Browsing by Author "Lago, P."
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- Association between Polymorphisms in Antioxidant Genes and Inflammatory Bowel DiseasePublication . Costa-Pereira, C.; Durães, C.; Coelho, R.; Grácio, D.; Silva, M.; Peixoto, A.; Lago, P.; Pereira, M.; Catarino, T.; Pinho, S.; Teixeira, J.; Macedo, G.; Annese, V.; Magro, F.Inflammation is the driving force in inflammatory bowel disease (IBD) and its link to oxidative stress and carcinogenesis has long been accepted. The antioxidant system of the intestinal mucosa in IBD is compromised resulting in increased oxidative injury. This defective antioxidant system may be the result of genetic variants in antioxidant genes, which can represent susceptibility factors for IBD, namely Crohn's disease (CD) and ulcerative colitis (UC). Single nucleotide polymorphisms (SNPs) in the antioxidant genes SOD2 (rs4880) and GPX1 (rs1050450) were genotyped in a Portuguese population comprising 436 Crohn's disease and 367 ulcerative colitis patients, and 434 healthy controls. We found that the AA genotype in GPX1 is associated with ulcerative colitis (OR = 1.93, adjusted P-value = 0.037). Moreover, we found nominal significant associations between SOD2 and Crohn's disease susceptibility and disease subphenotypes but these did not withstand the correction for multiple testing. These findings indicate a possible link between disease phenotypes and antioxidant genes. These results suggest a potential role for antioxidant genes in IBD pathogenesis and should be considered in future association studies.
- Calprotectin and the Magnitude of Antibodies to Infliximab in Clinically-stable Ulcerative Colitis Patients are More Relevant Than Infliximab Trough Levels and Pharmacokinetics for Therapeutic EscalationPublication . Magro, F.; Afonso, J.; Lopes, S.; Coelho, R.; Gonçalves, R.; Caldeira, P.; Lago, P.; Sousa, H.; Ramos, J.; Gonçalves, A.; Ministro, P.; Rosa, I.; Vieira, A.; Andrade, P.; Soares, J.; Carvalho, D.; Sousa, P.; Meira, T.; Lopes, J.; Moleiro, J.; Dias, C.; Falcão, A.; Geboes, K.; Carneiro, F.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.
- Clinical performance of an infliximab rapid quantification assayPublication . Magro, F.; Afonso, J.; Lopes, S.; Coelho, R.; Gonçalves, R.; Caldeira, P.; Lago, P.; Sousa, H.; Ramos, J.; Gonçalves, A.; Ministro, P.; Rosa, I.; Meira, T.; Andrade, P.; Soares, J.; Carvalho, D.; Sousa, P.; Vieira, A.; Lopes, J.; Dias, C.; Geboes, K.; Carneiro, F.BACKGROUND: Therapeutic drug monitoring (TDM)-based algorithms can be used to guide infliximab (IFX) adjustments in inflammatory bowel disease (IBD) patients. This study aimed to explore a rapid IFX-quantification test from a clinical perspective. METHODS: This manuscript describes a prospective cohort study involving 110 ulcerative colitis (UC) patients on the maintenance phase of IFX. IFX trough levels were quantified using a rapid quantification assay and a commonly-used reference kit. RESULTS: Irrespective of the assay used to measure IFX, its through levels were statistically different between patients with and without endoscopic remission (Mayo endoscopic score = 0), as well as between patients stratified by their faecal calprotectin (FC) levels. Despite the fact that the two methods correlated well with each other [Spearman's rank correlation coefficient = 0.843, p < 0.001; intraclass correlation coefficients = 0.857, 95% confidence interval (CI): 0.791-0.903], there was a discernible systematic variation; values obtained with the reference kit were on average 2.62 units higher than those obtained with the rapid assay. Notwithstanding, 3 µg/ml was shown to be an acceptable cut-off to assess endoscopic status and inflammatory burden levels using both assays. The percentage of patients that had a positive outcome when the IFX concentration measured by the rapid assay ranked above 3 µg/ml was 88% both for a Mayo endoscopic score ⩽ 1 and for an FC concentration <250 µg/g. CONCLUSIONS: Based on this study, we concluded that using the rapid IFX assessment system with a 3 µg/ml threshold is a reliable alternative to the time-consuming enzyme-linked immunosorbent assays in patients on the maintenance phase of IFX.
- Crohn's disease and systemic lupus erythematosus: A rare and challenging associationPublication . João-Magalhães, M.; Lago, P.; Pedroto, I.
- Metabolic control of T cell immune response through glycans in inflammatory bowel diseasePublication . Dias, A.; Correia, A.; Pereira, M.; Almeida, C.; Alves, I.; Pinto, V.; Catarino, T.; Mendes, N.; Leander, M.; Oliva-Teles, M.; Maia, L.; Delerue-Matos, C.; Taniguchi, N.i; Lima, Margarida; Pedroto, I.; Marcos-Pinto, Ricardo; Lago, P.; Reis, C.; Vilanova, M.; Pinho, S.Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5-/-, MGAT5+/-) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.
