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1.
J Crohns Colitis ; 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38243908

RESUMO

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.

2.
Dig Liver Dis ; 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37980274

RESUMO

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.

3.
United European Gastroenterol J ; 11(6): 531-541, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37318072

RESUMO

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.


Assuntos
Doença de Crohn , Humanos , Infliximab/uso terapêutico , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Doença de Crohn/metabolismo , Estudos Prospectivos , Biomarcadores , Prognóstico , Progressão da Doença
4.
Artigo em Inglês | MEDLINE | ID: mdl-36915954

RESUMO

INTRODUCTION: Inflammatory Bowel Disease (IBD) patients may have an increased risk of neoplasia. The aim was to evaluate the incidence of malignant neoplasia in IBD patients, associated risk factors and therapy adjustments. METHODS: Unicentric retrospective cohort study. All patients followed for IBD in a tertiary portuguese hospital and oncological centre during 2015-2020 were included. RESULTS: 318 patients were included female 55.0%, age at diagnosis = 37.24(±15,28), Crohn's disease 52.5%, Primary Sclerosing Cholangitis n = 7, family history of cancer n = 12, previous diagnosis of neoplasia n = 23(7.2%). 42 cancers were diagnosed in 35 patients (11.0%) - median of 12.0(IQR = 7.5-21.0) years after IBD diagnosis. Most affected organs were the skin (n = 15 in 11 patients; melanoma = 1), colon/rectum (n = 8 in 6 patients), prostate (n = 4), breast (n = 3) and anal canal (n = 2). In those with non-melanoma skin cancer, 6 were under active treatment with azathioprine and 2 had stopped it for more than two years. In the univariate analysis, the occurrence of neoplasia was positively associated with tobacco exposure (p = 0.022), age at IBD diagnosis (p = 0.021), and negatively with infliximab exposure (p = 0.046). In 9 cases, cancer treatment was different because of the IBD, while IBD treatment was changed in 9 patients. In those affected by cancer, in the univariate analysis, its cure/remission was negatively associated with tobacco exposure (p = 0.004) and positively with salicylates use (p = 0.007). CONCLUSION: In IBD patients, cancer mostly affected the skin and the lower digestive system. As in the general population, tobacco exposure was a risk factor for the development of neoplasia.

5.
Clin Gastroenterol Hepatol ; 20(9): 2059-2073.e7, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-34896644

RESUMO

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.


Assuntos
Doença de Crohn , Adulto , Biomarcadores , Proteína C-Reativa , Progressão da Doença , Fezes , Humanos , Inflamação , Infliximab , Complexo Antígeno L1 Leucocitário , Estudos Prospectivos , Fatores de Risco , Inibidores do Fator de Necrose Tumoral
6.
GE Port J Gastroenterol ; 28(2): 97-105, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33791396

RESUMO

INTRODUCTION: Patients with colonic inflammatory bowel disease (IBD) are at an increased risk for colorectal cancer (CRC), whereby surveillance colonoscopy is recommended. AIM: To study the clinical and endoscopic variables associated with dysplasia in IBD patients. METHODS: A cohort study was conducted on IBD patients who were part of a colonoscopy surveillance program between 2011 and 2016. RESULTS: A total of 342 colonoscopies were performed on 162 patients (105 with ulcerative colitis [UC] and 57 with Crohn's disease). Random biopsies were performed at least once on 81.5% of patients; 33.3% of the patients underwent chromoendoscopy (CE) at least once. Endoscopically resectable lesions were detected in 55 patients (34%), and visible lesions deemed unfit for endoscopic resection were found in 5 patients (3.1%). Overall, 62 dysplastic visible lesions (58 with low-grade dysplasia and 3 with high-grade dysplasia) and 1 adenocarcinoma were found in 34 patients. Dysplasia in random biopsies was present in 3 patients, the yield of random biopsies for dysplasia being 1.85%/patient (3/162), 1.75%/colonoscopy (6/342), and 0.25%/biopsy (9/3,637). Dysplasia detected in random biopsies was significantly associated with a personal history of visible dysplasia (p = 0.006). Upon univariate analysis, dysplasia was significantly associated with the type of IBD, the performance of random biopsies, and CE (p = 0.016/0.009/0.05, respectively). On multivariate analysis, dysplasia was associated with duration of disease. CONCLUSION: Our data confirm that patients with long-standing IBD, in particular UC, should be enrolled in dysplasia surveillance programs, and that performing CE and random biopsies seems to help in the detection of colonic neoplastic lesions.


