bluuebunny/crossref_metadata_2025 huggingface dataset:
P888 Evaluating patient access to infliximab subcutaneous in inflammatory bowel disease
Authors: Jang M , Yoo H , Kwon T
Published: January 2023

Background

Infliximab(IFX) subcutaneous(SC) was developed as a novel formulation biosimilar added to the intravenous(IV) infliximab. Infliximab is one of the most effective treatments in IBD and approval of subcutaneous formulation was expected to bring greater patient convenience, yet it had to overcome its hurdles in Health Technology Assessment (HTA) in the absent of the SC originator. This research aims to evaluate patient access to IFX SC based on time-to-reimbursement decision post market authorization in July of 2021.

Methods

The pricing database, IQVIA MIDAS® data and epidemiology data were combined to analyze patient access in 32 countries. We evaluated 1) status of the reimbursement 2) volume consumed in a country 3) average period from marketing authorisation to positive reimbursement decision 4) reason for delayed access.

Results

Since the market authorization, positive reimbursement decisions were made in 18 countries among 31 European countries including UK. Among them, patients who reside in 15 countries had records of utilization of IFX SC in the year of 2022. About 74.76% of IBD patients is eligible for reimbursement of CT-P13 SC among the assumed 1,023,765 IBD patients in Europe. Average time from market authorisation to positive reimbursement decision by health authorities were 9 months(2-17) in the case of IFX SC which suggests delayed reimbursement compared to biosimilars. Although most of the European countries offered shortened or simplified HTA pathways to biosimilars, most of the countries did not have clear guidance on pricing of the novel biosimilars. Several countries failed to provide IFX SC after a positive reimbursement decision because the procurement system failed to differentiate a novel biosimilar with different strength and form from the existing biosimilars in same molecule. This may have deterred the market entry; countries where adopted national tender grouped IFX SC with IFX IV(Norway, Hungary) or extended procurement basket to all available IBD treatment(Denmark and Lithuania).

Figure: Reimbursement status of infliximab subcutaneous in European countries

Conclusion

There are apparent differences in patient access to IFX SC among European countries. Biosimilars promises to bring improved patient access to biologics, however, pricing of bio-betters or bio-innovators could be convoluted that efforts are still warranted in order to bring the drug into the market within shortest possible time. Although IBD treatment options are expanding, IFX is still widely used. Adding another SC treatment may improve patient convenience and quality of life and thus, overall improved access to the drug is imperative for equitable use.
P890 Prevalence and Characteristics of Extra-intestinal Manifestations in a single cohort of Italian Patients with Inflammatory Bowel Disease
Authors: Marino M , Sigura E , Castagnaviz E , Dottor F , Colombo A , Solito S , Terrosu G , Buda A , Berretti D
Published: January 2023

Background

Inflammatory bowel disease (IBD) is a chronic immune-mediated disorder comprised of Crohn disease (CD) and ulcerative colitis (UC). Patients with IBD may present extraintestinal manifestations (EIMs) that may affect different district such as joints, skin, eyes, and hepatobiliary area. Our objective is to characterize and determine the prevalence of EIMs in our cohort of patients affected with IBD

Methods

The study population consisted of IBD patients who were followed in one single tertiary Centre in North East Italy. Retrospectively demographic and clinical characteristics of patients were analysed. The diagnosis of EIMs was based on standard criteria and on specialist consultation.

Results

Our registry has 904 patients with IBD (M/F 484/420), 536 have UC (59,29%), 355 CD (39,26%) and 13 unclassified IBD (1.43%). Among them 170 patients (18,80%) presented at least one EIMs, 82 of 536 (15,29%) with UC and 81 of 335 (24,17%) with CD. The median age of these patients was 48 years old (36-57) and EIMs were more prevalent in females (55.6%) and in patients with younger age (57.7% with age range between 17-40 y.o.). In most of the patients (67.64%) were present more than one EIMs. Regarding the type of EIMs, the articular ones were by far the most frequent (67.7%) than followed by other manifestations: mucocutaneous (32.4%), hepatobiliary (11.2%), ocular (10.0%), pancreatic (5.9%), coagulation (3.5%), pulmonary (2.4%), muscular (1.2%), hearing loss (1.2%) and cardiac (1.2%). Furthermore EIMs were also more prevalent in smokers [p <0.001], patients with extensive UC [p = 0.008] and patients with major IBD-related surgery [p = 0.015]

Conclusion

Our study confirm that about one-fifth of patients with IBD may have associated EIMs with rheumatic manifestations, by far, the most frequent symptom. CD and female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs followed by smokers, extensive UC and with previous major IBD surgery. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.
P892 Characteristics and trend of Inflammatory Bowel Disease epidemiology for 30 years from 1991 to 2020: A single-center experience analysis in Incheon, Korea
Authors: Na S Y , Choi H , Ji J S , Kim S Y
Published: January 2023

Background

Inflammatory bowel disease (IBD) in Asia is different from that of the West in incidence, prevalence, clinical features, and genetic mutations. The purpose of this study was to investigate changes in the characteristics and trends in patients with IBD over 30 years in a single center in Incheon, Korea.

Methods

Among 1,070 IBD patients (Crohn’s disease [CD] 286; ulcerative colitis [UC] 784) who visited from Jan 1991 to Dec 2020, 773 patients (CD 204; UC 569) who were first diagnosed and followed for more than 1 year were enrolled. The demographic characteristics and trends of IBD patients for 30 years of IBD were analyzed retrospectively by dividing them into three periods.

