bluuebunny/crossref_metadata_2025 huggingface dataset:
P494 Can Patients Monitor Response To Ustekinumab In The Real World?
Authors: Walsh A J , Matini L , Kormilitzin A , Wilson J , Lyden S , Al-Hillawi L , Kantschuster R , White L , Payton S , Brain O , Palmer R , Ambrose T , Satsangi J , Travis S P L
Published: May 2021

Background

Real time monitoring of patients with Crohn’s disease (CD) gives us the opportunity to examine disease trajectory. We have demonstrated the feasibility of using a monitoring platform with patient reported data, collected prospectively and routinely in clinical practice. The question is whether it can be used for specific drugs

Methods

TrueColours-IBD (TC-IBD)is a real time, web based platform that through email prompts linked to questionnaires, collects longitudinal patient reported outcome measures (for CD, symptoms measured by Harvey Bradshaw Index (HBI) and quality of life by IBD Control-8). It is routinely used by >2000 patients in Oxford. This study examined 114 patients with Crohn’s: 45 males (median age 36, IQR 28–51) and 69 females (median age 34.8, IQR 28–47), treated with ustekinumab for a maximum of 16 months (range -2 months to 14 months). A linear mixed-effects model was used to approximate longitudinal trends of HBI and IBD Control-8. 3 individual items of the HBI scale (general well-being, abdominal pain & stool frequency) were also assessed. The TC-IBD platform has the capacity to analyse and show patients’ data automatically, using customised models and algorithms through the feedback loop (Fig 1). Model coefficients, intercept and slope were estimated using the restricted maximum likelihood (REML) approach. The intercept corresponds to the expected cohort mean value of the scale (e.g. HBI, IBD Control-8) at baseline (time zero) and the slope describes the rate of the change over time

Results

The models’ coefficients, the intercept and slope of both HBI and IBD Control-8 scales were statistically significant and are summarised in Table 1 with confidence intervals. Both linear trends (slopes) describing HBI (p<0.001) and IBD Control-8 (p<0.001) confirmed improvements for patients. The bowel movement component of the HBI dominated over general well-being and abdominal pain, while keeping a similar downward trend over time ( Fig 2 and Fig 3a,b)

Conclusion

Patient reported data through the TC-IBD platform can be used for statistical analyses and continuous monitoring of drug effect over time. This analysis is limited by a lack of comparator group, but the models may be used with the TrueColours platform as a decision support tool for other drugs
P497 The value of endoscopic healing index monitoring for guiding infliximab dosing in patients with Crohn’s disease
Authors: Kantasiripitak W , Mathôt R , Oldenburg B , Buisson A , Ferrante M , Laharie D , D’Haens G , Vermeire S , Dreesen E
Published: May 2021

Background

The endoscopic healing index (EHI) is a novel multi-protein serum biomarker test developed and validated to assess endoscopic disease activity in patients with Crohn’s disease (CD). Evidence for the use of EHI to guide decision-making during infliximab (IFX) treatment remains scarce. Therefore, we aimed to characterise the relationships between IFX dose, serum IFX concentrations, EHI, and endoscopic remission (ER).

Methods

Data were obtained from 118 biologic naïve adult patients with CD enrolled in the phase 4 TAILORIX trial (EudraCT 2011 003038 14). All patients had confirmed active CD at baseline based on clinical, biological, and endoscopic criteria. IFX and EHI (scores ranging from 0–100) were measured using a homogenous mobility shift assay (HMSA) and immunoassay, respectively (Prometheus Laboratories). First, the previously published population pharmacokinetic (popPK) model of the TAILORIX study population was revisited to describe the HMSA data. The effect of EHI, faecal calprotectin (FC), C-reactive protein (CRP), and serum albumin (ALB) on IFX clearance was evaluated. Next, a minimal continuous-time Markov model was developed to describe the time course of EHI within patients. EHI was considered as a three-stage ordinal variable (scores 0–19, 20–49, and 50–100) with the lowest score stage (0–19) indicative of ER. The course-modifying effect of IFX on EHI was assessed. Finally, a generalised linear model was used to describe the relationship between EHI and the probability of attaining ER (Simple Endoscopic Score for CD [SES-CD] ≤2). The predictive ability of EHI for ER was compared with that of FC, CRP, ALB, and IFX using a receiver operating characteristic (ROC) curve analysis.

Results

The revisited two-compartment popPK model described the IFX data with adequate descriptive and predictive accuracies. EHI, FC, CRP, and ALB at week (w)0 were not found to explain interpatient variability in IFX clearance. In contrast, higher IFX at w14 was associated with a higher probability of achieving EHI <20 at w14 (Figure 1). The probability of attaining EHI <20 at w14 was predicted to increase more than four-fold when IFX at w14 was targeted at 10 mg/L instead of 5 mg/L (Table 1). EHI and FC equally well predicted the probability of attaining ER at the same time point (Figure 2, Table 2).

Conclusion

EHI, FC, ALB, and CRP at w0 should not be considered for a priori IFX dose optimisation. Nevertheless, a posteriori IFX dose optimisation (based on IFX concentrations measurements) towards a predefined IFX concentration at w14 may lead to lower post-induction EHI scores and thus improved ER rates. An IFX target of 10 mg/L at w14 is associated with four-fold higher normalisation of EHI as compared to the commonly used target of 5 mg/L.
P504 Effectiveness and safety of ustekinumab maintenance therapy in 103 patients with real-world ulcerative colitis: A GETAID multicentre cohort study
Authors: Fumery M , Filippi J , Abitbol V , Biron A , Laharie D , Serrero M , Altwegg R , Bouhnik Y , Peyrinbiroulet L , Gilletta C , Roblin X , Pineton de Chambrun G , Vuitton L , Bourrier A , Nancey S , Gornet J M , Nahon S , Bouguen G , Viennot S , Pariente B , Amiot A
Published: May 2021

Background

Phase III trials have demonstrated the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis (UC), but no real-life long-term data is currently available.

