The influence of subclinical active inflammation on IFX pharmacokinetic modeling and disease progression assessment: findings from a prospective real-world study in inflammatory bowel disease patients.

BACKGROUND AND AIMS: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment. METHODS: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model. RESULTS: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in all its different definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression. CONCLUSION: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance.

Thiopurines have no impact on outcomes of Crohn's disease patients beyond 12 months of maintenance treatment with infliximab.

BACKGROUND: The emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines. AIMS: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab. METHODS: In this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug-related items was used to define treatment failure. RESULTS: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub-analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021). CONCLUSION: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration.

Safety of Endoscopy Units during the COVID-19 Pandemic.

Introduction: The COVID-19 pandemic drastically changed the daily routine of all healthcare systems worldwide, and endoscopy units were no exception. Endoscopic exams were considered to have a high risk of transmission, and therefore, the safety of endoscopy units and the consequent need for pre-endoscopy SARS-CoV-2 screening were questioned early on. The aim of our study was to assess the safety of endoscopy units during the COVID-19 pandemic, as well as the effectiveness/necessity for SARS-CoV-2 screening prior to endoscopies. Material and Methods: This is a retrospective and single-center study carried out in a Portuguese tertiary hospital. All patients who underwent endoscopic procedures between September 1, 2020 and February 28, 2021 were included. The pre-endoscopy screening consisted of a specific questionnaire or a RT-PCR test for SARS-CoV-2 (nasal and oropharyngeal swab). Data were obtained through patient's clinical records and the Trace COVID platform. Results: A total of 2,166 patients were included. Patients had a mean age of 61.8 years and were predominantly male (56.2%, n = 1,218). Eighty-one (3.7%) patients had previous SARS-CoV-2 infection, with a median difference of 74 days (IQ 40.5:160.5) between infection and endoscopy. Most patients (70.2%, n = 1,521) underwent PCR screening for SARS-CoV-2 up to 72 h before the procedure, with the remaining patients (29.8%, n = 645) answering a questionnaire of symptoms and risk contacts up to 3 days before endoscopy. Of the patients who underwent RT-PCR screening for SARS-CoV-2, 21 (1.4%) tested positive, and all were asymptomatic at the time of the screening. The evaluation for SARS-CoV-2 infection up to 14 days after the endoscopic exams identified 9 positive patients (0.42%) for SARS-CoV-2. The median difference in days between endoscopy and the diagnosis of infection was 10 days. Discussion/Conclusion: Pre-endoscopy screening with RT-PCR test for SARS-CoV-2 identified a very small number of patients with COVID-19 infection as well as patients with COVID-19 infection in the following 14 days. Therefore, the risk of infection in endoscopy units is negligible if screening of symptoms and risk contacts is applied and individual protective equipment is used.

Introdução: A pandemia COVID-19 mudou drasticamente o dia-a-dia de todos os sistemas de saúde a nível mundial e as unidades de endoscopia não foram exceção. Os exames endoscópicos foram considerados exames com alto risco de transmissão pelo que desde cedo se questionou a segurança das unidades de endoscopia e a consequente necessidade de rastreio SARS-CoV-2 pré-endoscopia. O objetivo do estudo foi avaliar a segurança das unidades de endoscopia durante a pandemia por COVID-19 bem como a eficácia/necessidade de rastreio SARS-CoV-2 prévio aos exames endoscópicos. Material e métodos: Foi desenvolvido um estudo retrospetivo e unicêntrico, no qual todos os doentes submetidos a exames endoscópicos entre 1 de setembro de 2020 e 28 de fevereiro de 2021 foram incluídos. Como estratégia de rastreio pré endoscopia foram aplicados questionários específicos de sintomas e contactos de risco, ou teste PCR de SARS-CoV-2 (zaragatoa nasal e orofaríngea). Os dados clínicos foram obtidos através do processo clínico do doente e da plataforma Trace COVID-19. Resultados: Foram incluídos um total de 2,166 doentes submetidos a exames endoscópicos durante o período de estudo. Os doentes incluídos apresentaram uma média de idades de 61.8 anos e eram maioritariamente do sexo masculino (56.2%, n = 1,218). 3.7% (n = 81) dos doentes já tinha tido infeção por COVID-19 no passado, sendo a mediana da diferença de dias entre a infeção e a data do exame de 74 dias. A maioria dos doentes (70.2%, n = 1,521) foi submetido a rastreio por PCR de SARS-CoV-2 até 72 horas antes do procedimento, sendo os restantes doentes (29.8%, n = 645) submetidos a um questionário de sintomas e contactos de risco realizado até 3 dias antes do procedimento. Dos doentes que realizaram rastreio por PCR de SARS-CoV-2, 21 (1.4%) apresentaram teste positivo, estando todos assintomáticos à data do teste. Aquando da verificação de infeção por SARS-CoV-2 até 14 dias após a realização dos exames endoscópicos apurou-se que apenas 9 doentes (0.42%) testaram positivo para SARS-CoV-2, sendo a mediana da diferença de dias entre a data do exame e o diagnóstico de infeção de 10 dias. Discussão/Conclusão: O rastreio pré-endoscopia com teste PCR de SARS-CoV-2 identificou um número reduzido de doentes infetados com COVID-19 e o número de doentes com infeção por COVID-19, nos 14 dias seguintes aos exames endoscópicos, foi muito baixo. Assim, se aplicado o rastreio de sintomas e contactos de risco, usados os equipamentos de proteção individual adequados, o risco de infeção nas unidades de endoscopia torna-se negligenciável.

