bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Procedures for Evaluating Laboratory Performance in External Quality Assessment Schemes for Lead in Blood and Aluminum in Serum Demonstrates the Need for Common Quality Specifications
Authors: Taylor Andrew , Angerer Jurgen , Claeys Francoise , Kristiansen Jesper , Mazarrasa Olav , Menditto Antonio , Patriarca Marina , Pineau Alain , Schoeters Ilse , Sykes Christophe , Valkonen Sinikka , Weykamp Cas
Published: January 2020

Background: The different scoring methods used by eight European External Quality Assessment Schemes (EQASs) for occupational and environmental laboratory medicine were compared to develop suitable quality specifications as a step toward harmonization.

Methods: Real results for blood lead and serum aluminum assays, reported by participants in Italian and United Kingdom EQASs, were evaluated according to individual scheme scoring criteria. The same results were then used to produce z scores using scheme-based between-laboratory SDs as the estimate of variability to determine whether simple performance-derived quality specifications produced better agreement among schemes.

Results: The schemes gave conflicting assessments of participants’ performance, and participants judged to be successful by one scheme could be defined as performing inadequately by another. An approach proposed by Kenny et al. (Scand J Clin Lab Invest 1999;59:585), which uses clinical inputs to set targets for analytical imprecision, bias, and total error allowable, was then used to elaborate quality specifications.

Conclusions: We suggest that the CLIA ′88 recommendations for blood lead (± 40 μg/L or ± 10% of the target concentration, whichever is the greater) could be used as a quality specification, although a revision to ± 30 μg/L or ± 10% is recommended. For serum aluminum, a suitable quality specification of ± 5 μg/L or ± 20% of the target concentration, whichever is the greater, is suggested. These specifications may be used to compare laboratory performance across schemes.
Clinical Performance of an In-Line, ex Vivo Point-of-Care Monitor: A Multicenter Study
Authors: Billman Glenn F , Hughes Amy B , Dudell Golde G , Waldman Elizabeth , Adcock Lisa M , Hall Dan M , Orsini Edmund N , Koska Adolph J , Van Marter Linda J , Finer Neil N , Kulhavy Jeff C , Feld Ronald D , Widness John A
Published: January 2020

Background: The management of critically ill infants and neonates includes frequent determination of arterial blood gas, electrolyte, and hematocrit values. An objective of attached point-of-care patient monitoring is to provide clinically relevant data without the adverse consequences associated with serial phlebotomy.

Methods: We prospectively determined the mean difference (and SD of the difference) from laboratory methods of an in-line, ex vivo monitor, the VIA LVM Blood Gas and Chemistry Monitoring System® (VIA LVM Monitor; Metracor Technologies, Inc.), in 100 critically ill neonates and infants at seven children’s hospitals. In doing so, we examined monitor stability with continuous use. In vivo patient test results from laboratory benchtop analyzers were compared with those from the VIA LVM Monitor on paired samples. In a separate in vitro comparison, benchtop analyzer and monitor test results were compared on whole-blood split samples.

Results: A total of 1414 concurrent, paired-sample measurements were obtained. The mean differences (SD of differences) from laboratory methods and r values for the combined data for the VIA LVM Monitor from the seven sites were 0.001 (0.026) and 0.97 for pH, 0.7 (3.6) mmHg and 0.94 for Pco2, 4.2 (9.6) mmHg and 0.98 for Po2, 0.0 (2.9) mmol/L and 0.87 for sodium, 0.1 (0.2) mmol/L and 0.96 for potassium, and 0.3% (2.9%) and 0.90 for hematocrit. Performance results were similar among the study sites with increasing time of monitor use and between in vivo paired-sample and in vitro split-sample test results.

Conclusion: The VIA LVM Monitor can be used to assess critically ill neonates and infants.
Reagent-free, Simultaneous Determination of Serum Cholesterol in HDL and LDL by Infrared Spectroscopy
Authors: Liu Kan-Zhi , Shaw R Anthony , Man Angela , Dembinski Thomas C , Mantsch Henry H
Published: January 2020

Background: The purpose of this study was to assess the feasibility of infrared (IR) spectroscopy for the simultaneous quantification of serum LDL-cholesterol (LDL-C) and HDL-cholesterol (HDL-C) concentrations.

Methods: Serum samples (n = 90) were obtained. Duplicate aliquots (5 μL) of the serum specimens were dried onto IR-transparent barium fluoride substrates, and transmission IR spectra were measured for the dry films. In parallel, the HDL-C and LDL-C concentrations were determined separately for each specimen by standard methods (the Friedewald formula for LDL-C and an automated homogeneous HDL-C assay). The proposed IR method was then developed with a partial least-squares (PLS) regression analysis to quantitatively correlate IR spectral features with the clinical analytical results for 60 randomly chosen specimens. The resulting quantification methods were then validated with the remaining 30 specimens. The PLS model for LDL-C used two spectral ranges (1700–1800 and 2800–3000 cm−1) and eight PLS factors, whereas the PLS model for HDL-C used three spectral ranges (800–1500, 1700–1800, and 2800–3500 cm−1) with six factors.

Results: For the 60 specimens used to train the IR-based method, the SE between IR-predicted values and the clinical laboratory assays was 0.22 mmol/L for LDL-C and 0.15 mmol/L for HDL-C (r = 0.98 for LDL-C; r = 0.91 for HDL-C). The corresponding SEs for the test spectra were 0.34 mmol/L (r = 0.96) and 0.26 mmol/L (r = 0.82) for LDL-C and HDL-C, respectively. The precision for the IR-based assays was estimated by the SD of duplicate measurements to be 0.11 mmol/L (LDL-C) and 0.09 mmol/L (HDL-C).