Methods

From January to September 2019, all consecutive patients with active UC treated with ustekinumab in a GETAID centre were included. Patients were evaluated at week 52. Remission was defined by a partial Mayo Clinic score ≤ 2. The aim of the present study was to assess long-term effectiveness and safety of ustekinumab in UC.

Results

103 UC patients (62 men; mean age: 41.2 ± 16.2 years; 52% pancolitis E3) were included in 21 centres. History of immunomodulator, anti-TNF and vedolizumab therapies was noted in 84.5%, 99.0% and 85.4% of the cases, respectively. At week 54, 44 (43%) patients discontinued ustekinumab, for lack of efficacy (n=41), pregnancy (n=1), persistence of eczematiform lesions (n=1) or personal decision (n=1). Cumulative probabilities of ustekinumab persistence were 96.1%, 81.6%, 71.7%, and 58.4% after 3, 6, 9, and 12 months, respectively. In multivariate analysis, a CRP>5 mg/L at week 0 (OR=2.91, CI95%[1.15–7.36]; p=0.02) and concomitant steroids at week 0 (OR=3.05, CI95%[1.30–7.14]; p=0.01) were significantly associated with ustekinumab discontinuation within one year. The overall rate of steroid-free clinical remission at week 52 was 32% of whom 71% had null rectal bleeding and stool frequency subscores. Ten patients (9.7%) underwent colectomy within a median of 6.7 [4.3–10.6] months. Adverse events were observed in 15 (16.9%) patients, of whom 4 (4.5%) had severe adverse events including three patients with exacerbation of UC leading to hospitalization, and a 62 years-old men who died from a myocardial infarction four months after ustekinumab initiation.

Conclusion

In this real-world cohort study that included patients with refractory ulcerative colitis to multiple therapies, more than one-half of patients were still treated by ustekinumab and one-third were in steroid-free clinical remission, after 52 weeks.
P505 Early therapeutic drug monitoring after induction therapy with infliximab: correlation with intestinal ultrasound
Authors: Nascimento C , Morão B , Frias Gomes C , Cúrdia Gonçalves T , Castro F , Moreira M , Cotter J , Pereira F , Caldeira A , Sousa R , Coelho R , Macedo G , Macedo C , Ferreira M , Cravo M , Glória L , Torres J , Palmela C
Published: May 2021

Background

Therapeutic drug monitoring (TDM) in patients receiving infliximab (IFX) has a role in assessing treatment and managing outcomes. Infliximab trough levels (ITL) have been suggested as useful markers for treatment optimization in Crohn’s disease (CD).Our goals were: to assess the relationship between ITL and transmural inflammation as assessed by intestinal ultrasound(IUS), following induction therapy with IFX; to assess which clinical, laboratorial or IUS parameters better predicted adequate levels by the end of induction therapy.

Methods

Prospective multicentric cohort study including patients with active CD starting IFX therapy. Clinical disease activity assessed using the Harvey-Bradshaw index (HBI), C-reactive protein (CRP), fecal calprotectin (FC) were measured at week 0 and after induction therapy (week 14). IUS was performed at week 0 and 14, bowel wall thickness (BWT) from the worst segment was selected for analysis. Ileocolonoscopy was performed at W0 and SES-CD was registered. ITL were measured at W14.

Results

We included 36 patients with CD (61% male; median age 30 years (range 16–73)). According to Montreal classification, most patients were A2 (69%), had ileocolonic disease (L3 56%) and an inflammatory phenotype (B1 58%).Perianal disease was present in 42%. Combination therapy was used in 61%. After induction therapy, 81% were in clinical remission (HBI <5) and 43% had laboratorial remission (normal CRP and FC). IUS response (decrease >25% in BWT) was observed in 24% of patients and remission (BWT normalization) in 11%. Median ITL were 4.3 (IQR 2.3–8.1) and 64% had ITL >3 ug/ml. There was a good negative correlation between ITL and SES-CD (r=-0.492, p=0.003). Adequate ITL were associated with lower HBI (1.5 vs 4.5, p=0.052), laboratory remission (61% vs 15%, p=0.014), lower BWT (4 vs 5.5 mm, p=0.009) and sonographic response (39% vs 0%, p=0.014) at W14. At the end of induction, we found a fair to good correlation between ITL and HBI (r=-0.430, p=0.009),CRP (r=-0,510, p=0.001), FC (r=-0.590, p=0.001) and BWT (R=-0.506, p=0.002). Receiver operating characteristic (ROC) curve analysis showed that FC at W14 had the largest area under the curve (AUC) in predicting adequate ITL (0.813 vs 0.716 vs 0.739 vs 0.772, p<0.05).

Conclusion

Patients with higher disease burden measured by ileocolonoscopy at baseline had lower ITL after induction. Adequate ITL were associated with laboratorial remission and sonographic response at the end of induction, with a good correlation with clinical, laboratorial and sonographic parameters. These findings suggest that adequate IFX levels after induction are associated with a better control of inflammation in IBD, so early proactive TDM during induction may be helpful in treatment management.
P545 Calprotectin at week 12 is a predictor for histological remission in ulcerative colitis patients treated with Vedolizumab
Authors: Rubstov D , Kakkadasam Ramaswamy P , Edwards J , Shukla D , Willmann L , Moattar H , Bhullar M , Ishaq N , Dorrington A , Mohsen W
Published: May 2021

Background

Vedolizumab (VDZ) is a gut-specific α4β7 integrin antagonist that has demonstrated efficacy for induction and maintenance of remission in moderate to severe ulcerative colitis (UC). The aim of this study was to assess the rates of histological remission (HR) in a real-world setting and to identify predictors for histological remission.

