoscopic disease activity (MES 2) (P < 0.001). In the multivariate analysis, therapeutic non-adherence (HR 24.6 CI 95% 2.0–296.6; P = 0.012) and MES > 0 (HR 16.6; CI 95% 2.9–94.2; P = 0.002) were the only independent risk factors associated with relapse.
P074 Review of patients with inflammatory bowel disease at the university hospital of the West Indies between 1980-June 2018
Authors: Yvonne Dawkins , Michael Lee , Trevor Ferguson , Mike Mills , Milton Arthurs , Kildare Donaldson , Trevor Murphy
Published: July 2019

BACKGROUND:

There are limited data on the incidence and prevalence of Inflammatory bowel disease (IBD) in Jamaica and other Caribbean countries. The aim of this study is to determine the clinical features, course and outcomes of patients with IBD in Jamaica.

METHODS:

A retrospective chart review of patients who were diagnosed with IBD and seen at the University Hospital of the West Indies between the period January 1980 to June 2018 was conducted. Data collected included: demographic characteristics and symptoms, endoscopic disease activity at last endoscopy, treatment and response to therapy, and surgical requirement. Descriptive statistics was computed using Stata 14 statistical software.

RESULTS:

We identified 115 patients with IBD during the study period. Mean age was 48.2 ± 17.7 years, 61.7% were females and mean disease duration was 12.5 ± 10.2 years. Forty-three patients (37.4%) had Crohn's disease (CD) and 72 (62.6%) had ulcerative colitis (UC). The most common presenting symptom was diarrhea (86 patients, 78.2%) and was more common in females (88% vs 62%; P value 0.001). Most patients with UC had pancolitis (54.2%), 19.4% left sided colitis and 18.1% had proctitis/proctosigmoiditis. Disease distribution in CD was mainly ileal in 37.2%, ileo-colonic in 34.9% and colonic in 23.3%. CD phenotype was inflammatory in 37.2% of patients, stricturing in 25.6% and penetrating in 32.6%. The majority of patients had moderate/high risk disease (66.1%). Eighty-nine patients (78.1%) were treated with 5-aminosalicylates, 37 (32.2%) with immunomodulators, 1 (0.9%) with a biologic agent, 48 (41.7%) were on chronic steroids and 7 (6.1%) were not on any medications. Chronic steroid use was associated with side effects in 36.4% of patients with steroid induced diabetes mellitus being the most frequent side effect occurring in 9 patients, all of whom were females (16.4% vs 0%; P value 0.007). Twenty six patients required surgical therapy for IBD. The most common indication for surgery in patients with CD was bowel obstruction (45.8%) whereas 2 patients with UC had surgery for failed medical management and spontaneous perforation respectively. Over the last 2 years patients with CD required more frequent hospital admissions for disease flares than patients with UC (0.9 ± 1.3 vs 0.3 ± 0.7; P value 0.005). Clinical remission was achieved by 75% of patients at their last clinic visit.

CONCLUSION(S):

Only 115 patients with IBD were identified over a 38 year period at a single referral center in Jamaica. UC was more commonly diagnosed than CD. The most common presenting symptom was diarrhea. Most patients with UC had pancolitis whereas most patients with CD had inflammatory ileal disease. A third of patients were maintained on chronic steroids. Most patients achieved clinical remission at their last clinic visit.
P075 Prospective validation of CD4+CD25+FOXP3+ T-regulatory cells as an immunological marker to differentiate intestinal tuberculosis from Crohn's disease
Authors: Ritika Rampal , Saurabh Kedia , Deepak Madhu , Govind Makharia , Vineet Ahuja
Published: July 2019

BACKGROUND:

Crohn’s disease (CD) and intestinal tuberculosis (ITB) are difficult to differentiate. We have previously documented high diagnostic accuracy of peripheral blood frequency of CD4+CD25+FOXP3+ T-regulatory cells (T-regs) in differentiating CD and ITB. The present study was designed to validate the results of the previous study prospectively. Crohn’s disease (CD) and intestinal tuberculosis (ITB) are difficult to differentiate. We have previously documented high diagnostic accuracy of peripheral blood frequency of CD4+CD25+FOXP3+ T-regulatory cells (T-regs) in differentiating CD and ITB. The present study was designed to validate the results of the previous study prospectively.

