bluuebunny/crossref_metadata_2025_split huggingface dataset:
A229 USTEKINUMAB FOR THE TREATMENT OF REFRACTORY PEDIATRIC CROHN’S DISEASE: A SINGLE CENTRE EXPERIENCE
Authors: Cohen A , Sant’Anna A , Ahmed N 
Published: February 2020

Abstract

Background
Despite the well-established efficacy of Tumor Necrosis Factor (TNF) antagonists as treatment options for Crohn’s Disease, many pediatric patients need a change in therapy due to adverse events, as well as primary and secondary loss of response, highlighting the necessity for medications with a different mechanism of action. Ustekinumab, a monoclonal antibody targeting IL-12 and IL-23, has been approved to treat psoriatic arthritis, plaque psoriasis, and adults with Crohn’s disease. While utekinumab has been shown to be effective in inducing clinical remission in adults with Crohn’s disease refractory to anti-TNF agents, minimal data exists in the pediatric population.

Aims
We retrospectively describe 11 pediatric patients who received ustekinumab at the Montreal Children’s Hospital with the goal of assessing its efficacy in inducing clinical, biochemical, and endoscopic remission.

Methods
We abstracted baseline data, prior treatment and response, indications for starting ustekinumab, clinical response, endoscopic data, and laboratory parameters pre- and post- therapy. Clinical response was defined as decrease in abbrPCDAI (Pediatric Crohn’s Disease Activity Index) score.

Results
Patients ranged in age from 12–17 years old upon initiation of treatment with ustekinumab and had all previously failed either one (N=8) or both (N=3) anti-TNF therapies. Follow-up ranged from 6 to 22 months. We examined three indices of response to ustekinumab: symptomatic improvement, biomarker normalization, and endoscopic changes. Five of eleven patients demonstrated a clinical response – two maintained clinical remission across available follow-up data, while the remaining three experienced a secondary loss of response. The other six patients studied were primary non-responders. Two of these patients had normal abbrPCDAI scores upon initiation of ustekinumab and terminated therapy due to persistent stricturing disease. The other four non-responders either remained unwell or demonstrated clinical worsening, as measured by the abbrPCDAI. Of the clinical responders, 3/5 had elevated CRP values prior to initiating ustekinumab therapy, all of which normalized within one month of clinical improvement. Endoscopic data both pre- and post- ustekinumab was available in two responders and two non-responders, with endoscopic improvement seen in both of the responders and in one of the two non-responders.

Conclusions
These results demonstrate that ustekinumab has the potential ability to induce not only clinical and biochemical remission, but also endoscopic improvement, in the pediatric population. An area of concern is the fact that only one patient maintained remission for longer than one year. Future research should focus on maximizing and lengthening the effect of ustekinumab, as well as determining factors that influence response to therapy.

Funding Agencies
None
A232 EFFICACY OF TOFACITINIB FOR THE TREATMENT OF MODERATE-TO-SEVERE ULCERATIVE COLITIS: REAL-WORLD DATA
Authors: Xiao Y , Lakatos P L , Bourdages R , Bitton A , Afif W , Kohen R , Berberi M , Bessissow T 
Published: February 2020

Abstract

Background
A significant proportion of patients with moderate to severe ulcerative colitis (UC) do not respond to therapy, which includes thiopurines, glucocorticoids, and antagonists to tumour necrosis factor-α and integrin. Tofacitinib, a Janus Kinase inhibitor, has emerged as an efficacious and safe treatment for moderate to severe ulcerative colitis. However, it is not known if this efficacy translates into real-life effectiveness in a regular clinical practice.

Aims
We aimed to assess the rate of clinical response and clinical remission at 3 and 6 months after tofacitinib initiation. Secondary endpoints included rate of biomarker normalization, corticosteroids-free clinical remission and severe infections.

Methods
We conducted a multi-center retrospective observational study of adult patients with active UC started on tofacitinib from January 1, 2015 to October 1, 2019 at the McGill University Health Center and Hotel-Dieu de Lévis. A positive clinical response was defined as a decrease of ≥3 in the partial Mayo score. Clinical remission was defined as partial Mayo score of ≤2. Biomarker normalization was defined as fecal calprotectin ≤250ug/g. Severe infection was defined as an infection requiring hospitalization.