Methods

Retrospective cohort study of all UC patients (≥18 years) initiated on VDZ from 2016 to 2020 was completed. Clinical, biochemical, endoscopic and histologic data were collected. All patients received standard induction therapy with VDZ 300 mg IV at Weeks 0, 2, and 6 and maintained on an 8-weekly regimen. Dose was escalated to a every 4-weekly regimen as per physician’s discretion. A 52-week follow-up was completed on all patients. Endoscopic assessment was carried out between 24 and 52 weeks after commencing VDZ. Histological activity was graded as per Nancy index and histological remission was defined as Nancy grade 0. Endoscopic remission was defined as Mayo endoscopic score = 0. Clinical remission was defined as SCCAI ≤ 5.

Results

A total of 51 patients [55% female, median age 48 years (IQR 35–60)] were included. 16/51 (34%) were anti-TNF exposed. In 30/51 (59%) patients VDZ was combined with steroids at induction and by week 12 steroids were completely tapered in 14/30 (46.7%) patients. At weeks 12, 24 and 52, 89.6%, 87% and 97.5% of patients, respectively, were in clinical remission. 19/37 (51.3%) patients were in endoscopic remission at end of follow up. Median Nancy score prior to commencing VDZ was 3 (IQR: 2–4) and the median Nancy score at end of follow up was 1 (IQR: 0–2). 19/37 (51.3%) patients achieved HR; 3 patients who were in HR at the time of commencement of VDZ remained in HR at the end of follow up. Median baseline faeces calprotectin (FC) was 320 mcg/g (IQR 45–1000) and was similar in patients who achieved HR and those who did not. Median FC at 12 weeks was 155 mcg/g (45–720) and was significantly lower in patients who achieved HR when compared to patients who did not achieve histological remission (45 vs 420, p 0.028). FC at week 12 predicted histological remission (AUC =0.8667). FC ≥ 200mcg/g at week 12 predicted failure to achieve HR with sensitivity 70%, specificity 100%, PPV 100%, NPV 75%, accuracy 84%.

Conclusion

Vedolizumab is effective in achieving histological remission and FC ≥ 200 mcg/g at week 12 accurately predicts failure to achieve HR in patients treated with VDZ.
P570 Prediction of achieving remission in Crohn’s disease patients by abdominal Imaging
Authors: Meringer H , Tzadok R , Mercer D , Handler M , Barnes S , Waterman M , Abadi S , Margalit Yehuda R , Kopylov U , Amitai M M , Bar-Gil Shitrit A , Sheynkman G , Zittan E , Maharshak N
Published: May 2021

Background

Vedolizumab (VDZ) is an effective therapy in patients with Crohn’s disease (CD). Early prediction of response remains an unmet need. We aimed to evaluate whether abdominal imaging can predict response to VDZ.

Methods

Abdominal imaging [Computed tomography enterography (CTE) or magnetic resonance enterography (MRE)] of CD patients initiating therapy with VDZ was evaluated, up to 4 months before VDZ initiation. Response to VDZ was determined at week 26 using the Harvey–Bradshaw index (HBI) or the Crohn’s Disease Activity Index (CDAI), in cases no objective score was available it was defined based on the physician assessment.

Results

Thirty-three CD patients were included. At week 26, clinical response and remission were achieved in 20(60.6%) and 14(42.4%) patients, respectively. CRP and Calprotectin levels were available for 22/33 and 7/33 patients at week 26. As expected, levels trended lower in remission versus no remission- median CRP 2.41mg/L [IQR 1.3–4.5] vs 10.2[1.6–44.6], p=0.11 and 23.5 µg/g [5–42] vs 2002.8[191–2003], p=0.095, though this did not reach statistical significance. Clinical remission versus no remission was significantly associated with being biologic naïve, 8/14 vs 2/19 (p=0.01) and no prior CD surgeries, 10/14 vs 6/19 (p=0.04). Characteristics of local inflammation as mural edema, fibrofatty proliferation or lymphadenopathy were higher in patients achieving remission versus non-remission. The presence of either mural edema or fibro-fatty proliferation was significantly associated with remission (12/14 vs 9/19, p=0.03). The presence of stenosis in imaging was nominally higher in patients failing to achieve remission (14/19 vs 6/14, p=0.15). Number of diseased segments, length of inflammation or the maximal bowel thickness were similar in remission and no-remission.

Conclusion

Baseline imaging may help to predict remission based on the presence of either mural edema or fibrofatty proliferation and the absence of stenosis
P609 Impact of accessibility of medical care and socioeconomic class on outcomes of IBD – a nationwide population study
Authors: Ledder O , Harel S , Orlanski-Meyer E , Yogev D , Loewenberg Weisband Y , Greenfeld S , Kariv R , Lederman N , Matz E , Schwartz D , Focht G , Dotan I , Turner D
Published: May 2021

Background

Despite ongoing improvements in Inflammatory Bowel Disease (IBD) therapeutics, timely access to quality medical care likely impacts patient outcomes. Physical distance from specialty care and socioeconomic status (SES) may impact quality of care. In a nationwide population study we aimed to assess the impact of patient location and SES on IBD outcomes.

Methods

This Epi-IIRN project utilized a meta-database incorporating patient data of all four health maintenance organisations (HMO) in Israel, representing 98% of the population. All patients identified on the incidence cohort were followed from diagnosis until end of 2018. Regions in Israel were defined as central (coastal plain and Jerusalem corridor), northern region and southern region. SES class were defined by postcode as per Israel bureau of statistics data from SES 1 (lowest) to SES 4 (highest). Primary outcome was steroid dependency, with secondary outcomes of biologic therapy use during first year of diagnosis, surgery, gastroenterology visits, hospitalizations and mortality. Analysis was performed separately for Crohn’s disease (CD) and ulcerative colitis (UC).