METHODS:

Seventy treatment naïve patients of CD (n = 23) and ITB (n = 47) (diagnosed by standard criteria) were recruited prospectively from October 2016 till May 2017. Patients with history of ant-tubercular therapy in the past were excluded. The frequency of T-reg cells in peripheral blood as determined by flow cytometry and was compared between CD and ITB.

RESULTS:

Frequency of T-reg cells in peripheral blood was significantly increased in ITB as compared to CD [40.9 (IQR: 33–50) vs 24.9 (IQR: 14.4–29.6), P < 0.001]. There was good diagnostic accuracy of T-reg cell frequency in differentiating CD and ITB with an area under the curve (AUC) on ROC curve of 0.77 (0.65p0.9). The cut-off obtained on the ROC curve, to differentiate CD and ITB in the present study (32%) was like the previous study (32.5%) with a sensitivity, specificity, positive and negative predictive value of 81%, 83%, 90%, 65% respectively for the diagnosis of ITB.

CONCLUSION(S):

CD4+CD25+FOXP3+ T-regulatory cells frequency in peripheral blood has a good diagnostic accuracy and can be used as a simple test in differentiating CD and ITB.
P083 Improvement in thiopurine dosing in pediatric inflammatory bowel disease by participation in a national collaborative
Authors: Christina Lowrance , Keith Hanson , anshu Maheshwari , Christopher Mullett , Mohammad Yaseen , Sandeep Gupta , Ian Kang
Published: July 2019

BACKGROUND:

Pediatric Inflammatory Bowel Disease (IBD) is a chronic disease with several treatment options. Medication optimization is key to patient-centered, efficacious management of IBD. Thiopurines, including azathioprine and 6-mercaptopurine, are a mainstay of treatment and are dosed based on weight. As part of a national IBD collaborative, ImproveCareNow, we identified an opportunity to improve weight-based dosing in this patient population. The specific aim of the project was to increase the percentage of patients meeting weight-based thiopurine dosing targets to 80%.

METHODS:

We undertook a rapid quality improvement project to improve this metric, using standard quality improvement techniques and resources from the ImproveCareNow collaborative. Inclusion criteria were IBD patients with a clinic visit in the preceding 13 months and known weight and medication dose. Exclusion criteria included patients with low or unknown TMPT activity, treatment with a biologic agent, and treatment with allopurinol. Interventions focused on pre-visit planning, standardized visit templates, increasing frequency of visits, obtaining labs prior to the visit, and provider/patient education. Performance was continually monitored via ImproveCareNow's data management program, which tracks metrics on a monthly basis.

RESULTS:

This study was conducted over a 20-month period (June 2016 to January 2018). 31 unique patients on thiopurine therapy met study criteria and were enrolled. 19 (61%) were males, with ages ranging from 2.4 to 21.7 years (mean age 15.0 years). Since patients both started and stopped thiopurine therapy during the study, the total number of patients varied over time; the number of patients per month on thiopurines ranged from 16 to 21 during the study period. On average approximately 30% of IBD patients at our center were on thiopurines each month. The percentage of patients who met weight-based dosing guidelines increased from 56% at the start of the project to the target of 80% within 15 months, exceeding performance from the national cohort. Target performance was maintained for the remainder of the study period.

CONCLUSION(S):

Participation in a national collaborative allowed the identification of an unmet need in our IBD clinic, as we were not consistently meeting weight-based dosing recommendations for thiopurines. Using standard quality improvement methodology and resources from a national collaborative, we not only improved our weight-based dosing recommendations for thiopurines but also exceed that of the national cohort and maintained this for duration of study. Future work will examine whether these changes led to improvements in thiopurine serum metabolite levels and disease control.
P089 Small bowel Clostridium difficile masquerading as Crohn's disease
Authors: Cecelia Zhang
Published: July 2019

CASE:

A 38-year old man with a history of perforated diverticulitis s/p sigmoid colectomy presented to the emergency room with 2 days of abdominal pain. He was without any symptoms of diarrhea, hematochezia or melena. He was previously admitted to the hospital for 4 days approximately one month prior to presentation with similar symptoms of abdominal pain. He had a CT scan of the abdomen and pelvis performed during that admission with wall thickening of the terminal ileum, but no colonic inflammation seen. He was treated with a week of ciprofloxacin and metronidazole with transient improvement in his symptoms. He denied any significant social history. Family history was negative for inflammatory bowel disease. He denied any NSAID use, but he did report a 3-day course of clindamycin approximately 3 weeks ago for a dental procedure. His lab values were notable for a mild leukocytosis of 12.6 × 109/L (ref range 4.8–10.8 × 109/L), elevated C-reactive protein at 1.89 mg/dL (ULN ≤ 0.60 mg/dL), normal lactate at 1.0 mmol/L (ref range 0.6–2.2 mmol/L), and a negative QuantiFERON TB Gold Plus. He had CT imaging repeated of his abdomen and pelvis that was significant for multiple loops of ileal wall thickening consistent with severe ileitis without any inflammation of the large intestine. Given the concern for Crohn's disease, a colonoscopy was performed and a normal terminal ileum was seen for 30 cm. There were multiple small-mouth diverticula seen in the descending, transverse and ascending colon along with a prior end-to-end colo-colonic anastomosis in the sigmoid colon. The mucosa appeared to be normal and healthy in the colon. Random biopsies taken of the terminal ileum and colon were negative for any significant pathological diagnosis. No antibiotics were given prior to colonoscopy. Stool studies returned with a positive Clostridium difficile result, but negative stool culture and parasite screen. He was treated with a 14-day course of metronidazole 500 mg Q8H with resolution of his symptoms.

DISCUSSION:

This case is atypical given the patient's lack of significant diarrhea, CT imaging findings of distal ileal involvement without any colonic inflammation, and normal findings on both endoscopic evaluation and pathology. While C. difficile is the most common cause of healthcare associated infectious diarrhea, small bowel infection with C. difficile is a rare presentation. The pathophysiology of C. difficile enteritis is not well understood, but most cases reported in the literature have been described in patients with altered bowel anatomy such as colectomy, pouch construction or other large and small bowel surgery. In these cases, the small bowel is postulated to be more susceptible to colonization and infection in the setting of surgical intervention. This case highlights that C. difficile can solely affect the small bowel of patients with limited colonic resections which is important for practicing gastroenterologists.
P093 Stressful events possibly related to the onset of IBD
Authors: Beatriz Pernalete , Guillermo Veitia
Published: July 2019

BACKGROUND:

Inflammatory Bowel Disease (IBD) is a multifactorial disease. There may be mentioned a bacterial antigen act as trigger the clinical picture in a genetically predisposed patient with a mucosal permeability altered by an inappropriate immune response. Often stress is perceived by patients with IBD as the leading cause of their disease, as Psychosomatic theory says. Studies have shown that chronic stress have a significant effect on the immune system illness as its ultimate manifest. It rises catecholamines and suppressor T cells levels, which suppresses the immune system. So we asked the question: was there be a stressful event that may have been related to the onset of IBD in our patients? The aim of study was to assess whether stress, though life events, are associated with onset IBD.

METHODS:

112 patients with IBD (83 with ulcerative colitis (UC) and 29 with Crohn´s Disease (CD), aged between 18 and 65 years, from 3 university hospitals in 2 cities of Venezuela (Caracas and Maracaibo) were given a survey with dichotomous items, simple selection and filling of information, easy management, simple language and short duration. The study of the collected data was performed using the statistical method of frequency analysis.

RESULTS:

16.7% of the sample analyzed denied stressful event before the start of IBD. 83.03% reported stressful situations during the year before the onset of the disease (35 patients reported stress economic situation, labor problems 21, lost close family member 17, divorce 13, domestic violence 8, sexual abuse 3).

CONCLUSION(S):

Due to the high percentage of patients reporting stressful events prior to the onset of IBD stressful events, when we talk about the theories related to the pathogenesis of these diseases, it would be interesting to mention the psychosomatic theory. We recommend that all Multidisciplinaries IBD teams should have a psychologist and/or psychiatrist conducting psychiatric and/or psychological evaluation to conclude the presence or absence of psychological disorders i IBD patients and give them appropriate treatment. This would help significantly to patient management and most likely to get that improvement related to the comprehensive evaluation over all.
P102 Young Investigator, Top Clinical Abstract Combined therapy with adalimumab and mesenchymal stromal cells contributes to reduction in the degree of inflammation in ulcerative colitis
Authors: Oleg Knyazev , Anna Kagramanova , Albina Lishchinskaya , Dmitriy Kulakov , Anatoliy Konoplyannikov , Mariya Zvyaglova , Sergey Khomeriki , Asfold Parfenov
Published: July 2019

