bluuebunny/crossref_metadata_2025 huggingface dataset:
FEASIBILITY OF A NURSE AND DIETITIAN-LED IBD SURGICAL PREHABILITATION PROGRAM
Authors: Banty Andrea , Issokson Kelly , Fleshner Phil , Melmed Gil , Zaghiyan Karen , Ha Christina
Published: January 2023

BACKGROUND

Surgery activates catabolic pathways that lead to loss of lean body mass and physical deconditioning, which can predispose to complications and delayed healing. Prehabilitation addresses modifiable risk factors, provides nutrition and functional status optimization, and has been shown to optimize surgical outcomes after cancer and/or orthopedic surgery. This includes decreased hospital length of stay (LOS), postoperative complications, readmission rates, and accelerated return to pre-surgical functional capacity. We assessed the feasibility of a structured, multidisciplinary prehabilitation program for patients with inflammatory bowel disease (IBD) undergoing abdominal surgery.

METHODS

We developed a nurse-practitioner and dietitian-led IBD prehabilitation program for patients undergoing ileal-cecal resection (ICR) or colectomy. Perioperative nutrition and medications were addressed during two clinic visits (4 weeks before and after surgery). The Global Leadership Initiative on Malnutrition (GLIM) criteria were used to define malnutrition. Sarcopenia was defined as either (1) two standard deviations below the norm for age and gender as assessed by dynamometry or (2) skeletal muscle index (SMI) <55 cm2/m2 for males and <39 cm2/m2 for females at the L3 region as assessed by computerized tomography. Micronutrients (iron profile, vitamin D, B6, zinc) were assessed and corrected if a deficiency was found. Patients were provided personalized diet recommendations for optimizing nutrition and were counseled on preoperative carbohydrate loading, and pre- and post-operative immunonutrition (IN). We assessed post-operative outcomes including post-operative length-of-stay (LOS), 30-day readmission, and perioperative complications of infection, abscess, and leak.

RESULTS

Ten patients (70% female, mean age 41 years) completed the program between 3/2021 and 5/2022. 9 underwent ICR and 1 underwent colectomy. 9 completed IN pre-operatively (90%); 9 (90%) completed carbohydrate loading pre-operatively, and 4 (40%) completed IN post-operatively. Upon initial assessment, 6 patients (60%) had malnutrition, and among the 4 patients with sarcopenia assessments, all 4 met criteria for sarcopenia. Forty percent had at least one micronutrient deficiency. Median post-operative LOS was 3.5 days. There were no readmissions within 30 days, and one patient had a postoperative infection.

CONCLUSION

A nurse practitioner- and dietician-led structured prehabilitation program is feasible. We hypothesize that low compliance with post-operative IN was due to formula not being available for inpatients at our facility; the impact of IN on post-operative outcomes should be evaluated in future studies. Further evaluation of outcomes associated with structured, multidisciplinary prehabilitation in IBD relative to usual care is warranted.
USING R TO ADVANCE PATIENT-CENTRIC RESEARCH IN THE STUDY OF A PROSPECTIVE ADULT RESEARCH COHORT
Authors: Fehlmann Tara , Harvey Sarah , Deepak Parakkal , O'Charoen Sirimon
Published: January 2023

OBJECTIVE

IBD Plexus is a data exchange platform that houses four cohorts, including The Study of a Prospective Adult Research Cohort with IBD (SPARC IBD). SPARC IBD is a multicentered, longitudinal cohort that follows patients through their standard of care. In IBD Plexus, patient reported data (eCRF) is linked with clinical and electronic medical record (EMR) data. Biospecimens are continuously collected and have been used to generate a myriad of molecular and biomarker data. To facilitate inflammatory bowel disease (IBD) research, we built an R package ‘ibdplexus’ (https://github.com/ccf-tfehlmann/ibdplexus), with multiple functions to load, filter and subset the data in IBD Plexus. Currently, this R package focuses primarily on SPARC IBD, with a future goal to expand to incorporate other studies. Each function is designed to help understand an IBD patient’s journey including their treatment use and disease activity over time.

PRIMARY FUNCTIONS

Three main functions help navigate the prescription information from the eCRF and structured EMR data. ‘Sparc_medication_filter’ filters the prescription data to generate a dataset with medication(s) of interest from eCRF and EMR data. For long-term medications including biologics, aminosalicylates, and immunomodulators, `sparc_medication_starts’ extracts the first instance of a medication start date from eCRF and EMR data. Sparc_medication_at_index’ generates a dataset with each participant and their medication at a specified time-point (e.g., enrollment, at time of biosample collection, etc.). Another set of functions map out a patient’s disease activity over the course of their enrollment. ‘Calculate_disease_scores’ creates a list of dataframes and an optional spreadsheet containing multiple tabs with disease activity and endoscopy scores for participants. Calculations include the short Crohn’s Disease activity index and the patient reported outcome (PRO) derivations PRO2 and PRO3, as well as the simple endoscopic score for Crohn’s Disease. For ulcerative colitis patients, the disease activity measures include the 6 and 9-point Mayo score and Mayo endoscopy score. ’Sparc_scores’ generates a dataset with each SPARC participant and their disease activity scores at a specified time-point.