Results

A total of 30,167 IBD patients (16,936 (56%) CD and 13,231 (44%) UC) were included: 74% of patients were in central region, 12% southern region and 14% northern region. 21% were in SES class 1 and 12% in SES 4.

In CD, lower SES was associated with higher steroid dependency (37% vs 30%, p=0.002), higher surgery rates (21% vs 12%, p<0.001), more hospitalizations (2.4 vs 1.1, p<0.001), more emergency department (ER) visits (2.9 vs 1.9, p<0.001) and higher mortality (3.3% vs 2.5%, p=0.03). Regarding region, steroid dependency, hospitalization rate, ER visits and surgery rate were all lower in central regions compared to both northern and southern region (p<0.001 for both central vs northern, and central vs southern regions). Similarly, gastrointestinal specialized clinic visits were more frequent in central regions (p=0.01).

In UC, lower SES was associated with lower frequency of gastrointestinal clinic visits (5.0 vs 8.5, p<0.001). This was associated with more hospitalizations (1.6 vs 0.7, p<0.001), ER visits (2.1 vs 1.6, p=0.002), surgeries (7.6% vs 5.0%, p=0.014) and higher mortality (5.1% vs 4.2%, p=0.026). By region, gastrointestinal clinic visits were more frequent, and ER visits, hospitalizations (all p<0.001) and surgeries (p=0.001) were all lower in central compared to both northern and southern regions.

Conclusion

In this nationwide analysis we show deleterious impact of both lower SES and peripheral residence on outcomes of CD and UC. Policy makers should consider these data to facilitate improved access to medical care and maximize IBD outcomes in a standardized way.
P612 Lower incidence of COVID-19 in patients with Inflammatory Bowel Diseases treated with non-gut-selective biologic therapy: an observational multicentre study
Authors: Ferretti F , Monico M C , Carvalhas Gabrielli A M , Carmagnola S , Bezzio C , Saibeni S , Bosani M , Caprioli F , Mazza S , Casini V , Cortelezzi C , Parravicini M , Cassinotti A , Cosimo P , Indriolo A , Di Sabatino A , Lenti M V , Pastorelli L , Conforti F , Ricci C , Sarzi-Puttini P , Vecchi M , Maconi G , Ardizzone S
Published: May 2021

Background

Since the outbreak of COVID-19, concerns have been raised as to whether IBD patients under biologic therapy might be more susceptible to the disease and its complications. This study aimed to determine the incidence and outcomes of COVID-19 in a large cohort of IBD patients on biologic therapy in Lombardy, the hardest-hit Italian region by the pandemic.

Methods

This is an observational retrospective multicentre study collecting data about COVID-19 in IBD patients on biologic therapy in regular clinical follow-up at 11 IBD referral units in Lombardy, between February 20th and May 20th, 2020. The main endpoints were to assess the cumulative incidence of COVID-19 and its outcome (hospitalization/death) among IBD patients on biologic therapy and to identify any variations among the different classes of biologic agents. Secondarily, we compared the results with the incidence of COVID-19 in the general population of Lombardy in the same period and the incidence of symptoms suggestive of COVID-19 in our study population compared with those of a second cohort of IBD patients undergoing non-biological therapies and coming from the same geographic area.

Results

Overall, 1816 IBD patients on biologic therapy were enrolled. The cumulative incidence of COVID-19 was 3.9 per 1000 (7/1816) with a hospitalization rate of 57% and a case-fatality rate (CFR) of 29%. In our Cohort, the gut-selective therapy (Vedolizumab and Etrolizumab) was the only risk factor of developing symptomatic COVID-19 (OR 8.7, 95% CI 1.7–45.0, p = 0.01). Conversely, non-gut selective anti-cytokine agents were associated with a lower incidence of infection (OR 0.13, 95%CI 0.02–0.74) and development of symptoms (OR 0.60, 95%CI 0.37–0.98). Compared to the general population of Lombardy, a lower incidence of COVID-19 was observed (3.9 vs 8.5 per 1000 with a RR 0.45, 95%CI 0.21–0.95); conversely, in terms of hospitalization rate and CFR, the clinical outcome was not statistically different. Finally, compared to a second cohort of 565 IBD patients treated with non-biologic conventional therapies, a significantly lower risk of symptomatic disease was observed in patients on biologic agents (OR 0.3, 95%CI 0.2–0.4, p<0.01).

Conclusion

Compared to the general population, IBD patients on biologic therapy are not exposed to a higher risk of COVID-19; compared to gut-selective agents, cytokine blockers are associated with a lower incidence of symptomatic infection, supporting the decision of maintaining the ongoing treatment.
P616 Sustainability of thiopurines monotherapy in ulcerative colitis: a nationwide analysis from the epi-IIRN cohort
Authors: Atia O , Friss C , Mendelovici A , Shteyer E , Orlanski-Meyer E , Ledderman N , Greenfeld S , Kariv R , Loewenberg Weisband Y , Gabay H , Nevo D , Matz E , Dotan I , Turner D
Published: May 2021

Background

Thiopurines have been long used to maintain remission in ulcerative colitis (UC) but are also associated with toxicity and therapeutic failure. We aimed to assess the sustainability rate of thiopurines commenced as monotherapy in UC, and to explore predictors of sustainability.

Methods

This study was performed on data from four Health Maintenance Organizations (HMOs), covering 98% of the Israeli population. We included all biologic-naïve UC patients diagnosed after 2005 and treated with thiopurines monotherapy for at least three months. Treatment with 5- aminosalicylic acid (ASA) was allowed if initiated prior to or during the first three months from initiation of thiopurines. Sustainability was defined as continued thiopurines treatment without switching therapy, adding biologics or requiring surgery. At most one short steroid course was allowed. Cox regression model was used to explore estimated predictors to sustainability.

