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1.
Pharmacol Res ; 197: 106948, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37806602

ABSTRACT

The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed. The minor isoform of the complement inhibitor C4b-binding protein, C4BP(ß-), has been shown to confer a robust anti-inflammatory and immunomodulatory phenotype over inflammatory myeloid cells. Here we show that C4BP(ß-)-mediated immunomodulation can significantly attenuate the histopathological traits and preserve the intestinal epithelial integrity in dextran sulfate sodium (DSS)-induced murine colitis. C4BP(ß-) downregulated inflammatory transcripts, notably those related to neutrophil activity, mitigated circulating inflammatory effector cytokines and chemokines such as CXCL13, key in generating ectopic lymphoid structures, and, overall, prevented inflammatory immune cell infiltration in the colon of colitic mice. PRP6-HO7, a recombinant curtailed analogue with only immunomodulatory activity, achieved a similar outcome as C4BP(ß-), indicating that the therapeutic effect is not due to the complement inhibitory activity. Furthermore, both C4BP(ß-) and PRP6-HO7 significantly reduced, with comparable efficacy, the intrinsic and TLR-induced inflammatory markers in myeloid cells from both ulcerative colitis and Crohn's disease patients, regardless of their medication. Thus, the pleiotropic anti-inflammatory and immunomodulatory activity of PRP6-HO7, able to "reprogram" myeloid cells from the complex inflammatory bowel environment and to restore immune homeostasis, might constitute a promising therapeutic option for IBD.


Subject(s)
Colitis , Inflammatory Bowel Diseases , Animals , Humans , Mice , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Colitis/chemically induced , Colitis/drug therapy , Immunomodulation , Inflammation , Inflammatory Bowel Diseases/chemically induced , Inflammatory Bowel Diseases/drug therapy , Myeloid Cells
2.
Am J Gastroenterol ; 118(7): 1237-1247, 2023 07 01.
Article in English | MEDLINE | ID: mdl-36716287

ABSTRACT

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.


Subject(s)
Colitis, Ulcerative , Humans , Colitis, Ulcerative/drug therapy , Treatment Outcome , Remission Induction , Retrospective Studies
5.
Gastroenterol. hepatol. (Ed. impr.) ; 45(1): 9-17, Ene. 2022. tab, graf
Article in Spanish | IBECS | ID: ibc-204124

ABSTRACT

Introducción: La pandemia producida por el virus SARS-CoV-2 ha generado un grave impacto en el funcionamiento de las unidades de endoscopia digestiva. La Asociación Española de Gastroenterología y la Sociedad Española de Endoscopia Digestiva (AEG-SEED) han propuesto la utilización de la guía European Panel on the Appropriateness of Gastrointestinal Endoscopy II (EPAGE) para la gestión de las colonoscopias pospuestas.Objetivo: Evaluar la guía EPAGE como herramienta de gestión en comparación con el test de sangre oculta en heces inmunológico (TSOHi) y con una calculadora de riesgo (CR), que incluye la edad, el sexo y el TSOHi, para la detección de cáncer colorrectal (CCR) y lesión significativa colónica (LSC).Métodos: Estudio unicéntrico prospectivo. Se incluyeron 743 pacientes derivados para una colonoscopia diagnóstica. Se clasificó cada solicitud según EPAGE en apropiada, indeterminada e inapropiada. Se les entregó un TSOHi y se calculó el valor de la CR.ResultadosEl TSOHi (p<0,001), pero no EPAGE (p = 0,742), fue una variable independiente de riesgo de CCR. El área bajo la curva receiver operating characteristic (ROC) de EPAGE, TSOHi y CR fue: 0,61(IC 95% 0,49 a 0,75), 0,95 (0,93 a 0,97) y 0,90 (0,87 a 0,93) para CCR; y 0,55 (0,49 a 0,61), 0,75 (0,69 a 0,813) y 0,78 (0,73 a 0,83) para LSC, respectivamente. El número necesario de colonoscopias para detectar un CCR y una LSC fue de 38 y siete para EPAGE, de siete y dos para TSOHi, y de 19 y cuatro para CR ≥ cinco puntos, respectivamente.Conclusión: La EPAGE, a diferencia del TSOHi, no es adecuada para seleccionar a los pacientes candidatos a colonoscopia diagnóstica para la detección de CCR. El TSOHi, en combinación con la edad y el sexo, es la estrategia correcta para gestionar la demanda de endoscopia en un escenario de acceso restrictivo.