- Preoperative Enteral Nutrition and Surgical Outcomes in Adults with Crohn's Disease: A Systematic ReviewPublication . Rocha, A.; Bessa, I.; Lago, P.; Santos, Marisa D.; Leite, J.; Castro-Poças, F.Background and aim: Enteral nutrition (EN) is applicable to adult Crohn's disease (CD) in treating malnutrition and in inducing remission - here as a less effective alternative than corticosteroids. The purpose of this review is to determine whether preoperative EN impacts postoperative complications of adult CD, either by means of nutritional or therapeutic effects. Summary: A systematic review of English written full-text research articles published between January 1990 and November 2017, including adult patients undergoing abdominal surgery for complicated CD after EN, was performed. Four studies out of 22 were selected, all of which institutional, retrospective, case-control cohorts, one classified as "good quality" and three as "poor quality," as rated by the Newcastle-Ottawa Scale. The application of inclusion and exclusion criteria resulted in a non-intentional absence of studies referring to supplemental EN among those reviewed. The reduced number of heterogeneous eligible studies impeded meta-analysis. In all studies, exclusive EN (EEN) was used and well tolerated, allowing to defer or even avoid surgery altogether, improving patients' global state. The two studies with the greatest number of patients found preoperative EEN to be an independent factor against infectious and non-infectious complications in 219 patients and against anastomotic leaks or abscesses in 38 patients. Also, in univariate analysis, EEN was found to increase preop-erative immunosuppressant-free intervals and to protect against anastomotic dehiscences, intra-abdominal abscesses, surgical wound infections, ileus, stomas, and reoperations in the largest study; in another study it was related to fewer intra-abdominal septic complications. Key messages: All reviewed studies are retrospective and, consequently, of limited relevance. Nonetheless, all of them call the attention of the scientific community to the potential benefits of preoperative EEN on postoperative outcomes in adult CD, calling for prospective multi-institutional studies and randomized controlled trials.
- Primary intestinal Hodgkin's lymphoma associated with Crohn's diseasePublication . Salgueiro, P.; Lago, P.; Farrajota, P.; Santos, M.; Pedroto, I.
- The importance of ultrasound findings in the study of anal painPublication . Vieira, A.; Castro-Poças, F.; Lago, P.; Pimentel, R.; Pinto, R.; Saraiva, M.; Areias, J.ABSTRACT Objective: endoanal ultrasonography can detect organic causes of anal pain without pathology on physical examination. The aim of this study is to evaluate the importance of endoanal ultrasonography in the diagnosis and therapeutic management of idiopathic and functional anal pain. Material and methods: retrospective study, between 15 March 2005 and 15 June 2008, of all patients with proctalgia and normal examination or with alterations not responsible for anal pain at proctologic exam that have undergone an endoanal ultrasonography. Results: a total of 90 patients were analyzed, with a mean age of 50.5 years, 58% were female. Twenty-three patients had functional anal pain clinic criteria. Endoanal ultrasonography revealed alterations in 49% of patients. The primary findings were changes in sphincters in 14 patients, followed by anal sepsis in 12 patients, anal fissure in 10 patients, perirectal lesions in 6 patients and ulcer of the anal canal in 2 patients. Of the patients with sphincter defects, 5 patients had criteria of chronic anal pain. In this group of patients, no differences were found in manometric and defecographic results between the different ultrasound abnormalities. Conclusions: the endoanal ultrasonography detected occult organic lesions to proctologic examination, in half the patients with anal pain. Ultrasound abnormalities were found in 22% of patients with functional anal pain. However, there was no correlation between ultrasound findings and physiological studies, and therefore could not find etiological or pathogenic factors of functional anal pain.
- The risk of disabling, surgery and reoperation in Crohn's disease - A decision tree-based approach to prognosisPublication . Dias, C.; Pereira Rodrigues, P.; Fernandes, S.; Portela, F.; Ministro, P.; Martins, D.; Sousa, P.; Lago, P.; Rosa, I.; Correia, L.; Moura Santos, P.; Magro, F.INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory bowel disease known to carry a high risk of disabling and many times requiring surgical interventions. This article describes a decision-tree based approach that defines the CD patients' risk or undergoing disabling events, surgical interventions and reoperations, based on clinical and demographic variables. MATERIALS AND METHODS: This multicentric study involved 1547 CD patients retrospectively enrolled and divided into two cohorts: a derivation one (80%) and a validation one (20%). Decision trees were built upon applying the CHAIRT algorithm for the selection of variables. RESULTS: Three-level decision trees were built for the risk of disabling and reoperation, whereas the risk of surgery was described in a two-level one. A receiver operating characteristic (ROC) analysis was performed, and the area under the curves (AUC) Was higher than 70% for all outcomes. The defined risk cut-off values show usefulness for the assessed outcomes: risk levels above 75% for disabling had an odds test positivity of 4.06 [3.50-4.71], whereas risk levels below 34% and 19% excluded surgery and reoperation with an odds test negativity of 0.15 [0.09-0.25] and 0.50 [0.24-1.01], respectively. Overall, patients with B2 or B3 phenotype had a higher proportion of disabling disease and surgery, while patients with later introduction of pharmacological therapeutic (1 months after initial surgery) had a higher proportion of reoperation. CONCLUSIONS: The decision-tree based approach used in this study, with demographic and clinical variables, has shown to be a valid and useful approach to depict such risks of disabling, surgery and reoperation.
- Type 2 Autoimmune Pancreatitis: A Challenge in the Differential Diagnosis of a Pancreatic MassPublication . Martins, C.; Lago, P.; Sousa, P.; Araújo, T.; Davide, J.; Castro-Poças, F.; Pedroto, I.Autoimmune pancreatitis is a rare entity of unknown etiology that can mimic pancreatic cancer and whose diagnosis involves clinical, serological, imagiological, and histological findings. There are two types of autoimmune pancreatitis: type 1, in which the pancreas is involved as one part of a systemic immunoglobulin G4-related disease, and type 2, generally without immunoglobulin G4-positive cells and without systemic involvement.