Conclusions: IR spectroscopy has the potential to become the clinical method of choice for quick and simultaneous determinations of LDL-C and HDL-C.
Homogeneous Amplification and Mutation Scanning of the p53 Gene Using Fluorescent Melting Curves
Authors: Millward Haleigh , Samowitz Wade , Wittwer Carl T , Bernard Philip S
Published: January 2020

Background: In malignancy, gene mutations frequently occur in tumor suppressor genes such as p53 and are sporadically located. We describe a homogeneous method for amplification and mutation scanning, and apply the method to the p53 gene.

Methods: Using a series of overlapping fluorescein-labeled oligonucleotides complementary to a wild-type p53 sequence, we detected somatic mutations in colorectal cancers by aberrant probe:target melting temperatures (Tm). The probes were designed so that fluorescence decreased on target annealing as a result of deoxyguanosine quenching. Probes were walked along the sequence to be scanned, using two to three probes per cuvette and placing overlapping probes in separate reactions. After amplification, the reaction was cooled to anneal probes and then slowly heated (0.1 °C/s) while fluorescence was continuously monitored. Somatic mutations in tumor tissue were detected by changes from a characteristic wild-type melting curve profile using leukocyte DNA.

Results: A complete scanning of the DNA binding domain (exons 5–8) of the p53 gene was completed in a single run (∼30 min) starting from genomic leukocyte DNA. To show proof-of-principle, p53 exons 6–8 from 63 colon cancers were probe-scanned and showed 100% agreement with direct sequencing for detecting alterations from wild-type DNA.

Conclusions: p53 mutation scanning by single-labeled hybridization probes is a homogeneous, rapid, and sensitive method with application in both research and clinical diagnostics.
Genotyping of the Common Haptoglobin Hp 1/2 Polymorphism Based on PCR
Authors: Koch Werner , Latz Wolfgang , Eichinger Marianne , Roguin Ariel , Levy Andrew P , Schömig Albert , Kastrati Adnan
Published: January 2020

Background: A genetically defined molecular heterogeneity of haptoglobin, characterized by the major phenotypic forms Hp 1-1, Hp 2-1, and Hp 2-2, has been associated with distinct clinical manifestations. To enable the use of DNA samples for the study of this polymorphism, we established a haptoglobin genotyping method based on PCR.

Methods: Taking advantage of the selectivity of PCR, we amplified DNA segments specifically representing haptoglobin alleles Hp 1 and Hp 2 from genomic DNA. The products were analyzed by agarose gel electrophoresis. Haptoglobin phenotyping of plasma samples was performed by polyacrylamide gel electrophoresis and peroxidase staining.

Results: Exploiting the known size difference between Hp 1 and Hp 2, we amplified allele-specific DNA molecules with one pair of oligonucleotide primers. As an alternative, we used separate primer pairs to generate amplification products indicative of alleles Hp 1 and Hp 2. Because of the primer design, genotype determination was not compromised by sequence variations specifying haptoglobin allele subtypes S and F. For the same reason, the sequence similarity between the haptoglobin gene and the haptoglobin-related gene did not interfere with the accuracy of genotyping. Analysis with restriction enzymes demonstrated the authenticity of the allele-specific DNA products. Haptoglobin DNA genotyping and protein phenotyping, performed in parallel, yielded fully corresponding results. In a group of 249 individuals, the haptoglobin genotype distribution was as follows: 14.5% Hp 1-1, 48.2% Hp 2-1, and 37.3% Hp 2-2.

Conclusion: The new method can be used for genotyping of a common haptoglobin polymorphism.
Expanding Tiny Earth to genomics: a bioinformatics approach for an undergraduate class to characterize antagonistic strains
Authors: Basalla Joseph , Harris Ryan , Burgess Elizabeth , Zeedyk Nicholas , Wildschutte Hans
Published: January 2020

The evolution of multidrug resistant pathogens and the diminishing supply of effective antibiotics are global crisis. Tiny Earth (TE) is undergraduate curriculum that encourage students to pursue science careers by engagement in authentic drug discovery research. Through the TE program, students identify environmental strains that inhibit other bacteria. Although these isolates may produce antibiotics based on the antagonistic phenotype, understanding the activity in regard to genome content remains elusive. Previously, we developed a transposon mutagenesis module for use with TE to identify genes involved in antibiotic production. Here, we extend this approach to a second semester undergraduate course to understand the origin of antagonism and genome diversity. Using a bioinformatics strategy, we identified gene clusters involved in activity, and with annotated genomes in hand, students were able to characterize strain diversity. Genomes were analyzed using different computational tools, including average nucleotide identity for species identification and whole genome comparisons. Because the focus of TE involves the evolution of drug resistance, predicted products in strains were identified and verified using a drug susceptibility assay. An application of this curriculum by TE members would assist in efforts with antibiotic discovery.
Metabolites Associated with Walking Ability Among the Oldest Old from the CHS All Stars Study
Authors: Marron Megan M , Wendell Stacy G , Boudreau Robert M , Clish Clary B , Santanasto Adam J , Tseng George C , Zmuda Joseph M , Newman Anne B
Published: January 2020

Background

Low walking ability is highly prevalent with advancing age and predicts major health outcomes. Metabolomics may help to better characterize differences in walking ability among older adults, providing insight into potentially altered molecular processes underlying age-related decline in functioning. We sought to identify metabolites and metabolic pathways associated with high versus low walking ability among 120 participants ages 79–95 from the CHS All Stars study.