Introduction: The pandemic caused by the SARS-CoV-2 virus has had a serious impact on the functioning of gastrointestinal endoscopy Units. The Asociación Española de Gastroenterología (AEG) and the Sociedad Española de Endoscopia Digestiva (SEED) have proposed the EPAGE guidelines for managing postponed colonoscopies.ObjectiveTo evaluate the EPAGE guidelines as a management tool compared to the immunologic faecal occult blood test (iFOBT) and compared to risk score (RS) that combines age, sex and the iFOBT for the detection of colorectal cancer (CRC) and significant bowel disease (SBD).Methods: A prospective, single-centre study enrolling 743 symptomatic patients referred for a diagnostic colonoscopy. Each order was classified according to the EPAGE guidelines as appropriate, indeterminate or inappropriate. Patients underwent an iFOBT and had their RS calculated.Results: The iFOBT (p<0.001), but not the EPAGE guidelines (p = 0.742), was an independent predictive factor of risk of CRC. The ROC AUCs for the EPAGE guidelines, the iFOBT and the RS were 0.61 (95% CI 0.49-0.75), 0.95 (0.93-0.97) and 0.90 (0.87-0.93) for CRC, and 0.55 (0.49-0.61), 0.75 (0.69-0.813) and 0.78 (0.73-0.83) for SBD, respectively. The numbers of colonoscopies needed to detect a case of CRC and a case of SBD were 38 and seven for the EPAGE guidelines, seven and two for the iFOBT, and 19 and four for a RS ≥5 points, respectively.Conclusion: The EPAGE guidelines, unlike the iFOBT, is not suitable for screening candidate patients for a diagnostic colonoscopy to detect CRC. The iFOBT, in combination with age and sex, is the most suitable strategy for managing demand for endoscopy in a restricted-access situation


Subject(s)
Humans , Colonoscopy , Pandemics , Betacoronavirus , Spain , Intestinal Diseases/diagnosis , Prospective Studies , Data Interpretation, Statistical , Gastroenterology , Disease
6.
Gastroenterol Hepatol ; 45(1): 9-17, 2022 Jan.
Article in English, Spanish | MEDLINE | ID: mdl-33545240

ABSTRACT

INTRODUCTION: The pandemic caused by the SARS-CoV-2 virus has had a serious impact on the functioning of gastrointestinal endoscopy Units. The Asociación Española de Gastroenterología (AEG) and the Sociedad Española de Endoscopia Digestiva (SEED) have proposed the EPAGE guidelines for managing postponed colonoscopies. OBJECTIVE: To evaluate the EPAGE guidelines as a management tool compared to the immunologic faecal occult blood test (iFOBT) and compared to risk score (RS) that combines age, sex and the iFOBT for the detection of colorectal cancer (CRC) and significant bowel disease (SBD). METHODS: A prospective, single-centre study enrolling 743 symptomatic patients referred for a diagnostic colonoscopy. Each order was classified according to the EPAGE guidelines as appropriate, indeterminate or inappropriate. Patients underwent an iFOBT and had their RS calculated. RESULTS: The iFOBT (p<0.001), but not the EPAGE guidelines (p = 0.742), was an independent predictive factor of risk of CRC. The ROC AUCs for the EPAGE guidelines, the iFOBT and the RS were 0.61 (95% CI 0.49-0.75), 0.95 (0.93-0.97) and 0.90 (0.87-0.93) for CRC, and 0.55 (0.49-0.61), 0.75 (0.69-0.813) and 0.78 (0.73-0.83) for SBD, respectively. The numbers of colonoscopies needed to detect a case of CRC and a case of SBD were 38 and seven for the EPAGE guidelines, seven and two for the iFOBT, and 19 and four for a RS ≥5 points, respectively. CONCLUSION: The EPAGE guidelines, unlike the iFOBT, is not suitable for screening candidate patients for a diagnostic colonoscopy to detect CRC. The iFOBT, in combination with age and sex, is the most suitable strategy for managing demand for endoscopy in a restricted-access situation.