BACKGROUND:

One of the new promising methods of treatment of patients with ulcerative colitis (UC) is biological therapy using bone marrow mesenchymal stromal cells (MCS). In some cases, simultaneously with MCS, patients receive concomitant anticytokine therapy. Currently, a new strategy for UC therapy is to achieve a deep remission of the disease. Objective: to compare the level of immunobiological and histological markers of inflammation – C-reactive protein (CRP), the Histological Geboes Score (GS) and fecal calprotectin (FCP) - in patients with UC receiving cell therapy MSC, anticytokine therapy with adalimumab (ADA) and combined therapy of bone marrow MSC and ADA.

METHODS:

60 patients with total ulcerative colitis of moderate severity were divided into groups depending on the therapy. The first group of patients with UC aged from 19 to 56 years (Me-29) (n = 20) received anti-inflammatory therapy with the use of the culture of 2 million MSC/kg according to the scheme the second group of patients with UC (n = 20) aged 23 to 62 years (Me-41) received ADA in accordance with the recommended scheme, the third group of patients with UC (n = 20) aged 20 to 59 years (Me-33) received the MSC + ADA. The level of CRP, PCF and is was assessed 26 weeks after initiation of therapy. The baseline CRP was 25.0 ± 1.9; 26.5 ± 2.1 and 24.0 ± 2.4 mg/L, respectively. Baseline GS in the groups of patients was 4.4 ± 0.2; 4.35 ± 0.2 and 4.5 ± 0.3 points, respectively. The initial level of the FCP made 890.8 ± 88,8; 850.3 ± 83.9 and 910.5 ± 120.5 μg/g, respectively.

RESULTS:

After 26 weeks from the start of therapy in the 1-st group of patients, the level of CPP was 6.8 ± 1.1 mg/L, in the 2-nd group-7.4 ± 1.3 mg/L, in the 3-rd group-7.9 ± 1.0 mg/L (P > 0.05). After 26 weeks from the start of therapy in the 1-st group of patients, the level of FCP was 108.8 ± 9.3 μg/g, in the 2-nd group-90.6 ± 6.5 μg/g, in the 3-rd group - 96.8 ± 6.3 μg/g (P < 0.05 compared to the 1-st and 2-nd groups). After 26 weeks from the start of therapy in the 1-st group of patients with GS was 0.7 ± 0.1 points, in the 2-nd group-0.65 ± 0.1 points, in the 3-rd-0.5 ± 0.06 points (P < 0.001 compared with the 1-st and 2-nd groups).

CONCLUSION(S):

Combined cell and anti-cytokine therapy with adalimumab contributes to a more pronounced reduction in the degree of inflammation of the intestinal mucosa.
P104 Branded infliximab still predominantly used over biosimilars in patients with IBD
Authors: Lynn Price
Published: July 2019

BACKGROUND:

Despite the availability of 2 infliximab biosimilars in the US market, the vast majority of bio-naïve patients being placed on infliximab are prescribed the reference brand.

METHODS:

In April 2018, we conducted a retrospective patient chart audit of 1,005 patients with IBD who were started on a biologic agent for the first time. 209 US gastroenterologists submitted patient-level data via a HIPAA-compliant audit form which included both clinical and non-clinical data. The collaborating physicians also completed a brief survey about their practices and their opinions regarding IBD patient management. The data were collected and analyzed in SPSS.

RESULTS:

30% of the patients starting on a biologic for the first time were initiated on infliximab. Of those, 16% were placed on a biosimilar and 84% were placed on the reference brand. When presented with the statement, “I trust that infliximab biosimilars are clinically comparable to the reference brand,” 46% of the physicians expressed agreement, 36% were neutral, and 18% disagreed. In 90% of the cases where the patient was placed on the reference brand, the physician was not contacted by a pharmacist or insurance company about using a biosimilar in place of the reference brand. If they had been contacted, in 43% of the cases they would have switched to a biosimilar, in 51% they would have pressed to use the reference brand, and in 6% they would have chosen a non-infliximab alternative.