Infliximab Induction Strategies in Corticosteroid-Refractory Acute Severe Ulcerative Colitis: A Case Series and Literature Review.

Acute severe ulcerative colitis (ASUC) is an emergent medical condition and particularly challenging to treat efficaciously. Infliximab is one of the medical salvage treatment options after corticosteroid refractoriness, but the best induction strategy is not yet defined. With this case series, the authors intend to describe three corticosteroid-refractory ASUC cases with different intensified/accelerated infliximab induction approaches and review the literature on this topic. The first case describes an 18-year-old girl with ASUC at disease onset with rapid progression to toxic megacolon, complicated also with anemia, hypoalbuminemia, and coagulopathy. After corticosteroid failure, both accelerated and intensified (10 mg/kg) infliximab regimen was completed within 11 days, with solid clinical response and colon imaging normalization. Second, we present a 26-year-old male with left-sided ulcerative colitis known for 2 years, under mesalazine, who developed a moderate flare and was started on infliximab after partial and inconsistent response to corticosteroids. During the induction period, he presented this time an ASUC episode, which motivated an early and intensified third dose with good clinical response. Finally, we describe the case of a 78-year-old man with ulcerative proctitis for 12 years presenting ASUC with proximal disease extension as well. After unsatisfactory response to corticosteroids, infliximab was initiated on an accelerated induction regimen, completed in 13 days, with the standard dose, achieving clinical remission. Accelerated or intensified infliximab induction plans are becoming current clinical practice in corticosteroid-refractory ASUC. Current guidelines refer to the possibility of this type of strategies, not determining the optimal regimen due to lack of solid evidence. Literature is mainly based on retrospective studies, not randomized, with heterogeneous groups according to disease severity, and the effect on colectomy rates, mainly on the long term, is not clear. Additional well-supported studies are needed on this subject in order to seek a more widely uniform approach.