Subject(s)
COVID-19/epidemiology , Colonoscopy/standards , Colorectal Neoplasms/diagnosis , Occult Blood , Pandemics , Practice Guidelines as Topic , Adult , Age Factors , Aged , Analysis of Variance , COVID-19/prevention & control , Colonoscopy/statistics & numerical data , Endoscopy, Gastrointestinal/standards , Female , Gastroenterology/standards , Humans , Intestinal Diseases/diagnosis , Male , Middle Aged , Predictive Value of Tests , Prospective Studies , Risk Factors , Sex Factors , Societies, Medical
7.
Clin Chem Lab Med ; 58(2): 232-239, 2020 01 28.
Article in English | MEDLINE | ID: mdl-31785194

ABSTRACT

Background Blood loss from the gastrointestinal (GI) tract is the most common cause of iron deficiency anaemia (IDA) in adult men and postmenopausal women. Gastroduodenal endoscopy (GDE) and colonoscopy are frequently recommended, despite uncertainty regarding the coexistence of lesions in the upper and lower GI tract. The faecal immunochemical test (FIT) measures the concentration of faecal haemoglobin (f-Hb) originating only from the colon or rectum. We aimed to assess whether the FIT was able to select the best endoscopic procedure for detecting the cause of IDA. Methods A prospective study of 120 men and postmenopausal women referred for a diagnostic study of IDA were evaluated with an FIT, GDE and colonoscopy. The endoscopic finding of a significant upper lesion (SUL) or a significant bowel lesion (SBL) was considered to be the cause of the IDA. Results The diagnoses were 35.0% SUL and 20.0% SBL, including 13.3% GI cancer. In the multivariate analysis, the concentration of blood haemoglobin (b-Hb) <9 g/dL (OR: 2.60; 95% CI 1.13-6.00; p = 0.025) and non-steroidal anti-inflammatory drugs NSAIDs (2.56; 1.13-5.88; p = 0.024) were associated with an SUL. Age (0.93; 0.88-0.99; p = 0.042) and f-Hb ≥ 15 µg Hb/g faeces (38.53; 8.60-172.50; p < 0.001) were associated with an SBL. A "FIT plus gastroscopy" strategy, in which colonoscopy is performed only when f-Hb ≥15 µg Hb/g faeces, would be able to detect 92.4% of lesions and be 100% accurate in the detection of cancer while avoiding 71.6% of colonoscopies. Conclusions The FIT is an accurate method for selecting the best endoscopy study for the evaluation of IDA. An FIT-based strategy is more cost-effective than the current bidirectional endoscopy-based strategy and could improve endoscopic resource allocation.


Subject(s)
Anemia, Iron-Deficiency/diagnosis , Feces/chemistry , Hemoglobins/analysis , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Colonoscopy , Endoscopy, Gastrointestinal , Female , Follow-Up Studies , Gastrointestinal Neoplasms/pathology , Humans , Male , Middle Aged , Prospective Studies , Risk Factors
8.
United European Gastroenterol J ; 6(5): 765-772, 2018 Jun.
Article in English | MEDLINE | ID: mdl-30083339

ABSTRACT

BACKGROUND: Histological remission has been proposed as a new treatment goal in patients with ulcerative colitis (UC) although no universal definition for microscopic activity exists. AIM: We evaluated the accuracy of histological activity to predict clinical relapse in UC patients with both clinical and endoscopic remission. METHODS: Asymptomatic UC patients in endoscopic remission (Mayo endoscopic sub-score 0 or 1) undergoing surveillance colonoscopy in two referral hospitals were prospectively recruited. All colonic biopsies were analyzed according to the Geboes' score (GS) and the presence of basal plasmacytosis (BP). RESULTS: Ninety-six patients were included (38% women, median (interquartile range) age 50.0 (39.0-58.5) years, median disease duration 12.0 (6.5-19.5) years). Histological activity defined as GS ≥ 2B.1, GS ≥ 3.1, or BP was present in, respectively, 26%, 23% and 12%. Within 12 months from index endoscopy, 23% of the patients presented with clinical relapse. In multivariate analysis, active histological disease was the only risk factor predicting clinical relapse (odds ratio (95% confidence interval) 4.29 (1.55-11.87); p = 0.005 for GS ≥ 2B.1 and 4.31 (1.52-12.21); p = 0.006 for GS ≥ 3.1). CONCLUSIONS: In patients with UC in clinical and endoscopic remission, histological activity is an independent risk factor for clinical relapse. Further prospective studies need to clarify whether treatment optimization is justified in this context.