Methods

Using a nested case–control design, 60 randomly selected participants with low walking ability were matched one-to-one on age, gender, race, and fasting time with 60 participants with high walking ability. High versus low walking ability was defined as being in the best versus worst tertiles for both gait speed (≥0.9 vs <0.7 m/s) and the Walking Ability Index (7–9 vs 0–1). Using liquid chromatography-mass spectrometry, 569 metabolites were identified in overnight-fasting plasma.

Results

Ninety-six metabolites were associated with walking ability, where 24% were triacylglycerols. Triacylglycerols that were higher among those with high walking ability consisted mostly of polyunsaturated fatty acids, whereas triacylglycerols that were lower among those with high walking ability consisted mostly of saturated or monounsaturated fatty acids. Body composition partly explained associations between some metabolites and walking ability. Proline and arginine metabolism was a top pathway associated with walking ability.

Conclusion

These results may partly reflect pathways of modifiable risk factors, including excess dietary lipids and lack of physical activity, contributing to obesity and further alterations in metabolic pathways that lead to age-related decline in walking ability in this older adult cohort.
An approximate fast-mapping approach to the surface NMR forward problem
Authors: Grombacher Denys , Kass Mason Andrew , Auken Esben , Larsen Jakob Juul
Published: January 2020

A surface nuclear magnetic resonance (NMR) forward model based on the full-Bloch equation improves the accuracy of the forward response given an arbitrary excitation pulse and a wider range of relaxation conditions. However, the full-Bloch solution imposes a significant slowdown in inversion times compared to the traditional forward model. We present a fast-mapping approach capable of dramatic increases in inversion speeds with minimal sacrifices in forward response accuracy. We show that the look-up tables used to calculate the transverse magnetization and the full surface NMR forward response are smoothly varying functions of the underlying T2* and T2 values. We exploit this smoothness to form a polynomial representation of the look-up tables and surface NMR forward responses, where a fast-mapping approximation of each are reduced to a simple matrix multiplication. Accurate approximations with less than 1 per cent error can be produced using 21 coefficient representations of the look-up tables for each B1 value and for the signal expected from a particular depth layer for a particular pulse moment. In essence, the proposed fast-mapping approach front-loads all expensive calculations and stores the results in a compressed form as a coefficient matrix containing less than a half a million elements. This allows all subsequent inversions to be performed at greatly improved speeds.
The centre in British politics since 1906
Authors: Nuttall Jeremy
Published: January 2020

The modern British ideological centre has been neglected and its impact underestimated. This article highlights the persistence of the centre’s moderating influence and its progressive, indeed at times radical, contribution. This ideological dynamism emanated from centrists’ synthesis of objectives often considered to conflict. Notably, centrists sought social justice alongside individual aspiration, albeit that this cross-ideological marriage was partial and incomplete. The article also examines the relationship between the centre and the people – presently portrayed as one of popular disconnection from an aloof elite. Yet, centrists have received considerable electoral sustenance from voters, and in turn demonstrated an appreciation of the contradictory ‘mix’ in many people, conservatism and progressivism in complex co-existence. Centrist history points to the contemporary political challenge as being one of raising the sights of a collective national ‘us’, rather than demonizing a variously targeted ‘other’.
P095 AMISELIMOD SAFETY PROFILE FOR CROHN’S DISEASE, STRATIFIED BY PREVIOUS TREATMENT WITH ANTI-TNF AGENTS
Authors: D’Haens Geert R A M , Slatkin Neal , Israel Robert , Heimanson Zeev
Published: January 2020

Background

Anti-TNF agents are an established treatment modality for ulcerative colitis (UC); however, as many as 30% of patients do not respond to anti-TNF agents, and almost 50% of responders lose clinical benefits after a year of treatment. Furthermore, numerous safety concerns are associated with long-term use of anti-TNF agents. An alternative treatment in development for autoimmune-mediated diseases, including Crohn’s disease (CD) and UC, are sphingosine 1-phosphate receptor modulators such as amiselimod (AMS).

Methods

The safety and efficacy of oral AMS 0.4 mg/d in adults with moderate to severe active CD over 14 wks were evaluated in a multicenter, randomized, double-blind, parallel-group, placebo (PBO)-controlled (DBPC), phase 2a clinical trial, followed by an open-label extension (OLE) study with AMS for up to 36 wks. Patients had previously used anti-TNF-α agents, immunosuppressants, or corticosteroids. Safety data (adverse events [AEs]) were stratified by patients with and without prior anti-TNF treatment.

Results

Of the 78 patients randomized 1:1 to receive AMS (n=40) or PBO (n=38), 78% (n=61) completed the DBPC treatment phase. Of those patients continuing into the OLE, 26 patients (AMS/AMS [n=14]; PBO/AMS [n=12]) completed it. Oral AMS 0.4 mg for 12 wks did not have a significant effect on clinical disease activity in CD. Patients previously treated with anti-TNF agents had more serious AEs (SAEs) (27% AMS [n=22]; 4% PBO [n=25]) than did patients without prior anti-TNF treatment (0 AMS and 0 PBO patients). Relative numbers of treatment-emergent AEs (TEAEs) were similar between groups receiving prior anti-TNF agents (68% AMS [n=22]; 68% PBO [n=25]) and no prior treatment (65% AMS [n=17]; 31% PBO [n=13]). There was a trend toward more mild TEAEs and less severe AEs in patients not previously treated with anti-TNF agents compared to those previously treated. Conversely, in the OLE, patients not previously treated with anti-TNF agents had more AEs (100% AMS/AMS [n=11]; 67% PBO/AMS [n=9]) than those with prior treatment (60% AMS/AMS [n=10]; 87% PBO/AMS [n=16]). All of these TEAEs were mild or moderate. In the OLE, only 1 patient receiving AMS/AMS with no prior anti-TNF treatment had an SAE versus no patients with prior treatment.