Results

In CD, the age at diagnosis gradually decreased from 24.7±5.1 years in 1990-2000 to 21.9±9.5 years in 2011-2020 (p-trend=0.025), but there was no significant change in UC (p-trend=0.177). The male-to-female ratio showed a tendency to increase from 0.7 to 1.5 in UC (p-trend=0.002) over 30 years. The UC/CD ratio gradually decreased from 6.4 in 1991-2000, 2.6 in 2001-2010, and 2.5 in 2011-2020. In CD, the colonic phenotype gradually decreased with the recent period (35.7%, 26.2%, and 15.2%, respectively; p<0.01), but there was no difference in disease behavior (p=0.482). At the time of diagnosis, 35.8% of CD patients had a history of perianal abscess/fistula. In UC, there was no change in disease extent according to the periods, and the overall proctitis, left-sided, and pancolitis were 46.2%, 30.2%, and 23.6%, respectively. For the severity of UC, mild disease gradually increased; by 34.4% in 1991-2000, 47.0% in 2001-2010, and 60.1% in 2011-2020, respectively (p<0.001).

Conclusion

The incidence and prevalence of IBD in Korea have continued to increase over the past three decades. Age, male-to-female ratio, phenotype, and severity at the time of diagnosis of IBD in Korea are constantly changing.
P896 Inflammatory Bowel Disease in the elderly, a survey of elderly patient demographics, disease-related complications and compliance with vaccination and screening services
Authors: Elwood S , Clarke M , Lukose T , Lardner C , Mc Gettigan N , Boland K , Patchett S
Published: January 2023

Background

Inflammatory Bowel Disease (IBD) in the elderly (>60yrs) is becoming more prevalent in concordance with the ageing population and the rising incidence of IBD. An increasing number of patients are receiving a diagnosis of IBD in later years in addition to those with known IBD transitioning to elderly. The presentation, disease course, risk of complications and choice of medical therapies differ in this group from younger cohorts. We aimed to examine patient demographics and the incidence of adverse effects/complications amongst elderly IBD patients. We also sought to identify appropriate vaccination rates and uptake with screening services.

Methods

In a single tertiary centre, IBD patients aged >60 attending the outpatient clinic or admitted acutely were invited to complete an anonymous written survey.

Results

28 patients surveyed to date. 61% (n=17) had a diagnosis of UC. 54% were female (n=15). Mean age was 67.5, while mean age at diagnosis was 50 (range 19-65). 25% (n=7) received a diagnosis of IBD after 60 years, of which 57% were female. Mean BMI was 25.9. 25% (n=7) reported an infection in the last 6 months, all of whom required treatment with antibiotics. There was only one case of infection requiring hospitilisation, a patient on biologic therapy who developed a clostridium difficile infection. COVID-19 affected 39% (n=11), none required hospitilisation. 21% (n=6) report 2 or more comorbidities, of which 50% report a recent infection requiring treatment. All patients who required IBD surgery (n=5) had a high BMI. 57% (n=16) had a smoking history, with 14% (n=4) being active smokers. Infliximab and salofalk granules were the most prescribed IBD treatments. 46% were on biologics (n=13), with anti-TNF being the most common (29%). 25% (n=7) reported steroid use in the last year while 14% were not currently on IBD treatment. 21.4% (n=6) reported prior malignancy, skin cancer being most common. 50% of cancer sufferers were smokers. 100% have had a minimal of two COVID-19 vaccines. 64% (n=18) have had a flu-vaccine in the last 12 months with 75% (n=21) report annual flu-vaccine uptake. 61% (n=17) had the pneumococcal vaccine. Bowel screening participation was 46.5% (n=13).

Conclusion

Smoking, high BMI and multiple comorbidities were common in elderly IBD patients. Infections were common in this cohort and typically required treatment with antibiotics, however, were rarely severe or required hospitalisation. Severe infections were seen in those on biologic therapy. Biologics were commonly prescribed to elderly IBD patients. Skin cancer was the most common malignancy. There was suboptimal uptake with vaccinations and bowel screening.
P897 Longitudinal multi-tissue transcriptomic study reveals patient-specific drug response determinants in Inflammatory Bowel Disease patients
Authors: Cervera Seco L M , Sánchez Mayor M , Corraliza A M , Salas A , Panés J , Marigorta U M
Published: January 2023

Background

Despite the lack of understanding of Inflammatory Bowel Disease (IBD) pathogenesis, association studies have made inroads into the elucidation of the genetic component of disease diagnosis. The corresponding determinants of drug response, in turn, remain obscure. Primary response is low, secondary loss of response is prevalent and remission rates are low (30% of patients roughly). Along with the expanding repertoire of drugs, it is critical to develop a strategy to reveal the factors contibuting to drug response at the patient level. Our goal is to understand drug response in IBD looking to establish a precision medicine strategy to assign patients a specific treatment based on their transcriptomic profile.

Methods

We carried out a longitudinal follow-up of 147 IBD patients, from whom we sampled 264 intestinal biopsies and 119 blood extracts. Patients were exclusively treated with one of the three main available biologics: 248 with infliximab (anti-TNF), 47 with ustekinumab (anti-IL12/IL23) and 88 with vedolizumab (anti-α4β7). RNA-seq profiles were obtained at three different times (baseline, 14 weeks and 46 weeks after treatment initiation), resulting in 232, 92 and 59 samples, respectively. Differential expression analysis and pathway enrichment analysis were performed to get drug-specific genes and response signatures.

