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.

Burden of Disease and Cost of Illness of Inflammatory Bowel Diseases in Portugal.

Background: Inflammatory bowel diseases' (IBD) increasing incidence and prevalence place a heavy health and economic burden on society. Objectives: This study assesses the burden and cost of IBD in Portugal to support the definition of health policies, resource allocation, and patient care. Methods: The burden of disease was expressed using disability-adjusted life years (DALY). Costs were estimated considering the societal perspective, using a prevalence-based model and prices established by law. An expert panel composed of 5 expert Portuguese gastroenterologists and a patient-reported study were conducted to support the cost analysis and fill in information gaps. Results: In Portugal, with a prevalence of 24,069 IBD patients and an incidence of 15/100,000, the burden of disease was estimated at 6,067 DALYs: 507 resulting from premature deaths and 5,560 from disability. Total cost was estimated at EUR 146 million per year, with direct costs representing 59%. Average yearly cost per IBD patient is EUR 6,075, where 60% is related to Crohn's disease and 40% to ulcerative colitis (UC). Conclusion: This study estimates the annual health burden and cost of IBD in Portugal, thus generating information with the intent to raise awareness of the need to advance health policies as well as better clinical and economic decisions in this pathology.

Contexto: A crescente incidência e prevalência das Doenças Inflamatórias Intestinais (DII) representam um pesado fardo para a saúde e economia na sociedade. Objetivos: Este estudo avalia o custo e a carga da DII em Portugal, com o objetivo de suportar a definição de políticas de saúde, alocação de recursos e cuidados com o doente. Métodos: A carga da doença foi calculada utilizando anos de vida ajustados à incapacidade (DALY). Os custos foram estimados tendo em conta a perspetiva da sociedade, utilizando um modelo baseado na prevalência e preços estabelecidos por lei. Foi realizado um painel de peritos, composto por 5 gastroenterologistas portugueses, assim como um estudo de mercado a doentes, de forma a suportar a análise de custos e colmatar lacunas de informação. Resultados: Em Portugal, com uma prevalência de 24,069 doentes e uma incidência de 15/100,000, o peso das DII foi estimado em 6.067 DALYs: 507 dos quais resultantes de mortes prematuras e 5.560 de incapacidade. O custo total foi estimado em 146 milhões de euros por ano, com os custos diretos a representarem 59% do total. O custo médio anual por doente de DII é de 6.075 EUR, onde 60% está relacionado com Doença de Crohn (DC) e 40% com Colite Ulcerosa. Conclusão: Este estudo estima os encargos anuais para a saúde e o custo da DII em Portugal, gerando informação relevante, com o intuito de alertar para a necessidade de uma evolução nas políticas de saúde, assim como como suportar melhores decisões clínicas e económicas nesta patologia.

Tofacitinib-induced eosinophilia.

Tofacitinib is an oral small molecule JAK inhibitor approved for the treatment of moderate to severe ulcerative colitis (UC). Its efficacy and safety have been demonstrated in phase III clinical trials and supported by real-life data. We report the case of an 18-year-old woman with a 1-year diagnosis of left-sided UC, with multiple admissions due to disease exacerbation or infections, refractory to infliximab (with azathioprine) and currently under treatment with vedolizumab and tacrolimus. She was admitted due to a severe disease exacerbation and, because of a previous history of neuropsychiatric side effects to corticotherapy, tofacitinib was initiated. In the following 6 days, there was no clinical improvement of UC, and serial blood work-up revealed moderate grade persistent peripheral eosinophilia (3000 cells/mm3) and acute kidney injury grade 1 KDIGO. Tofacitinib temporary suspension was decided, with a rapid normalization of renal function/eosinophil levels. Tofacitinib was restarted 2 days after its suspension. However, she developed moderate eosinophilia (2000 cells/mm3) again, which was considered an adverse effect (AE) to tofacitinib, leading to its suspension with eosinophilia resolution. Given the severity of the disease, after a multidisciplinary discussion, it was decided to start high-dose corticotherapy and ustekinumab with maintenance therapy every 4 weeks, and to add tacrolimus. Clinical and biochemical remission were achieved, and the patient was discharged. Three-month follow-up after tofacitinib suspension showed no recrudescence of eosinophilia. Tofacitinib represents a significant advance in the management of UC patients. The drug has a good safety profile with few related AE. This case aims to warn about an adverse reaction to tofacitinib not reported so far, including in a multicenter real-life setting recently published by Hernández et al where eosinophilia is also not described, thus emphasizing the rarity of this AE. To our knowledge this is the first case of tofacitinib-induced eosinophilia in the context of UC. .