A agudização grave de colite ulcerosa é uma emergência médica, particularmente difícil de tratar de forma eficaz. O infliximab é uma das opções de tratamento médico de resgate após refractariedade aos corticosteróides, porém a melhor estratégia de indução ainda não está definida. Com este relato de série de casos, os autores pretendem descrever três casos de agudização grave de colite ulcerosa refratária a corticosteróides com diferentes abordagens de indução intensificada/acelerada de infliximab e rever a literatura sobre este tópico. O primeiro caso descreve uma jovem de 18 anos com agudização grave de colite ulcerosa, à apresentação da doença, com rápida progressão para megacólon tóxico, complicada também com anemia, hipoalbuminemia e coagulopatia. Após ausência de resposta a corticosteróides, foi iniciado regime acelerado e intensificado (10 mg/kg) de infliximab, concluído em 11 dias, com resposta clínica e normalização das alterações imagiológicas do cólon. Em segundo lugar, apresentamos um homem de 26 anos com colite ulcerosa esquerda conhecida há 2 anos, sob messalazina, que apresentou uma agudização moderada da doença e iniciou infliximab após resposta parcial e inconsistente aos corticosteróides. Durante o período de indução, apresentou desta vez um episódio de agudização grave, o que motivou uma terceira dose precoce e intensificada com boa resposta clínica. Por fim, descrevemos o caso de um homem de 78 anos com proctite ulcerosa há 12 anos apresentando agudização grave de colite ulcerosa, também com extensão proximal da doença. Após resposta insatisfatória a corticosteróides, foi iniciado infliximab em regime de indução acelerada, completado em 13 dias, com a dose padrão, obtendo remissão clínica. Os esquemas de indução de infliximab acelerados ou intensificados têm vindo a tornar-se prática clínica habitual nos casos de agudização grave de colite ulcerosa refratária a corticosteróides. As diretrizes atuais referem a possibilidade deste tipo de estratégias, não indicando qual o regime ideal por falta de evidência sólida. A literatura baseia-se principalmente em estudos retrospetivos, não randomizados, com heterogeneidade de grupos de estudo de acordo com a gravidade da doença e o efeito nas taxas de colectomia, sobretudo a longo prazo, não é claro. Estudos mais fundamentados são necessários sobre esta matéria de modo a que seja possível uma abordagem amplamente mais uniforme.

How many biomarker measurements are needed to predict prognosis in Crohn's disease patients under infliximab?-A prospective study.

BACKGROUND: Timely stratification of Crohn's disease (CD) is essential for patients' management. The use of noninvasive accurate biomarkers is key to monitor treatment and to pursue mucosal healing, the ultimate treatment endpoint in CD. OBJECTIVE: We aimed to evaluate the performance of readily available biomarkers and develop risk matrices to predict CD progression. METHODS: Data from 289 CD patients receiving infliximab (IFX) maintenance therapy for 2 years was collected; those patients were included in DIRECT, a prospective multicenter observational study. Disease progression was evaluated using two composite outcomes incorporating clinical and drug-related factors, the first including IFX dose and/or frequency adjustments. Univariate and multivariable logistic regressions were used to calculate the odds ratios (OR) and to develop risk matrices. RESULTS: The isolated presence of anemia at least once during follow-up was a significant predictor of disease progression (OR 2.436 and 3.396 [p ≤ 0.001] for composite outcomes 1 and 2, respectively) regardless of confounding factors. Isolated highly elevated C-reactive protein (CRP; >10.0 mg/L) and fecal calprotectin (FC; >500.0 µg/g) in at least one visit were also significant predictors, while milder elevations (3.1-10.0 mg/L and 250.1-500.0 µg/g) were only relevant when detected in at least two visits (consecutive or not). The combination of biomarkers in risk matrices had good ability to predict progression; patients simultaneously presenting anemia, highly elevated CRP and FC at least once had 42%-63% probability of achieving the composite outcomes. CONCLUSION: The combined evaluation of hemoglobin, CRP, and FC in at least one time point and their incorporation into risk matrices seems to be the optimal strategy for CD management, as data from additional visits did not meaningfully influence the predictions and may delay decision-making.

Terminal ileitis - When all factors come together.

A 45-year-old male, with a recent surgery for odontoid fracture, presented to the emergency department with a 15-days history of abdominal pain associated with fever and weight loss. He reported a recent history of antibiotic therapy due to respiratory infection and a frequent use of anti-inflammatory drugs (NSAIDs) in the last three months.

Esophagopleural fistula due to empyema necessitans.

Empyema necessitans is a rare entity that consists on the development of an abscess that begins in the pleural space and then extends to the adjacent tissues. This case shows a rare and very late complication of a total pneumonectomy, emphasizing the importance of the multidisciplinary approach and the potential of endoscopic therapy with over-the-scope clips.

Colitis due to Cytomegalovirus and Herpes Simplex Type 2 as a Complication of a First Presentation of Inflammatory Bowel Disease.