Conclusions

Previous treatment with anti-TNF agents did not significantly affect the TEAEs associated with AMS. While SAEs appeared to be more common in previously treated patients in the DBPC, patients had fewer AEs during the OLE. This analysis suggests that previous treatment with anti-TNF agents should be considered when assessing the AE profile of AMS in future trials.
P152 EVALUATING THE EFFICACY OF GLUTAMATE CARBOXYPEPTIDASE II (GCPII) INHIBITORS IN “WILD-TYPE” MICE: LESSONS LEARNED FROM THE DEDICATOR OF CYTOKINESIS 2 MUTANT MOUSE
Authors: Peters Diane , Norris Lauren , Slusher Barbara
Published: January 2020

Background

Glutamate carboxypeptidase II (GCPII) is highly upregulated in human IBD and is a therapeutic target under active investigation by our laboratory. We recently published that a spontaneously occurring loss-of-function mutation in dedicator of cytokinesis 2 (Dock2Hsd) that was present in commercially-purchased “wild-type” C57Bl6/NHsd mice increased their sensitivity to DSS-colitis and caused them to closely resemble human IBD with respect to GCPII. The DSS-exposed Dock2Hsd mice had significantly elevated colon GCPII activities and were sensitive to treatment with the GCPII inhibitor, 2-PMPA. We hypothesized that if colitis of the same severity were to be induced in Dock2WT mice, that they would also exhibit heightened colon GCPII activity and would be equally sensitive to 2-PMPA treatment.

Methods

DSS-colitis was induced in weight-, age- and gender-matched C57Bl/6NHsd mice (Dock2Hsd and Dock2WT). Increasing concentrations of DSS were utilized (2.5%-4.0%) and disease activity index was monitored daily. Mice received once daily treatment with vehicle or GCPII inhibitor 2-PMPA (IP).

Results

With increased DSS concentrations (4%), a severe colitis could be established in the Dock2WT mice which closely resembled the disease seen in Dock2Hsd mice induced with 2.5% DSS. Interestingly, despite similarity in DAI scores and disease progression, the GCPII activity in colons of Dock2WT mice (4% DSS) remained significantly lower than that of Dock2Hsd mice (2.5% DSS) (p<0.001, t-test). Further, while 2-PMPA was effective in both groups, higher systemic doses were required in the IBD-resistant Dock2WT mice.

Conclusions

Following identification that the spontaneously occurring mutation Dock2Hsd influences murine DSS-colitis sensitivity and alters the activity of our therapeutic target protein, GCPII, in the colon, we sought to re-establish our DSS model using Dock2WT mice. While we were successfully able to recapitulate disease severity in the Dock2WT mice by increasing the DSS concentration from 2.5% to 4%, the underlying disease biology was not conserved. Despite having comparable DAI scores at study termination, Dock2WT mice had decreased GCPII activity in their colons relative to Dock2Hsd mice and were less sensitive to inhibition with the GCPII inhibitor, 2-PMPA. These data caution that target protein expression must be verified even with subtle changes to experimental method when utilizing the DSS-colitis model.
P157 FBXO3-FBXL2 AXIS MODULATORS AS A NOVEL CLASS OF ORAL SMALL MOLECULE COMPOUNDS FOR THE TREATMENT OF CROHN’S DISEASE
Authors: Angeli Franca , Wyborski Russell , Chen Bill , Mallampalli Rama , Lark Michael
Published: January 2020

Background

Ubiquitination is a common post-translational modification, tagging proteins for degradation. The ubiquitin proteasome system is activated in Crohn’s Disease (CD), and modulation of its components might be a novel strategy for therapeutic intervention to control inflammation. The conjugation of ubiquitin to a target protein is orchestrated by a series of enzymatic reactions, the last step being catalyzed by a selective ubiquitin E3 ligase. Among ubiquitin E3 ligases, Fbxl2 serves as a sentinel gatekeeper to limit inflammation by targeting and enhancing the degradation of tumor necrosis factor receptor associated factors (TRAF) proteins, which link cell surface signals (through NFkB signaling) to cytokine secretion. In addition, Fbxl2 controls the ubiquitination of the inflammasome, NOD-like receptor protein 3 (NLRP3), which mediates the release of interleukin (IL)1β and IL18 (Fig.1). Fbxl2 protein itself is ubiquitinated and degraded by another protein, called Fbxo3. Inhibition of Fbxo3 results in increased Fbxl2 levels and decreased TRAF and NLRP3. Individuals with a natural occurring polymorphism within Fbxo3V221Ihave decreased lipopolysaccharide(LPS)-induced cytokine (TNFα, IL1β & IL6) production, Fbxo3 and TRAF levels and increased Fbxl2, providing human genetic target validation for Fbxo3-Fbxl2 axis modulation in inflammatory conditions. BC1261 is a first-in-class, selective, orally available Fbxo3 inhibitor in clinical development for the treatment of CD.