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.

Positioning Aeromonas Infection in Inflammatory Bowel Disease: A Retrospective Analysis.

Background and Aim: Aeromonas are Gram-negative rods known to cause a spectrum of diseases. Inflammatory bowel disease (IBD) is an idiopathic complex condition resulting from interaction of multiple factors. Aeromonas infection in association with IBD is still largely unknown. We aim to look for the significance of Aeromonas infection and for significant differences between IBD and non-IBD patients. Methods: A retrospective observational analysis was performed of all patients positive for Aeromonas in stool cultures, during a 10-year period, from a tertiary and university hospital. Results: Fifty patients were included, 56% male with a mean age of 42.1 years. Thirty-eight (76%) were non-IBD and 12 (24%) IBD patients. IBD patients were more frequently under immunosuppressors. Two patients were asymptomatic and 44% developed mild, 44% moderate, and 16.7% severe infection. The main strains isolated were Aeromonas hydrophila/caviae. Bacterial co-isolation was found in 4 non-IBD and histological findings of cytomegalovirus in 2 IBD patients. Non-IBD patients presented more frequently with fever and IBD patients with bloody diarrhea and abdominal pain. There was higher tendency for severe infection rate in IBD patients with higher antimicrobial therapy use. Steroids were exclusively used in the IBD group. From IBD, 4 patients had the diagnosis of ulcerative colitis and 9 of Crohn's disease with colonic involvement. Of these patients, 5 received IBD diagnosis after the acute episode of Aeromonas infection. Conclusions: Clinical presentation of Aeromonas infection differs between IBD and non-IBD patients. Non-IBD patients had milder severity of infection with less use of antibiotics. Aeromonas infection seems to greatly contribute to IBD manifestation.

Introdução: A etiologia da Doença Inflamatória Intestinal (DII) é complexa e resultante da interação de diversos fatores, nomeadamente microbiológicos. A infeção por Aeromonas caracteriza-se por um espectro alargado de manifestações clínicas. O papel da infeção por Aeromonas na DII não está caracterizado. Objetivos: Avaliar o significado da infeção por Aeromonas na DII e as diferenças com a infeção em doentes não-DII. Métodos: avaliação retrospetiva e observacional de todos os doentes com isolamento microbiológico de Aeromonas em amostras fecais num período de 10 anos, num hospital terciário. Resultados: foram avaliados 50 doentes, 56% do sexo masculino, com idade média de 42.1 anos. Doze (24%) com diagnóstico de DII e trinta e oito (76%) não-DII. Os doentes com DII encontravam-se mais frequentemente sob imunossupressão. Dois doentes foram assintomáticos, 44% desenvolveram doença ligeira, 44% moderada e 16.7% severa, havendo maior tendência para infeção severa nos DII. Os doentes não-DII apresentaram mais frequentemente febre e os DII diarreia sanguinolenta e dor abdominal. O uso de antimicrobianos foi superior no grupo DII e a utilização de corticoesteroides foi exclusiva nestes doentes. Isolamento concomitante de outros agentes microbiológicos ocorreu em 4 doentes não-DII e 2 com DII tinham histologia compatível com infeção por Citomegalovírus. Da população DII, 4 eram Colite Ulcerosa e 9 Doença de Crohn com envolvimento cólico. Destes, 5 receberam o diagnóstico após a infeção por Aeromonas. Conclusão: A apresentação clínica da infeção por Aeromonas foi distinta entre as populações DII e não-DII, sendo que os doentes DII apresentaram doença mais severa e maior utilização de antimicrobianos. A infeção na DII ocorreu essencialmente em doentes com envolvimento cólico.

Composite outcomes in observational studies of Crohn's disease: a systematic review and meta-analysis.