INTRODUCTION: The first presentation of ulcerative colitis may be an acute flare in about 15% of patients, requiring hospital admission. In acute severe steroid-refractory ulcerative colitis, cytomegalovirus (CMV) should be sought because it is a frequent cause of refractory disease. Herpes simplex colitis constitutes a rarer event in ulcerative colitis patients and it is usually associated with immunosuppression. CASE PRESENTATION: We report a case of a first presentation of ulcerative colitis complicated by CMV and herpes simplex type 2 coinfection. After a long period of systemic corticosteroids, the diagnosis of both CMV and herpes colitis was made. Despite antiviral treatment, colectomy was required due to a contained perforation. DISCUSSION/CONCLUSION: This report highlights the importance of a high degree of suspicion for opportunistic infections in steroid/immunomodulator refractory ulcerative colitis, even in the first flare.

INTRODUÇÃO: A Colite Ulcerosa pode apresentar-se de forma aguda em até 15% dos casos, com necessidade de internamento hospitalar. Na agudização severa de Colite Ulcerosa refractária a corticoterapia deve ser excluída a infeção por Citomegalovirus (CMV), dado tratar-se de uma causa frequente de doença refractária. A colite por Herpes simplex é mais rara nos doentes com Colite Ulcerosa e associa-se frequentemente a imunossupressão. DESCRIÇÃO DO CASO: Relata-se a apresentação inaugural de Colite Ulcerosa complicada por co-infeção por CMV e herpes simplex tipo 2. Após terapêutica prolongada com corticoids sistémicos, foi diagnosticada colite tanto por CMV como Herpes simplex. Apesar de tratamento anti-vírico, foi necessária colectomia por perfuração cólica. DISCUSSÃO/CONCLUSÃO: Este caso sublinha a importância de um alto grau de suspeição para infeções oportunistas em doentes com doença refractária a corticóide/imunomoduladores, mesmo na primeira agudização.

Subclinical Persistent Inflammation as Risk Factor for Crohn's Disease Progression: Findings From a Prospective Real-World Study of 2 Years.

BACKGROUND AND AIMS: Subclinical intestinal inflammation is common in Crohn's disease (CD). We aimed to explore its impact in the disease progression of infliximab-treated patients and the usefulness of fecal calprotectin (FC) and C-reactive protein (CRP) as surrogate minimally invasive biomarkers. METHODS: The registry-based, prospective, observational, multicenter DIRECT (study to investigate the correlation of fecal calprotectin with serum Drug levels and development of an antI-dRug antibodiEs among adult patients with inflammatory bowel disease reCeiving anti-TNF-alfa treatment or vedoluzimab treatment) study followed infliximab-treated CD patients for 2 years in a tertiary care setting. Persistent inflammation definition was based on FC (>150 µg/g, >250 µg/g, or >350 µg/g) or serum CRP (>3 µg/mL) concentrations over 2 consecutive or at least 3 visits. Patients were categorized according to a composite outcome reflecting disease progression that incorporated surgery; hospitalizations; new fistulae, abscess, or stricture; and treatment escalation. RESULTS: Of 322 DIRECT study patients, 180 asymptomatic, infliximab treated on maintenance regimen were included in the analysis. Patients developing the composite endpoint (n = 96) presented higher median levels of FC (205 [interquartile range, 98-515] µg/g; P = .045) but not of CRP (2.50 [interquartile range, 0.80-6.00] µg/mL; P = .895). Biomarker-defined persistent subclinical inflammation prevalence ranged from 24% to 81%. Considering FC >250 µg/g in 2 consecutive visits, prevalence was 50%, odds of achieving the endpoint were increased 3-fold (odds ratio, 2.996 [95% confidence interval, 1.557-5.776]), and time-to-outcome occurrence was significantly lower among subjects with persistent inflammation (median time: 11 months). Both clinical-related and treatment-related components were significantly associated with persistent inflammation. Definitions based on CRP >3 µg/mL, FC >150 µg/g, FC >350 µg/g, double biomarkers (FC >250 µg/g and/or CRP >3 µg/mL), or more visits did not improve predictive ability. CONCLUSIONS: Persistent inflammation, defined simply and readily by FC >250 µg/g over 2 consecutive visits, was associated with a significantly higher risk and shorter time to occurrence of a composite outcome reflecting disease progression in asymptomatic infliximab-treated CD patients.

Validation of the IBD-Disk in a Portuguese cohort.