INTRODUÇÃO: Nos doentes com doença inflamatória intestinal (DII) está recomendada vigilancia por colonoscopia para detetar e tratar lesões neoplásicas iniciais, dado o risco aumentado de cancro colo-rectal (CCR). O objetivo do trabalho foi estudar variáveis clínicas e endoscópicas associadas a displasia. MÉTODOS: Estudo coorte − doentes com DII integrados num programa de vigilância de displasia entre 2011­2016. RESULTADOS: Um total de 342 colonoscopias foi realizado em 162 doentes, 105 com colite ulcerosa (CU) e 57 com doença de Crohn (DC). Foram efetuadas biopsias aleatorias (BA) em 81,5% dos doentes (média: 27.5 ± 6.4 biopsias/colonoscopia) e 33.3% realizaram cromoendoscopia. 55 doentes apresentaram lesões endoscopicamente ressecáveis e 5 doentes lesões irressecáveis. No total, em 34 doentes, foram identificadas 6 lesões displásicas visíveis (58 com displasia de baixo grau e 3 com displasia de alto grau) e um adenocarcinoma. Foi detetada displasia em BA em 3 doentes sendo o rendimento das BA de 1.85% por doente (3/162), 1.75% por colonoscopia (6/342) e 0.25% por biopsia (9/3,637). A displasia em BA associou-se à historia pessoal de lesões displásicas (p = 0.006). A presença de displasia associouse, na análise univariada, com: tipo de DII (p = 0.016), realização de BA (p = 0.009) e cromoendoscopia (p = 0.05). Na anàlise multivariada, verificou-se associação com a duração da doença. CONCLUSÃO: Doentes com DII de longa duração deverão ser incluidos num programa de vigilància de displasia. A realizado de cromoendoscopia e BA é útil na deteção de lesões displásicas do cólon.

7.
Scand J Gastroenterol ; 55(6): 646-655, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32456486

RESUMO

Background and aims: Inflammatory Bowel Disease (IBD) with colonic involvement increases colorectal cancer risk. However, the distinction between IBD related and sporadic dysplasia in IBD patients is difficult. Some data favors the importance of abnormal DNA methylation in IBD-related carcinogenesis. We aimed to define methylation patterns in patients with colonic cancer or dysplasia diagnosis following an IBD diagnosis.Methods: Multicentric cross-sectional study-91 samples from colonic mucosa with/without dysplasia from 9 patients with IBD-related dysplasia/cancer and 26 patients with IBD and sporadic dysplasia/cancer were included. Methylation patterns of CpG islands in the promoter regions of 67 genes were studied by Methylation-specific Multiplex Ligation-dependent Probe Amplification.Results: Mean age at IBD diagnosis: 42 ± 16 years;at dysplasia diagnosis: 56 ± 14 years. Twenty-ninepatients had ulcerative colitis. Twenty-five patients had at least 1 lesion endoscopically described as adenoma-like, 4 at least 1 non-adenoma like, 3 had cancer and 3 had dysplasia in flat mucosa. No patient had both adenoma-like and non-adenoma-like lesions. Patients with an IBD-related lesion were significantly younger at IBD diagnosis (p = .003) and at dysplasia/cancer diagnosis (p = .039). Promoter methylation of IGF2, RARB, ESR1, CHFR, CDH13, WT1, GATA5, WIF1genes was significantly associated to dysplasia/cancer; methylation of MSH6, TIMP3 was significantly associated to IBD-related dysplasia/cancer. Promoter methylation of MSH6, MSH3, RUNX3, CRABP1, TP73, RARB, CDH13, PAX5, WT1, THBS1, TP53, SFRP1, WIF1, APAF1, BCL2 genes was significantly associated to active IBD.Conclusions: Methylation analysis, namely of MSH6, may contribute to the classification of dysplastic lesions in IBD- to be further tested in prospective studies.