CONCLUSION

The ibdplexus R package has increased the speed and efficiency with which the SPARC IBD data can utilized for research projects. Twenty domains can now be easily collapsed into one table mapped to a date of interest. These reference tables are then used to complete multiple queries, reducing the time per query from up to a day to an hour. The results from the medication functions are well aligned with a subset of patients that underwent chart review. In the few cases where the medication at index date did not align, the information was only available in progress notes or other forms of unstructured EMR data.
AMINOSALICYLATE USE IN PEDIATRIC PATIENTS WITH CROHN’S DISEASE
Authors: Patel Perseus , Kaplan Jess , Moses Jonathan , Pasternak Brad , Samson Charles , Suskind David , Ali Sabina , Adler Jeremy
Published: January 2023

INTRODUCTION

Societal guidelines recommend against the use of 5-aminosalicylate (5-ASA) therapy for pediatric patients with Crohn’s Disease (pCD). Previous trials showed no benefit of 5-ASAs for inducing remission and similar one-year relapse rates when compared with placebo. Conversely, biologics are recommended as first-line therapy due to higher remission rates, corticosteroid-sparing effects, and potential to alter disease progression.

AIMS

We aimed to describe the use of 5-ASAs in pCD and the associated patterns of biologic and corticosteroid use in a large multi-center patient cohort.

METHODS

We used data from the Biologic dISContinUation sTudy (BISCUIT), a multi-center study in which retrospective medical record abstraction from 7 US centers supplemented prospectively collected data from the ImproveCareNow (ICN) Network Registry. We included patients newly diagnosed with pCD (<18 years old) and compared patients who were prescribed a 5-ASA within 90 days of diagnosis to those who were not exposed to 5-ASAs. We used Student’s t-tests, chi-squared tests, and Wilcoxon rank sum to compare baseline characteristics, including demographics (age, gender, race, ethnicity, insurance status); disease characteristics (age at diagnosis, Paris classification, concomitant liver disease, extraintestinal manifestations); and disease activity measures (labs, disease activity indices, and extraintestinal manifestations).

RESULTS

Our study included 608 patients, 142 of whom (23.4%) were treated with 5-ASAs within 90 days after CD diagnosis. At baseline, younger patients (p<0.01), those with colonic disease (L2) (p=0.03), and those with Medicaid as their primary insurance (p=0.05) were more likely to receive 5-ASAs (Table 1). There was no difference in 5-ASA use by disease severity (p=0.52). Those on 5-ASA therapy had an 84-day longer delay in initiation of their first biologic medication, with 56.1% of patients starting a biologic at least 90 days after diagnosis (p<0.001). There were no differences in corticosteroid use (p=0.08) or dietary therapy (p=0.90) (Table 2).

CONCLUSIONS

We found 5-ASA use was common in pCD and was associated with a near 4-month delay in initiating biologic therapy. These results are a call-to-action to improve guideline dissemination and examine barriers such as insurance status in the evidence-based treatment of pCD. Our future work will evaluate differences in outcomes, biologic durability, and disease complication rates between these groups.
CHARACTERIZING THE JOHNS HOPKINS INFLAMMATORY BOWEL DISEASE COHORT USING OMOP CDM
Authors: Haas Leonard , Nagy Paul , Bowring Mary , Cook Michael , Magen-Rimon Ramit , Weisshof Roni , Yanover Chen , Miller Steven
Published: January 2023

BACKGROUND

Inflammatory Bowel Disease (IBD) is an increasingly prevalent condition that results in weight loss, bloody diarrhea, and poor quality of life. Traditional population-based research on patients with IBD has involved use of relatively shallow claims data that is deficient in precise demographics. IBD research using richly detailed electronic health record (EHR) data has been difficult due to the need for laborious manual chart review to extract information, but new methods and technology allow for rapid EHR data extraction. We present here the results of the extraction of IBD patient data from our EHR into the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM).

METHODS

This study is an observational cohort study using patient health care data from our EHR extracted into the OMOP CDM. Transforming data into the standard CDM format allows for information from different databases and coding schema to be compared and aggregated. We used a de-identified dataset of all patients seen at Johns Hopkins Medicine since 2016. Our cohort of IBD, Crohn’s disease (CD), and Ulcerative Colitis (UC) patients were stratified by age, sex, race, weight, and pregnancy status. Within the cohorts, we obtained demographics, comorbidities, symptoms, labs, medications, and other data. We validated the extraction by comparison with EHR queries using Slicer/Dicer (SD).

RESULTS

There were 11,357 IBD patients including 6,512 CD patients and 4,224 UC patients. There were more female patients for both CD and UC (56.4% v 57.5%) and more white patients for both CD and UC (55.4% v 56.7%) compared to black (23.5% v 22.6%) and Asian patients (5.6% v 4.9%). CD and UC patients were treated with systemic steroids (49.1% v 51.5%), 5-ASA (24.9% v 47.2%) anti-TNF inhibitors (24.0% v 12%), IL12/23 inhibitors (8.4% v 2.7%), and JAK inhibitors (0.3% v 1.8%). Using SD queries, the percent differences were determined between the OMOP and EHR data, revealing a 0.54% difference in the number of CD patients and 10.36% difference in the number of UC patients (Table 1).

CONCLUSION

Using OMOP CDM to analyze clinical characteristics and outcomes for patients with IBD is a valuable method for obtaining de-identified patient data, reducing patient risk, and facilitating rapid creation of on-demand cohorts for multi-institutional research studies. This advantage is balanced by the lack of access to row-level data to validate cohorts. Local validation of data extraction through SD queries can allow for rapid creation of cohorts for big data research. The most significant differences between SD queries and OMOP CDM was in the calculation of prevalence of medications and race, suggesting that differing data extraction coding methods could result in queries that underestimate rates of treatment due to proprietary local coding schema.
PERSISTENCE WHILE ON LABELED MAINTENANCE DOSE AMONG BIO-EXPERIENCED PATIENTS WITH CROHN'S DISEASE INITIATED ON USTEKINUMAB COMPARED TO ADALIMUMAB
Authors: Zhdanava Maryia , Ding Zhijie , Manceur Ameur , Kachroo Sumesh , Holiday Christopher , Zhao Ruizhi , Pilon Dominic
Published: January 2023

BACKGROUND

In Crohn’s disease (CD), dose escalation on biologic therapy may be required to maintain effectiveness, while adverse events or non-response, among other factors, may lead to lack of persistence. Understanding persistence while on labeled maintenance dose is particularly important in bio-experienced patients with CD, as they may have reduced response to subsequent lines of therapy. This analysis compared persistence while on labeled maintenance dose among bio-experienced patients on ustekinumab versus adalimumab in the United States (US).