Results

The initial exploratory analysis confirms that tissue is the main determinant of expression variability among patients. As for longitudinal response, anti-TNF-specific features are quintessentially inflammatory, especially involved in translation and immune pathways, while response to ustekinumab is associated with extracellular recognition. Of note, vedolizumab-specific profiles strikingly differ between biopsy and blood samples. We also revealed that drug response is determined during first weeks of treatment, as up- and down-regulated genes are shared across time points. This may entail huge consequences in the clinic since the determination of response could be assessed earlier. Using clinical activity to define responders, we identified around 200 differentially expressed genes that could predict response to infliximab at time zero. We also improved our understanding regarding individual response by carrying out trend analyses based on connectivity scores that identify individual-specific regulated pathways.

Conclusion

While we identified common patterns across time in enriched pathways, we could discern specific drug response profiles. Besides providing a renewed understanding of the molecular effects of biological drugs, we propose that personalised models predicting response are feasible, and a promising venue to develop therapeutic guidelines of biologics in IBD.
P902 Native American Mapuche ancestry is related to higher IBD risk in Chileans
Authors: Pérez T , Bustamante M L , Magne F , Travisany D , Alvarez-Lobos M , Hernandez-Rocha C , Azocar L , Aguilar N , Espino A , Estela R , Escobar S , Zazueta A , Baez P , Silva V , Arriagada E , Barahona C , Zollner L , Miquel J F , Lorenzo-Bermejo J
Published: January 2023

Background

Most genetic association studies rely on Caucasian, African and Asian individuals with inconsistent results depending on the population investigated, suggesting that genetic susceptibility to inflammatory bowel disease (IBD) may depend on interactions between ethnicity and genetic-environmental factors. Aim: To explore the contribution of genetic ancestry to IBD risk in Chileans. Aim: To explore the contribution of genetic ancestry to IBD risk in Chileans.

Methods

192 Chilean IBD patients were genotyped using Illumina’s Global Screening Array. Genotype data was combined with similar information from 3147 population-based Chilean controls from a published study on gallstones, body mass index, c-reactive protein and gallbladder cancer in Chileans (Barahona et al., Hepatology 2021). The individual proportions of Aymara, African, European and Mapuche ancestry were estimated using the software ADMIXTURE (supervised estimation). Using the statistical software R version 4.2.1, we calculated the odds ratios (OR) and 95% confidence intervals (CI) for gender, as well as age and ancestry proportions grouped into quartiles using the library “epitools”.

Results

Table 1 shows the investigated characteristics of the study population and their association with IBD risk. For example, the 1st and 3rd quartiles of the proportion of Mapuche ancestry in IBD patients were 24.7% and 34.2%, respectively, and the corresponding OR was 2.30 (95%CI 1.52-3.48) for the lowest versus the highest group.

Conclusion

The type and proportion of Native American ancestry in Chileans seems to be associated with IBD risk.
P907 NOD2 mutations are associated with the development of inflammatory and progressive digestive tract damage in Crohn’s disease
Authors: Behnisch S , Reiner J , Witte M , Holle A , Schäffler H , Huth A , Jaster R , Lamprecht G
Published: January 2023

Background

Single-nucleotide polymorphisms (SNP) of the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) gene are associated with higher risk for Crohn′s disease (CD). It has also been reported that they are more likely to associate with specific phenotypes such as stricturing or perianal disease and the need for resection surgery. The aim of our study was to investigate if these NOD2 variants are associated with higher cumulative bowel damage in Crohn’s disease.

Methods

We performed NOD2 genotyping in a cohort of 150 patients with CD from a tertiary care center in Germany. The risk polymorphisms SNP 8 (R702W, rs2066844), SNP 12 (G908R, rs2066845), and SNP 13 (1007fs, rs2066847) were screened for. The Lémann-Index (LI) was calculated to estimate digestive tract damage of each patient. Additionally, we collected the following data: age at diagnosis, disease location and behaviour using the Montréal classification, and the disease duration.

Results

Fifty patients carried at least one of the three SNPs. In the univariate analysis, the LI of patients with at least one risk-SNP was not significantly different from the LI in patients without a risk-SNP (NOD2 WT), 13.62 ± 15.10 vs. 11.57 ± 13.08, p=0.196. Also, after stratification for the single polymorphisms, the LI was not significantly different in patients with vs. patients without SNP. However, variants of NOD2 were associated with a higher LI in patients with non-stricturing, non-penetrating disease behavior (Montréal classification B1), 2.61 ± 2.80 vs. 0.85 ± 1.82, p=0.007. Importantly, in the presence of SNP13 a strong correlation between the LI and disease duration was found, rp = 0.69. In contrast, only a weak correlation was detectable in the presence of NOD2 WT, rs = 0.30 (figure 1). The LI was significantly higher in patients with SNP13 and an early disease onset than in patients who were first diagnosed at a higher age.