Assuntos
Adenoma/genética , Colite Ulcerativa/genética , Colo/patologia , Neoplasias do Colo/genética , Metilação de DNA/genética , Mucosa Intestinal/patologia , Adenoma/patologia , Adulto , Biomarcadores Tumorais/genética , Carcinogênese/genética , Colite Ulcerativa/patologia , Neoplasias do Colo/patologia , Estudos Transversais , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal , Regiões Promotoras Genéticas/genética
8.
J Crohns Colitis ; 14(2): 169-175, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31504348

RESUMO

BACKGROUND AND AIMS: The histological status of ulcerative colitis [UC] patients in clinical and endoscopic remission has gained space as an important prognostic marker and a key component of disease monitoring. Our main aims were to compare two histological indexes-the continuous Geboes score [GS] and the Robarts Histopathology index [RHI]-regarding their definitions of histological remission and response, and the ability of faecal calprotectin [FC] levels to discriminate between these statuses. METHODS: This was an analysis of three prospective cohorts including 422 patients previously enrolled in other studies. RESULTS: The two continuous scores [GS and RHI] were shown to be significantly correlated [correlation coefficient of 0.806, p < 0.001] and particularly close regarding their definition of histological response: 95% and 88% of all patients classified as having/not having [respectively] histological response according to RHI also did so according to GS. Moreover, median FC levels in patients with histological response were lower than those in patients without histological response [GS: 73.00 vs 525.00, p < 0.001; RHI: 73.50 vs 510.00, p < 0.001]; a similar trend was observed when FC levels of patients in histological remission were compared to those of patients with histological activity [GS: 76.00 vs 228.00, p < 0.001; RHI: 73.50 vs 467.00, p < 0.001]. FC levels allowed us to exclude the absence of histological remission [according to RHI] and absence of histological response [according to RHI and GS], with negative predictive values varying from 82% to 96%. However, optimization of the FC cut-off to exclude the absence of histological remission, as for the continuous GS, falls within values that resemble those of the healthy population. CONCLUSION: The continuous GS and RHI histological scores are strongly correlated in their definitions of histological response. An absence of histological remission could only be excluded at physiological levels of FC.


Assuntos
Colite Ulcerativa/diagnóstico , Complexo Antígeno L1 Leucocitário/análise , Biomarcadores/análise , Colite Ulcerativa/patologia , Colo/patologia , Colo Sigmoide/patologia , Fezes/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reto/patologia , Indução de Remissão , Índice de Gravidade de Doença , Sigmoidoscopia
9.
J Crohns Colitis ; 14(4): 480-489, 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31602473

RESUMO

BACKGROUND: Interstitial lung [ILD] disease and granulomatous lung disease [GLD] are rare respiratory disorders that have been associated with inflammatory bowel disease [IBD]. Clinical presentation is polymorphic and aetiology is unclear. METHODS: This was an ECCO-CONFER project. Cases of concomitant ILD or GLD and IBD, or drug-induced ILD/GLD, were collected. The criteria for diagnosing ILD and GLD were based on definitions from the American Thoracic Society and the European Respiratory Society and on the discretion of reporting clinician. RESULTS: We identified 31 patients with ILD. The majority had ulcerative colitis [UC] [n = 22]. Drug-related ILD was found in 64% of these patients, 25 patients [80.6%] required hospitalisation, and one required non-invasive ventilation. The causative drug was stopped in all drug-related ILD, and 87% of patients received systemic steroids. At follow-up, 16% of patients had no respiratory symptoms, 16% had partial improvement, 55% had ongoing symptoms, and there were no data in 13%. One patient was referred for lung transplantation, and one death from lung fibrosis was reported. We also identified 22 GLD patients: most had Crohn's disease [CD] [n = 17]. Drug-related GLD was found in 36% of patients and 10 patients [45.4%] required hospitalisation. The causative drug was stopped in all drug-related GLD, and 81% of patients received systemic steroids. Remission of both conditions was achieved in almost all patients. CONCLUSIONS: ILD and GLD, although rare, can cause significant morbidity. In our series, over half of cases were drug-related and therefore focused pharmacovigilance is needed to identify and manage these cases.


Assuntos
Anti-Inflamatórios , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Doenças Inflamatórias Intestinais , Doenças Pulmonares Intersticiais , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/classificação , Comorbidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/terapia , Feminino , Saúde Global/estatística & dados numéricos , Glucocorticoides/administração & dosagem , Hospitalização/estatística & dados numéricos , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/terapia , Doenças Pulmonares Intersticiais/induzido quimicamente , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/terapia , Transplante de Pulmão/métodos , Transplante de Pulmão/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Avaliação de Sintomas/estatística & dados numéricos
10.
GE Port J Gastroenterol ; 26(5): 314-323, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31559322