METHODS

Adults with CD initiated on ustekinumab or adalimumab (index date) between 09/23/2016 (ustekinumab approval for CD in the US) and 08/01/2019 were selected from IBM® MarketScan® Commercial Database. Patients were bio-experienced (≥1 claim for another CD-indicated biologic in the 12 months baseline period pre-index date). Patients with other auto-immune diseases at baseline were excluded. Cohorts were balanced on baseline characteristics using inverse probability of treatment weights. Persistence to the index agent while on labeled maintenance dose was defined as (1) no gaps between days of therapy supply >120 days for ustekinumab (2 x 8-week on-label maintenance dose interval) or >60 days for adalimumab (2 x days of supply mode) and (2) no dose change relative to the US label maintenance dose. It was assessed from index date until the earliest of discontinuation (event), dose change during maintenance phase (censoring), or last day of supply (censoring). Weighted Kaplan-Meier and Cox proportional hazards models adjusted for baseline classes of biologics were used to assess the outcome at 12 months post-index.

RESULTS

903 bio-experienced patients with CD were included in the ustekinumab cohort (mean age 40.9 years old; 57.1% female) and 525 in the adalimumab cohort (mean age 41.3; 56.3% female). During the baseline period, 71.1% and 72.6% used corticosteroids, 41.2% and 40.8% used immunomodulators, and 11.1% and 12.6% had a prior CD-related surgery, in the ustekinumab and adalimumab cohorts, respectively. At 12 months post-index, the probability of persisting on the index biologic while on labeled maintenance dose was higher in the ustekinumab cohort versus adalimumab cohort (78.8% vs. 67.8%; Fig. 1). Patients in the ustekinumab versus adalimumab cohort had a 71% higher rate of persistence while on labeled maintenance dose (hazard ratio [HR] 1.71; 95% confidence interval: 1.31-2.23; P-value: <0.001*).

CONCLUSIONS

Bio-experienced patients with CD initiated on ustekinumab were significantly more persistent while on labeled maintenance dose compared to patients initiated on adalimumab. These results confirm results on persistence to biologics in bio-experienced patients with CD from a prior study.
ASSESSMENT OF THE IMMUNE CELL LANDSCAPE IN INFLAMMATORY BOWEL DISEASE
Authors: Martinez Evelyn Calderon , Zevallos-Delgado Christian , Ng Wern Lynn , Gautam Seema Sharma , Joseph Maria
Published: January 2023

INTRODUCTION

Inflammatory Bowel Disease (IDB) is a chronic and sometimes refractory group of gastrointestinal conditions that can cause enormous medical and socioeconomic burdens. [1] Both, innate and adaptive immune cells play a crucial role in the pathogenesis of IBD, but the exact mechanisms are not totally well understood [2] An improved understanding of the immune cell landscape behind IBD is necessary for identifying novel diagnostic and therapeutic targets.

OBJECTIVE

The aim of this study was to evaluate and compare the immune cell composition between healthy patients and patients with Ulcerative Colitis (UC) and Chron’s Disease (CD) in peripheral blood and colon biopsy samples.

METHODOLOGY

The immune cell landscape in peripheral blood and colon biopsy samples was determined using CIBERSORT and gene expression data from the study submitted by Argmann et al obtained via Gene Expression Omnibus (peripheral blood: GSE186507 and colon biopsies: GSE193677). In this study the biopsies were obtained from ileum, colon, and rectum. T-test was used to estimate the differences among the groups.

RESULTS

The immune cell landscape of peripheral blood showed more resting T CD4 memory cells in the control group (p=0.009), while the number of activated T CD4 memory cells was greater in IBD patients (p= 0.01). The frequency of B cells naïve was higher in CD than in UC (p= 0.03), and CD8 T cells were more in UC (p=0.04). In terms of biopsies, the samples from the rectum showed the highest infiltration of immune cells. Macrophages M1 are present with higher numbers in rectum samples from CD vs UC (p=0.0026) and CD vs control group (p=8e-10).

CONCLUSIONS

The results showed significant differences in the immune cell composition among the control group, UC, and CD patients, not only in peripheral blood but also in biopsy samples. In both cases, Macrophages M1 were the most common cells found. These findings suggest that immune cell landscape could be used as a potential biomarker of the progression of IBD.
A NURSE LED INTERVENTION TO IMPROVE ACCESS TO CARE USING A TELEPHONE TRIAGE ALGORITHM
Authors: Banty Andrea , Solomon Theodore , Lee Susie , Castelan Viankail Cedillo , Parry Alyssa , Davey Joseph , Paredes Jovina , Farrior Sharmayne , Torres Daisy , Savoy Rochelle , Martirosyan Lilly , Melmed Gil
Published: January 2023

BACKGROUND

Inflammatory bowel disease is a chronic inflammatory condition for which patients may require care on a more urgent basis. Response times can be delayed when clinics are inundated with calls or when providers are not available for immediate patient care. We developed and tested an algorithm to empower nurses to effectively triage phone calls and improve access.