9.
Dig Liver Dis ; 49(9): 991-996, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28587751

ABSTRACT

The aim of our work was to test the usability of fecal calprotectin (FC) home-based test in inflammatory bowel disease (IBD) patients. METHODS: IBD patients were prospectively recruited. They had to measure FC with a dedicated tool and smartphone application, 5 times at two weeks intervals over an 8 weeks period. They had to fill in a usability questionnaire at the first and the last FC measurement. A System Usability Scale (SUS: 0-100) and the Global Score of Usability (GSU: 0-85) were calculated. FC was also centrally measured by ELISA. RESULTS: Fifty-eight patients were recruited. Forty-two performed at least one FC measurement and 27 performed all the FC requested measurements. The median (IQR) SUS (0-100) at the first and last use were 85 (78-90) and 81 (70-88), respectively; the median (IQR) GSU (0-85) at the first and last use were 74 (69-80) and 77 (68-83), respectively. Adherence to the planned measurements and usability of the tool were higher in females and in less severe disease. The intra-class correlation coefficient between home-based and centrally measured FC was 0.88. CONCLUSION: The adherence to home-based measurement of FC was fair. Usability scores for the home-based test were high. There was a good correlation with the centrally measured FC by ELISA.


Subject(s)
Feces/chemistry , Inflammatory Bowel Diseases/diagnosis , Leukocyte L1 Antigen Complex/analysis , Self Care , Adult , Asymptomatic Diseases , Belgium , Biomarkers/analysis , Female , Humans , Linear Models , Logistic Models , Male , Norway , Patient Compliance , Predictive Value of Tests , Severity of Illness Index , Spain , Surveys and Questionnaires
10.
Dig Liver Dis ; 49(9): 973-977, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28457904

ABSTRACT

BACKGROUND: Controlled studies show high efficacy of budesonide in inducing short-term clinical remission in collagenous colitis (CC), but relapses are common after its withdrawal. AIM: To evaluate the need for high-dose budesonide (≥6mg/d) to maintain clinical remission in CC. METHODS: Analysis of a multicentre retrospective cohort of 75 patients with CC (62.3±1.5years; 85% women) treated with budesonide in a clinical practice setting between 2013 and 2015. Frequency of budesonide (9mg/d) refractoriness and safety, and the need for high-dose budesonide to maintain clinical remission, were evaluated. Drugs used as budesonide-sparing, including azathioprine and mercaptopurine, were recorded. Logistic regression analysis was performed to evaluate the risk factors associated with the need for high-dose budesonide (≥6mg/d) to maintain clinical remission. RESULTS: Budesonide induced clinical remission in 92% of patients, with good tolerance. Fourteen of 68 patients (21%; 95% CI, 13-32%) needed high-dose budesonide to maintain remission. Only intake of NSAIDs at diagnosis (OR, 8.6; 95% CI, 1.6-44) was associated with the need for high-dose budesonide in the multivariate analysis. TREATMENT: with thiopurines was effective in 5 out of 6 patients (83%; 95% CI, 44-97%), allowing for withdrawal from or a dose decrease of budesonide. CONCLUSIONS: One fifth of CC patients, especially those with NSAID intake at diagnosis, require high-dose budesonide (≥6mg/d) to maintain clinical remission. In this setting, thiopurines might be effective as budesonide-sparing drugs.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Budesonide/administration & dosage , Colitis, Collagenous/drug therapy , Maintenance Chemotherapy , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Azathioprine/therapeutic use , Dose-Response Relationship, Drug , Female , Humans , Logistic Models , Male , Mercaptopurine/therapeutic use , Middle Aged , Multivariate Analysis , Recurrence , Remission Induction , Retrospective Studies , Risk Factors , Spain
11.
Gastroenterol. hepatol. (Ed. impr.) ; 39(8): 535-559, oct. 2016. tab, graf
Article in Spanish | IBECS | ID: ibc-156244