RESUMO

BACKGROUND: Narrow-band imaging (NBI) allows "in vivo" classification of colorectal polyps. OBJECTIVES: We evaluated the optical diagnosis by nonexpert community-based endoscopists in routine clinical practice, the impact of training, and whether the endoscopists could achieve the threshold for the "do not resect" policy. METHODS: This was an observational study performed in two periods (P1 and P2). Endoscopists had no prior experience in NBI in P1 and applied the technique on a daily basis for 1 year before participation in P2. Lesions were classified by applying the NBI International Colorectal Endoscopic (NICE) and Workgroup serrAted polypS and Polyposis (WASP) classifications, simultaneously. RESULTS: A total of 290 polyps were analyzed. The overall accuracy of optical diagnosis was 0.75 (95% CI 0.68-0.81) in P1, with an increase to 0.82 (95% CI 0.73-0.89) in P2 (p = 0.260). The accuracy of the NICE/WASP classifications to differentiate adenomatous from nonadenomatous histology was 0.78 (95% CI 0.72-0.84) in P1 and 0.86 (95% CI 0.77-0.92) in P2 (p = 0.164); assignments made with a high confidence level achieved statistical significance (13% improvement, 95% CI 3-22%; p = 0.022). The negative predictive value for adenomatous histology of diminutive rectosigmoid polyps was 81% (95% CI 64-93%) and 80% (95% CI 59-93%) in P1 and P2, respectively. CONCLUSIONS: Nonexpert endoscopists achieved moderate accuracy for real-time optical diagnosis of colorectal lesions with the NICE/WASP classifications. The overall performance of the endoscopists improved after sustained use of optical diagnosis, but did not achieve the standards for the implementation of the "do not resect" strategy.


INTRODUÇÃO: O narrow-band imaging (NBI) permite a classificação "in-vivo" dos pólipos colo-rectais. OBJECTIVOS: Avaliámos o diagnóstico óptico na prática clínica diária em endoscopistas da comunidade, sem experiência prévia em NBI, o impacto do treino e se estes conseguiam atingir o limiar da estratégia de "não ressecar". MÉTODOS: Estudo observacional, realizado em dois períodos (P1 e P2). Os endoscopistas não apresentavam experiência prévia em NBI em P1 e aplicaram a técnica diariamente durante um ano antes da participação em P2. As lesões foram classificadas aplicando as classificações NBI International Colorectal Endoscopic (NICE) e Workgroup serrAted polypS and Polyposis (WASP), simultaneamente. RESULTADOS: Foram analisados 290 pólipos. A acuidade global do diagnóstico óptico foi de 0.75 (IC 95%, 0.68-0.81) em P1, aumentando para 0.82 (IC 95%, 0.73-0.89) em P2 (p = 0.260). A acuidade das classificações de NICE/WASP na diferenciação de histologia adenomatosa de não-adenomatosa foi de 0.78 (IC 95%, 0.72-0.84) em P1, e 0.86 (IC 95%, 0.77-0.92) em P2 (p = 0.164); as predições realizadas com alto grau de confiança alcançaram significado estatístico (melhoria de 13%, IC 95%, 3-22%; p = 0.022). O valor preditivo negativo para histologia adenomatosa dos pólipos diminutos recto-sigmóides foi de 81% (IC 95%, 64-93%) e 80% (IC 95%, 59-93%), em P1 e P2, respetivamente. CONCLUSÕES: Endoscopistas sem experiência em NBI alcançaram acuidade moderada no diagnóstico óptico em tempo real de lesões colo-rectais, utilizando as classificações de NICE/WASP. O desempenho global melhorou após a utilização contínua do diagnóstico óptico, mas não alcançou o limiar definido para a implementação da estratégia de "não ressecar".

11.
Scand J Gastroenterol ; 54(4): 465-470, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31012338

RESUMO

Background: Fatigue is a common symptom reported in inflammatory bowel disease (IBD) patients. It can be severe and modify the self-perception of disease. Objective: To evaluate the contribution of clinical and demographic factors to the level of fatigue in IBD patients. Methods: Patients consecutively observed in an outpatient IBD clinic during a 9-month period were studied. Demographic and clinical data were collected. Fatigue was assessed using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F). A FACIT-F score <30 was considered as severe fatigue. Results: One hundred and five patients were evaluated. Of them, 57.1% had Crohn´s Disease (CD) and 42.9% had Ulcerative Colitis. Also 85.0% and 77.8% were in clinical remission, respectively. The mean FACIT-F score was 39.63 ± 9.67. Severe fatigue was observed in 17.1% of patients. Female gender and active CD were significantly associated with a severe level of fatigue (p = .05 and p = .04). There was no significant correlation between the level of fatigue (severe vs. non-severe) and type of IBD, hemoglobin, C-reactive protein, ferritin levels or previous surgeries. Patients under biological therapy had a significantly higher level of fatigue and a higher rate of previous hospitalizations (p = .02). Conclusions: Fatigue level is a simple and useful tool to evaluate the disease's impact in patients' life, and it should, therefore, be included in clinical practice. Biological therapy was associated to higher levels of fatigue. Future studies should evaluate the impact of therapy on the level of fatigue.