METHODS

We created an algorithm for nurses handling phone calls and electronic messages to a tertiary care IBD clinic. Calls were divided into four categories: Needs Immediate Response, Disease Flare, Routine and Other. IBD nurses triaged calls to facilitate urgent visits with a nurse practitioner (NP) when deemed appropriate, bypassing physician review or response. We compared the time from call-to-visit during the 3 months before and 3 months after implementation of the algorithm. We also assessed clinical outcomes of these urgently scheduled visits including visit type (in-person or virtual), and whether there was a change in dose or type of therapy, new prescription of steroids, or emergency room referral. We used the Mann Whitney U Test to assess for pre-post changes.

RESULTS

We randomly assessed 60 visits per month in the 3 months before and 3 months after the algorithm was implemented (June 1, 2022), for a total of 360 visits. The median time from call-to-visit improved from 5 days during the 3 months prior to the algorithm implementation to 3.5 days during the 3 months after algorithm implementation (p=0.016). There was no significant change in visit type pre- and post-intervention. Overall clinical interventions during these visits included therapy change (36%), a new prescription of corticosteroids (9%), new diagnostic testing ordered (67%) and ER referral (1%); these did not significantly differ in the pre- and post-intervention periods.

CONCLUSION

Utilization of a phone call triage algorithm by nurses can help improve the time from call-to-visit without involvement of a physician. Urgently scheduled NP visits result in important clinical interventions including changes to therapy and diagnostic testing. Implementation of nurse-led triage algorithms can improve access to care in a tertiary IBD clinic.
THE ONSET AND SEVERITY OF ULCERATIVE COLITIS IN IL-10 -/- MICE IS NOT DEPENDENT ON FECAL MICROBIOTA TRANSPLANTATION FROM ULCERATIVE COLITIS PATIENTS
Authors: Roy Kayla , Moncada Edward , Reddivari Lavanya
Published: January 2023

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects around 1% of the U.S population. IBD is comprised of Chron’s Disease and Ulcerative Colitis (UC), with UC having a higher incidence rate. IBD is believed to be caused by immune dysfunction and several environmental factors. Specifically in UC, bacterial dysbiosis is positively correlated with colitis severity and incidence. Thus, we propose that genetically susceptible mice colonized with human colitis-associated bacteria will exhibit early onset and increased colitis severity compared to mice colonized with fecal microbiota from healthy individuals. To test this hypothesis, germ-free IL-10-/- mice of an average age of 20 weeks were gavaged orally with fecal samples from healthy individuals and a severe colitis patient with a fecal calprotectin level of 1947 ug/mg. The Disease Activity Index (DAI) was calculated based on occult blood, weight loss, stool consistency, and grimace. DAI was used to assess colitis severity weekly in transplanted mice for eight weeks.16S rRNA sequencing analysis showed a significant difference in alpha (Shannon Index) and beta diversity (unweighted UniFrac) between the colitis patient and healthy donors indicating dysbiosis (p=.0001; p=.001). The colitis donor had a reduction in species richness. Furthermore, recipient mice clustered with the donors in their bacterial composition. Compared to mice with healthy individual-associated bacteria, colitic-associated bacteria did not significantly increase the colitis incidence or severity in IL-10 -/- mice. Furthermore, there were no significant differences in DAI scores, organ weights, and gut permeability between the treatments. Thus, this study demonstrates that bacterial dysbiosis alone is not sufficient to induce colitis in genetically predisposed mice.
REAL-WORLD EXPERIENCE FOR BIOLOGIC USE IN IBD IN THAI: A SINGLE-CENTER EXPERIENCE
Authors: Limsrivilai Julajak , Chaemsupaphan Thanaboon , Sattayalertyanyong Onuma , Subdee Nichcha , Permpim Parinya , Pausawasdi Nonthalee
Published: January 2023

BACKGROUND

Biologics have been used for the treatment of inflammatory bowel disease (IBD) worldwide; however, their use is still limited in Southeast Asia. This study aimed to describe the pattern of biologic use and outcomes in a tertiary referral center in Thailand.

METHOD

All patients with IBD who used biologics from the first case in 2012 to present in our center were enrolled. The data were prospectively collected since 2017; the data of patients before 2017 were retrospectively reviewed. The treatment outcomes comprised cumulative clinical, endoscopic, radiologic response or remission, and quality of life assessed by SIBDQ. Furthermore, the biologic persistence was reported.

RESULTS

Of 296 cases currently in the IBD clinic, 85 used biologics, including infliximab (IFX), vedolizumab (VDZ), and ustekinumab (UST). The mean age was 44.4 years, and 62% were male. Fifty-eight (68.2%) had Crohn’s disease (CD) and 27 (31.8%) had ulcerative colitis (UC). In CD, 58% had ileocolonic disease, 48% had bowel stricture, 29% had fistula, and 19% had perianal diseases. In UC, 19% had left-sided colitis, and 81% had extensive colitis. Most patients (97%) failed conventional treatment. In CD, 60%, 31%, and 8.6% use IFX, VDZ, and UST as the first biologic, respectively. While 81.5% of UC used VDZ and 18.5% used IFX. Concomitant immunomodulator was used in 77.6%. The median duration of the first biologic use was 12.6 months. The outcomes of the treatment were shown in Table 1. The overall cumulative clinical response and remission at 1 year were 94% and 63%, respectively, without significant differences among each biologic. The cumulative rate of endoscopic remission was 29%, 64%, and 82% at 1, 3, and 5 years, respectively, also without significant differences among each biologic (p=0.21). However, subgroup analysis in Crohn’s disease showed a trend of a better endoscopic remission rate for IFX and UST when compared to VDZ (p=0.15). The radiologic remission rate was only 12% of 25 patients who underwent CT enterography. The SIBDQ increased from 52.0 to 57.4 after 1 year of treatment. Thirty-six (42%) stopped the medicine. As shown in Figure 1, the overall cumulative rate of biologic discontinuation was 19% and 39% in the first and second year, respectively, without significant differences among biologics. However, the reason for drug discontinuation was different as all adverse events occurred in only patients using IFX.