Results

A total of 1,897 (370 [20%] pediatric-onset and 1,527 [80%] adults) thiopurines-treated patients were included with a 15,033 person-years of follow-up. The median time from UC diagnosis to initiation of thiopurines was 12.7 months (IQR 4.6–30.9), and the median treatment duration was 13.0 months (6.3–28.4). Sustainability rate was evident in 92% of patients after 6 months from initiation of thiopurines and 83%, 65% and 42% at one, three and five years, thereafter. Sustainability was associated with early initiation of thiopurines during disease course (HR 0.99 [95%CI 0.985–0.995]) and lack of 5-ASA at initiation of thiopurines (HR 0.7 [95%CI 0.6–0.8]).

Conclusion

As many as two thirds of biologic-naïve UC patients treated with thiopurines monotherapy sustain this treatment after five years, especially when initiated early and without 5-ASA.
P626 SARS-CoV-2 seroprevalence in patients with Inflammatory Bowel Disease
Authors: García Mateo S , Martínez-Domínguez S J , Aso Gonzalvo M C , Gargallo-Puyuelo C J , Gallego Llera B , Arroyo Villarino M T , Laredo de la Torre V , Nocito Colon M M L , Lario Quilez L , Refaie E , Latre Santos M , Gomollón García F
Published: May 2021

Background

Patients with Inflammatory Bowel Disease (IBD) suffer from a chronic illness and many of them need immunosuppressive therapy throughout the course of the disease. Consequently, COVID-19 pandemic has caused uncertainty about the possible increased risk of suffering SARS-CoV-2 infection that could confer IBD or its treatments.

The aim of this study is to assess SARS-CoV-2 seroprevalence in patients with IBD as well as the existence of potential risk factors for its development.

Methods

This is a unicentric cross-sectional study developed in IBD unit of University Hospital “Lozano Blesa” of Zaragoza. Patients older than 18 years with established diagnosis of Crohn′s Disease (CD), Ulcerative Colitis (UC) or Indeterminate Colitis (IC) have been included. A blood sample has been drawn from each patient to detect IgG against SARS-CoV-2 (ELISA method) and each patient has completed a questionnaire to know symptoms related to infection and previous comorbidity. We have performed a descriptive analysis and a univariate analysis to study relationship between potential risk factors and seroconversion against SARS-CoV-2.

Results

431 patients have been included, with a mean age of 50.2 ± 14.1 years and a 51.3% of women. Of them, 49.7% suffer from UC, 49.2% CD and 1.2% IC. Related to the treatment, 23.5% receive anti-TNF biologic agents, 13.1% other kind of biologic agents, 9.3% immunomodulators, 7.7% combined treatment (biologic agent and immunomodulator), 33.1% other treatment and 13.3% no treatment.

According to World Health Organization (WHO) definitions, 85.6% had not suffered the infection, 7.7% were confirmed cases (only 3 admitted patients) and 6.7% were probable cases. The seroprevalence of SARS-CoV-2 obtained is 8.8%, being significantly higher among confirmed cases than among probable cases (71.0% in confirmed vs 6.9% in probable; RR 10.3; p<0.001). A higher risk of seroconversion has been detected among patients without biologic agents (11.8% in patients without biologic agents vs 5.3% in patients with biologic agents; RR 2.2; p=0.021). No differences have been observed in the seroprevalence of patients with other treatments for IBD or in terms of age, active smoking, level of inflammation markers, the presence of symptoms of infection or hospital admission.

Conclusion

The seroprevalence of SARS-CoV-2 of Aragon′s patients with IBD is similar to that described in national seroprevalence study of Ministry of Health for the region (8.8%). The treatment with biologic agents is associated with a lower risk of seroconversion
P655 Insulin Resistance Prevalence is Not Increased in Patients with Inflammatory Bowel Disease: a case-control study
Authors: Carrillo Palau M , Hernández-Camba A , Hernández Álvarez-Buylla N , Ramos L , Alonso-Abreu I , Vela M , Hernández-Pérez A , Arranz L , Hernández-Guerra M , Ferraz-Amaro I
Published: May 2021

Background

Inflammatory bowel disease (IBD) is considered a chronic inflammatory state that has been associated with nonalcoholic fatty liver disease (NAFLD). Insulin resistance (IR) has been linked to NAFLD and inflammation. Whether if IR is prevalent in IBD and increases the risk of NAFLD in these patients is unknown. We aimed to study if IR is prevalent in a cohort of patients with IBD and associated risk factors.

Methods

This multicentric cross-sectional study compared 151 IBD patients with 174 age matched non-diabetic controls. Insulin and C-peptide serum levels and IR and beta cell function (%B) indices by homoeostatic model assessment (HOMA2) were evaluated. In the IBD patients fatty liver disease (FLD) was assessed by ultrasound (Grade I-IV) and Transition elastography (Fibroscan ®, values were correlated to liver fibrosis as: <7.6 KPa=F0-F1, 7.7–9.4 KPa=F2, 9.5-14KpPa =F3, >14KPa =F4). .Anthropometric, IBD characteristics, biochemical parameters and concomitant diseases were registered as predictive factors for having IR among IBD patients and assessed by multivariable regression analysis.

Results

IBD patients (57% female, mean age 48 years(SD 10)), compared to matched controls (68% female, mean age 50 years(SD 16)) exhibited similar HOMA2-IR (0.97 ± 0.64 vs 1.31 ± 0.80, p=0.19) and HOMA2-%B indexes (126 ± 49 vs 134 ± 47, p=0.31) after adjusting by confounders. Obesity, abdominal circumference and triglycerides were associated with the presence of IR in IBD patients, whereas IBD disease patterns, disease activity and inflammatory markers were not related to IR. Mild and moderate FLD was present in 26% and 13 % of IBD patients, respectively. FLD grades correlated with a higher insulin and C-peptide and IR indices as observed in the univariable analysis for HOM2-IR (0.06 (0.01–0.11)) and for HOM2-%B 6(3–10) indices.