Assuntos
Fadiga/diagnóstico , Doenças Inflamatórias Intestinais/diagnóstico , Perfil de Impacto da Doença , Adulto , Idoso , Doença Crônica , Fadiga/fisiopatologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Qualidade de Vida , Reprodutibilidade dos Testes , Índice de Gravidade de Doença
12.
Gut ; 68(4): 594-603, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29437913

RESUMO

OBJECTIVE: Histological remission is being increasingly acknowledged as a therapeutic endpoint in patients with UC. The work hereafter described aimed to evaluate the concordance between three histological classification systems-Geboes Score (GS), Nancy Index (NI) and RobartsHistopathologyIndex (RHI), as well as to evaluate their association with the endoscopic outcomes and the faecal calprotectin (FC) levels. DESIGN: Biopsy samples from 377 patients with UC were blindly evaluated using GS, NI and RHI. The results were compared with the patients' Mayo Endoscopic Score and FC levels. RESULT: GS, NI and RHI have a good concordance concerning the distinction between patients in histological remission or activity. RHI was particularly close to NI, with 100% of all patients classified as being in remission with NI being identified as such with RHI and 100% of all patients classified as having activity with RHI being identified as such with NI. These scores could also predict the Mayo Endoscopic Score and the FC levels, with their sensitivity and specificity levels depending on the chosen cut-offs. Moreover, higher FC levels were statistically associated with the presence of neutrophils in the epithelium, as well as with ulceration or erosion of the intestinal mucosa. CONCLUSIONS: GS, NI and RHI histopathological scoring systems are comparable in what concerns patients' stratification into histological remission/activity. Additionally, FC levels are increased when neutrophils are present in the epithelium and the intestinal mucosa has erosions or ulcers. The presence of neutrophils in the epithelium is, indeed, the main marker of histological activity.


Assuntos
Biomarcadores/análise , Colite Ulcerativa/patologia , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Sigmoidoscopia , Adulto , Idoso , Biópsia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão
13.
GE Port J Gastroenterol ; 25(3): 117-122, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29761147

RESUMO

BACKGROUND/OBJECTIVES: Vitamin B12 (VB12) deficiency is a common complication after total gastrectomy which may be associated with megaloblastic anemia and potentially irreversible neurologic symptoms. Intramuscular supplementation of VB12 has been considered the standard treatment, although it is associated with high costs and patient discomfort. PATIENTS/METHODS: We performed a prospective uncontrolled study (ACTRN12614000107628) in order to evaluate the clinical and laboratory efficacy of long-term oral VB12 supplementation in patients submitted to total gastrectomy. All patients received daily oral VB12 (1 mg/day) and were evaluated every 3 months (clinical and laboratory evaluation: hemoglobin, VB12, total iron, ferritin, and folate). RESULTS: A total of 26 patients were included with a mean age of 64 years (29-79). Patients were included with a mean period of 65 months (3-309) after total gastrectomy. At inclusion time, 17/26 patients were under intramuscular VB12, and 9 had not started supplementation yet. There were normal serum VB12 levels in 25/26 patients (mean VB12 serum levels: 657 pg/mL). The mean follow-up period was 20 (8.5-28) months. During follow-up, all patients had normal VB12 levels and there was no need for intramuscular supplementation. The patient with low VB12 levels had an increase to adequate levels, which remained stable. There were no differences with statistical significance among VB12 levels at 6 (867 pg/mL), 12 (1,008 pg/mL), 18 (1,018 pg/mL), and 24 (1,061 pg/mL) months. Iron and folate supplementation was necessary in 21 and 7 patients, respectively. CONCLUSIONS: Oral VB12 supplementation is effective and safe in patients who underwent total gastrectomy and should be considered the preferential form of supplementation.