CONCLUSION

Biologics were mostly used in refractory patients in this cohort. The outcomes were comparable to those previously reported in western. Current biologics could significantly improve patients’ symptoms, quality of life, and mucosal healing, but not transmural healing. The adverse events were less in newer biologics.
HLA-DQA1*05 ASSOCIATES WITH IMMUNOGENICITY AND LOSS OF RESPONSE TO ANTI-TNF THERAPY IN THE IBD POPULATION: A META-ANALYSIS
Authors: Bergstein Suzannah , Spencer Elizabeth
Published: January 2023

BACKGROUND

The human leukocyte antigen (HLA) allele group HLA-DQA1*05 has been associated with the development of antidrug antibodies (ADA) to tumor necrosis factor antagonists (anti-TNF)1 in the inflammatory bowel disease (IBD) population, except in the setting of proactive optimization2. We performed a meta-analysis to determine the prevalence of HLADQA1*05 carriage, to define the association of HLA-DQA1*05 on immunogenicity and loss of response (LOR) to anti-TNF, and to explore the impact of therapeutic drug monitoring (TDM) on this association.

METHODS

A systematic search of EMBASE, MEDLINE, Web of Science, and SCOPUS was conducted and identified 49 studies. Fourteen studies were included in the meta-analysis according to our inclusion and exclusion criteria. Two reviewers independently assessed eligibility and extracted data. Data extraction focused on the prevalence of HLADQA1*05 carriage, management style of the subjects (proactive TDM vs not), use of combination therapy with immunomodulators (IMM), and association of the variant with ADA and LOR. To examine the potential mitigating effect of management style, three forest plots were generated for each outcome including: 1. all studies, 2. studies using solely proactive TDM, and 3. studies where TDM was either not defined or not performed.

RESULTS

The prevalence of HLADQA1*05 carriage was 43.3% across the 14 manuscripts. Ten studies used data from adult populations, 2 reported on pediatrics only, and 2 reported on a mix of pediatrics and adults. Nine studies took place in Europe, and 5 occurred in North America. A little over half (57%) were abstracts. All studies included some patients on combination therapy with IMM. Data analysis confirmed that possessing the HLADQA1*05 variant leads to an increased ADA risk (OR 1.63 [95% CI: 1.35 - 1.98]). When focusing on the studies that used proactive optimization of anti-TNF therapy, the variant was no longer a risk factor for developing ADA (OR 0.37 [95% CI: 0.19 - 0.70]). Without proactive optimization, the carriage of HLADQA1*05 appears to consistently be associated with a higher risk of immunogenicity (OR 1.93 [95% CI: 1.58 - 2.36]) (Figure 1). HLADQA1*05 was also found to be a risk factor for LOR (HR 1.84 [95% CI: 1.53 - 2.22]) (Figure 2); insufficient data were available for the studies with proactive TDM on LOR.

CONCLUSION

Prevalence of HLADQA1*05 carriage is consistent across studies from both North America and Europe. This variant increases the risk of ADA and LOR to anti-TNF. However, in studies that used solely proactive TDM, variant carriage no longer conferred a risk for ADA.

1. Sazonovs A, et al. Gastro. 2020;158(1):189-199.

2. Spencer EA, et al. Gastro. 2022;162(6):1746-1748.e1743.
SPATIAL CONCORDANCE OF LEFT AND RIGHT COLON FINDINGS IN PEDIATRIC PATIENTS WITH ULCERATIVE COLITIS AFTER TREAMTENT
Authors: Thadasina Meenal , Ammoun Alwalid , Perry Sharon , Patil Nirav , Young Denise , Saab Shahrazad , Moses Jonathan
Published: January 2023

OBJECTIVES

Achieving endoscopic remission has become the preferred clinical endpoint in the care of inflammatory bowel disease (IBD) patients. This requires repeat colonoscopy in patients with ulcerative colitis (UC) after initiation of therapy. Recent adult data suggests findings in the left colon on flexible sigmoidoscopy can be highly predictive of the findings if a full colonoscopy was performed; however, pediatric data is lacking for this association. The primary aim our study to assess the accuracy of findings on the left colon with the right colon for repeat endoscopy in pediatric patients with UC.

METHODS

This was a retrospective chart review of pediatric patients with UC seen at a single, academic center between 2010-2021. Patient demographics, clinical disease activity, laboratory values and endoscopic findings were collected. The Mayo Endoscopy Score (MES) was used to assess the findings in the right and left colon by a single reader (JM). Histologic findings were assessed using the Geobes index by a pathology resident (AKA) and over-read by an attending pathologist (SS). Weighted kappa correlation was used to assess concordance between left and right colon endoscopic and histologic findings. Receiver operator curve (ROC) analysis was used to assess the accuracy of left-sided findings predicting right-sided findings.

RESULTS

We analyzed repeat endoscopies from 57 patients, of which 31 (54.4%) were male, mean age at UC diagnosis was 13.5 ± 4.1 years, 53 (93%) were Caucasian. Most common medication was oral mesalamine (67.2%) and most common distribution was pancolitis (53.4%). Mean time between index and repeat colonoscopy was 11.3 months. On repeat colonoscopy, endoscopic findings on the left colon moderately correlated with findings on the right colon [(κ = 0.53 (0.30-0.75)], similarly histologic findings for the left and right colon had a moderate correlation [(κ = 0.41 (0.17-0.64)]. Area under the ROC (AUC) was 0.89 for endoscopic remission anywhere in the colon and 0.98 for complete endoscopic healing anywhere in the colon. Longer interval between the index and follow-up colonoscopy did not affect odds of concordance.