Patients with severe fat infiltration had higher serum levels of insulin and C-peptide and a superior HOM2-IR (2.4 ± 1.6, p=0.01) and HOMA2-%B (251 ± 40, p<0.001) indices compared to mild steatosis. Moreover, adjusted trend analysis showed significant values for C-peptide and HOMA2-%B, showing, therefore, that as FLD grades increases higher values of both also rises.

Conclusion

IBD patients show a similar prevalence of IR compared to controls. However, likewise in the general population, metabolic syndrome factors are associated with IR and FLD, so metabolic syndrome assessment is mandatory among IBD patients.
Corporate Human Rights?
Authors: Kulick Andreas
Published: May 2021

Do corporations have human rights? This article addresses, to date, a rather understudied issue of the corporations and human rights debate: whether and to what extent corporations can be bearers of human rights, with a focus on the European Convention on Human Rights and the European Court of Human Rights (ECtHR) jurisprudence. In a nutshell, it argues that what subsequently will be called ‘the individualistic approach’ – that is, purporting that the corporate form itself cannot be bearer of human rights – counter-intuitively leads to almost unfettered human rights entitlements of corporations. Thereby, this article provides a critique of both established corporate law thinking as well as the dominant view in human rights scholarship. Instead, it is submitted that taking the corporate form seriously and granting it some entitlements to some extent under a functionalist theory emerges as the preferable approach – theoretically, doctrinally and practically. The article draws on ECtHR jurisprudence, general legal as well as corporate law theory and comparative constitutional law in order to corroborate its argument.
Genome-wide association study suggests an independent genetic basis of zinc and cadmium concentrations in fresh sweet corn kernels
Authors: Baseggio Matheus , Murray Matthew , Wu Di , Ziegler Gregory , Kaczmar Nicholas , Chamness James , Hamilton John P , Buell C Robin , Vatamaniuk Olena K , Buckler Edward S , Smith Margaret E , Baxter Ivan , Tracy William F , Gore Michael A
Published: May 2021

Despite being one of the most consumed vegetables in the United States, the elemental profile of sweet corn (Zea mays L.) is limited in its dietary contributions. To address this through genetic improvement, a genome-wide association study was conducted for the concentrations of 15 elements in fresh kernels of a sweet corn association panel. In concordance with mapping results from mature maize kernels, we detected a probable pleiotropic association of zinc and iron concentrations with nicotianamine synthase5 (nas5), which purportedly encodes an enzyme involved in synthesis of the metal chelator nicotianamine. In addition, a pervasive association signal was identified for cadmium concentration within a recombination suppressed region on chromosome 2. The likely causal gene underlying this signal was heavy metal ATPase3 (hma3), whose counterpart in rice, OsHMA3, mediates vacuolar sequestration of cadmium and zinc in roots, whereby regulating zinc homeostasis and cadmium accumulation in grains. In our association panel, hma3 associated with cadmium but not zinc accumulation in fresh kernels. This finding implies that selection for low cadmium will not affect zinc levels in fresh kernels. Although less resolved association signals were detected for boron, nickel, and calcium, all 15 elements were shown to have moderate predictive abilities via whole-genome prediction. Collectively, these results help enhance our genomics-assisted breeding efforts centered on improving the elemental profile of fresh sweet corn kernels.
Energy use in hotels: a case study in Gran Canaria
Authors: Santiago Dunia E
Published: May 2021

In this paper, the energy models of six hotels were compared. Food and beverage (F&B) service demands the highest amount of energy (over 50%), followed by the hot water system. A regression analysis revealed that, among 31 different characteristics, the revenue per available room, the pool volume, the number of diners and the mean number of guests per occupied room can explain the total energy demand of the studied hotels. The possibility of including photovoltaic solar energy could increase the renewable contribution of the energy mix by 8–30%, but this highly depends on the available surface for this installation in each hotel.
Stable gradient flow discretizations for simulating bilayer plate bending with isometry and obstacle constraints
Authors: Bartels Sören , Palus Christian
Published: May 2021

Bilayer plates are compound materials that exhibit large bending deformations when exposed to environmental changes that lead to different mechanical responses in the involved materials. In this article a new numerical method that is suitable for simulating the isometric deformation induced by a given material mismatch in a bilayer plate is discussed. A dimensionally reduced formulation of the bending energy is discretized generically in an abstract setting and specified for discrete Kirchhoff triangles; convergence towards the continuous formulation is proved. A practical semi-implicit discrete gradient flow employing a linearization of the isometry constraint is proposed as an iterative method for the minimization of the bending energy; stability and a bound on the violation of the isometry constraint are proved. The incorporation of obstacles is discussed and the practical performance of the method is illustrated with numerical experiments involving the simulation of large bending deformations and investigation of contact phenomena.
Validating Threat: IO Approval and Public Support for Joining Military Counterterrorism Coalitions
Authors: Recchia Stefano , Chu Jonathan
Published: May 2021