OBJECTIVE: The aim of this study was to validate the IBD-Disk in a Portuguese cohort according to the COnsensus-based Standards for the selection of the health Measurement INstruments (COSMIN) recommendations. METHODS: After translation of the original IBD-Disk to Portuguese, a group of IBD patients was invited to complete the IBD-Disk at baseline (T0), after 1-4 weeks (T1) and after more than 3 months (T2), from July 2020 to February 2021. At T0 and T2, the patients also completed the IBD Disability Index. We evaluated reliability (internal consistency, test-retest, interrater reliability and measurement error), construct validity, responsiveness, interpretability of IBD-Disk, sociodemographic and clinical factors associated with IBD-Disk. RESULTS: At T0, 154 patients (107 - Crohn's disease; 46 - ulcerative colitis) completed the IBD-Disk; 1 - IBD-unclassified). At T1 and T2, 64 and 114 patients repeated the questionnaire, respectively. Factor analysis confirmed the unidimensionality of the scale and reduced the final version to 10 items. Internal consistency was excellent with a Cronbach's α of 0.916. The intraclass correlation coefficient was 0.95 for test-retest (T0 and T1). To evaluate construct validity, the IBD-Disk was compared with the IBD Disability Index and Manitoba IBD Index with a significative positive correlation (r = 0.850 and r = 0.459, respectively; P < 0.001 for both). IBD-Disk scores ranged from 0 to 93 with a mean of 38.18 ± 25.39. Female sex, professional inactivity, longer IBD duration and clinical activity were associated with significantly higher IBD-Disk scores. CONCLUSION: The Portuguese version of IBD-Disk is a reliable and valid tool to assess disability in Portuguese IBD patients.

Clinical Performance of New Software to Automatically Detect Angioectasias in Small Bowel Capsule Endoscopy.

BACKGROUND: Video capsule endoscopy (VCE) revolutionized the diagnosis and management of obscure gastrointestinal bleeding, though the rate of detection of small bowel lesions by the physician is still disappointing. Our group developed a novel algorithm (CMEMS-Uminho) to automatically detect angioectasias which display greater accuracy in VCE static frames than other methods previously published. We aimed to evaluate the algorithm overall performance and assess its diagnostic yield and usability in clinical practice. METHODS: Algorithm overall performance was determined using 54 full-length VCE recordings. To assess its diagnostic yield and usability in clinical practice, 38 VCE examinations with the clinical diagnosis of angioectasias consecutively performed (2017-2018) were evaluated by three physicians with different experiences. The CMEMS-Uminho algorithm was also applied. The performance of the CMEMS-Uminho algorithm was defined by a positive concordance between a frame automatically selected by the software and a study independent capsule endoscopist. RESULTS: Overall performance in complete VCE recordings was 77.7%, and diagnostic yield was 94.7%. There were significant differences between physicians in regard to global detection rate (p < 0.001), detection rate per capsule (p < 0.001), diagnostic yield (p = 0.007), true positive rate (p < 0.001), time (p < 0.001), and speed viewing (p < 0.001). The application of CMEMS-Uminho algorithm significantly enhanced all readers' global detection rate (p < 0.001) and the differences between them were no longer observed. CONCLUSION: The CMEMS-Uminho algorithm detained a good overall performance and was able to enhance physicians' performance, suggesting a potential usability of this tool in clinical practice.

