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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.
- An exceptional cause of drug-induced colitis: cholestyramine.Publication . Branco, J; Alexandrino, G; Alves, A; Reis, J
- Association between transient acute kidney injury and morbidity and mortality after lung transplantation: a retrospective cohort study.Publication . Fidalgo, P; Ahmed, M; Myer, S; Lien, D; Weinkauf, J; Kapasi, A; Cardoso, F; Jackson, K; Bagshaw, SAcute kidney injury (AKI) is a common occurrence after lung transplantation (LTx). Whether transient AKI or early recovery is associated with improved outcome is uncertain. Our aim was to describe the incidence, factors, and outcomes associated with transient AKI after LTx. MATERIALS AND METHODS: We performed a retrospective cohort study of all adult recipients of LTx at the University of Alberta between 1990 and 2011. Our primary outcome transient AKI was defined as return of serum creatinine below Kidney Disease-Improving Global Outcome AKI stage I within 7days after LTx. Secondary outcomes included occurrence of postoperative complications, mortality, and long-term kidney function. RESULTS: Of 445 LTx patients enrolled, AKI occurred in 306 (68.8%) within the first week after LTx. Of these, transient AKI (or early recovery) occurred in 157 (51.3%). Transient AKI was associated with fewer complications including tracheostomy (17.2% vs 38.3%; P<.001), reintubation (16.4% vs 41.9%; P<.001), decreased duration of mechanical ventilation (median [interquartile range], 69 [41-142] vs 189 [63-403] hours; P<.001), and lower rates of chronic kidney disease at 3 months (28.5% vs 51.1%, P<.001) and 1 year (49.6% vs 66.7%, P=.01) compared with persistent AKI. Factors independently associated with persistent AKI were higher body mass index (per unit; odds ratio [OR], 0.91; 95% confidence interval, 0.85-0.98; P=.01), cyclosporine use (OR, 0.29; 0.12-0.67; P=.01), longer duration of mechanical ventilation (per hour [log transformed]; OR, 0.42; 0.21-0.81; P=.01), and AKI stages II to III (OR, 0.16; 0.08-0.29; P<.001). Persistent AKI was associated with higher adjusted hazard of death (hazard ratio, 1.77 [1.08-2.93]; P=.02) when compared with transient AKI (1.44 [0.93-2.19], P=.09) and no AKI (reference category), respectively. CONCLUSIONS: Transient AKI after LTx is associated with fewer complications and improved survival. Among survivors, persistent AKI portends an increased risk for long-term chronic kidney disease.
- C-reactive protein may influence decisively the prescription of prophylactic antibiotics in acute pancreatitis: a population-based cohort studyPublication . Cardoso, F; Ricardo, L; Gondar, P; Deus, JR; Horta, DOBJECTIVES: Prescription of prophylactic antibiotics in acute pancreatitis (AP) is controversial. We aimed to identify the patients' characteristics that may prompt clinicians to prescribe prophylactic antibiotics in AP. METHODS: This single-center retrospective cohort study included 299 consecutive patients with AP from a Portuguese hospital in 2009 to 2010. Logistic regression was used to study the association of patients' characteristics with prescription of prophylactic antibiotics in AP. RESULTS: Persistent organ failure developed in 7% of patients (9/136). The median C-reactive protein at 48 hours after hospital admission was 154 mg/L (interquartile range, 55-271 mg/L). Bedside Index for Severity in AP score greater than or equal to 3 occurred in 14% of patients (42/299). Pancreatic necrosis was diagnosed in 21% of the patients (35/169). Computerized Tomography Severity Index score greater than 3 occurred in 23% of patients (38/169). In-hospital mortality rate was 4% (10/299). Prophylactic antibiotics were prescribed to 14% of patients (42/299). After adjusting for persistent organ failure and Computerized Tomography Severity Index score greater than 3, C-reactive protein at 48 hours after hospital admission greater than or equal to 150 mg/L was significantly associated with higher likelihood of receiving prophylactic antibiotics (odds ratio, 12.2). Prophylactic antibiotics did not improve in-hospital mortality rate (P = 0.637). CONCLUSIONS: C-reactive protein was the most influential in prescribing prophylactic antibiotics in AP. Clinicians may need better tools to support the decision to prescribe prophylactic antibiotics in AP.