Recent scholarship has fruitfully investigated the effect of international organization (IO) approval on public support for military intervention. Following Jentleson and Britton [Bruce W. Jentleson and Rebecca L. Britton, “Still Pretty Prudent: Post-Cold War American Public Opinion on the Use of Military Force,” Journal of Conflict Resolution 42, no. 4 (1998): 395–417], scholars argue that IO approval does not increase already high public support for “foreign policy restraint” (FPR) operations intended to coerce “aggressively threatening” opponents, including terrorists. We challenge this argument, focusing on public support for contributing to military coalitions. The public may wonder whether leaders are sincere when they frame a coalition military operation as having FPR objectives; this may lead the public to put a premium on multilateral validation. We also question the common argument that UN Security Council approval necessarily has a greater positive effect on public support for intervention than approval from regional IOs. Approval from broad-based regional IOs, such as the African Union (AU), may be just as consequential. Data from survey experiments that we conducted in three countries confirm our principal hypotheses: (1) IO approval consistently increases public support for contributing to military coalitions even in counterterrorism cases and (2) the UN and AU approval effects are of comparable magnitude. These findings expand our theoretical understanding of the conditions under which IO approval can increase public support for military intervention.
The Footprint of the Prophet at the Gate to Mecca: Mediating Empire, Pilgrimage, and Prophetic Piety in Mughal Gujarat
Authors: Hamid Usman
Published: May 2021

This article unpacks the connections between empire, piety, and pilgrimage in the early modern western Indian Ocean world by examining the history of a reliquary shrine dedicated to a qadam, or footprint relic of the Prophet Muḥammad located in Ahmedabad, Gujarat. Classified by the Archeological Survey of India as the ‘Tomb of Mir Abu Turab’ (ASI Monument no. N-GJ-44), the site was a qadamgāh in the Mughal period and from the late-sixteenth to the early-eighteenth centuries functioned as a place of visitation (mazār) for pilgrims eager to see the naqsh-i qadam-i sharīf (the impression of the noble foot), whose white appearance stood in stark contrast against the black stone. By examining Persian historical narratives, including one authored by the man responsible for the relic’s arrival to South Asia, this article demonstrates how relics mediated Mughal imperium, devotion to the Prophet Muḥammad, and sayyid identity in early modern Gujarat.
China and International Adjudication—Picking Up Steam?
Authors: Hao Yayezi , de la Rasilla Ignacio
Published: May 2021

This article examines the gradual shift from outright rejection of legal methods of international dispute settlement towards greater acceptance of it in certain contexts on the part of China in recent years using a tripartite typology. The first type includes analysis of a minor softening of its traditional strategic detachment from some international adjudicative systems in general public international law, international criminal law and international human rights law. The second type focuses on China’s deepening engagement with adjudicative systems in the areas of international trade law and international commercial and investment law. The third category analyses its exploratory accommodation to adjudicative settlement mechanisms in the law of the sea and in newer areas. The article fleshes out this classification by examining the roots of both historical and contemporary attitudes underlying China’s asymmetrical and regime-specific approach to international adjudication with reference to Chinese major policy initiatives including the Belt and Road Initiative.
Transfiguring Theaters for Disrespectable Leisure: An Ethnography on Black Womxn’s Ratchet Performances in Movie Showings ofGirls Trip
Authors: Davis Shardé M , Tounsel Timeka N
Published: May 2021

This ethnographic study considers how Black womxn audiences collectively negotiated the politics of respectability in the movie theater, anecdotally referred to as cinema etiquette, in showings of the film Girls Trip. Data were collected in two local theaters in a Northeastern city using field interviews, follow-up telephone interviews, and participant observation. Findings revealed that Black womxn audiences (from various age groups) embodied an intersectional resistance discourse of disrespectability ( Cooper, 2012, 2017, 2018) through their (non)verbal behaviors and an ecology of the senses (i.e., sight and sound) that were situated at the intersection of ratchetness, playfulness, and informality. In doing so, they created a “homeplace,” making an otherwise uncomfortable and highly regulated public space suitable for their collective spectatorship of the film. We argue that Black womxn’s embodiment of ratchetness is not necessarily a unidimensional endeavor, but rather an ever-evolving, multifaceted resource that enables Black womxn to reach political and pleasurable ends.
Efficacy of antiepileptic drugs in glioma patients with epilepsy: a systematic review
Authors: de Bruin Marjolein E , van der Meer Pim B , Dirven Linda , Taphoorn Martin J B , Koekkoek Johan A F
Published: May 2021

Background

Comprehensive data on the efficacy and tolerability of antiepileptic drugs (AED) treatment in glioma patients with epilepsy are currently lacking. In this systematic review, we specifically assessed the efficacy of AEDs in patients with a grade II-IV glioma.

Methods

Electronic databases PubMed/MEDLINE, EMBASE, Web of Science, and Cochrane Library were searched up to June 2020. Three different outcomes for both mono- and polytherapy were extracted from all eligible articles: (i) seizure freedom; (ii) ≥50% reduction in seizure frequency; and (iii) treatment failure. Weighted averages (WA) were calculated for outcomes at 6 and 12 months.

Results

A total of 66 studies were included. Regarding the individual outcomes on the efficacy of monotherapy, the highest seizure freedom rate at 6 months was with phenytoin (WA = 72%) while at 12-month pregabalin (WA = 75%) and levetiracetam (WA = 74%) showed highest efficacy. Concerning ≥50% seizure reduction rates, levetiracetam showed highest efficacy at 6 and 12 months (WAs of 82% and 97%, respectively). However, treatment failure rates at 12 months were highest for phenytoin (WA = 34%) and pregabalin (41%). When comparing the described polytherapy combinations with follow-up of ≥6 months, levetiracetam combined with phenytoin was most effective followed by levetiracetam combined with valproic acid.