Conclusion

NOD2 risk polymorphisms are associated with a high LI during non-stricturing, non-penetrating disease behaviour. In line with this, we observed higher digestive tract damage in patients with CD diagnosis at a young age in patients with the polymorphism SNP13. Finally, our data suggest that particularly SNP13 predisposes to progressive damage accumulation over the disease course.
P916 Small bowel permeability improvement is associated with microbial changes seen in mild to moderate active paediatric Crohn’s disease patients on nutritional therapy
Authors: Verburgt C , Dunn K , Sigall Boneh R , Wine E , Benninga M , de Jonge W , Van Limbergen J
Published: January 2023

Background

Barrier disruption leading to impaired intestinal permeability in Crohn’s Disease (CD) has been associated with various processes, including (pro-inflammatory) cytokine production, impaired mucus production and altered tight junction protein expression. A recent study showed that healthy first-degree relatives of CD patients had abnormal intestinal permeability which was associated with altered gut microbiome composition. We have previously reported that intestinal permeability improves with nutritional therapy (by either Crohn’s disease exclusion diet (CDED) or exclusive enteral nutrition (EEN)). We hypothesized this improvement in permeability might be associated with changes in the gut microbiome caused by nutritional therapy.

Methods

Paediatric participants with mild-to-moderate CD from a prospective clinical trial evaluating nutritional therapy (with CDED+PEN or EEN) for induction of remission were included (NCT01728870). A lactulose/mannitol (L/M) test for intestinal permeability was performed at weeks 0 and 3 by administering a sugar solution containing lactulose (5 g) and mannitol (1 g) followed by urine collection for LC-MS/MS analysis. A cut-off L/M ratio 0.025 was used (Leibovitzh, Gastroenterology 2022). We compared 16S rRNA (V4V5) changes of dietary responders between weeks 0 and 6 to identify microbial changes associated with improved intestinal permeability.

Results

Paired L/M ratios were available for 53 patients (26 CDED+PEN and 27 EEN). Normal L/M ratios were seen in 15/26 (58%) of CDED+PEN patients and 15/27 (56%) of EEN patients at baseline, which improved to 19/26 (73%) in CDED+PEN and 17/27 (63%) in EEN (generalized linear model, p=0.574) at week 3. Notably, 7/11 (63%) CDED+PEN patients with abnormal intestinal permeability at baseline normalised, compared to 5/12 (41%) patients in the EEN group (NS). Dietary response has been shown to be associated with significant increases in Clostridia and decrease in Gammaproteobacteria (Gastroenterology 2019). Of dietary responders, intestinal permeability “non-improvers” showed no significant changes in microbial composition, whereas “improvers” showed significant increases in different genera of Eubacteriales (Clostridia), accompanied by increase in Alphaproteobacteria (all p<0.05,LDA >2) at week 6.

Conclusion

A subset of patients with paediatric CD have impaired intestinal barrier function and disrupted intestinal permeability. Achieving clinical remission and improvement in intestinal permeability share features of microbiome correction. Further study to characterise the effect of the microbiome and metabolome (including whole metagenome analysis) on intestinal permeability, particularly within a dysbiotic state such as CD, is warranted.
P929 Gut mucosal microbiota composition in Inflammatory Bowel Disease introduced to infliximab
Authors: Ventin-Holmberg R , Lindholm J , Eberl A , Taina S , Saavalainen P
Published: January 2023

Background

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastro-intestinal tract with the main subtypes Crohn’s disease (CD) and ulcerative colitis (UC). IBD is growing rapidly in incidence and prevalence throughout the world and is strongly associated with an imbalance of the gut microbiota, although the pathogenesis is unknown. There are multiple conventional treatments, but moderate to severe IBD is treated successfully with anti-tumor necrosis factor alpha (TNF-α) infliximab (IFX). Many have studied the fecal microbiota in relation to IFX treatment, but studies on the mucosal microbiota composition during IFX treatment are scarce. Additionally, there is a problem that up to half of the patients receiving IFX do not have a good long-term response. There are no methods available to predict the response to IFX, which would be crucial to save from both high costs and possible side-effects. Previously, predictive markers of IFX response have been mostly investigated from the fecal microbiota composition.

Methods

Here the aim was therefore to investigate the mucosal microbiota composition of the gut during IFX treatment and to determine whether the gut mucosal microbiota composition differed between responders and non-responders to IFX. This was investigated in an exceptional cohort including 72 IBD patients from whom biopsy samples from both small- and large intestine and fecal samples were collected before, during and after IFX treatment. The IFX response was determined clinically and by colonoscopy at week 12 after start of treatment.

The microbiota composition was determined by MiSeq sequencing targeting the 16S conserved rRNA regions of DNA extracted from the biopsies using an optimized repeated bead-beating isolation method. Additionally, the already published fecal fungal and bacterial microbiota composition was also included to get further comparison between these.

Results

Interestingly, the preliminary results of the mucosal bacterial microbiota also show that there is a significant difference between the response groups (p < 0.05), similar to the fecal microbiota composition. Thus, the IFX response groups could be distinguished based on the fecal and mucosal microbiota composition.

Conclusion

These results could, together with previously published results, provide an urgently needed diagnostic tool for IFX response prediction.
N06 The Introduction of Nurse Led Preconception and Pregnancy Education Clinics for patients with Inflammatory Bowel Disease
Authors: Gleeson S , Buckley P M , McCarthy D J , Moran D C , O'Sullivan C , O'Sullivan G , O'Grady D J , Sugrue K
Published: January 2023

Background

•The Inflammatory Bowel Disease Centre in the Mercy University Hospital ( MUH) has a patient population of approximately 4000 patients with IBD, of these roughly half are women and many are diagnosed during their reproductive years. • Caring for this patient cohort can be a challenge due to patient lack of knowledge surrounding IBD and pregnancy misinformation that can occur.