CONCLUSIONS

We found that endoscopic and histologic severity correlated between the right and left colon for repeat assessment after initiation of biologic therapy. Left sided findings were highly accurate for endoscopic remission and complete endoscopic healing anywhere in the colon. This data suggest a flexible sigmoidoscopy could be feasible in lieu of full colonoscopy when assessing for endoscopic remission in pediatric patients with UC, to reduce the burden to the family and healthcare system. Further, prospective studies with a central reading component for histology and endoscopy are needed to validate these findings.
A PHASE II OPEN LABEL STUDY OF NEIHULIZUMAB, AN ANTI-CD162 (PSGL-1) ANTIBODY, IN PATIENTS WITH MODERATE TO SEVERE ACTIVE, ANTI-TNFα AND/OR ANTI-INTEGRIN REFRACTORY ULCERATIVE COLITIS
Authors: Rubin David , Lee Scott D , Flores Lucky , Albizu-Angulo Gustavo , Scherl Ellen , Saini Surinder , Cho Iming , Lin Shih-Yao , Reed Simona , Hall Jesse
Published: January 2023

BACKGROUND

Neihulizumab (ALTB-168) is a novel immune checkpoint agonistic antibody that binds to human CD162 (PSGL-1), and leads to downregulation of activated T-cells. Early-phase trials of neihulizumab have suggested a benefit in patients with immune conditions, including psoriasis, psoriatic arthritis and steroid-refractory acute graft-versus-host disease. Here, we report the results of a Phase II study investigating the use of neihulizumab for ulcerative colitis (UC) (ClinicalTrials.gov Identifier: NCT03298022).

AIMS

The aims of this study were to evaluate efficacy, safety, tolerability and immunogenicity of neihulizumab in patients with moderate to severe active UC who are refractory or intolerant to anti-TNFα and/or anti-integrin therapy.

METHODS

Two regimens were tested: 5 weekly IV doses plus 3 bi-weekly IV doses of 9 mg/kg neihulizumab (5 + 3 regimen), and 8 weekly IV doses plus 2 bi-weekly IV doses of 9 mg/kg neihulizumab (8 + 2 regimen). The primary efficacy outcome is the proportion of patients with clinical response at Week 12. The key secondary efficacy outcomes are the proportion of patients with clinical remission, mucosa healing, histological healing and the change in Inflammatory Bowel Disease Questionnaire (IBDQ).

RESULTS

24 subjects enrolled in this study; study demographics and baseline disease characteristics are shown in Table 1.

In the 5 + 3 regimen, 10 subjects were enrolled into this study and 2 (20%) subjects completed the study. The mean duration of study treatment exposure was 59.5 days. Among 10 enrolled subjects, 9 subjects were included in the efficacy analysis: 2 (22%) subjects achieved clinical response at Week 12 and 1 (11%) subject achieved clinical response at Week 2. The overall efficacy is summarized in Table 2. In this regimen, 9/10 (90%) subjects reported an AE: 7 (70%) subjects with AEs related to study treatment, 9 (90%) subjects with AEs that were not related to study treatment, 1 (10%) subject with an SAE not related to study treatment, and no deaths were reported in this regimen.

In the 8 + 2 regimen, 14 subjects were enrolled into this study and 9 (64%) subjects completed the study. The mean duration of study treatment exposure was 78.1 days. Among 14 enrolled subjects, 7 (50%) subjects achieved clinical response at Week 12 and 5 (36%) subjects achieved clinical response at Week 26 (Table 2). In this regimen, 13/14 (93%) of subjects reported an AE: 2 (14%) subjects with AEs related to study treatment and 12 (86%) subjects with AEs that were not related to study treatment; there was no SAE reported and no deaths.

CONCLUSIONS

This phase 2 study of neihulizumab suggest efficacy and safety signals in treatment-refractory UC that warrant further investigation.
Justifying the Protection of Legitimate Expectations in International Investment Law: Legal Certainty and Arbitrary Conduct
Authors: Henckels Caroline
Published: January 2023

This article argues that legal certainty provides the most compelling justification for recognizing legitimate expectations in international investment law, and that the prohibition on arbitrary conduct provides the most persuasive reason for their protection. After considering other rationales for recognizing legitimate expectations, the article analyses the types of government action typically arising in investment cases through the lens of legal certainty, arguing that the strength of the claim for recognizing legitimate expectations depends on the government conduct at issue, with interference with legal rights or formal decisions generating the strongest claim for recognition, and changes to laws generating the weakest claim. The article discusses the prohibition on arbitrary conduct as the relevant touchstone for protecting legitimate expectations, demonstrates that this interpretation accords with recent treaty innovations, and explains how the expected degree of legal certainty correlates with the risk of arbitrariness in relation to different types of government conduct.
Does thoracoscopic basal pyramid segmentectomy really offer functional advantages in comparison with thoracoscopic lower lobectomy?
Authors: Bongiolatti Stefano , Salvicchi Alberto , Mugnaini Giovanni , Vokrri Eduart , Viggiano Domenico , Gonfiotti Alessandro , Lavorini Federico , Voltolini Luca
Published: January 2023

OBJECTIVES

The functional impact of thoracoscopic basal segmentectomy in comparison with lower lobectomy has not been investigated in-depth and the aim of this study was to clarify this topic.