Results
During the study period, 40 patients with UC were started on tofacitinib. Amongst the patients, 85% (n=34) had failed ≥1 biologic and 50% (n=20) had failed ≥3 biologics. At the time of this preliminary analysis, 38 patients had undergone 3 months of treatment and 30 patients had undergone 6 months of treatment. At 3 months, a clinical response was seen in 89.5% of patients (n=34) and clinical remission occurred in 63.2% (n=24). At 6 months, clinical response occurred in 73.3% of patients (n=22) and clinical remission was sustained in 53.33% (n=16). Biochemical normalization occurred in 29.0% (n=11) and 30.0% (n=9) at 3 and 6 months, respectively. Additionally, 63.2% (n=24) and 43.3% of patients (n=13) achieved steroid-free clinical remission at 3 and 6 months, respectively. In the interim, one patient developed a serious infection requiring discontinuation of drug.

Conclusions
Our preliminary analysis demonstrates that in a real-life setting, tofacitinib is an effective treatment for inducing clinical remission in refractory UC patients. Further data will be complied to better assess the efficacy over a longer follow up.

Funding Agencies
None
A240 ASSESSING THE IMPACT OF AGE AT DIAGNOSIS ON TRANSITION PROCESS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES FROM PEDIATRIC TO ADULT CARE
Authors: Yang X , Tchogna S A , Deslandres C , Jantchou P 
Published: February 2020

Abstract

Background
Twenty-five percent of pediatric patients with inflammatory bowel disease (IBD) are diagnosed between the age of 16 and 18 years. They represent a unique challenge associated with the short follow-up time between diagnosis and transition to adult care.

Aims
The primary aim was to compare the current practices related to the transitional process in adolescents diagnosed before 16 years (early-adolescence (EA)) or after 16 years (late-adolescence (LA)). The secondary aim was to investigate clinical factors associated with age at transfer.

Methods
Patients diagnosed between 2013 and 2015, at the IBD clinic of CHU Sainte-Justine were included in the study. The date of transfer to adult care was defined as the date of the last visit in the pediatric unit. The factors associated with transition process and transfer included: disease type, disease severity at diagnosis and last pediatric visit, age at diagnosis, treatment group, disease burden (hospitalizations/relapses) and disease education.

Results
We included 144 patients (77 males; median (interquartile range (IQR) age at diagnosis 15.2(14.3–16.2) years; Crohn’s disease (N=98), ulcerative colitis (N=31) and IBD-unclassified (N=15). The median (IQR) duration of pediatric follow-up was 3.6 (2.7–4.1) years in the EA group as compared to 1.4 (1.0–1.8) yrs in the LA group; P&lt; 0.01. While most of the patients completed the transition at a median (IQR) age of 18.0 (17.9–18.3) years, 15 % of patients were transferred at an older age (18.5 to 20 years). Overall, 75.7% were in remission, 13.9% with mild disease activity and 10.4% with moderate activity at the last pediatric visit. Patients with moderate activity at last pediatric visit tend to be transferred at an older age as compared to patients in remission or mild activity. The median (IQR) age were respectively 18.4 (18.2–19.1), 18.0 (17.9–18.1), 18.0 (17.9–18.3) years; P=0.024. There was a modest correlation between age at diagnosis and age at transfer (R = 0.22; P = 0.0068). Patients were transferred to adult gastroenterologists in academic hospitals (50.8%) or non-academic hospitals (43.1%). However, the disease activity at transfer was not associated with the adult care setting (academic vs non-academic). The number of relapses and hospitalizations during pediatric care were associated with older age at transfer: (&gt; 18.5 yrs vs &lt; 18.5 years): median(IQR) of 0.8(0.4–1.4) vs 0.3 (0.-0.6) for relapses; P=0.009 and 0.4 (0.0–1.1) vs 0.3 (0.0–0.7) for hospitalizations; P=0.009.