• The aim of this project was to identify the unmet education needs of patients in relation to pregnancy and IBD. Subsequent aims were to improve patient care through the establishment of IBD preconception and pregnancy education clinics

Methods

•An audit was carried out at the IBD infusion suite and Nurse led clinics over a 20-week period between April- August 2021. 448 patients between the ages of 18-45 were identified during this timeframe and asked to complete and IBD and pregnancy questionnaire. • The questions to assess education needs were Q1) Are you planning pregnancy in the next 2years? Q2 Has your diagnosis of IBD affected your family planning in any way? Q3) Do you feel well informed/prepared from an IBD perspective to start/continue your family? Q4) Do you have any questions or concerns regarding IBD and pregnancy e.g. Disease flare up impact on pregnancy, mediation queries/concerns, impact of pregnancy disease process Q5) What do you feel the percentage risk of your baby developing IBD would be ( 0-10%, 10-20%,20-40% or >40%) Q6 Would you be interested in attending a pregnancy education clinic led by and Advanced Nurse Practitioner?

Results

•55% of respondents were women. • 89% of respondents felt they needed more education on IBD and pregnancy. • 70% of respondents were concerned about the impact of an IBD flare up on fetal health with 19% remaining voluntarily childless. • 95% of patients had questions/concerns about the effects of biologic drugs on pregnancy outcomes. • 90% of patients said they would attend IBD ANP led preconception and pregnancy education clinics. • 84% of patients overestimated the percentage risk of their offspring developing IBD, with 59% estimating the risk to be greater than 20%

Conclusion

•This audit identified the need for preconception and pregnancy education clinics for patients with IBD to improve patient education, care and outcomes.

ANP led preconception and pregnancy education clinics have been established since October 2021 & are ongoing. Currently between 8-12 patients attend exclusively for preconception counselling per month. Referrals are received from Consultants within the IBD Centre MUH
N29 Audit of Inflammatory Bowel Disease Telephone Advice Line
Authors: Walsh C
Published: January 2023

Background

Inflammatory Bowel Disease (IBD) is a chronic unpredictable condition of the gastrointestinal tract and advice lines for chronic disease are well established. Advice lines are a fundamental part of the Inflammatory Bowel Disease services. They offer advice and support for patients and have been shown that early intervention via an advice line can have a major impact in avoiding hospitalisation due to a flare up. Inflammatory Bowel Disease advice lines provide for multiple queries in relation to IBD and increasing demands were observed. The introduction and increased use of biologic medication (subcutaneous and oral) requires a repeat Hi Tech prescription and this has increased the workload through the IBD advice line.

The aim was establish if aspects of the IBD advice line was in accordance with IBD Standards UK and to highlight any deficiencies that would require corrective action

Methods

Data was collected on all telephone calls received by the ANP IBD advice line during the data period 17/01/2022 to 11/02/2022 (n=80). The average number of monthly calls to the service is 146. Prospective data was collected by ANP IBD and analysed by the Clinical Audit Facilitator using IBM SPSS Statistics v 24.

Criteria used to measure against:

Rapid access to specialist advice should be available to patients to guide early flare intervention, including access to a telephone/email advice line with response by the end of the next working day ( IBD Standards UK)

Results

The highest number of calls to the advice line was 23/80 (29%) for a Hi Tech prescription. Flare up calls consisted of 21.2% of the calls and results investigations was equal to this. Administration queries and medication queries consisted of 7.5% of the calls. Clinical related queries were almost 9% of the calls.

59% of calls were returned within 36 hours. Mean interval of time call was returned was 34.7 hours and a median interval of 28 hours.

Conclusion

The audit indicates the highest number of calls are for repeat Hi tech prescriptions for medications. A Quality Improvement Plan includes the establishment of a dedicated Hi Tech Prescription Telephone/Virtual Clinic. This will also ensure an improved quality and a safer standard of care for patients. .

The audit further identifies the number of calls and the effectiveness of the Inflammatory Bowel Disease advice line e.g. the number of calls (17/80) that dealt with a flare up that would have possibly attended the Emergency Department. It also highlights the time intervals for return of calls (33/80) calls were returned > 36 hours. A new Clinical Nurse Specialist Inflammatory Bowel Disease would improve service outcomes.
Going under the bridge: unmasking ischaemia and endothelial dysfunction of myocardial bridging: a case report
Authors: Bhogal Sukhdeep , Waksman Ron , Hashim Hayder
Published: January 2023

Background

Physiological assessment of myocardial bridging prevents unnecessary interventions. Non-invasive workup or visual coronary artery compression may underestimate the underlying ischaemia associated with myocardial bridging in symptomatic patients.

Case summary

A 74-year-old male presented to the outpatient clinic with chest pain and shortness of breath on exertion. He underwent coronary artery calcium scan showing an elevated calcium score of 404. On follow-up, he endorsed progressive worsening of symptoms with chest pain and decreased exercise tolerance. He was then referred for coronary angiography that revealed mid-left anterior descending myocardial bridging with initial normal resting full-cycle ratio of 0.92. Further workup after ruling out coronary microvascular disease demonstrated abnormal hyperaemic full-cycle ratio of 0.80 with a diffuse rise across the myocardial bridging segment on pullback. Our patient also had increased spastic response to hyperaemia on angiography, supporting the presence of underlying endothelial dysfunction and ischaemia, likely contributing to his exertional symptomology. The patient was started on beta-blocker therapy with improvement in symptoms and resolution of chest pain on follow-up.