Background: This systematic review and meta-analysis aims to assess composite and aggregate outcomes of observational studies in Crohn's disease and to evaluate whether the number and type of variables included affect the frequency of the outcome. Methods: MEDLINE [via PubMed], Scopus and Web of Science were searched to identify observational studies that enrolled patients with Crohn's disease and evaluated a composite or aggregate outcome. The proportion of patients achieving the outcome was determined and a random-effects meta-analysis was performed to evaluate how the frequency of each outcome varies according to the reporting of predefined variables. Results: From 10,257 identified records, 46 were included in the qualitative analysis and 38 in the meta-analysis. The frequency for composite and aggregate outcomes was 0.445 [95% confidence interval (CI): 0.389-0.501] and 0.140 (95% CI: 0.000-0.211), respectively. When comparing composite outcomes by number of included variables, the frequency was 0.271 (95% CI: 0.000-0.405) and 0.698 (95% CI: 0.651-0.746), for one and six variables, respectively. The frequency of the composite outcome varied according to the identity of the variables being reported. Specific pairs of predefined variables had a significant effect in the frequency of composite outcomes. Conclusion: Composite outcomes with increasing number of predefined variables show an increase in frequency. Outcomes including variables such as 'Surgery' and 'Steroids' had higher frequencies when compared with the ones that did not include these variables. These results show that the frequency of composite outcomes is dependent on the number and type of variables being reported.

Incidence Trends of Inflammatory Bowel Disease in a Southern European Country: A Mirror of the Western World?

INTRODUCTION: Inflammatory bowel disease (IBD) affects people from all age categories worldwide. Although the incidence of the disease is stabilizing or decreasing in most Western world countries, its prevalence is still increasing because of the rise in life expectancy and better disease management. This work intends to identify the trends related to IBD incidence nationwide, analyzing regional, sex, and age distributions. METHODS: Data were provided by the Portuguese Shared Services of the Ministry of Health. This study consisted of a retrospective analysis of all first consultations coded for "Chronic enteritis/ulcerative colitis" (D94) in a primary healthcare setting, between 2017 and 2020, in Portugal. The primary outcome measure was the IBD incidence rate per 100,000 inhabitants. We also calculated the incidence rate per person-year and forecasted incidence until 2024. RESULTS: Between 2017 and 2019, the incidence rate of IBD in Portugal decreased from 54.9 to 48.6 per 100,000 inhabitants. The average incidence was 20 new cases of IBD per 1,000 person-year. It was predicted that, in December 2023, IBD incidence would reach 305.4 new cases (95% Prediction Interval 156.6-454.3), a similar result to the values forecasted for December 2021 (305.4, 95% Prediction Interval 197.3-413.6). DISCUSSION: The incidence of IBD slightly declined from 2017 to 2019, and it is posed to stabilize in the future. The presented data are of the utmost importance for the characterization of IBD in Southern European countries and the establishment of future health policies in the setting of compounding prevalence in the Western world.

The Magnitude of Crohn's Disease Direct Costs in Health Care Systems (from Different Perspectives): A Systematic Review.

BACKGROUND: The prevalence of inflammatory bowel disease (IBD) has been increasing worldwide, causing high impact on the quality of life of patients and an increasing burden for health care systems. In this systematic review, we reviewed the literature concerning the direct costs of Crohn's disease (CD) for health care systems from different perspectives: regional, economic, and temporal. METHODS: We searched for original real-world studies examining direct medical health care costs in Crohn's disease. The primary outcome measure was the mean value per patient per year (PPY) of total direct health care costs for CD. Secondary outcomes comprised hospitalization, surgery, CD-related medication (including biologics), and biologics mean costs PPY. RESULTS: A total of 19 articles were selected for inclusion in the systematic review. The studies enrolled 179 056 CD patients in the period between 1997 and 2016. The pooled mean total cost PPY was €6295.28 (95% CI, €4660.55-€8503.41). The pooled mean hospitalization cost PPY for CD patients was €2004.83 (95% CI, €1351.68-€2973.59). The major contributors for the total health expenditure were biologics (€5554.58) and medications (€3096.53), followed by hospitalization (€2004.83) and surgery (€1883.67). No differences were found between regional or economic perspectives, as confidence intervals overlapped. However, total costs were significantly higher after 2010. CONCLUSIONS: Our review highlighted the burden of CD for health care systems from different perspectives (regional, economic, and temporal) and analyzed the impact of the change of IBD treatment paradigm on total costs. Reducing the overall burden can depend on the increase of remission rates to further decrease hospitalizations and surgeries.

Composite outcomes in observational studies of ulcerative colitis: A systematic review and meta-analysis.