METHODS

We retrospectively analysed a cohort of patients who underwent surgery between 2015 and 2019 for non-small-cell lung cancer, peripherally located lung nodules, far enough from both the apical segment and the lobar hilum to allow an oncologically safe thoracoscopic lower lobectomy or basal segmentectomy. Pulmonary function tests (PFTs) including spirometry and plethysmography were performed 1 month after surgery and forced expiratory volume in 1 s, forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) were collected; the difference, the loss and the recovery rate of pulmonary function were calculated and compared with the Wilcoxon–Mann–Whitney test.

RESULTS

During the study period, n = 45 and n = 16 patients for video-assisted thoracoscopic surgery (VATS) lower lobectomy and for VATS basal segmentectomy, respectively, completed the study protocol: the 2 groups were homogeneous as to preoperative variables and PFT values. Postoperative outcomes were similar and PFTs revealed significant differences between postoperative forced expiratory volume in 1 s %, FVC%, ΔFVC and ΔFVC%. The loss percentage of FVC%, DLCO% and the recovery rate was better for FVC and DLCO in the VATS basal segmentectomy group.

CONCLUSIONS

Thoracoscopic basal segmentectomy seems to be associated with a more preserved lung function, maintaining more FVC and DLCO levels than lower lobectomy, and could be performed in selected cases ensuring also adequate oncological margins.
Characterization and analysis of fish waste as feedstock for biogas production
Authors: Ingabire Hortence , Ntambara Boniface , Mazimpaka Ezgad
Published: January 2023

Fish waste (FW) is biodegradable waste that remains underutilized and causes a problem to the environment since the existing disposal techniques result in health risks and environmental pollution. FW has significant potential for producing biogas that decreases the reliance on fossil fuels because it contains easily biodegradable organic matter. The physicochemical analysis of the FW such as moisture content of 61.78%, volatile solids (VS) of 93.94%, total solids of 38.21%, ash content (AC) of 0.52%, total organic carbon of 54.2%, total Kjeldahl nitrogen of 9.2% and carbon to nitrogen (C/N) ratio of 5.89% were considered and analyzed in this research. In addition, the methane potential was determined and obtained using gas detector. The results shown that the methane (CH4) content in FW was 50.12%, which was the potential feedstock of FW for biogas production. Nevertheless, the VS of FW was high, which was good for this feedstock to be easily digested as the sign of producing biogas and demonstrates 99.9985% of performance rate. Finally, the FW had a lower C/N ratio compared with other biogas production waste. Future work needs to consider co-digestion with higher C/N ratio feedstocks.
Teaching cultural competence to undergraduate pharmacy students using vignettes (case scenarios) as an innovative teaching intervention
Authors: Nkhoma Gloria , Lim Chiao Xin , Kennedy Gerard A , Stupans Ieva
Published: January 2023

Objective

Cultural competence is instrumental in reducing health equities. Addressing cultural competence at higher education level in healthcare students lays a solid cultural competence foundation for professional practice. The use of vignettes as a teaching intervention was effective because it allowed the use of role-modelling in real-life situations.

The study aimed to enhance cultural competence in undergraduate pharmacy students using a self-directed online interactive cultural competence module embedded with three vignettes (case scenarios).

Method

This study was an exploratory longitudinal mixed method (survey and written feedback) study and used a convenience sample of 90 pharmacy students at an Australian University. Students’ self-perceived transcultural self-efficacy was evaluated pre- and post-intervention using Jeffreys’ Transcultural Self-Efficacy Tool (TSET) which is a validated outcome measure.

Key findings

Vignettes were effective in teaching cultural competence as shown by significant (P < 0.0005) changes pre- to post-intervention in cognitive, practical and affective domains scores using TSET. The affective domain had the least positive mean score change. There was no significant association between any of the demographic factors such as age, gender or birthplace/parents’ birthplace and changes in any of the three domains. Cronbach’s alpha of >0.90 in all domains confirmed the test’s internal consistency and reliability.

Conclusions

The findings were indicative of the students’ positive receptivity to learning cultural competence and that they had a well-developed understanding of cultural competence. Further research is needed to determine why most cultural competence teaching methods produce little or no meaningful change in enhancing the affective domain.
Tautological classes on low-degree Hurwitz spaces
Authors: Canning Samir , Larson Hannah
Published: January 2023

Let ${\mathcal {H}}_{k,g}$ be the Hurwitz stack parametrizing degree $k$, genus $g$ covers of ${\mathbb {P}}^{1}$. We define the tautological ring of ${\mathcal {H}}_{k,g}$ and we show that all Chow classes, except possibly those supported on the locus of “factoring covers,” are tautological up to codimension roughly $g/k$ when $k \leq 5$. The set-up developed here is also used in our subsequent work [6], wherein we prove new results about the structure of the Chow ring for $k \leq 5$.
In vitroactivity of isavuconazole against clinically relevantTrichosporonspecies: a comparative evaluation of EUCAST broth microdilution and MIC Test Strip methods
Authors: Francisco Elaine Cristina , Dieleman Chendo , Hagen Ferry , Colombo Arnaldo Lopes ,   Trichosporon Brazilian Network, Chaves Guilherme M , Mendes Ana Verena A , de Oliveira Silva Marcio , de Andrade Barberino Maria Goreth , Neves Rejane Pereira , Botura Monica Borges , Hahn Rosane C , de Almeida Junior João Nóbrega , Ponzio Vinicius , de Tarso O e Castro Paulo , Guimarães Thais , Santos Daniel Wagner , de Miranda Bianca Grassi , Silva Ivan Leonardo A França E , Carlesse Fabianne , Ramos Jéssica Fernandes , Queiroz-Telles Flávio , Aquino Valério Rodrigues , Motta Fabio Araújo , Schwarzbold Alexandre Vargas , Perozin Jamile Sardi
Published: January 2023

Objectives

To evaluate the in vitro activity of isavuconazole on 154 clinical and reference strains of Trichosporon asahii, Trichosporon asteroides, Trichosporon coremiiforme, Trichosporon faecale and Trichosporon inkin by using the EUCAST broth microdilution method (BMD) and Liofilchem MIC Test Strips (MTS).