Conclusion

Our case highlights the importance of thorough workup of myocardial bridging in symptomatic patients to better understand the underlying physiology and endothelial function after ruling out microvascular disease and consideration of hyperaemic testing if symptoms are suggestive of ischaemia.
Transcatheter aortic valve implantation for patient with non-calcified bicuspid aortic valve: a case report
Authors: Nonaka Hideaki , Asami Masahiko , Miura Sumio , Tanabe Kengo
Published: January 2023

Background

Non-calcified aortic stenosis (AS) is rare and is associated with a high risk of transcatheter valve embolization and migration (TVEM) because aortic valve complex calcification is important for stable anchoring of the prosthesis. Therefore, transcatheter aortic valve implantation (TAVI) for non-calcified AS is not preferred. However, a universally accepted strategy for TAVI in such patients is not yet established.

Case summary

A 69-year-old woman with symptomatic severe AS and a high surgical risk was admitted to our institution for TAVI. Pre-procedural computed tomography (CT) revealed a non-calcified bicuspid aortic valve. Implantation of a 23 mm self-expandable valve (SEV) was planned according to the manufacturer’s recommended optimal size based on CT measurements. Intraoperatively, the 23 mm SEV did not snugly fit at the aortic apparatus level. Thus, we deployed a 26 mm SEV with stable anchoring because of the stronger radial force. She was discharged without any complication. Echocardiography at 3 months follow-up showed a well-functioning transcatheter heart valve (THV) without migration or paravalvular leakage.

Discussion

In our patient with non-calcified bicuspid AS, an SEV that was one size larger than the optimal as measured on CT was successfully implanted without THV embolization. An upsized SEV may be considered when performing TAVI in patients with severe non-calcified AS.
Prasugrel dose de-escalation in diabetic patients with acute coronary syndrome receiving percutaneous coronary intervention: results from the HOST-REDUCE-POLYTECH-ACS trial
Authors: Lee Kyu-Sun , Park Keun-Ho , Park Kyung Woo , Rha Seung-Woon , Hwang Doyeon , Kang Jeehoon , Han Jung-Kyu , Yang Han-Mo , Kang Hyun-Jae , Koo Bon-Kwon , Lee Nam-ho , Rhew Jay Young , Chun Kook Jin , Lim Young-Hyo , Bong Jung Min , Bae Jang-Whan , Lee Bong Ki , Kim Seok-Yeon , Shin Won-Yong , Lim Hong-Seok , Park Kyungil , Kim Hyo-Soo
Published: January 2023

Aims

The aim of this study was to evaluate the efficacy and safety of prasugrel dose de-escalation therapy in patients with diabetes mellitus (DM)–acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).

Methods and results

This was a post-hoc analysis of the HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases—Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) randomized trial. The efficacy and safety of prasugrel dose de-escalation therapy (prasugrel 5 mg daily) were compared with conventional therapy (prasugrel 10 mg daily) in patients with DM. The primary endpoint was net adverse clinical events (NACE), defined as a composite of all-cause death, non-fatal myocardial infarction (MI), stent thrombosis (ST), clinically driven revascularization, stroke, and Bleeding Academic Research Consortium (BARC) class ≥2 bleeding events. The secondary ischaemic outcome was major adverse cardiovascular and cerebrovascular events, defined as the composite of cardiac death, non-fatal MI, ST, or ischaemic stroke. Of 2338 patients randomized, 990 had DM. The primary endpoint of NACE occurred in 38 patients (7.6%) receiving prasugrel dose de-escalation and in 53 patients (11.3%) receiving conventional therapy among patients with DM [hazard ratio (HR) 0.66; 95% confidence interval (CI) 0.43–0.99; P = 0.049]. Prasugrel dose de-escalation as compared with conventional therapy did not increase the risk of ischaemic events (HR 1.03; 95% CI 0.56–1.88; P = 0.927) but decreased BARC class ≥2 bleeding in patients with DM (HR 0.44; 95% CI 0.23–0.84; P = 0.012).

Conclusion

Prasugrel dose de-escalation compared with conventional therapy may reduce the risk of net clinical outcomes, mostly driven by a reduction in bleeding without an increase in ischaemic events in patients with DM.

Trial Registration: HOST-REDUCE-POLYTECH-ACS, NCT02193971, https://clinicaltrials.gov/ct2/show/NCT02193971
LDL lowering effect of PCSK9 inhibition is reduced in women
Authors: Myasoedova Veronika A , Rimbert Antoine , Camera Marina , Le May Cedric , Capoulade Romain , Cariou Bertrand , Poggio Paolo
Published: January 2023

Aims

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of plasma low-density lipoprotein cholesterol (LDL-C) concentration, and its inhibition reduces the risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to assess the sex-differential effect of either pharmacological or genetic inhibition of PCSK9 on LDL-C levels.

Methods and results

We meta-analyzed six real-life studies (1216 men and 641 women) that investigated the effects of PCSK9 monoclonal antibodies (mAbs) on LDL-C reduction in men and women. Despite higher LDL-C levels in women at baseline [mean difference (MD) = 17.4 mg/dL, P < 0.0001, women = 175 mg/dL vs. men = 152 mg/dL], the LDL-C reduction under PCSK9 mAb treatment was significantly greater in men (MD = 7.6 mg/dL, 95% confidence interval: 2.7–12.4, P = 0.002) than in women.