BACKGROUND: Ulcerative colitis (UC) has been the focus of numerous observational studies over the years and a common strategy employed in their design is the use of composite and aggregate outcomes. OBJECTIVE: This systematic review and meta-analysis aims to identify composite and aggregate outcomes of observational studies in UC and to evaluate how the number and type of variables included and the length of follow-up affect the frequency of patients that achieve these outcomes. METHODS: A systematic literature search was carried out using MEDLINE [via PubMed], Scopus, and Web of Science online databases. Observational studies that included UC patients and reported composite or aggregate outcomes were identified. A set of variables considered to be representative of progressive or disabling UC was defined, the proportion of patients attaining the outcomes was determined and a random-effects meta-analysis was performed by dividing the identified studies into subgroups according to different criteria of interest. RESULTS: A total of 10,264 records were identified in the systematic search, of which 33 were retained for qualitative analysis and 20 were included in the meta-analysis. The mean frequency for composite outcomes was 0.363 [95% confidence interval (CI) 0.323-0.403]. The frequency of composite outcome for the subgroup of studies that included the variable "Biologics" was significantly higher than for those in which this variable was not reported [0.410; 95% CI 0.364-0.457 versus 0.298; 95% CI 0.232-0.364; p = 0.006]. Composite outcomes were also more frequent as the follow-up duration increased. CONCLUSION: The frequency of composite outcomes in observational studies of UC is dependent on the specific identity of the variables being reported. Moreover, longer follow-up periods are associated with higher frequencies of composite outcomes. The evidence provided here is useful for the design of future observational studies of UC that aim to maximize the frequency of patients that achieve composite outcomes.

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.

Bringing to Light the Risk of Colorectal Cancer in Inflammatory Bowel Disease: Mucosal Glycosylation as a Key Player.

Colitis-associated cancer is a major complication of inflammatory bowel disease remaining an important clinical challenge in terms of diagnosis, screening, and prognosis. Inflammation is a driving factor both in inflammatory bowel disease and cancer, but the mechanism underlying the transition from colon inflammation to cancer remains to be defined. Dysregulation of mucosal glycosylation has been described as a key regulatory mechanism associated both with colon inflammation and colorectal cancer development. In this review, we discuss the major molecular mechanisms of colitis-associated cancer pathogenesis, highlighting the role of glycans expressed at gut epithelial cells, at lamina propria T cells, and in serum proteins in the regulation of intestinal inflammation and its progression to colon cancer, further discussing its potential clinical and therapeutic applications.

Colitis-associated cancer (CAC) is a major complication of inflammatory bowel disease and the molecular mechanisms underlying CAC progression are still elusive. Protein glycosylation holds a great promise for improving the understanding of CAC immunopathogenesis, opening new avenues for clinical and therapeutic interventions.

Genetic and Bioinformatic Strategies to Improve Diagnosis in Three Inherited Bleeding Disorders in Bogotá, Colombia.

Inherited bleeding disorders (IBDs) are the most frequent congenital diseases in the Colombian population; three of them are hemophilia A (HA), hemophilia B (HB), and von Willebrand Disease (VWD). Currently, diagnosis relies on multiple clinical laboratory assays to assign a phenotype. Due to the lack of accessibility to these tests, patients can receive an incomplete diagnosis. In these cases, genetic studies reinforce the clinical diagnosis. The present study characterized the molecular genetic basis of 11 HA, three HB, and five VWD patients by sequencing the F8, F9, or the VWF gene. Twelve variations were found in HA patients, four in HB patients, and 19 in WVD patients. From these variations a total of 25 novel variations were found. Disease-causing variations were used as positive controls for validation of the high-resolution melting (HRM) variant-scanning technique. This approach is a low-cost genetic diagnostic method proposed to be incorporated in developing countries. For the data analysis, we developed an accessible open-source code in Python that improves HRM data analysis with better sensitivity of 95% and without bias when using different HRM equipment and software. Analysis of amplicons with a length greater than 300 bp can be performed by implementing an analysis by denaturation domains.

The Coronavirus Chasm in Inflammatory Bowel Disease: Report of Patient-Centered Care at a Hospital in Northern Portugal.