INTRODUÇÃO: A endoscopia por cápsula (EC) revolucionou o diagnóstico da hemorragia gastrointestinal obscura, porém a taxa de defeção de lesões no intestino delgado pelo endoscopista permanece insatisfatória. Desenvolveu-se um novo algoritmo para a defeção automática de angioectasias, que revelou uma melhor acuidade na avaliação de imagens de EC que outros métodos previamente publicados. Pretende-se avaliar agora a performance global do algoritmo, o seu rendimento diagnóstico e a utilidade na prática clínica. MÉTODOS: A performance global do algoritmo foi avaliada com 54 vídeos de EC. Para avaliar o seu rendimento diagnóstico e utilidade na prática clinica, 38 EC consecutivas com diagnóstico clínico de angiectasias (2017­2018) foram analisadas por três médicos com experiência distinta. A performance do algoritmo CMEMS-Uminho foi definida por uma concordância positiva entre um frame selecionado automaticamente pelo software e um endoscopista de cápsula independente do estudo. RESULTADOS: O algoritmo CMEMS-Uminho revelou uma performance global de 77,7% e um rendimento diagnóstico de 94,7%. Os médicos apresentaram diferenças significativas na taxa de defeção global (p < 0,001), taxa de deteção por cápsula (p < 0,001), rendimento diagnóstico (p = 0,007), taxa de verdadeiros positivos (p < 0,001), tempo (p < 0,001) e velocidade de visualização (p < 0,001). A aplicação do algoritmo CMEMS-Uminho melhorou significativamente a taxa de deteção dos médicos (p < 0,001) e as diferenças entre eles diluiram-se após a sua aplicado. CONCLUSÃO: O algoritmo CMEMS-Uminho deteve um bom desempenho global e foi capaz de melhorar o desempenho médico, sugerindo uma potencial utilidade desta ferramenta na prática clínica.

Gastrointestinal manifestations of COVID-19: results from a European centre.

BACKGROUND: Infection due to severe acute respiratory syndrome coronavirus 2 is typically associated with a respiratory syndrome, but gastrointestinal symptoms have been described in early reports from China. However, data from European centres are scarce. OBJECTIVES: We aimed to characterise the gastrointestinal manifestations of patients with coronavirus disease 2019 (COVID-19) and their disease course. METHODS: Patients admitted at our centre between March and April 2020 with diagnosis of COVID-19 were included. Asymptomatic patients or those without symptom information were excluded. Clinical features, laboratory data and disease severity (mechanical ventilation, intensive care admission or death) were analysed. RESULTS: Two-hundred one patients were included (median age 71 years; 56.2% male). Digestive symptoms were reported by 60 (29.9%) patients during the disease course, being part of the disease presentation in 34 (16.9%). The most frequent were diarrhoea in 36 patients (17.9%). Patients with gastrointestinal symptoms were younger (P = 0.032), had higher haemoglobin levels (P = 0.002) and lower C-reactive protein (P = 0.045) and potassium levels (P = 0.004). Patients with digestive symptoms had less severe disease (28.3 vs. 44.0%; P = 0.038). Regarding liver damage, aspartate aminotransferase (AST) was elevated in 65.2% of patients and alanine aminotransferase (ALT) in 62.7%, but these patients did not present a more severe disease (elevated AST P = 0.062; elevated ALT P = 0.276). CONCLUSION: A significant portion of COVID-19 patients have digestive symptoms, mostly at presentation. This should be taken into account in order to keep a high level of suspicion to reach an early diagnosis and setup infection control measures to control the transmission rate. This subgroup of patients appears to have a less severe disease course.

Sleep Disturbance in Inflammatory Bowel Disease Is Associated with Disease Activity and Adverse Outcome.

BACKGROUND: There is growing evidence about the relationship between sleep quality (SQ) and disease activity in inflammatory bowel disease (IBD). This study aimed to identify the prevalence of sleep disturbance in IBD and its predictive factors and to assess its association with worse outcome. METHODS: IBD patients were prospectively enrolled. Clinical activity, inflammatory activity (high C-reactive protein or fecal calprotectin), and SQ (assessed using the Pittsburgh Sleep Quality Index) were evaluated, and logistic regression was used to identify predictors of poor SQ at baseline. The development of disability or disease progression at 6 months (surgery, hospitalization, development of stenosis, penetrating or perianal disease, steroid dependency, or start/change immunosuppression) was compared between patients with and without poor SQ. RESULTS: Two hundred and five patients were enrolled, with 44.9% (n = 92) reporting poor SQ. On multivariate analysis, current smoking (OR 2.80), extraintestinal manifestations (OR 2.68), clinical activity (OR 3.31), and inflammatory activity (OR 4.62) were predictive factors of poor SQ. Cox proportional hazards model showed that poor SQ was predictive of worse prognosis at 6 months (HR 2.470). CONCLUSION: There is a high prevalence of poor SQ in IBD patients, highlighting the importance of its inclusion in patient-reported outcomes. Sleep disturbance seems to have prognostic value in IBD.