- C-reactive protein prognostic accuracy in acute pancreatitis: timing of measurement and cutoff points.Publication . Cardoso, F; Ricardo, L; Oliveira, AM; Canena, J; Horta, D; Papoila, A; Deus, JRC-reactive protein (CRP) has been used widely in the early risk assessment of patients with acute pancreatitis. This study evaluated the prognostic accuracy of CRP for severe acute pancreatitis (SAP), pancreatic necrosis (PNec), and in-hospital mortality (IM) in terms of the best timing for CRP measurement and the optimal CRP cutoff points. MATERIALS AND METHODS: This was a single-center retrospective cohort study including 379 patients consecutively admitted with acute pancreatitis. CRP determinations at hospital admission, 24, 48, and 72 h after hospital admission were collected. Discriminative and predictive abilities of CRP for SAP, PNec, and IM were assessed by the area under the receiver-operating characteristic curve and the Hosmer-Lemeshow test, respectively. To determine the optimal CRP cutoff points for SAP, PNec, and IM, the minimum P-value approach was used. RESULTS: In total, 11% of patients had SAP, 20% developed PNec, and 4.2% died. The area under the receiver-operating characteristic curves of CRP at 48 h after hospital admission for SAP, PNec, and IM were 0.81 [95% confidence interval (CI) 0.72-0.90], 0.77 (95% CI 0.68-0.87), and 0.79 (95% CI 0.67-0.91), respectively. The Hosmer-Lemeshow test P-values of CRP at 48 h after hospital admission for SAP, PNec, and IM were 0.82, 0.47, and 0.24, respectively. The optimal CRP at 48 h after hospital admission cutoff points for SAP, PNec, and IM derived were 190, 190, and 170 mg/l, respectively. CONCLUSION: CRP at 48 h after hospital admission showed a good prognostic accuracy for SAP, PNec, and IM, better than CRP measured at any other timing. The optimal CRP at 48 h after hospital admission cutoff points for SAP, PNec, and IM varied from 170 to 190 mg/l.
- Clinical and genetic factors predicting response to therapy in patients with Crohn's diseasePublication . Cravo, M; Ferreira, P; Sousa, P; Moura-Santos, P; Velho, S; Tavares, L; Deus, JR; Ministro, P; Silva, J; Correia, L; Velosa, J; Maio, R; Brito, MAIM:To identify clinical and/or genetic predictors of response to several therapies in Crohn's disease (CD) patients. METHODS:We included 242 patients with CD (133 females) aged (mean ± standard deviation) 39 ± 12 years and a disease duration of 12 ± 8 years. The single-nucleotide polymorphisms (SNPs) studied were ABCB1 C3435T and G2677T/A, IL23R G1142A, C2370A, and G9T, CASP9 C93T, Fas G670A and LgC844T, and ATG16L1 A898G. Genotyping was performed with real-time PCR with Taqman probes. RESULTS:Older patients responded better to 5-aminosalicylic acid (5-ASA) and to azathioprine (OR 1.07, p = 0.003 and OR 1.03, p = 0.01, respectively) while younger ones responded better to biologicals (OR 0.95, p = 0.06). Previous surgery negatively influenced response to 5-ASA compounds (OR 0.25, p = 0.05), but favoured response to azathioprine (OR 2.1, p = 0.04). In respect to genetic predictors, we observed that heterozygotes for ATGL16L1 SNP had a significantly higher chance of responding to corticosteroids (OR 2.51, p = 0.04), while homozygotes for Casp9 C93T SNP had a lower chance of responding both to corticosteroids and to azathioprine (OR 0.23, p = 0.03 and OR 0.08, p = 0.02,). TT carriers of ABCB1 C3435T SNP had a higher chance of responding to azathioprine (OR 2.38, p = 0.01), while carriers of ABCB1 G2677T/A SNP, as well as responding better to azathioprine (OR 1.89, p = 0.07), had a lower chance of responding to biologicals (OR 0.31, p = 0.07), which became significant after adjusting for gender (OR 0.75, p = 0.005). CONCLUSIONS:In the present study, we were able to identify a number of clinical and genetic predictors of response to several therapies which may become of potential utility in clinical practice. These are preliminary results that need to be replicated in future pharmacogenomic studies.
- Clinical and microbiological characteristics associated with mortality in spontaneous bacterial peritonitis: a multicenter cohort study.Publication . Oliveira, AM; Branco, JC; Barosa, R; Rodrigues, JA; Ramos, L; Martins, A; Karvellas, C; Cardoso, FOBJECTIVES: Spontaneous bacterial peritonitis (SBP) is a prevalent and high mortality complication of cirrhosis. We aimed to describe these patients' clinical and microbiological characteristics and evaluate their impact on outcomes. METHODS: This was a retrospective cohort study including 139 consecutive patients with positive culture SBP from three Portuguese centers diagnosed between 2009 and 2014. Multivariate logistic regression was used to study associations with 30-day mortality. RESULTS: The mean age of the patients was 62 years and 81% of patients were men. The mean model for end-stage liver disease score was 19. Hepatic encephalopathy, hepatorenal syndrome, and variceal bleeding developed in 47, 30, and 21% of patients, respectively. Gram-positive bacteria were isolated in the ascitic fluid of 42% of patients. Resistance to quinolones and multiresistance were found in 33 and 17% of patients, respectively. C-reactive protein level (adjusted odds ratio, 1.16 per 1 mg/l increment) and development of hepatorenal syndrome (adjusted odds ratio, 2.86) were associated independently with 30-day mortality (model's area under the curve, 0.78). CONCLUSION: In this cohort, SBP portended high early mortality. Gram-positive bacteria, bacteria resistant to quinolones, and multiresistant bacteria were identified in considerable proportions of patients. In the setting of the high early mortality and changing microbiological profile, SBP management strategies need to be improved.
- 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.
- Comparison of the AIMS65 Score with Other Risk Stratification Scores in Upper Variceal and Nonvariceal Gastrointestinal Bleeding.Publication . Alexandrino, G; Carvalho, R; Reis, J