Conclusions
Pediatric IBD diagnosed at late adolescence tend to have more active disease and older age at transfer. Therefore, efforts to design a structured transitional care program are needed in order to improve transition outcomes for IBD patients with a special focus for subjects diagnosed in late adolescence.

Funding Agencies
CAG
A241 PRICE: PREVENTING READMISSIONS IN IBD CENTRES OF EXCELLENCE
Authors: Dang F , Habashi P , Gallinger Z , Nguyen G C 
Published: February 2020

Abstract

Background
Hospital readmission rates are high in the IBD population, with 20% of patients readmitted within the same calendar year. Hospital discharge processes are not routinely standardized and deficiencies in the transition of care after discharge puts patients at increased risk of illness, hospital utilization and healthcare cost. In addition to increased healthcare expenditure, hospitalizations for IBD patients are associated with nosocomial complications such as venous thromboembolism and infection.

Aims
We hypothesize that implementing standardized follow-up by an IBD practice nurse and electronic health outcome monitoring through NoviSurvey can reduce the risk of hospital readmission compared to current approaches of hospital discharge alone.

Methods
This parallel randomized control trial is powered for N=400 and will include patients admitted for an IBD flare without requiring surgical intervention from the gastroenterology service or consulted from general internal medicine. Patients randomized to the control arm are discharged with usual standard of care. Patients in the intervention group will be eligible for usual post-discharge care in addition to organized telephone follow-up by an IBD practice nurse at 1, 7 and 30 days post-discharge. In addition, these patients will receive bi-weekly correspondence from NoviSurvey to complete a short questionnaire on clinical disease severity and medication adherence. Based on telephone interaction and survey scores, the IBD nurse may arrange readmission or expedited ambulatory visit for high-risk patients.

Results
15 patients are currently enrolled into our study, with 7 randomized to the intervention and 8 to the control group. In the control group, 25% of patients were readmitted to hospital within 30 days of discharge and 13% failed to follow their steroid taper. There were no patients in the intervention group who were readmitted to hospital within 30 days and none who failed their steroid taper. In both the control or intervention group, there were no occurrences of deep vein thrombosis within 30 days post-discharge.

Conclusions
The preliminary findings in our small sample study indicate that a nurse led post-discharge intervention may translate to benefits including decreased readmission rates to hospital, better patient satisfaction and better medication adherence.

Funding Agencies
CCC
A253 ADMINISTRATIVE DATA CAN ACCURATELY IDENTIFY PATIENTS WITH PERIANAL CROHN’S DISEASE
Authors: Fairclough J , Tang T , Fung M , Golden S , Kukaswadia A , Powers S , Ward R , McCurdy J 
Published: February 2020

Abstract

Background
Perianal fistulas (PAF) are a frequent complication of Crohn’s disease (CD) associated with substantial morbidity. Population-based studies with CD are lacking, in part due to the difficulty in identifying these patients from health administrative databases.

Aims
To determine if administrative claims and diagnostic codes can reliably identify patients with perianal fistulas in a cohort of patients with CD.

Methods
A retrospective cohort study was performed using data from The Ottawa Hospital (TOH), which was linked to The Institute for Clinical Evaluative Sciences (ICES) Ontario Crohn’s and Colitis Cohort (OCCC) data using Ontario Health Insurance Plan (OHIP) numbers. Patients admitted with CD from 1 Jan 2009 to 31 Dec 2016 were identified from TOH data warehouse using the ICD-10 code K50.x. Confirmation of CD diagnosis and determination of the presence or absence of PAF was achieved by a longitudinal, manual chart review. Patients with and without PAF were abstracted in a 1:2 ratio to serve as a reference gold standard for PAF status. ICES captures all publicly reimbursed diagnostic tests, interventional procedures and physician billing codes, including MRI pelvis utilization and surgical procedures associated with perianal fistulas in Ontario. Sixteen case definitions for PAF in ICES were specified a priori. Two by two contingency tables were constructed to assess the sensitivity, specificity, positive predictive value (PPV) and negative predicative value (NPV) of each case definition against the gold standard PAF status as determined by TOH data. Youden’s index and Kappa were used to select a case definition that best identified TOH PAF patients.
Results:
A total of 136 patients with active PAF and 351 without PAF were included in the linked analysis. There were a similar proportion of male patients with and without PAF (49% vs. 43%). Patients with PAF were slightly younger; 69% were aged 18–44 compared to 58% of patients without PAF. Sensitivity of the case definitions ranged from 0.44 to 0.98, and specificity from 0.45 to 1.00. A case definition that combined at least two of fistula diagnosis code, perianal surgical procedures associated with fistulas, and radiologic imaging codes of the pelvis, all within 2 years, had the best performance using Youden’s index and Kappa. It discriminated between patients with or without PAF with sensitivity of 0.80 and specificity of 0.92.

