Browsing by Author "Cotter, J"
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- Accuracy of Faecal Calprotectin and Neutrophil Gelatinase B-associated Lipocalin in Evaluating Subclinical Inflammation in UlceRaTIVE Colitis-the ACERTIVE study.Publication . Magro, F; Lopes, S; Coelho, R; Cotter, J; Castro, F; Sousa, H; Salgado, M; Andrade, P; Vieira, A; Figueiredo, P; Caldeira, P; Sousa, A; Duarte, M; Ávila, F; Silva, J; Moleiro, J; Mendes, S; Giestas, S; Ministro, P; Sousa, P; Gonçalves, R; Gonçalves, B; Oliveira, A; Chagas, C; Torres, J; Dias, C; Lopes, J; Borralho, P; Afonso, J; Geboes, K; Carneiro, F; Portuguese IBD Study Group [GEDII].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.
- Comparing the Continuous Geboes Score With the Robarts Histopathology Index: Definitions of Histological Remission and Response and Their Relation to Faecal Calprotectin LevelsPublication . Magro, F; Lopes, J; Borralho, P; Lopes, S; Coelho, R; Cotter, J; Oliveira, A, et al.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.
- Comparison of different histological indexes in the assessment of UC activity and their accuracy regarding endoscopic outcomes and faecal calprotectin levels.Publication . Magro, F; Lopes, J; Borralho, P; Lopes, S; Coelho, R; Cotter, J; Oliveira, A, et al.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.
- Health-Related Quality of Life in Patients with Moderate to Severe Ulcerative Colitis: Surgical Intervention versus Immunomodulatory Therapy.Publication . Portela, F; Ministro, P; Deus, JR; Cravo, M; Cotter, J; Duque, G, e outrosPURPOSE: Ulcerative colitis (UC) can be managed with immunomodulation or surgery. We aimed to understand whether these strategies had a different impact on patients' health-related quality of life (HRQoL). METHODS: This was a retrospective, cross-sectional study: patients who had a moderate to severe UC episode that prompted the utilization of immunomodulatory drugs or surgery were invited to complete a generic (short form [36] health survey [SF-36]) and a disease-specific (inflammatory bowel disease questionnaire [IBDQ]) survey. RESULTS: We included 157 patients, 65 (41.4%) surgically treated. The therapeutic procedure had a minimal impact on HRQoL: only the social dimension of the IBDQ and the physical function component of the SF-36 were significantly different between the study arms - lower for the surgically treated patients. The type of surgery had no impact, but the occurrence of pouchitis, namely, in a chronic form, was associated with a lower HRQoL. Regression analysis confirmed surgery as an independent predictor of lower scores in the social dimension of the IBDQ (-4.646, 95% CI -6.953 to -2.339) and in the physical functioning (-9.622, 95% CI -17.061 to -2.183) and physical role functioning (-3.669, 95% CI -7.339 to 0.001) dimensions of the SF36. CONCLUSIONS: Although usually feared by patients, surgery has a limited impact on UC patients HRQoL when compared to medical management with immunomodulatory drugs.
- One year of Lamivudine therapy for portuguese patients with chronic hepatitis B.Publication . Areias, J; Calinas, F; Porto, A; Carvalho, A; Freitas, D; Macedo, G; Noronha, R; Cotter, J; Meliço-Silvestre, A; Peixe, R; Pratas, J; Barrote, D; Teixeira, R; Augusto, F; Carrilho, I; Campante, F; Velosa, J; Carvalho, L; Duarte, M; Guerreiro, H; Pires, C; Silva, A; Cotrim, I; Guedes, F; Tomé, L; Marcelino, M; Gonçalves, C; Ferreira, E; Matos, L; Peixe, P; Esteves, J; Valente, T; Simões, C; Marinho, C; Jasmins, L; Vieira, M; Marinho, R; Matos, P; Estevans, J; Carrasquinho, J; Salsedo, G; Parada, P; Teixeira, COBJECTIVE: To further verify the efficacy and safety of locally manufactured lamivudine on patients with chronic hepatitis B (CHB). METHODS: 2200 patients with CHB were recruited and received lamivudine orally 100 mg once daily for 12 months. The efficacy assessments included virologic response rate (defined by the absence of serum HBV DNA, HBeAg loss and HBeAg/HBeAb seroconversion), percentage of patients with normalization of alanine aminotransferase (ALT). Meanwhile improvement of quality of life (QOL) measured by mos SF-36 QOL questionnaire and liver histology evaluation were conducted in some patients. The safety assessments included adverse events, serious adverse events and laboratory abnormalities. All 2200 patients received at least one dose of medication and were all included in the safety population. RESULTS: Ninety seven percent of patients (2137/2200) recruited were HBV DNA positive by dot blot (sensitivity GRT or equal to 1.0 pg/ml) at baseline. At the end of 12 months treatment, HBV DNA was undetectable in 80% patients (1538/1920) with HBV DNA positive before treatment. Among the 79%(1744/2200) of the patients recruited had positive HBV DNA accompanied abnormal ALT levels at baseline, 72% patients became ALT normal. And among the 84% (1843/2200) of the patients recruited were HBV DNA and HBeAg positive, anti-HBe negative, 16% (269/1650) patients achieved HBeAg/HBeAb seroconversion after 12 months of lamivudine treatment. The HBeAg/HBeAb seroconversion rate was positive correlation to the ALT level before treatment. A total of 304 patients completed the health-related QOL questionnaire. After 12 months treatment, lamivudine improved both their physical and mental health, especially for their mental health. 133 evaluable, paired liver biopsies were obtained for histological assessment, among whom 115 patients had abnormal ALT levels at baseline. Compared with pre-treatment most of their liver injury got alleviated (51.9%) or no further deterioration (36%), only 12% worsening. During the 12 months treatment, 9% patients withdrew from the study and 17% patients showed at least one adverse event, mild or moderate. There were no obvious difference between this study and the previously reported lamivudine Phase II or III study with regard to the kinds, incidence and severity of adverse events. CONCLUSION: The efficacy and safety profile of the locally manufactured lamivudine 100 mg tablets are similar with those of the previously reported available lamivudine tablets imported in treating Chinese chronic hepatitis B patients.
- Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).Publication . Durães, C; Machado, J; Portela, F; Rodrigues, S; Lago, P; Cravo, M; Ministro, P; Marques, M; Cremers, I; Freitas, J; Cotter, J; Tavares, L; Matos, L; Medeiros, I; Sousa, R; Ramos, J; Deus, JR, et al.BACKGROUND: About 70 loci are associated with susceptibility to Crohn's disease (CD), particularly in pathways of innate immunity, autophagy, and pathogen recognition. Phenotype-genotype associations are inconsistent. METHODS: CD susceptibility polymorphisms ATG16L1 rs2241880, ICAM1 rs5498, IL4 rs2070874, IL17F rs763780, IRGM rs13361189, ITLN1 rs2274910, LRRK2 rs11175593, and TLR4 rs4986790 were genotyped in a Portuguese population (511 CD patients, 626 controls) and assessed for association with CD clinical characteristics. RESULTS: There is a significant association of CD with the single nucleotide polymorphisms (SNPs) in ATG16L1 (odds ratio [OR] 1.36 [1.15-1.60], P = 2.7 × 10(-6) for allele G), IRGM (OR 1.56 [1.21-1.93], P = 3.9 × 10(-4) for allele C), and ITLN1 (OR 1.55 [1.28-1.88], P = 4.9 × 10(-4) for allele C). These SNPs are associated with ileal location (OR, respectively, 1.49, 1.52, and 1.70), ileocolonic location (OR, respectively, 1.31, 1.57, and 1.68), and involvement of the upper digestive tract (OR, respectively for ATG16L1 and IRGM, 1.96 and 1.95). The risk genotype GG in ATG16L1 is associated with patients who respond to steroids (OR 1.89), respond to immunosuppressants (OR 1.77), and to biologic therapy (OR 1.89). The SNPs in ITLN1 and IRGM are both associated with a positive response to biologic therapy. The risk for ileal, ileocolonic, and upper digestive tract locations increases with the number of risk alleles (OR for three alleles, respectively, 7.10, 3.54, and 12.07); the OR for positive response to biologic therapy is 3.66. CONCLUSIONS: A multilocus approach using autophagy-related genes provides insight into CD phenotype-genotype associations and genetic markers for predicting therapeutic responses.
- Ulcerative colitis in a Southern European country: a national perspectivePublication . Portela, F; Magro, F; Lago, P; Cotter, J; Cremers, I; Deus, JR; Vieira, A; Lopes, H; Caldeira, P; Barros, L; Reis, J; Carvalho, L; Gonçalves, R; Campos, M; Ministro, P; Duarte, M; Amil, J; Rodrigues, S; Azevedo, L; Costa-Pereira, ABACKGROUND: The incidence, prevalence, and even the clinical behavior of ulcerative colitis (UC) are highly variable in different world regions. In previous studies, Portugal was reported as having a milder clinical behavior. The aim of this study was to apply the Montreal Classification in a large group of UC Portuguese patients in order to describe their clinical characteristics and evaluate variables potentially useful for outcome prediction. METHODS: A cross-sectional study based on data collected from a nationwide online registry was undertaken. RESULTS: In all, 2863 patients with UC were included. Twenty-one percent had ulcerative proctitis, 52% left-sided colitis, and 28% extensive colitis. Sixty percent of patients had taken steroids, 14% immunosuppressors, 1% biologicals, and 4.5% were submitted to surgery. Patients with extensive colitis had more severe activity, needing more steroids, immunosuppressors, and surgery. At the time of diagnosis 61% were less than 40 years old and 5% less than 16. Younger patients also had a more aggressive initial course. Thirty-eight percent of patients had only taken salicylates during the disease course and were characterized by a lower incidence of systemic symptoms at presentation (3.8% versus 8.8%, P < 0.001), fewer extraintestinal manifestations (7.7% versus 24.0%, P < 0.001), and a higher prevalence of proctitis (32.1% versus 10.0%). CONCLUSIONS: A more aggressive phenotype was found in extensive colitis and in the initial course of younger patients, with an increased need for steroids and immunosuppressors. In addition, a significant percentage of patients, particularly with proctitis, showed a milder clinical evolution and were maintained in remission only with salicylates.