Methods

Antifungal susceptibility testing for isavuconazole, fluconazole, voriconazole and posaconazole was assessed by EUCAST E.DEF 7.3.2. MIC values of isavuconazole obtained by BMD after 48 h of incubation were compared with MTS MICs after 24 and 48 h of incubation.

Results

T. asahii and T. asteroides showed the highest isavuconazole MIC90 values (0.5 mg/L). In clinical isolates, T. asahii exhibited the highest MIC90 values (0.5 mg/L) compared with non-T. asahii (0.06–0.25 mg/L). The five non-WT T. asahii isolates for fluconazole, voriconazole and posaconazole also exhibited high MICs of isavuconazole (≥0.5 mg/L). A better correlation between MTS and BMD MICs was observed after 24 h incubation for all species tested. MTS measurements performed at 48 h increased by at least 122% the number of isolates with >2 dilutions compared with the standard method.

Conclusions

Isavuconazole exhibited variable in vitro activity among the Trichosporon species tested, showing higher or equal MICs than the other azoles. The five non-WT T. asahii clinical isolates tested also exhibited high isavuconazole MICs, suggesting the occurrence of triazole cross-resistance. Our MTS data indicate that there is no advantage in extended reading time for MTS from 24 to 48 h for Trichosporon yeasts.
Exploration of plasma metabolite levels in healthy nursery pigs in response to environmental enrichment and disease resilience
Authors: Dervishi Elda , Bai Xuechun , Cheng Jian , Fortin Frederic , Dyck Mike K , Harding John C S , Seddon Yolande M , Dekkers Jack C M , Canada PigGen , Plastow Graham
Published: January 2023

The purpose of this study was to explore plasma metabolite levels in young healthy pigs and their potential association with disease resilience and estimate genetic and phenotypic correlation with the change in lymphocyte concentration following disease challenge. Plasma samples were collected from 968 healthy nursery pigs over 15 batches at an average of 28 ± 3.23 d of age. Forty-four metabolites were identified and quantified by nuclear magnetic resonance. Pigs were then introduced into a natural disease challenge barn, and were classified into four groups based on the growth rate of each animal in the grow-to-finish phase (GFGR) and treatment rate (TR): resilient (RES), average (MID), susceptible (SUS), and dead (pigs that died before harvest). Blood samples were collected from all pigs before and 2 wk after disease challenge and complete blood count was determined. Environmental enrichment (inedible point source objects) was provided for half of the pigs in seven batches (N = 205) to evaluate its impact on resilience and metabolite concentrations. Concentration of all metabolites was affected by batch, while entry age affected the concentration of 16 metabolites. The concentration of creatinine was significantly lower for pigs classified as “dead” and “susceptible” when compared to “average” (P < 0.05). Pigs that received enrichment had significantly lower concentrations of six metabolites compared with pigs that did not receive enrichment (P ≤ 0.05). Both, group classification and enrichment affected metabolites that are involved in the same pathways of valine, leucine, and isoleucine biosynthesis and degradation. Resilient pigs had higher increase in lymphocyte concentration after disease challenge. The concentration of plasma l-α-aminobutyric acid was significantly negatively genetically correlated with the change in lymphocyte concentration following challenge. In conclusion, creatinine concentration in healthy nursery pigs was lower in pigs classified as susceptible or dead after disease challenge, whilst l-α-aminobutyric may be a genetic biomarker of lymphocyte response after pathogen exposure, and both deserve further investigation. Batch, entry age, and environmental enrichment were important factors affecting the concentration of metabolites and should be taken into consideration in future studies.
Post-operative progress of arm abduction function and rate of lymph node metastasis around the region of the accessory nerve: a multicentre prospective observational study
Authors: Tomioka Toshifumi , Beppu Takeshi , Onitsuka Tetsuro , Fujimoto Yasushi , Kawabata Kazuyoshi , Matsuura Kazuto , Fujii Takashi , Hayashi Ryuichi , Asakage Takahiro
Published: January 2023

Objective

Although neck dissection is an essential technique in the surgical treatment of head and neck carcinoma, arm abduction disorders occurring after neck dissection reduce the patient’s quality of life.

Methods

We prospectively evaluated the rate of lymph node metastasis in Levels IIB and V in head and neck cancer patients who underwent neck dissection at eight centres in Japan. In addition, post-operative arm abduction disability was classified according to functional assessment values at 1 month post-operatively, and the rate of maintained function at 6 and 12 months was evaluated.

Results

Lymph node metastasis occurred in Level IIB in 12 of 242 cases (4.9%) and in Level V in 5 cases (2.1%) during the 12-month post-operative course. In patients with preservation of the ipsilateral accessory nerve, arm abduction function was maintained in 142 of 209 patients (67.9%) at 12 months after surgery. Post-operative radiotherapy and Level V dissection had no statistically significant effect on the recovery of arm abduction function. Level V dissection caused a temporary loss of abduction function post-operatively. A higher arm abduction test score at 1 month post-operatively was associated with a higher rate of subsequent ability to maintain arm abduction function.

Conclusions

In patients classified as cN0, metastatic rate at Levels IIB and V was low. In this cohort, omitting Level V dissection may be an option in strategies aimed at maintaining arm abduction function.