Methods and Results

In vitro data demonstrated that BC1261 binds to Fbxo3, prevents Fbxo3/Fbxl2 association and produces a concentration-dependent inhibition of LPS-induced release of TNFα and IL1β from human peripheral blood mononuclear cells. In an acute DSS-mouse model, administration of BC-1261 via drinking water ad libitum (30 μg/ml) or by daily intraperitoneal (IP) injection (150 μg) for 5 days resulted in the attenuation of the shortening of colonic length, tissue damage (Fig2.A), and TNFα and IL6 tissue levels (Fig.2B). In a repeated DSS-mouse model, BC-1261 (10 mg/kg bid) given orally for 19 days was comparable to the positive control (anti-p40) in the DAI composite (Fig2.C), stool consistency (Fig2.D), and histopathology score in the proximal colon (Fig2.E). BC-1261 also lead to clinically relevant reductions on endoscopy score (Fig2.F).

Conclusion

BC1261, a Fbxo3 inhibitor, was efficacious in both acute and chronic preclinical models of colitis. Taken together, these results suggest the potential utility of selective Fbxo3-Fbxl2 modulation in the treatment of CD.
P068 MIRIKIZUMAB TREATMENT IMPROVES BOWEL MOVEMENT URGENCY IN PATIENTS WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
Authors: Dubinsky Marla , Lee Scott D , Panaccione Remo , Abreu Maria , Vermeire Séverine , Lissoos Trevor , Morris Nathan , Arora Vipin , Dong Yan , Naegeli April , Sands Bruce
Published: January 2020

Background

Mirikizumab (miri; LY3074828) is a humanized monoclonal antibody directed against the p19 subunit of IL-23, which demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial (NCT02589665) in patients with ulcerative colitis (UC). Bowel movement urgency is one of the most bothersome symptoms experienced by patients with UC with an often-overlooked impact of their quality of life (QoL). Here we show the effect of miri on patient-reported urgency.

Methods

Patients were randomized 1:1:1:1 to receive intravenous placebo (PBO), miri 50mg or 200mg with possibility of exposure-based dose increases, or fixed miri 600mg every 4 weeks (Q4W), with efficacy assessment at Week 12. Patients who achieved clinical response to miri at Week 12 (decrease in 9-point Mayo score ≥ 2 points and ≥ 35% from baseline, and either a decrease in rectal bleeding (RB) subscore ≥1 or RB subscore of 0 or 1) were re-randomized 1:1 to double-blind maintenance treatment with miri 200mg subcutaneously (SC) every 4 (Q4W) or 12 (Q12W) weeks and were treated through Week 52. Patients reported daily symptoms, including absence or presence of bowel movement urgency. Logistic regression analysis was conducted to evaluate the treatment differences in absence of urgency among patients who had urgency at baseline for the first 12 weeks, with absence of urgency defined as no urgency symptom for three consecutive days prior to each scheduled visit. The proportion of patients with no urgency was calculated for the maintenance period among patients who had urgency at baseline and reached clinical response at Week 12, irrespective of urgency status at Week 12. Patients who had missing urgency data were imputed as having experienced urgency.

Results

At Week 12 patients in the 200mg and 600mg miri groups showed significantly higher rates of achieving absence of urgency compared to the PBO group (PBO: 10/55, 18.2% [CI: 8.0–28.4]; miri 50mg: 18/59, 30.5% [CI: 18.8–42.3]; 200mg: 22/56, 39.3% [CI: 26.5, 52.1], p=0.016; 600mg: 22/51, 43.1% [CI: 29.5, 56.7], p=0.006, Figure 1). Induction clinical responders who continued onto the maintenance period sustained this improvement in urgency with minimal variation (Figure 2).

Conclusion

In patients who reported bowel movement urgency at baseline, mirikizumab treatment resulted in significantly higher proportions of patients with no bowel movement urgency compared to placebo at Week 12, with numerical improvement observed as early as Week 4 and statistically significant improvement by Week 8. The reduction in bowel movement urgency was sustained through Week 52.
P056 DISCRIMINATORY ROLE OF ANTI-MICROBIAL ANTIBODIES IN DIAGNOSIS OF CROHN’S DISEASE AGAINST NORMAL AND OTHER MIMICS
Authors: Zhang Peilin , Minardi Lawrence , Kuenstner J Todd , Zekan Steve , Kruzelock Rusty
Published: January 2020

Anti-microbial antibodies have been found useful for diagnosis of Crohn’s disease (CD) and Sjogren’s syndrome (Sjo). These antibodies are also elevated in other autoimmune disease such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and multiple sclerosis (MS). The prevalence of these antibodies in the normal healthy population is unknown. We set to survey the normal population for these anti-microbial antibodies in comparison with Crohn’s disease and others. Totally 288 blood samples from the donor units of the leukocyte-reduced red blood cells from the American Red Cross were examined for the presence of anti-microbial antibodies using direct ELISA assays established in our laboratory using the recombinant microbial protein antigens. Our results showed that the prevalence of RPOB antibody in the normal blood donor population is 2.4% (7 positive of 288 samples). The prevalence of EF-G antibody is 4.2% (12 positive of 288 samples), ATP5a 5.2% (15 positive), Hsp65 2.8% (8 positive), EF-Tu 5.6% (16 positive), and NMPC 4.2% (12 positive). Meanwhile, in 109 patients with Crohn’s disease and 28 patients with Sjogren’s syndrome, these anti-bacterial antibodies are significantly increased (p<0.001) (Figure 1). The anti-microbial antibodies were also elevated in ulcerative colitis (UC) and rheumatoid arthritis (RA). ROC curve analysis showed excellent sensitivity and specificity (Figure 2). These results indicate that the specific anti-microbial antibodies within the normal general population are uncommon, but frequent in chronic disease states. The presence of anti-microbial antibodies in patients but not in normal controls can serve as biomarkers for chronic diseases such as Crohn’s disease and Sjogren’s, and their presence indicates abnormal B-cell/plasma cell function in response to the commensal/pathogenic microbes. Since the antigens were derived from the common microbes present in normal population, the antimicrobial antibodies in patients with diseases but not in the normal population suggest a deficient clearance of the microbes from the circulation by the innate immunity system in chronic diseases. These results also raise questions of bacterial vaccination using whole bacterial extracts as these anti-bacterial antibodies appear pathogenic rather than protective, offering fresh thinking in designing bacterial vaccines as preventive or therapeutic measures in chronic diseases such as Crohn’s disease and Sjogren’s Disease.
P103 FULMINANT CLOSTRIDIUM DIFFICILE ENTERITIS IN A PATIENT WITH ULCERATIVE COLITIS FOLLOWING TOTAL COLECTOMY RELIEVED BY ILEAL DECOMPRESSION
Authors: Rolfsen Matthew , Forster Erin , George Virgilio , Curry Scott
Published: January 2020