We tested the sex-related association of the loss-of-function variant PCSK9-R46L with LDL-C plasma levels in 382 813 individuals (219 301 women and 163 512 men) free of lipid-lowering drugs from the UK Biobank general population cohort. The magnitude of LDL-C reduction was larger in men than in women (mean LDL-C difference: –35 mg/dL vs. –26 mg/dL, when comparing homozygous carriers with non-carriers in men and women, respectively). The relationship between PCSK9-R46L and LDL-C was significantly dependent on sex (P for interaction = 7.2e–04).

Conclusion

These results demonstrate by complementary approaches that the decrease in LDL-C mediated by PCSK9 inhibition is slightly, but significantly, less marked in women than in men. These data reinforce the need for specific studies to develop sex-specific recommendations for the management of ASCVD in women.
Conan Doyle and the rhetoric of genre
Authors: Kerr Douglas
Published: January 2023

Arthur Conan Doyle is recognized as a master of narrative. This essay argues that this mastery expresses itself in his management of genre, at a time when social and cultural changes had created a literary environment that saw the emergence of what is now called genre fiction. Crucial elements in the field of literary publishing which his stories served included the expansion of the monthly magazine market, the emergence of the short story as a popular form of fiction, and the appearance of a broad-based new reading public, well educated in the conventions of genre fiction and equipped with reading skills deriving from this ‘genre literacy’, which an author like Conan Doyle could foster and manipulate for rhetorical effect. I describe the conditions that created a taste for the popular genre fiction on which, somewhat to his chagrin, Conan Doyle’s reputation rested. He moved between genres with a versatility rivalled in his time only by Rudyard Kipling. But he also combined genres together in a single work, so as to satisfy or unsettle, disappoint, reward, or wrong-foot his readers pleasurably by playing on the expectations aroused by cues in the tales. Rather than the detective fiction which he made his own, I turn to his experiments in the genre of ‘imperial Gothic’ to illustrate this, and examine the rhetoric of three short stories with narrative tropes that depend for their effect on the genre literacy of the reading public to whom they were offered.
Hybridization in the absence of an ecotone favors hybrid success in woodrats (Neotomaspp.)
Authors: Klure Dylan M , Greenhalgh Robert , Parchman Thomas L , Matocq Marjorie D , Galland Lanie M , Shapiro Michael D , Dearing M Denise
Published: January 2023

Hybridization is a common process that has broadly impacted the evolution of multicellular eukaryotes; however, how ecological factors influence this process remains poorly understood. Here, we report the findings of a 3-year recapture study of the Bryant’s woodrat (Neotoma bryanti) and desert woodrat (Neotoma lepida), two species that hybridize within a creosote bush (Larrea tridentata) shrubland in Whitewater, CA, USA. We used a genotype-by-sequencing approach to characterize the ancestry distribution of individuals across this hybrid zone coupled with Cormack–Jolly–Seber modeling to describe demography. We identified a high frequency of hybridization at this site with ~40% of individuals possessing admixed ancestry, which is the result of multigenerational backcrossing and advanced hybrid-hybrid crossing. F1, F2, and advanced generation hybrids had apparent survival rates similar to parental N. bryanti, while parental and backcross N. lepida had lower apparent survival rates and were far less abundant. Compared to bimodal hybrid zones where hybrids are often rare and selected against, we find that hybrids at Whitewater are common and have comparable survival to the dominant parental species, N. bryanti. The frequency of hybridization at Whitewater is therefore likely limited by the abundance of the less common parental species, N. lepida, rather than selection against hybrids.
Weathering the Storm: Discordant Learning about Reputations for Reliability
Authors: Donahue Bailee , Crescenzi Mark J C
Published: January 2023

It is well established that state reputations impact international politics, but less is known about how these reputations change. We investigate one form of change by examining how individuals process new information. Using a logic of discordant learning, we expect good reputations to survive new and incongruent information that counters expectations. Good reputations can help states “weather the storm” in times of crisis. Such buffers have their limits, however, as strong incongruent signals can trigger large corrections in a state’s reputation. To analyze these expectations, we focus on alliance reliability. Using a pair of survey experiments, we find that individuals alter their perceptions of a state’s reputation when observing signals that deviate from the state’s prior reputation, and that good reputations are able to “weather the storm”. We also find that strongly incongruent signals affect good reputations more than others, suggesting “the bigger they are, the harder they fall” may also apply. Even in these large corrections, however, a reputation for reliability has lasting benefits. The analysis helps us understand when to expect changes in reputations for alliance reliability, which in turn may inform when reputation loss can influence alliance politics.
Sucrose enhances the chromogenic ability ofStaphylococcus xylosusby improving nitric oxide synthase activity
Authors: Xu Zhiqiang , Zheng Wenbin , Zhao Shang , Chen Yong , Yang Qingli , Zhu Yinglian
Published: January 2023