ABSTRACT

La diarrea crónica es un síntoma de presentación frecuente, tanto en las consultas de medicina de familia como en las de digestivo. Se estima que >5% de la población sufre diarrea crónica y que cerca del 40% de estos sujetos son mayores de 60 años. El clínico se enfrenta con frecuencia a la necesidad de decidir cuál es el mejor enfoque diagnóstico de estos pacientes y elegir entre las múltiples pruebas diagnósticas existentes. En 2014 la Societat Catalana de Digestologia creó un grupo de trabajo con el objetivo principal de crear algoritmos diagnósticos en base a la práctica clínica y evaluar las pruebas diagnósticas disponibles y la evidencia científica para su utilización. Para clasificar la evidencia científica y la fuerza de las recomendaciones se utilizó el sistema GRADE. Se han establecido 28 recomendaciones y 6 algoritmos diagnósticos. Se describen los criterios de derivación desde medicina primaria a digestivo de un paciente con diarrea crónica


Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care


Subject(s)
Humans , Diarrhea/classification , Chronic Disease , Dysentery/diagnosis , Evidence-Based Practice , Practice Patterns, Physicians' , Malabsorption Syndromes/diagnosis
12.
Dig Liver Dis ; 48(6): 608-12, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27012443

ABSTRACT

BACKGROUND AND AIM: Intravenous corticosteroids remain the first line therapy for severe attacks of ulcerative colitis although up to 30-40% of patients do not respond to treatment. The availability of alternative therapies to colectomy and the knowledge of early predictors of response to corticosteroids should have improved the clinical outcomes of patients with severe refractory ulcerative colitis. The aim of the study is to describe the current need, way of use, and efficacy of rescue therapies, as well as colectomy rates in patients with severe ulcerative colitis flares. METHODS: Between January 2005 and December 2011, all patients admitted in three referral centres for a severe ulcerative colitis flare who received intravenous corticosteroids were identified and clinical and biological data were accurately collected. Patients were followed-up until colectomy, death, or date of data collection. RESULTS: Sixty-two flares were included. Initial efficacy of intravenous corticosteroids (mild activity or inactive disease without rescue treatment, at day 7 after starting intravenous corticosteroids) was achieved in 50% of flares, and rescue therapies were used in 27 episodes (43%). After a median follow-up of 18 months, the colectomy rate was 6.5%. Failed oral corticosteroids for the index flare were the only baseline feature that predicted the need for rescue therapy and colectomy. CONCLUSIONS: There is a marked reduction in the colectomy rate and an increased use of medical rescue therapies as compared to historical series. Patients worsening while on oral corticosteroids for a moderate flare are at high risk of rescue therapy and colectomy and, therefore, should be directly treated with rescue therapies instead of attempting intravenous corticosteroids.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , Colitis, Ulcerative/therapy , Gastrointestinal Agents/therapeutic use , Immunosuppressive Agents/therapeutic use , Administration, Intravenous , Adult , Colectomy , Cyclosporine/therapeutic use , Female , Follow-Up Studies , Humans , Infliximab/therapeutic use , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Retrospective Studies , Severity of Illness Index , Spain , Tertiary Care Centers , Treatment Failure
13.
Gastroenterol Hepatol ; 39(8): 535-59, 2016 Oct.
Article in Spanish | MEDLINE | ID: mdl-26610769

ABSTRACT

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.


Subject(s)
Diarrhea , Algorithms , Antidiarrheals/therapeutic use , Chronic Disease , Colitis/complications , Colitis/diagnosis , Diagnostic Techniques, Digestive System , Diarrhea/classification , Diarrhea/diagnosis , Diarrhea/etiology , Diarrhea/therapy , Diet , Dietary Sugars/adverse effects , Disease Management , Exocrine Pancreatic Insufficiency/complications , Exocrine Pancreatic Insufficiency/diagnosis , Food Hypersensitivity/complications , Food Hypersensitivity/diagnosis , Gastrointestinal Diseases/diagnosis , Gastrointestinal Microbiome , Gastrointestinal Motility , Humans , Malabsorption Syndromes/complications , Malabsorption Syndromes/diagnosis
14.
Dig Liver Dis ; 47(9): 797-804, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26055489