A 20 year old female with a history of Ulcerative colitis status post total colectomy and end ileostomy was admitted to the intensive care unit with septic shock. She had initially been diagnosed with fulminant ulcerative pancolitis three months prior, and after failing to respond to dual therapy with high dose infliximab and azathioprine, she underwent total colectomy and end ileostomy as the first part of a staged ileal pouch-anal anastomosis procedure.

Upon presentation to the emergency department, she endorsed fevers, chills, abdominal pain, and decreased stomal output. Diagnostic workup was notable for polymerase chain reaction (PCR) positive for Clostridium difficile toxin A and toxin B. She began treatment with oral vancomycin and IV flagyl, but remained critically ill with persistent fevers, vasopressor requirement and imaging showing 4.1 cm dilation of her distal ileum. As such the decision was made to attempt decompression via placement of a rectal tube into her ileostomy, after which her ostomy output improved from <20cc/day to 7L in the ensuing 48 hours. During this time she defervesced, was taken off of vasopressors, and was able to be discharged from the hospital one week later.

Infectious agents are the most common cause of diarrhea worldwide. Amongst implicated culprits, C. difficile is both the most common nosocomial infection and the most common cause of death due to gastrointestinal infections. Mechanisms of infectious diarrhea include formation of various toxins as well as cellular adherence and invasion (1). In the case of C. difficile, the gram positive anaerobe produces both an enterotoxin (toxin A) and a cytotoxin (toxin B).

In patients found to have C. difficile infections (CDI), the vast majority are affected by colitis. There is a small prevalence of extracolonic CDI, including extraintestinal in a small subgroup (0.17%)(2). According to literature, extracolonic CDI carries a 20% mortality rate. Out of those cases of extracolonic CDI, the majority (4/7 in a small case series), had a history of a previous colonic surgery (3). It has been postulated that the reason for increased prevalence amongst patients with previous colonic surgery is the adaptation of ileal flora to resemble fecal flora following ileostomy (3).

Although not considered to be standard of care, colonic decompression has been described for patients with toxic megacolon refractory to medical therapy. In a seven patient series which looked at decompressive colonoscopy with intracolonic perfusion of vancomycin in patients with toxic megacolon, 57% had complete resolution (5). In a patient who has undergone ileostomy and who had a significant amount of dilation on her imaging, we felt that her clinical scenario was analogous to megacolon, and that an escalation in therapy was warranted.

Image 1. CT Abdomen showing diffuse ileal dilation
P104 PEDIATRIC CROHN’S DISEASE PRESENTINAG AS GENITAL EDEMA
Authors: Ebach Dawn , Storm Douglas , Gosse Matthew
Published: January 2020

Two 12 year old boys presented to pediatric urology with chief complaints of genital swelling who were eventually diagnosed with Crohn’s disease.

Patient 1 presented with swelling, erythema and discomfort of his penis. He did not respond to topical hydrocortisone or oral antibiotics. With history of short stature he was referred to pediatric GI. He had oral ulcerations and perianal skin tag, but denied abdominal pain or diarrhea. Weight was at the 3rd percentile height was at the 2nd percentile. He had Hgb of 12.2, and iron saturation of 8 with normal ESR and CRP. ASCA IgA was normal but IgG was elevated at 66 (normal <20). Endoscopy revealed erythema with linear ulcerations in the stomach and aphthous ulcerations of the colon with erythema and edema of the ileocecal valve with inability to intubate it. Pathology demonstrated mild chronic active gastritis and mild chronic active colitis with granulomas. Magnetic resonance enterography (MRE) showed mild enhancement at the ileocecal area. Budesonide improved the penile erythema but did not change the edema. He was then started on methotrexate and infliximab with no improvement of the edema. Topical tacrolimus did not resolve edema. At age 15 he had surgical resection of the indurated subcuticular penile tissues with pathology revealing fibrotic stroma with lymphoplasmacytic inflammation and rare granulomas. He has recovered well from his penile procedure with a dramatic improvement in the cosmetic appearance, with no recurrence of the penile edema.

Patient 2 had scrotal edema, erythema, and discomfort. A scrotal ultrasound demonstrated moderate to severe scrotal edema without epididymitis, orchitis, or abscess. He was prescribed a dose of prednisone and diphenhydramine. Swelling improved but he presented a month later with recurrent scrotal edema and pain and was prescribed doxycycline for a presumed diagnosis of cellulitis along with recommendations for ice, compression and elevation. He returned to the ER the next day due to serous seepage from the scrotum. Upon follow up in urology, a pediatric gastroenterology referral was performed as a family history of Crohn’s disease in the mother, maternal aunt, and maternal grandmother was noted. Labs revealed a slightly elevated ESR of 17, elevated CRP of 7.3 (normal <0.5), negative ASCA, and mildly elevated fecal calprotectin of 193. Endoscopy revealed aphthous ulcerations in the duodenal bulb and patchy erythema of the terminal ileum. Pathology revealed mild reflux esophagitis, mild reactive changes in the stomach, mild chronic duodenitis, and mild active ileitis. MRE was normal. He was treated with budesonide and mesalamine with subsequent improvement in the scrotal edema.