In this paper, the effect of different concentrations of sucrose stress on color formation of the Staphylococcus xylosus was investigated. The results showed that the highest a* value and the best coloring effect similar to those of nitrite were observed after the addition of 0.05 g/mL sucrose to stress the S. xylosus. UV-Vis and electron spin resonance spectra analysis showed that production of coloring product Mb-NO was significantly enhanced after 0.05 g/mL sucrose stress. The growth curve, reactive oxygen content, cell cycle, nitric oxide synthase (NOS) activity, zeta potential, cell size, and protein composition of S. xylosus were investigated to reveal the mechanism of sucrose stress to enhance the coloring effect of the strain. The result showed that sucrose inhibited the growth of S. xylosus, which changed the physiological state by activating the oxidative stress response. The stress altered the rate of intracellular metabolism of S. xylosus by delaying the cell cycle and increasing cell surface zeta potential and cell particle size. These changes altered the protein composition of the cells and significantly enhanced the activity of intracellular NOS, which could improve the chromogenic ability of S. xylosus. This study will provide theoretical support for sucrose stress on S. xylosus to enhance its coloring effect, and sucrose stress for S. xylosus might be a promising biological alternative to nitrite in meat products.
Dual Roles of Cardiorespiratory Fitness and Fatigability in the Life-Space Mobility of Older Adults: The Study of Muscle, Mobility and Aging (SOMMA)
Authors: Moored Kyle D , Qiao Yujia (Susanna) , Rosso Andrea L , Toledo Frederico G S , Cawthon Peggy M , Cummings Steven R , Goodpaster Bret H , Kritchevsky Stephen B , Glynn Nancy W
Published: January 2023

Background

Cardiorespiratory fitness and perceived fatigability are interrelated components of physical capacity that may jointly influence movement within one’s living environment (life-space mobility). We examined whether fitness and fatigability were associated with life-space mobility in community-dwelling older adults, and whether the association of fitness with life-space varied by the level of perceived fatigability.

Methods

Participants were from the Study of Muscle, Mobility and Aging (SOMMA) baseline cohort (N = 775, mean age 76.1 years). Life Space Assessment scores incorporated level, frequency, and assistance used (personal, devices) for life-space mobility. Fitness was measured as VO2peak from symptom-limited treadmill testing. Fatigability cut-points included: (i) Borg Rating of Perceived Exertion (RPE) ≥ 10 after a fixed-speed (1.5 mph) treadmill test, (ii) the Pittsburgh Fatigability Scale (PFS) Physical ≥ 15, and (iii) PFS Mental ≥ 13. The total count of cut-points was used as a composite fatigability measure (range: 0–3). Linear regressions were adjusted for demographic, lifestyle, and health confounders.

Results

Better fitness was associated with greater life-space, but the association plateaued at higher fitness levels (VO2peak > 18). Life-space was significantly lower for individuals meeting ≥2 fatigability criteria (vs none), attributable mainly to more severe physical, but not mental, fatigability. In moderation analyses, the fitness–life-space association was significant only for those with RPE ≥ 10 but did not differ by PFS.

Conclusion

Fitness below a critically low threshold was associated with limited life-space mobility, suggesting that certain older individuals may need to operate close to their maximum aerobic capacity to traverse daily environments; these associations were driven by those with more severe physical fatigability.
A Novel Probiotic Combination Ameliorates Crohn’s Disease–Like Ileitis by Increasing Short-Chain Fatty Acid Production and Modulating Essential Adaptive Immune Pathways
Authors: Di Martino Luca , Osme Abdullah , Ghannoum Mahmoud , Cominelli Fabio
Published: January 2023

BACKGROUND

Crohn’s disease (CD) represents a significant public health challenge. We identified a combination of beneficial probiotic strains (Saccharomyces boulardii, Lactobacillus rhamnosus, Lactobacillus acidophilus, and Bifidobacterium breve) and amylase that may antagonize elevated bacterial pathogens in the inflamed gut. Our aim was to characterize the effect(s) of this novel probiotic supplement in SAMP1/YitFc (SAMP) mice with CD-like ileitis.

METHODS

Three groups of 7-week-old SAMP mice were used in this study. The first experimental group was administered 1 dose of the probiotic supplement (probiotic strains + amylase) diluted in sterile phosphate-buffered saline (PBS) (0.25 mg in 100 µL of PBS) every day for 56 days through the gavage technique, the second group had a probiotic supplement (probiotic strains without amylase), and the third group was a control group in which animals were administered sterile PBS. At the end of the treatment, mice were sacrificed and ilea were collected for histological scoring of ileitis and NanoString analysis. Stool samples were evaluated by 16S ribosomal RNA and gas chromatography–mass spectrometry analyses.

RESULTS

Histology scores showed that mice treated with probiotics + amylase had a significant decrease of ileitis severity compared with the other 2 groups. 16S ribosomal RNA and gas chromatography–mass spectrometry analysis showed that abundance of species belonging to genus Lachnoclostridium and Mucispirillum schaedleri were significantly increased compared with the other 2 groups, and this increase was associated with augmented production of short-chain fatty acids. NanoString data showed that 21 genes involved in B memory cell development and T cell infiltration were significantly upregulated in probiotic-treated mice and that 3 genes were significantly downregulated.

CONCLUSIONS

Our data provide experimental proof for a beneficial effect of the designed probiotic formulation on the severity of CD-like ileitis in the SAMP mouse model, involving both alteration of intestinal genetic pathways and microbial rearrangements. Thus, we propose that this novel probiotic mixture should be further tested as an adjuvant therapy in the treatment of biofilm-associated disorders such as CD, in which it has been proven that polymicrobial imbalance plays a critical role in dysbiosis and gut inflammation.