Histologic Features of Colon Biopsies (Geboes Score) Associated With Progression of Ulcerative Colitis for the First 36 Months After Biopsy.

BACKGROUND & AIMS: In addition to findings from endoscopy, histologic features of colon biopsies have been associated with outcomes of patients with ulcerative colitis (UC). We investigated associations between Geboes scores (a system to quantify structural changes and inflammatory activity in colon biopsies) and UC progression, and the time period over which this association is valid. METHODS: We analyzed data from 399 asymptomatic patients with UC enrolled in the ACERTIVE study, followed at 13 inflammatory bowel disease (IBD) centers in Portugal through 31 December 2019. Blood and stool samples were collected and analyzed, and all patients underwent sigmoidoscopy within 24 h of sample collection. We assessed baseline endoscopic status (Mayo endoscopic subscore), histologic features of 2 sigmoid and 2 rectal biopsies (Geboes score), and concentration of fecal calprotectin (FC). The primary outcome was UC progression (surgical, pharmacologic, and clinical events). We generated survival curves for 36 months or less and more than 36 months after biopsy according to Geboes score using the Kaplan-Meier method and compared findings with those from a log rank test. Cox regression was adjusted for Mayo endoscopic subscore, Geboes score, and level of FC; results were expressed as adjusted hazard ratios (HR) with 95% CIs. RESULTS: Patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 had a higher frequency of, and a shorter time to UC progression, than patients with Geboes scores ≤2B.0, Geboes scores ≤3.0, or Geboes score ≤4.0 (P < .001). Disease progression occurred earlier in patients with Geboes scores >2B.0, Geboes scores >3.0, or Geboes scores >4.0 compared with patients with Geboes scores ≤2B.0 (HR, 2.021; 95% CI, 1.158-3.526), Geboes scores ≤3.0 (HR, 2.007; 95% CI, 1.139-3.534), or Geboes scores ≤4.0 (HR, 2.349; 95% CI, 1.269-4.349), respectively, in the first 36 months after biopsy. Similar results were found for patients with concentrations of FC below 150 µg/g. CONCLUSIONS: We found histologic features of colon biopsies (Geboes score) to be an independent risk factor for progression of UC in the first 36 months after biopsy.

Rapid test detection of anti-infliximab antibodies: performance comparison with three different immunoassays.

BACKGROUND AND AIMS: Therapeutic drug monitoring (TDM) of infliximab (IFX) and anti-infliximab antibodies (ATIs) is essential for treatment optimisation in inflammatory bowel disease (IBD) patients. The aim of this study was to estimate and compare the agreement and accuracy between a new rapid test and three established enzyme-linked immunosorbent assays (ELISAs) to quantify ATIs levels, and to evaluate the impact of exogenous IFX on the performance of these assays. METHODS: We analysed 200 serum samples from 57 IBD outpatients in IFX induction or maintenance therapy at six IBD centres in Portugal. ATI levels were quantified using the rapid test Quantum Blue® (QB) Anti-Infliximab (Bühlmann) and three established ELISAs: In-House, Theradiag (Lisa Tracker Anti-Infliximab), and Immundiagnostik (IDKmonitor Infliximab). ATIs were quantified in patients' serum samples and spiked samples with exogenous IFX, based on analytical and clinical cutoffs. Qualitative agreement and accuracy were estimated by Cohen's kappa (k) with 95% confidence intervals. RESULTS: ATIs quantification with clinical cutoffs showed a slight agreement between QB rapid test and In-House [k = 0.163 (0.051-0.276)] and Immundiagnostik [k = 0.085 (0.000-0.177)]. Regarding IFX/ATIs status, the QB rapid test showed a substantial agreement with Theradiag [k = 0.808 (0.729-0.888)] and a fair agreement with In-House [k = 0.343 (0.254-0.431)] and Immundiagnostik [k = 0.217 (0.138-0.297)]. The QB rapid test could not detect ATI-positive levels in samples with exogenous IFX at 5-300 µg/ml. Interference on ATIs detection was observed at exogenous IFX ⩾30 µg/ml for In-house and Immundiagnostik assays. CONCLUSION: QB rapid test is only suitable to detect ATI-positive levels in the absence of IFX.