INTRODUCTION: Although patient-centered care can be found in the mission statement of nearly every hospital, it is not always put into practice, and COVID-19 brings new challenges even to the best-organized hospitals and well-developed health care systems. METHODS: In the current COVID-19 pandemic, inflammatory bowel disease (IBD) patients have a potentially higher risk of complications from this infectious disease due to the use of immunosuppressant and/or biologic treatments and due to flares of this chronic illness, which often require urgent care and sometimes hospitalization. Moreover, patients undergoing biologic intravenous (IV) treatment visit the hospital for scheduled IV infusions. DISCUSSION: In hospitals like ours, where COVID-19 patients are treated, the organization of "clean circuits" is essential to minimize the risks of infection for non-COVID-19 patients, such as patients in IBD infusion units. In our hospital, the IBD infusion unit is located within the gastroenterology department, which, under normal circumstances, is very advantageous for patients but in the current context is not. Our goal was to maximize adherence to biologic IV treatment and clinical safety at a time of profound changes in gastroenterology activity and in a department with daily increases in the number of COVID-19 patients. CONCLUSION: To this end, we initiated proactive COVID-19 testing in IBD patients undergoing biologic IV treatment and changed the location of the infusion unit to a "COVID-free" institution, maintaining the care of these patients by the dedicated IBD team of our department. The purpose of this report is to show that a patient-centered care strategy allowed us to reach very high levels of patient comfort, satisfaction, and compliance with therapeutics.

INTRODUÇÃO: Os cuidados centrados no doente são uma intenção de quase todas as declarações de missão de um hospital. No entanto, nem sempre são colocados em prática. A doença por COVID-19 trouxe novos desafios, mesmo para os hospitais mais bem organizados e com sistemas de saúde desenvolvidos. MÉTODOS: Na atual pandemia COVID-19, os doentes com doença intestinal inflamatória (DII), têm um risco potencialmente maior de complicações desta doença infeciosa, quer pelo uso de tratamentos imunossupressores e/ou biológicos, quer pela natureza crónica da doença, que evolui com agudizações, que frequentemente requerem cuidados urgentes e, às vezes, hospitalização. Os doentes sob biológicos intravenosos (IV) necessitam de recorrer ao hospital para infusão programada. DISCUSSÃO: Em hospitais como o nosso, onde doentes com COVID-19 são recebidos e tratados, a organização de "circuitos limpos" é essencial para minimizar os riscos de infeção em doentes não-COVID-19, nomeadamente nas unidades de infusão de biológicos. No nosso Hospital, a unidade de infusão localiza-se dentro do Departamento de Gastrenterologia, o que em circunstâncias normais é muito vantajoso para os doentes, mas não o foi no contexto da atual pandemia. O nosso objetivo, num momento de profunda mudança da atividade da Gastrenterologia e num Departamento com aumento diário do número de doentes COVID-19, foi o de maximizar a adesão aos tratamentos biológicos IV e a sua segurança clínica. CONCLUSÃO: Para isso iniciamos um programa proactivo de teste a COVID-19, nos doentes com DII, sob biológicos IV, e mudamos a unidade de infusão para uma Instituição "COVID free," mantendo a habitual orientação destes doentes pela equipe diferenciada de DII do nosso Serviço. O objetivo deste trabalho é mostrar que, com uma estratégia de cuidados centrados no doente, foi possível atingir níveis elevados de adesão à terapêutica, de conforto e satisfação.

Age at Diagnosis Is Determinant for the Outcome of Inflammatory Bowel Disease: Is It a Myth?

INTRODUCTION: Patients with elderly-onset inflammatory bowel disease were previously associated with a less aggressive course of the disease. However, there are conflicting data that need further validation. We aimed to determine the association between age at diagnosis and the development of progressive disease in patients with Crohn's disease (CD) and ulcerative colitis (UC). METHODS: This cohort study included patients with CD and UC followed in 6 secondary and tertiary care centers in mainland Portugal. Patients were divided into a derivation (80%) cohort and a validation (20%) cohort. The primary outcome was progressive disease. Logistic regression analysis, receiver operating characteristic curves, and the areas under the curve (AUC) were performed. Odds ratios with 95% confidence intervals (CIs) were estimated. RESULTS: The derivation cohorts included 1245 patients with CD (68% with progressive disease) and 1210 patients with UC (37% with progressive disease), whereas the validation cohorts included 302 patients with CD and 271 patients with UC, respectively, with similar outcome proportions. In our final model, age at diagnosis older than 60 years was significantly associated with a lower risk of developing progressive disease (odds ratio 0.390, 95% CI 0.164-0.923, P = 0.032), with a high discriminative power (AUC 0.724, 95% CI 0.693-754) in patients with CD. However, according to this model, no significant associations were found between age at diagnosis and the risk of developing progressive disease in patients with UC. No differences were observed in the AUC values between the validation and the derivation cohorts. DISCUSSION: Patients with elderly-onset CD, but not patients with UC, were associated with a less progressive course of the disease.

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.