INTRODUÇÃO: O défice de vitamina B12 (vitB12) ocorre de forma quase universal e precocemente após gastrectomia total (GT), podendo associar-se a anemia megaloblástica e alterações neurológicas potencialmente irreversíveis. A administração intramuscular de vitB12 é considerada a forma de suplementação adequada, sendo, contudo, desconfortável, dispendiosa e, atualmente, de acesso difícil. MÉTODOS/OBJETIVO: Estudo prospetivo, não controlado (ACTRN12614000107628), cujo objetivo principal foi avaliar a eficácia clínica e laboratorial a longo prazo da suplementação oral com vitB12 em doentes com GT. O objetivo secundário foi avaliar outros défices nutricionais (ferro e folatos). Os doentes foram medicados com vitB12 oral (1mg/dia) e sujeitos a avaliação clínica e laboratorial trimestral (hemoglobina, vitB12, ferro, ferritina e ácido fólico). SPSS 23 (Wilcoxon test). RESULTADOS: Incluídos 26 doentes (M-18; F-8), idade média 64 anos (29­79), com diagnósticos de adenocarcinoma (n = 25) e linfoma MALT (n = 1). Os doentes foram incluídos em média 65 meses (3­309) após GT. À data de inclusão, 17/25 doentes encontravam-se medicados com vitB12 intramuscular e 9 ainda não tinham iniciado suplementação, verificando-se níveis séricos adequados de vitB12 em 25/26 doentes (1/26 com níveis de vitB12 baixos por incumprimento da terap'utica intramuscular), sendo o valor médio de 657 pg/mL (136­1,642). Os doentes foram avaliados durante uma mediana de 23 meses (IQR 8,8). No follow-up todos os doentes apresentaram níveis normais de vitB12, não sendo necessária terap'utica intramuscular. O doente com vitB12 baixa registou um incremento para níveis adequados, que se mantiveram estáveis. Não houve diferenças com significado estatístico nos níveis de vitB12 aos 6 (867 pg/mL), 12 (1,008 pg/mL) e 24 (1,061 pg/mL) meses, embora com aumento progressivo dos mesmos. A suplementação com ferro e folatos foi necessária em 21 e 7 doentes, respetivamente. CONCLUSÃO: A suplementação oral de vitB12 é eficaz e segura em doentes com GT, pelo que esta deve ser considerada a forma preferencial de administração neste grupo de doentes.

14.
EBioMedicine ; 21: 123-130, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28629912

RESUMO

Although infliximab (IFX) is an efficient therapy for ulcerative colitis (UC) patients, a considerably high rate of therapeutic failures still occurs. This study aimed at a better understanding of IFX pharmacokinetics and pharmacodynamics among clinically-asymptomatic UC patients. This was a multicentric and prospective study involving 65 UC patients in the maintenance phase of IFX therapy. There were no significant differences between patients with positive and negative clinical, endoscopic and histological outcomes concerning their IFX trough levels (TLs), area under the IFX concentration vs. time curve (AUC), clearance and antibodies to infliximab (ATI) levels. However, the need to undergo therapeutic escalation later in disease development was significantly associated with higher ATI levels (2.62µg/mL vs. 1.15µg/mL, p=0.028). Moreover, and after adjusting for disease severity, the HR (hazard ratio) for therapeutic escalation was significantly decreased for patients with an ATI concentration below 3µg/mL (HR=0.119, p=0.010), and increased for patients with fecal calprotectin (FC) level above 250µg/g (HR=9.309, p=0.018). In clinically-stable UC patients, IFX pharmacokinetic features cannot predict therapeutic response on a short-term basis. However, high levels of ATIs or FC may be indicative of a future therapeutic escalation.


Assuntos
Anticorpos/imunologia , Colite Ulcerativa/imunologia , Colite Ulcerativa/metabolismo , Fatores Imunológicos/efeitos adversos , Infliximab/efeitos adversos , Complexo Antígeno L1 Leucocitário/metabolismo , Anti-Inflamatórios/efeitos adversos , Anti-Inflamatórios/uso terapêutico , Anticorpos/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Endoscópios , Feminino , Humanos , Fatores Imunológicos/farmacocinética , Fatores Imunológicos/uso terapêutico , Infliximab/farmacocinética , Infliximab/uso terapêutico , Estimativa de Kaplan-Meier , Masculino , Razão de Chances , Modelos de Riscos Proporcionais
15.
Inflamm Bowel Dis ; 23(2): 289-297, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28107278

