bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt;5) and 43% had laboratorial remission (normal CRP and FC). IUS response (decrease &gt;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 &gt;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&lt;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

Abstract

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

Abstract

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

Abstract

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&lt;0.001), more hospitalizations (2.4 vs 1.1, p&lt;0.001), more emergency department (ER) visits (2.9 vs 1.9, p&lt;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&lt;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&lt;0.001). This was associated with more hospitalizations (1.6 vs 0.7, p&lt;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&lt;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

Abstract

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&lt;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

Abstract

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

Abstract

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&lt;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

Abstract

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: &lt;7.6 KPa=F0-F1, 7.7–9.4 KPa=F2, 9.5-14KpPa =F3, &gt;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&lt;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

Abstract
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.