Conclusions
Using a cohort of CD patients from a single tertiary care center we derived a case definition that could accurately distinguish CD patients with and without PAF in a provincial health administrative database. Once validated this will allow for future population-based studies to assess trends in PAF.

Funding Agencies
Takeda Pharmaceuticals
A257 NEW ONSET ULCERATIVE COLITIS IN A PATIENT WITH KNOWN AUTOIMMUNE HEPATITIS TYPE 1
Authors: Hasan M , Gallinger Z 
Published: February 2020

Abstract

Background
Elevated transaminases can occur in up to 17 per cent of cases of Inflammatory Bowel Disease (IBD)1, with many cases related to concurrent autoimmune conditions of the liver. Primary Sclerosing Cholangitis (PSC) is the most common autoimmune disease of the liver that is associated with IBD. Other causes of liver inflammation in patients with IBD can include Autoimmune Hepatitis (AIH).

Aims
We aim to report a case of new onset ulcerative colitis in a patient with autoimmune hepatitis type 1 in the absence of concomitant PSC.

Methods
Case report and review of literature.

Results
A 25-year-old male with painless jaundice and was found to have Autoimmune hepatitis type 1 with typical morphological changes, positive Antinuclear antibodies and elevated IgG levels. Histopathological exam of the liver did not show any direct changes to the bile ducts to suggest PSC. The patient was started on steroids and Mycophenolate Mofetil (MMF) and developed new onset diarrhea. Colonoscopy was performed and both endoscopic and pathological findings were suggestive of likely inflammatory bowel disease, although drug induced colitis (MMF) could not be excluded.

Conclusions
We conclude that there is a link between autoimmune hepatitis with IBD, in absence of concomitant PSC.

Funding Agencies
None
A277 DISCREPANCIES IN EUS-FNA CYTOPATHOLOGY AND SURGICAL SPECIMEN PATHOLOGY FOR HIGH RISK PANCREATIC MUCINOUS CYSTIC LESIONS: A CASE SERIES
Authors: Li S , Monachese M , James P 
Published: February 2020

Abstract

Background
Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) is the primary method of sampling pancreatic cystic lesions with reported specificity near 100% for diagnosing malignancy. Discrepant positive malignant cytopathology with final surgical pathology of pancreatic cystic lesions has not previously been described.

Aims
To present a case series and review the literature regarding the implications of positive malignant cytology with discrepant surgical pathology for high risk pancreatic mucinous cystic lesions.

Methods
Patient demographics, clinical history, procedure details, pathology evaluations and follow-up were collected. A thorough literature review was performed.

Results
Three patients with high-risk pancreatic cystic lesions on cross-sectional imaging underwent EUS-FNA evaluation. None of these patients had a history of pancreatitis. Cytology was reported as positive for adenocarcinoma in all patients by separate gastrointestinal cytopathologists. All patients underwent surgical resection. The pathology for all resected specimens were reported as intraductal papillary mucinous neoplasm. The resected cysts for two patients demonstrated foci of high-grade dysplasia and the third noted low grade dysplasia. All surgical pathology underwent consensus review by three separate gastrointestinal pathologists. None of the patients were treated with adjuvant chemotherapy. All patients have been followed post-operatively with surveillance magnetic resonance imaging with no evidence of recurrence to date (median follow-up time 239 days, range 133 – 447 days).