Clinical, Endoscopic and Histological Outcomes in Induction of Moderate-to-Severe Ulcerative Colitis: A Systematic Review with Meta-Analysis.

BACKGROUND AND AIMS: Interest in histology for ulcerative colitis [UC] has increased recently. This systematic review and meta-analysis aims to assess, for the first time, whether histological outcomes are more informative than endoscopic and clinical outcomes in distinguishing the impact of intervention over placebo in induction trials. METHODS: MEDLINE, ScienceDirect and Cochrane Central Register of Controlled Trials were searched to identify randomized placebo-controlled trials [RCTs] enrolling moderate-to-severe UC patients. Studies were assessed using the Quality Assessment Tool for Studies with Diverse Designs. We analysed the pooled proportion of patients achieving clinical, endoscopic and histological remission and response after a pharmacological intervention and compared the results with those of placebo-treated patients by using a random-effects model. RESULTS: From 889 identified records, 13 RCTs were included. The odds ratio [OR] for remission was higher in patients receiving intervention than in those under placebo for clinical (OR 2.13, 95% confidence interval [CI] 1.33-3.43), endoscopic [OR 1.46, 95% CI 0.19-11.18] and histological remission [OR 1.85, 95% CI 1.20-2.84]. Significant differences were observed for all response outcomes [clinical: OR 2.27, 95% CI 1.84-2.85; endoscopic: OR 2.16, 95% CI 1.51-3.10; histological: OR 3.63, 95% CI, 1.41-9.36]. No significant heterogeneity existed; no subgroup effects were found for duration of the induction or histological scale [p > 0.05]. Clinical and histological remission and endoscopic response were concordant in discriminating interventions from placebo. CONCLUSION: Histological outcomes are informative in trials of moderate-to-severe UC. Further studies analysing histology at the end of induction are needed to confirm its relevance in distinguishing the efficacy of an intervention over placebo in comparison to clinical and endoscopic outcomes and to explore its prognostic value.

A rare cecal subepithelial tumor in a Crohn´s Disease patient

Appendiceal tumors comprise a variety of histologic types, including appendiceal mucinous neoplasms, which can be grouped as premalignant lesions, tumors of uncertain malignant potential, and malignant lesions. The appendiceal mucinous neoplasms are characterized by mucinous epithelial proliferation with extracellular mucin and pushing tumor margins, commonly an incidental finding during operative exploration. We report the case of a low-grade appendiceal mucinous neoplasm presenting as a subepithelial lesion in Crohn´s Disease patient. The diagnosis was not straightforward, and only surgical resection allowed an accurate diagnosis. Although Inflammatory Bowel Disease is a risk factor for the development of colorectal neoplasms, the absolute risk for appendiceal tumors is uncertain. The frequency of progression to malignancy remains to be determined.

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.

Inflammatory Bowel Disease Reoperation Rate Has Decreased Over Time If Corrected by Prevalence.

INTRODUCTION: Despite the recent emergence of expensive biologic therapies, hospitalization and surgery remain important contributors for the overall costs of inflammatory bowel disease (IBD). In this study, we aimed to describe the burden of reoperations in patients with IBD by evaluating reoperation rates, charges, and risk factors over 16 years. METHODS: We performed a retrospective analysis of all hospital discharges, with focus on reoperations and with a primary diagnosis of IBD, in public hospitals between 2000 and 2015 in mainland Portugal from the Central Administration of the Health System's national registry. We collected data on patient, clinical, and healthcare charges. We used multivariate regressions to estimate the risk factors of IBD-related reoperations. RESULTS: We found that 5% of IBD-related hospitalizations were related to reoperations. The number of reoperations per year increased by approximately 200%. However, when corrected by the prevalence of the disease, IBD reoperation rates decreased. Mean IBD-related charges per hospitalization were 7,780 &OV0556; in 2000 and 10,592 &OV0556; in 2015, with total charges reaching 6.7 million euros by the end of the study. Risk factors for reoperation include urgent hospitalization, in patients with ulcerative colitis (odds ratio 1.94, 95% confidence interval 1.19-3.17, P = 0.008), and colic disease, in patients with Crohn's disease (odds ratio 1.57, 95% confidence interval 1.06-2.34, P = 0.025). DISCUSSION: To obtain an accurate scenario of reoperations among patients with IBD, it is mandatory to adjust the number of reoperations to the prevalence of the disease. Reoperation and its risk factors should be closely monitored to decrease the burden of IBD to the healthcare system.