RESUMO

BACKGROUND AND AIMS: The definition of early therapeutic strategies to control Crohn's disease aggressiveness and prevent recurrence is key to improve clinical practice. This study explores the impact of early surgery and immunosuppression onset in the occurrence of disabling outcomes. METHODS: This was a multicentric and retrospective study with 754 patients with Crohn's disease, who were stratified according to the need for an early surgery (group S) or not (group I) and further divided according to the time elapsed from the beginning of the follow-up to the start of immunosuppression therapy. RESULTS: The rate of disabling events was similar in both groups (S: 77% versus I: 76%, P = 0.700). The percentage of patients who needed surgery after or during immunosuppression therapy was higher among group S, both for first surgeries after the index event (38% of groups S versus 21% of group I, P < 0.001) and for reoperations (38% of groups S versus 12% of group I, P < 0.001). The time elapsed to reoperation was shorter in group I (HR = 2.340 [1.367-4.005]), stratified for the onset of immunosuppression. Moreover, reoperation was far more common among patients who had a late start of immunosuppression (S36: 50% versus S0-6: 27% and S6-36: 25%, P < 0.001) and (I36: 16% versus I0-6: 5% and I6-36: 7%, P < 0.001). CONCLUSIONS: Although neither early surgery nor immunosuppression seem to be able to prevent global disabling disease, an early start of immunosuppression by itself is associated with fewer surgeries and should be considered in daily practice as a preventive strategy.


Assuntos
Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Terapia de Imunossupressão/estatística & dados numéricos , Imunossupressores/administração & dosagem , Tempo para o Tratamento , Idoso , Feminino , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
17.
J Crohns Colitis ; 11(4): 445-453, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27683799

RESUMO

INTRODUCTION: The establishment of prognostic models for Crohn's disease [CD] is highly desirable, as they have the potential to guide physicians in the decision-making process concerning therapeutic choices, thus improving patients' health and quality of life. Our aim was to derive models for disabling CD and reoperation based solely on clinical/demographic data. METHODS: A multicentric and retrospectively enrolled cohort of CD patients, subject to early surgery or immunosuppression, was analysed in order to build Bayesian network models and risk matrices. The final results were validated internally and with a multicentric and prospectively enrolled cohort. RESULTS: The derivation cohort included a total of 489 CD patients [64% with disabling disease and 18% who needed reoperation], while the validation cohort included 129 CD patients with similar outcome proportions. The Bayesian models achieved an area under the curve of 78% for disabling disease and 86% for reoperation. Age at diagnosis, perianal disease, disease aggressiveness and early therapeutic decisions were found to be significant factors, and were used to construct user-friendly matrices depicting the probability of each outcome in patients with various combinations of these factors. The matrices exhibit good performance for the most important criteria: disabling disease positive post-test odds = 8.00 [2.72-23.44] and reoperation negative post-test odds = 0.02 [0.00-0.11]. CONCLUSIONS: Clinical and demographical risk factors for disabling CD and reoperation were determined and their impact was quantified by means of risk matrices, which are applicable as bedside clinical tools that can help physicians during therapeutic decisions in early disease management.


Assuntos
Doença de Crohn/diagnóstico , Adulto , Teorema de Bayes , Doença de Crohn/tratamento farmacológico , Doença de Crohn/cirurgia , Feminino , Humanos , Imunossupressores/uso terapêutico , Masculino , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
18.
J Crohns Colitis ; 11(4): 435-444, 2017 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-27664275

RESUMO

BACKGROUND AND AIMS: Mucosal healing and histological remission are different targets for patients with ulcerative colitis, but both rely on an invasive endoscopic procedure. This study aimed to assess faecal calprotectin and neutrophil gelatinase B-associated lipocalin as biomarkers for disease activity in asymptomatic ulcerative colitis patients. METHODS: This was a multicentric cross-sectional study including 371 patients, who were classified according to their endoscopic and histological scores. These results were evaluated alongside the faecal levels of both biomarkers. RESULTS: Macroscopic lesions [i.e. endoscopic Mayo score ≥1] were present in 28% of the patients, and 9% had active disease according to fht Ulcerative Colitis Endoscopic Index of Severity. Moreover, 21% presented with histological inflammation according to the Geboes index, whereas 15% and 5% presented with focal and diffuse basal plasmacytosis, respectively. The faecal levels of calprotectin and neutrophil gelatinase B-associated lipocalin were statistically higher for patients with endoscopic lesions and histological activity. A receiver operating characteristic-based analysis revealed that both biomarkers were able to indicate mucosal healing and histological remission with an acceptable probability, and cut-off levels of 150-250 µg/g for faecal calprotectin and 12 µg/g for neutrophil gelatinase B-associated lipocalin were proposed. CONCLUSIONS: Faecal calprotectin and neutrophil gelatinase B-associated lipocalin levels are a valuable addition for assessment of disease activity in asymptomatic ulcerative colitis patients. Biological levels of the analysed biomarkers below the proposed thresholds can rule out the presence of macroscopic and microscopic lesions with a probability of 75-93%. However, caution should be applied whenever interpreting positive results, as these biomarkers present consistently low positive predictive values.