Conclusions
This phenomenon sheds light on the potential for variable interpretations of EUS-FNA cytopathology and surgical resection pathology for high risk pancreatic cystic neoplasms. EUS-FNA may identify foci of adenocarcinoma that is not seen on surgical pathology specimens. Further research is required to examine the long-term outcomes of these patients.

Funding Agencies
None
A279 EUS-GUIDED BILIARY DRAINAGE IN MALIGNANT DISTAL BILIARY OBSTRUCTION: AN INTERNATIONAL SURVEY TO IDENTIFY BARRIERS OF TECHNOLOGY IMPLEMENTATION
Authors: Palmieri V , Ramana-Kumar A , Martel M , Forbes N , Mohamed R , Chatterjee A , Kenshil S , Desilets E , Donnellan F , Gan I , Lam E , Telford J J , Sandha G S , Teshima C W , May G , Mosko J , Paquin S , Sahai A , Barkun A N , Chen Y 
Published: February 2020

Abstract

Background
Endoscopic ultrasound-guided biliary drainage (EUS-BD) is a promising alternative to endoscopic retrograde cholangiopancreatography (ERCP) in malignant distal biliary obstruction (MDBO). Recent small randomized controlled trials comparing EUS-BD with ERCP suggest that EUS-BD achieves a similar technical success rate and safety profile while potentially being associated with lower rates of stent dysfunction However, its application in clinical practice has been impeded by various undefined barriers.

Aims
To evaluate the current practice of EUS-BD and the determinants for its clinical implementation in MDBO.

Methods
An online survey was generated using Google Forms. Five endoscopy societies have distributed the survey as of October 10th, 2019. Survey questions measured participant characteristics, EUS-BD in different clinical scenarios, and potential barriers to implementation. Descriptive statistics were calculated using frequencies, chi-square statistics were used for inferential analysis, and a standard step-wise multivariable analysis was performed to identify independent variables for and against the use of EUS-BD.

Results
To date, 102 physicians have participated in the survey (response rate 7.97%). The majority of participants are from North America (39.2%), Asia (31.4%), and Europe (19.6%). Most participants are gastroenterologists with formal therapeutic endoscopy training (66.7%), though only 28.4% have received EUS-BD training. In unresectable cancer, 85.1% of respondents favoured EUS-BD over percutaneous biliary drainage following ERCP failure (p&lt;0.0001), while in borderline resectable disease, 72.3% preferred EUS-BD. On multivariable analysis, male gender, formal training in EUS-BD, and unresectable cancer were independent variables for the use of EUS-BD. Conversely, independent discouraging factors for EUS-BD included fear of adverse events, limited high-quality data, lack of local expertise, and inadequate access to EUS technology.

Conclusions
In this international survey, it appears that EUS-BD is gaining traction, especially in the setting of unresectable disease following ERCP failure. However, barriers to implementation include the lack of high-quality data, fear for adverse events, limited experts in the field, and inadequate access to EUS technology. This suggest the need for high-quality clinical trials, increased endoscopist training in this field, and further technology development in EUS-BD in order to increase its uptake in clinical practice.

Funding Agencies
None
Dispatches from Cairo to India: Editors, Publishing Houses, and a Republic of Letters
Authors: Khan Ahmad 
Published: February 2020

Abstract
This article documents the existence of a vibrant republic of letters stretching from Cairo to Karachi in the middle of the twentieth century. On the basis of private letters, memoirs, and modern editions of classical texts, this article recreates the scholarly and personal commitments of a new class of professional editors (muḥaqqiqūn). These editors were responsible for the emergence of some of the most influential publishing houses in the Islamic world, and their contribution to the production and circulation of pre-modern texts has had a profound impact on the intellectual development of Islam in the twentieth and twenty-first centuries. They believed that cultivating a republic of letters was necessary because it served the world of learning and scholarship. In this way was fashioned a virtual community, separated by national and political borders, but united by visions of history and a shared sense of moral and intellectual duty.