CONCLUSION(S):

Until gastroenterologists are encouraged or mandated to use biosimilars, use of the reference brand is anticipated to remain dominant. Based on physician feedback, about half appear to be very willing to use biosimilars, but despite this, continue to prescribe the more familiar reference brand.
P105 Biologic/JAK preference in different IBD patient types
Authors: Lynn Price
Published: July 2019

BACKGROUND:

The IBD market is rapidly evolving as new biologic and small molecule agents are being approved such as ustekinumab in Crohn's disease and tofacitinib in ulcerative colitis (UC). This study sought to understand gastroenterologists' product preferences for certain patient types and to understand any shifts in preference with new agents to consider.

METHODS:

Each quarter, an independent healthcare agency surveys approximately 100 US gastroenterologists about the evolving treatment of IBD. To qualify, gastroenterologists must spend the majority of time in clinical practice, must be managing a minimum of 50 patients with IBD, and must be in practice between 2 and 35 years. Regional and practice setting quotas are applied in order to obtain a representative sample. The survey is administered online and respondents are compensated for their participation. The data are collected and analyzed in SPSS.

RESULTS:

Gastroenterologists describe over half of their UC patients as being “young, with active lifestyles”. This patient type has historically been strongly associated with adalimumab over other biologic agents, with 64% (n = 100) of respondents surveyed in April 2018 indicating that they would be most likely to use adalimumab for this patient category. However, with the availability of tofacitinib, which was approved in June 2018, preference for this large patient segment is changing. In the July 2018 wave of the survey, nearly one-quarter (23%) of gastroenterologists selected the new, oral JAK inhibitor as their most likely agent of choice for young, active patients, with adalimumab preference dipping to 54%. Tofacitinib was also selected by 16% of the gastroenterologists as being the drug of choice in patients with secondary TNF failures (waning efficacy), though the majority still prefer vedolizumab in this scenario (58%). When directly comparing adalimumab with tofacitinib in UC, gastroenterologists view adalimumab outperforming tofacitinib on all attributes associated with length of time in the market, but tofacitinib is already matching, or outpacing, adalimumab on many key attributes for treatment success including efficacy, adherence, tolerability, and sustained response. Analysis of the most recent prescription patterns, as assessed by physician allocation of their last 5 biologic/JAK prescriptions between April 2018 and July 2018 shows declining use of adalimumab (34% to 30%) with an increase of tofacitinib (0% to 5%).

CONCLUSION(S):

Adalimumab has long been the preferred biologic agent for the treatment of UC in younger, active patients, relatively unchallenged by any of the other biologics for this large patient sub-type. Early use of tofacitinib suggests that the advent of an oral advanced therapy option may soon rival adalimumab for preference in younger, active patients.
INFLUÊNCIA DO EL NIÑO-OSCILAÇÃO SUL NA PRECIPITAÇÃO EM MARINGÁ-PR, NO PERÍODO DE 1980 A 2016
Authors: Minaki Cíntia , Montanher Otávio Cristiano
Published: July 2019

O El Niño-Oscilação Sul influencia o clima de diferentes regiões do mundo, das quais o Sul do Brasil é um exemplo. Assim, buscou-se compreender a influência do ENOS nas anomalias pluviométricas do município de Maringá-PR, localizado na Mesorregião Norte Central Paranaense. Com a série de dados mensais de precipitação, de 1980 a 2016, da Estação Climatológica Principal de Maringá (ECPM), calculou-se as anomalias locais de chuva. Utilizou-se também os dados do Índice Oscilação Sul (IOS) e da Temperatura da Superfície do Mar (TSM), divulgados pela National Oceanic and Atmospheric Administration (NOAA). Para compreender se as anomalias de chuva podem ser explicadas pelo ENOS, com base no IOS, aplicou-se as correlações de Pearson (r) e de Kendall (τ). Aplicou-se também testes de mediana entre as anomalias de precipitação de três grupos: meses com influência do El Niño, La Niña e em condições neutras. Os resultados indicaram meses do outono e da primavera como os de maior correlação entre as variáveis, e a defasagem temporal variou de zero a cinco meses entre os coeficientes utilizados. Os testes estatísticos demonstraram a anomalia positiva de chuva em meses de El Niño, não sendo possível concluir o inverso, na mesma intensidade, para o La Niña.