ABSTRACT

BACKGROUND: European health systems have developed referral guidelines for the selection of patients for the urgent investigation of suspected colorectal cancer. AIM: To evaluate whether quantitative faecal immunochemical testing performs better than commonly used high-risk symptoms based strategies for fast-tracking cancer referrals. METHODS: We prospectively studied 1054 symptomatic patients referred for a colonoscopy who provided a sample for faecal immunochemical testing. The usefulness of faecal immunochemical testing and two current guidelines for urgent referral were compared for their efficacy in the detection of colorectal cancer and advanced neoplasia. RESULTS: The guidelines detected 46.7% and 43.3% of cases of colorectal cancer while faecal haemoglobin concentration ≥15µg Hb/g detected 96.7% of cases. The diagnostic accuracy of both the guidelines and faecal haemoglobin concentration ≥15µg Hb/g for the detection of advanced neoplasia was: sensitivity 38.3%, 36.1%, 57.1% and specificity 71.8%, 69.5%, 86.6%, respectively. Male gender (OR 2.35; p<0.001), age (1.34; p=0.002), and faecal haemoglobin concentration ≥10µg Hb/g (7.81; p<0.001) were independent predictive factors of advanced neoplasia. CONCLUSIONS: A faecal immunochemical test based-strategy performs better than current high-risk symptoms based strategies for fast-tracking cancer referrals. A score that combines gender, age and a faecal immunochemical test could accurately estimate the risk of advanced neoplasia.


Subject(s)
Colorectal Neoplasms/diagnosis , Occult Blood , Practice Guidelines as Topic/standards , Referral and Consultation/standards , Adult , Aged , Colonoscopy , Female , Humans , Male , Mass Screening , Middle Aged , Multivariate Analysis , Prospective Studies , ROC Curve , Sensitivity and Specificity
15.
J Crohns Colitis ; 8(11): 1523-8, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25066954

ABSTRACT

BACKGROUND: Oral corticosteroids remain the mainstay of treatment for moderately active ulcerative colitis (UC). In patients who fail to respond to oral corticosteroids, attempting the intravenous route before starting rescue therapies is an alternative, although no evidence supports this strategy. AIM: To evaluate clinical outcomes after a course of intravenous corticosteroids for moderate attacks of UC according to the failed oral corticosteroids or not. METHODS: All episodes of active UC admitted to three university hospitals between January 2005 and December 2011 were identified and retrospectively reviewed. Only moderately active episodes treated with intravenous corticosteroids were included. Treatment outcome was compared between episodes which failed to outpatient oral corticosteroids for the index flare and those directly treated by intravenous corticosteroids. RESULTS: 110 episodes were included, 45% of which failed to outpatient oral corticosteroids (median dose 60mg/day [IQR 50-60], median length of course 10days [IQR 7-17]). Initial response (defined as mild severity or inactive disease at day 7 after starting intravenous corticosteroids, without rescue therapy) was achieved in 75%, with no between-group differences (78% vs. 75%). After a median follow-up of 12months (IQR 4-24), 35% of the initial responders developed steroid-dependency and up to 13% required colectomy. Unsuccessful response to oral corticosteroids was the only factor associated with steroid-dependency in the long term (P=0.001). CONCLUSIONS: Intravenous corticosteroids are efficient for inducing remission in moderately active UC unresponsive to oral corticosteroids, but almost half of these patients develop early steroid-dependency. Alternative therapeutic strategies should be assessed in this clinical setting.


Subject(s)
Anti-Inflammatory Agents/administration & dosage , Colitis, Ulcerative/drug therapy , Methylprednisolone/administration & dosage , Administration, Intravenous , Administration, Oral , Adult , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Antibodies, Monoclonal/therapeutic use , Colectomy , Colitis, Ulcerative/surgery , Cyclosporine/therapeutic use , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/therapeutic use , Infliximab , Male , Methylprednisolone/adverse effects , Middle Aged , Prednisone/administration & dosage , Retreatment , Retrospective Studies , Severity of Illness Index , Treatment Failure
16.
Inflamm Bowel Dis ; 20(8): 1375-81, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25046008