Patients presenting as genital edema as their initial Crohn’s presentation is rare and it is important for providers to be aware of this rare manifestation.

Epitheliod granuloma in the bowel.

Epitheliod granuloma in penile tissue.
P108 TEDUGLUTIDE USE IN CROHN’S DISEASE: A CASE SERIES
Authors: Chiplunker Adeeti , Ha Christina , Paski Shirley
Published: January 2020

Background

Teduglutide is a glucagon-like peptide-2 (GLP-2) analogue with trophic effects on the intestinal mucosa to increase the absorptive surface area and enhance nutrient and fluid absorption of the small bowel (SB).1 It has been shown to reduce parenteral nutrition (PN) and intravenous fluid (IVF) requirements and is an important adjunct in the medical management of short bowel syndrome (SBS).1–2 Crohn’s disease (CD) is an important etiology of SBS but use of teduglutide in this population can be challenging.

Aim

The aim of this case series was to describe the use of teduglutide in CD patients.

Methods

A retrospective case series of all CD patients with SBS who used teduglutide at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center. Age, duration of SBS, length of remaining SB and colonic continuity status were recorded. BMI, average daily PN kilocalories (kcal), and IVF requirements were recorded at the time of teduglutide initiation. The duration of teduglutide use was calculated. Teduglutide dose, dose adjustment history, reason for dose adjustment, and therapy complications were noted.

Results

9 patients were included (5 male/4 female). Median age was 57 years (IQR 32). Median length of remaining small bowel was 60cm (IQR 27.5) and median duration of SBS was 8 years (IQR 9.83). Median BMI at teduglutide initiation was 18.66 (IQR 4.29) with a median duration of PN of 4.5 years (IQR 9.42) and median PN kcal/day of 971.43 (IQR 518). The median duration of teduglutide was 1.1 years (IQR 3.4).

4 patients (44%) had a teduglutide dose change. 2 patients had dose interval extended from daily to every other day to reduce injection burden. 1 patient developed obstructive symptoms on daily dosing, which resolved when the dose interval was extended to every other day. 1 patient had to stop therapy due to a small bowel obstruction requiring hospitalization. 8 patients (88%) were able to wean or stop PN/IVF with addition of teduglutide. 1 patient had to restart PN despite teduglutide therapy. Table 1.

Discussion

Teduglutide is effective in Crohn’s disease patients and facilitates weaning of PN and IVF requirements. Most patients tolerate the recommended dose with daily injections, but the dose interval can be extended to every other day to reduce obstructive symptoms or reduce the injection burden without affecting ability to wean PN/IVF.

References
P124 COMPARISONS OF HOLISTIC PATIENT-REPORTED OUTCOMES BY BIOLOGIC DRUG CLASS IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A REAL-WORLD STUDY IN IBD PARTNERS
Authors: Long Millie , Zhang Xian , Chen Wenli , Lissoos Trevor
Published: January 2020

Background

Increasing numbers of biologic agents are now available for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC). Limited data are available on clinical characteristics of populations initiating these therapies and relevant holistic patient-reported outcomes (PROs) in the real-world.

Methods

We used data from IBD Partners from May 2014-May 2019. Individuals initiating an anti-tumor necrosis factor (anti-TNF) agent or vedolizumab (VDZ) were included. A subgroup with at least 6 months of follow-up who had baseline data within 90 days of therapy initiation were included in longitudinal analyses. We aimed to: 1) compare clinical characteristics of patients initiating each biologic therapy and 2) compare PROs at follow-up by drug class. Outcomes included Patient-Reported Outcomes Measurement Information System (PROMIS) T scores for anxiety, depression, fatigue, pain interference, and social satisfaction. We used logistic regression models controlling for prior biologic exposure, age, sex, prior hospitalization, disease duration, surgery (for CD), and baseline values of each PRO to compare PROs at follow-up by drug class. Levels of each PRO within a half standard deviation of the general population T score represented wellness.

Results

A total of 878 patients initiating anti-TNF (625 CD, 253 UC) and 651 initiating VDZ (415 CD, 236 UC) were included. Patients with CD initiating VDZ were more likely to be older, had longer disease duration, increased IBD-related hospitalization, more prior surgeries, and were more likely to be biologic exposed (P<0.05 for all). Patients with UC initiating VDZ were more likely to be male and biologic exposed (P<0.05 for both) (Table 1). In longitudinal analyses, a total of 198 patients on anti-TNF and 168 on VDZ were included for CD; a total of 85 on anti-TNF and 96 on VDZ were included for UC. Individuals with CD initiating VDZ had significantly greater fatigue, pain interference, and reduced social satisfaction at baseline compared with the anti-TNF population. For UC, PROs at baseline were similar across drug groups. In both CD and UC, there were no significant differences in adjusted odds of wellness for each PRO at follow-up by drug class (Table 2).