Assuntos
Colite Ulcerativa/patologia , Fezes/química , Complexo Antígeno L1 Leucocitário/análise , Lipocalina-2/análise , Neutrófilos/química , Adulto , Colite Ulcerativa/metabolismo , Colo/patologia , Feminino , Humanos , Complexo Antígeno L1 Leucocitário/metabolismo , Lipocalina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Neutrófilos/metabolismo
19.
United European Gastroenterol J ; 4(3): 395-402, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27403306

RESUMO

INTRODUCTION AND AIMS: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is closely associated with Helicobacter pylori (HP) infection. Our aim was to evaluate demographic, clinical and endoscopic characteristics of gastric MALT lymphoma patients, as well as to analyse response to treatment and factors that affect complete remission (CR) and relapse. We also assessed the long-term prognosis. METHODS: The study involved a retrospective evaluation of consecutive patients admitted with gastric MALT lymphoma (1993-2013). RESULTS: A total of 144 patients (76 men; mean age 56) were included. At stage EI, 94/103 patients (92%) received HP eradication and 78 (83%) achieved CR after a mean period of 7 months (2-63 months) and 67 (86%) remained in CR after a mean follow-up time of 105 months. HP infection status (p = 0.004) and lymphoma localisation to the antrum plus body (p = 0.016) were associated with higher and lower CR rates, respectively. Relapse occurred in 11/78 (14%) patients after a mean period of 21 months. The absence of HP re-infection (p = 0.038), the need of only one eradication regimen (p = 0.009) and antrum lymphomas (p = 0.031) correlated with lower relapse rates. At stage EII, HP eradication was performed in 17/24 patients but only five experienced CR (30%). Among 16 patients diagnosed at stage EIV, nine achieved CR after chemotherapy ± surgery and 3/7 without remission died due to disease progression. The 5- and 10-year overall disease free survival rates were 90.5% and 79.1%, respectively. CONCLUSIONS: Most patients were diagnosed at an early stage. Eradication therapy was highly effective in inducing complete remission. Long-term evaluation showed that the long-term prognosis was very favourable.

20.
Endosc Int Open ; 4(1): E1-E16, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26793777

RESUMO

BACKGROUND AND AIMS: Submucosal injection is standard practice in endoscopic mucosal resection of gastrointestinal lesions. Several solutions are used. Our aim was to systematically review their efficacy and safety. PATIENTS AND METHODS: We performed a systematic review and meta-analysis using a random effects model of randomized controlled trials (RCTs) from MEDLINE. Studies in animal models were qualitatively assessed for efficacy and safety. RESULTS: In total, 54 studies were qualitatively assessed. Eleven RCTs were analyzed, two of which were on endoscopic submucosal dissection (ESD). The quantitative synthesis included nine RCTs on endoscopic mucosal resection (EMR), comprising 792 subjects and 793 lesions. Mean lesion size was 20.9 mm (range 8.5 - 46 mm). A total of 209 lesions were randomized to sodium hyaluronate (SH) vs normal saline (NS), 72 to 50 % dextrose (D50) vs NS, 82 to D50 vs SH, 43 to succinylated gelatin, 25 to hydroxyethyl starch and 36 to fibrinogen. In total, 385 were randomized to NS as controls. NS and SH are the best studied solutions and seem to be equally effective in achieving complete resection (OR 1.09; 95 %CI 0.82, 1.45). No solution was proven to be superior in complete resection rate, post-polypectomy bleeding or coagulation syndrome/perforation incidence. Many solutions have been tested in animal studies and most seem more effective for mucosal elevation than NS. CONCLUSIONS: There are several solutions in clinical use and many more under research, but most are poorly studied. SH seems to be clinically equivalent to NS. There are no significant differences in post-polypectomy complications. Larger RCTs are needed to determine any small differences that may exist between solutions.

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