Conclusion

Given the heterogeneous patient populations and the low scientific quality across the different studies, seizure rates need to be interpreted with caution. Based on the current limited evidence, with the ranking of AEDs being confined to the AEDs studied, levetiracetam, phenytoin, and pregabalin seem to be most effective as AED monotherapy in glioma patients with epilepsy, with levetiracetam showing the lowest treatment failure rate, compared to the other AEDs studied.
Polar or nonpolar? That is not the question for perovskite solar cells
Authors: Huang Boyuan , Liu Zhenghao , Wu Changwei , Zhang Yuan , Zhao Jinjin , Wang Xiao , Li Jiangyu
Published: May 2021

Perovskite solar cells (PSC) are promising next generation photovoltaic technologies, and there is considerable interest in the role of possible polarization of organic-inorganic halide perovskites (OIHPs) in photovoltaic conversion. The polarity of OIHPs is still hotly debated, however. In this review, we examine recent literature on the polarity of OIHPs from both theoretical and experimental points of view, and argue that they can be both polar and nonpolar, depending on composition, processing and environment. Implications of OIHP polarity to photovoltaic conversion are also discussed, and new insights gained through research efforts. In the future, integration of a local scanning probe with global macroscopic measurements in situ will provide invaluable microscopic insight into the intriguing macroscopic phenomena, while synchrotron diffractions and scanning transmission electron microscopy on more stable samples may ultimately settle the debate.
Visceral Adiposity and Severe COVID-19 Disease: Application of an Artificial Intelligence Algorithm to Improve Clinical Risk Prediction
Authors: Goehler Alexander , Hsu Tzu-Ming Harry , Seiglie Jacqueline A , Siedner Mark J , Lo Janet , Triant Virginia , Hsu John , Foulkes Andrea , Bassett Ingrid , Khorasani Ramin , Wexler Deborah J , Szolovits Peter , Meigs James B , Manne-Goehler Jennifer
Published: May 2021

Background

Obesity has been linked to severe clinical outcomes among people who are hospitalized with coronavirus disease 2019 (COVID-19). We tested the hypothesis that visceral adipose tissue (VAT) is associated with severe outcomes in patients hospitalized with COVID-19, independent of body mass index (BMI).

Methods

We analyzed data from the Massachusetts General Hospital COVID-19 Data Registry, which included patients admitted with polymerase chain reaction–confirmed severe acute respiratory syndrome coronavirus 2 infection from March 11 to May 4, 2020. We used a validated, fully automated artificial intelligence (AI) algorithm to quantify VAT from computed tomography (CT) scans during or before the hospital admission. VAT quantification took an average of 2 ± 0.5 seconds per patient. We dichotomized VAT as high and low at a threshold of ≥100 cm2 and used Kaplan-Meier curves and Cox proportional hazards regression to assess the relationship between VAT and death or intubation over 28 days, adjusting for age, sex, race, BMI, and diabetes status.

Results

A total of 378 participants had CT imaging. Kaplan-Meier curves showed that participants with high VAT had a greater risk of the outcome compared with those with low VAT (P < .005), especially in those with BMI <30 kg/m2 (P < .005). In multivariable models, the adjusted hazard ratio (aHR) for high vs low VAT was unchanged (aHR, 1.97; 95% CI, 1.24–3.09), whereas BMI was no longer significant (aHR for obese vs normal BMI, 1.14; 95% CI, 0.71–1.82).

Conclusions

High VAT is associated with a greater risk of severe disease or death in COVID-19 and can offer more precise information to risk-stratify individuals beyond BMI. AI offers a promising approach to routinely ascertain VAT and improve clinical risk prediction in COVID-19.
Photometric follow-up observations and transit timing analysis of HAT-P-37b
Authors: Yang Jia-Mei , Wang Xian-Yu , Li Kai , Liu Yuan
Published: May 2021

We performed follow-up photometric observations on exoplanetary system HAT-P-37 from 2011 February to 2019 September. The nine new transit light curves of the R and V bands are presented in this work. Based on the new light curves and published literature data, the physical and orbital parameters of HAT-P-37 are refined. In addition, mid-transit times are obtained to update the linear ephemeris, Tc[0] = 2456478.57916 ± 0.00077 [BJDTDB], P = 2.7974415 ± 0.0000025 d. Moreover, the transit timing variations (TTVs) have an rms of 57 s and there is no significant TTV signal. According to dynamic analysis, we excluded the possibility of perturbers with a mass larger than 200M⊕, when located in 1 : 3, 1 : 2, 2 : 3 (interior) or 3 : 2, 2 : 1, 5 : 2, 3 : 1 (exterior) orbital resonance, respectively.
Simultaneous imaging of ER and cytosolic Ca2+ dynamics reveals long-distance ER Ca2+ waves in plants
Authors: Resentini Francesca , Grenzi Matteo , Ancora Daniele , Cademartori Mara , Luoni Laura , Franco Marianna , Bassi Andrea , Bonza Maria Cristina , Costa Alex
Published: May 2021

Calcium ions (Ca2+) play a key role in cell signaling across organisms. In plants, a plethora of environmental and developmental stimuli induce specific Ca2+ increases in the cytosol as well as in different cellular compartments including the endoplasmic reticulum (ER). The ER represents an intracellular Ca2+ store that actively accumulates Ca2+ taken up from the cytosol. By exploiting state-of-the-art genetically encoded Ca2+ indicators, specifically the ER-GCaMP6-210 and R-GECO1, we report the generation and characterization of an Arabidopsis (Arabidopsis thaliana) line that allows for simultaneous imaging of Ca2+ dynamics in both the ER and cytosol at different spatial scales. By performing analyses in single cells, we precisely quantified (1) the time required by the ER to import Ca2+ from the cytosol into the lumen and (2) the time required to observe a cytosolic Ca2+ increase upon the pharmacological inhibition of the ER-localized P-Type IIA Ca2+-ATPases. Furthermore, live imaging of mature, soil-grown plants revealed the existence of a wounding-induced, long-distance ER Ca2+ wave propagating in injured and systemic rosette leaves. This technology enhances high-resolution analyses of intracellular Ca2+ dynamics at the cellular level and in adult organisms and paves the way to develop new methodologies aimed at defining the contribution of subcellular compartments in Ca2+ homeostasis and signaling.