ABSTRACT

BACKGROUND: The short-term efficacy of infliximab (IFX) and cyclosporine A (CsA) in steroid-refractory ulcerative colitis (SRUC) has been recently shown to be similar, but long-term outcomes are still unclear. Moreover, the need for further rescue therapies in patients treated with IFX or CsA for SRUC has not been reported. The aims of our study were to compare short-term and long-term efficacy between 2 different strategies based on initial treatment with CsA or IFX for SRUC attacks. PATIENTS AND METHODS: Between January 2005 and December 2011, all patients admitted for SRUC who required medical rescue therapy were identified from the electronic databases of 3 referral centers and grouped according to whether they received CsA or IFX as first-line rescue therapy, and retrospectively reviewed. RESULTS: Among 50 SRUC attacks, 20 were treated with CsA as first-line rescue therapy and 30 with IFX. The CsA group had a higher proportion of patients with severe UC activity immediately before rescue therapy (P = 0.03) and a shorter median time from intravenous corticosteroids to rescue therapy (P = 0.03). A higher proportion of patients in the CsA group received second-line drug therapy (switch) as compared with the IFX group (P = 0.04). Fifteen patients (30%) were colectomized during the study period, with no between-group differences. Previous thiopurine exposure (P = 0.004; odds ratio = 6.1 [1.7-20.9]) was the only independent predictor of colectomy. CONCLUSIONS: CsA- and IFX-based strategies for SRUC seem similarly effective in preventing colectomy in the short and long term, although second-line drug therapy is more often required with CsA-based strategies.


Subject(s)
Adrenal Cortex Hormones/pharmacology , Antibodies, Monoclonal/therapeutic use , Colitis, Ulcerative/drug therapy , Cyclosporine/therapeutic use , Drug Resistance, Neoplasm/drug effects , Adult , Aged , Disease Management , Female , Follow-Up Studies , Gastrointestinal Agents/therapeutic use , Hospitalization , Humans , Immunosuppressive Agents/therapeutic use , Infliximab , Male , Middle Aged , Prognosis
17.
Clin Gastroenterol Hepatol ; 12(11): 1865-70, 2014 Nov.
Article in English | MEDLINE | ID: mdl-24993368

ABSTRACT

BACKGROUND & AIMS: Histologic recovery of patients with ulcerative colitis (UC) often is incomplete, even among those in clinical and endoscopic remission. Persistent active microscopic inflammation is associated with an increased risk of relapse and colorectal neoplasia. A high level of fecal calprotectin (FC) is a reliable marker of endoscopic lesions in patients with UC. We evaluated the accuracy of FC in identifying patients with UC in clinical and endoscopic remission who still have histologic features of inflammation. METHODS: We performed a prospective observational study of 59 patients with UC in clinical and endoscopic remission undergoing colonoscopy. Several biopsy specimens were collected from each colonic segment. Endoscopic remission was defined as a Mayo endoscopic subscore with a grade of 0 or 1. Active histologic inflammation was defined by the presence of neutrophils infiltrating crypt epithelial cells. FC was determined by enzyme-linked immunosorbent assay analysis. RESULTS: Eighteen patients (30.5%) showed evidence of active histologic inflammation. Patients with active histologic inflammation had a significantly higher median level of FC (278 µg/g; interquartile range, 136-696 µg/g) than those without active histologic inflammation (68 µg/g; interquartile range, 30-172 µg/g) (P = .002). In multivariate analysis, the FC and Mayo endoscopic subscore (0 or 1) were each independent predictors of histologic inflammation. The level of FC identified active histologic inflammation in patients in clinical and endoscopic remission, with an area under the receiver operator characteristic curve value of 0.754. CONCLUSIONS: Histologic inflammation is common among patients with UC in clinical and endoscopic remission. Patients with histologic features of inflammation can be identified reliably based on their fecal level of calprotectin.


Subject(s)
Biomarkers/analysis , Colitis, Ulcerative/diagnosis , Colitis, Ulcerative/pathology , Feces/chemistry , Leukocyte L1 Antigen Complex/analysis , Adolescent , Adult , Aged , Biopsy , Colonoscopy , Female , Histocytochemistry , Humans , Male , Middle Aged , Prospective Studies , Young Adult
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