Conclusions

CD patients initiating VDZ in this real-world cohort had multiple factors consistent with more severe disease compared with those initiating anti-TNF. In longitudinal analyses after at least 6 months of treatment with VDZ or anti-TNF, there were no differences in wellness of PROs, such as anxiety, depression, fatigue, pain interference, or social satisfaction by drug class for CD or UC.
P129 INPATIENT OUTCOMES OF SEPSIS IN INFLAMMATORY BOWEL DISEASE PATIENTS: A 2016 NATIONWIDE INPATIENT SAMPLE ANALYSIS
Authors: Vohra Ishaan , Attar Bashar , Sharma Sachit , Katiyar Vatsala , Jaiswal Manthan
Published: January 2020

Introduction

Patients with inflammatory bowel disease are at increased risk of infections due to the immunosuppressive drugs used for its treatment and by the virtue of the disease itself. The risk of infection is further exacerbated by decreased host response to vaccines.

Objective

The objective of this study is to determine the outcomes of sepsis in patients with Inflammatory bowel disease (IBD).

Methods

The 2016 National Inpatient Sample database was used to identify patients admitted with primary diagnosis of sepsis using ICD 10 code. The subgroup analysis was done to identify patients with IBD. IBD patients were further subdivided into Ulcerative colitis and Crohn’s disease. We analyzed inpatient demographics using chi-square. Predictors of inpatient mortality were calculated using univariate and multivariable regression models.

Results

1,899,169 patients were admitted for sepsis in 2016. 10,485 UC and 13,879 CD patients with sepsis were identified. UC patients admitted with sepsis had a higher mortality (47.9%) compared to CD patients (37.8%). After adjusting for potential confounders, CD was associated lower odds of mortality as compared to UC (aOR 0.77, 95% CI 0.60–0.97, P=0.031). Independent predictors of mortality were Age (aOR 1.02, 95% CI 0.60–0.97, P=0.031) and increased Charlson comorbidity index (aOR 1.76, 95%CI 1.27–2.44 P=0.001). Acute renal failure patients requiring inpatient hemodialysis (aOR 2.8, 95% CI 1.9–4.1,P=0.000) and patients with septic shock requiring pressor support(aOR 1.6 95% CI 1.01–2.51, P=0.044) were also associated with higher odds of mortality. Severe malnourishment (aOR 0.005, 95% CI 1.18–2.62, P=0.005) and patients who developed obstruction (aOR 1.9, 95% CI 1.3–2.7, P=0.001) were also associated independent predictors of mortality on multivariate logistic regression.

Conclusions

Sepsis admissions in CD patients had better outcomes compared with UC patients. Age, Charlson comorbidity index, renal function and nutritional status of patient were useful tools to predict mortality. Further, research is needed to identify other predictors and to determine the mechanisms of underlying clinical differences.
P134 PREVALENCE OF LACTOSE INTOLERANCE IN INFLAMMATORY BOWEL DISEASE IN THE UNITED STATES BETWEEN 2014 AND 2019: A POPULATION-BASED STUDY
Authors: Mansoor Emad , Abou-Saleh Mohannad , Sarmini Muhammad Talal , Chouhan Vijit , Regueiro Miguel , Katz Jeffry , Cooper Gregory
Published: January 2020

Background

The role of dairy foods in the continued symptomatology of patients with IBD is unclear. This is in part due to limited data on epidemiology of lactose intolerance (LI) in IBD. We sought to utilize a large population based database to evaluate the prevalence of LI in IBD.

Methods

We queried a commercial database (Explorys Inc, Cleveland, OH), an aggregate of Electronic Health Record data from 26 major integrated healthcare systems in the US from 1999 to 2019. We identified an aggregated patient cohort of eligible patients with a diagnosis of “Crohn’s disease” (CD) and “Ulcerative Colitis” (UC) between June 2014 and 2019, based on Systematized Nomenclature Of Medicine – Clinical Terms. We calculated the prevalence LI in IBD overall, and among different age, race and gender based sub-groups and identified risk factors for LI in IBD.

Results

Of the 35,521,930 individuals in the database from October 2014–2019, we identified 165,750 and 140,640 individuals with a diagnosis of CD and UC with overall prevalence rates of 0.47% and 0.4% respectively. The prevalence of LI in individuals without IBD was 0.2%. Compared to individuals without IBD, the prevalence of LI in CD was increased at 0.9% [OR: 4.56, 95% CI: 4.33–4.81, p<0.0001] and prevalence of LI in UC was increased at 0.8% [OR: 4.03, 95% CI: 3.80–4.28, p<0.0001] (Figure 1).

The prevalence of LI in CD was increased in: females at 0.98% vs males at 0.77% [OR: 1.27, 95% CI: 1.14–1.41, p<0.0001]; African-Americans at 1.52% vs Caucasians at 0.87% [OR: 1.73, 95% CI: 1.50–2.00, p<0.0001] and children (<18yo) at 2.39% vs adults (≥18yo) at 0.88% [OR: 2.77, 95% CI: 2.13–3.60, p<0.0001].

The prevalence of LI in UC was increased in: females at 0.91% vs males at 0.64% [OR: 1.41, 95% CI: 1.25–1.60, p<0.0001]; African-Americans at 1.45% vs Caucasians at 0.78% [OR: 1.84, 95% CI: 1.55–2.19, p<0.0001] and children (<18yo) at 1.8% vs adults (≥18yo) at 0.79% [OR: 2.28, 95% CI: 1.46–3.57, p=0.0003].

Conclusions

This is one of the first large studies to date that has described the prevalence of LI in IBD in the United States. We found that the prevalence of LI to be increased nearly 4-fold in IBD. We recommend screening for LI in IBD patients with active symptoms to delineate active disease from symptomatology due to LI.