Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Increased risk of MAFLD and Liver Fibrosis in Inflammatory Bowel Disease Independent of Classic Metabolic Risk Factors.

BACKGROUND & AIMS: There is conflicting evidence regarding the prevalence of and risk factors for metabolic-associated fatty liver disease (MAFLD) in patients with inflammatory bowel disease (IBD). We aimed to determine MAFLD prevalence and risk factors in IBD patients. METHODS: Cross-sectional, case-control study included all consecutive IBD patients treated at 2 different university hospitals. Controls were subjects randomly selected from the general population and matched by age, sex, type 2 diabetes status, and body mass index in a 1:2 ratio. MAFLD was confirmed by controlled attenuation parameter. Liver biopsies were collected when MAFLD with significant liver fibrosis was suspected. In addition, age- and fibrosis stage-paired non-IBD patients with biopsy-proven MAFLD served as a secondary control group. RESULTS: Eight hundred thirty-one IBD patients and 1718 controls were included. The prevalence of MAFLD and advanced liver fibrosis (transient elastography ≥9.7 kPa) was 42.00% and 9.50%, respectively, in IBD patients and 32.77% and 2.31%, respectively, in the general population (P < .001). A diagnosis of IBD was an independent predictor of MAFLD (adjusted odds ratio, 1.99; P < .001) and an independent risk factor for advanced liver fibrosis (adjusted odds ratio, 5.55; P < .001). Liver biopsies were obtained from 40 IBD patients; MAFLD was confirmed in all cases, and fibrosis of any degree was confirmed in 25 of 40 cases (62.5%). Body mass index and type 2 diabetes prevalence were significantly lower in IBD-MAFLD patients than in severity-paired patients with biopsy-proven MAFLD. CONCLUSIONS: MAFLD and liver fibrosis are particularly prevalent in IBD patients, regardless of the influence of classic metabolic risk factors.

Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis.

INTRODUCTION: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. METHODS: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). RESULTS: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). DISCUSSION: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.

Consequences and management of COVID-19 on the care activity of an Inflammatory Bowel Disease Unit.

INTRODUCTION: COVID-19 has altered the usual practice of medicine and the state of emergency declared in Spain on March 14th has considerably changed the activity of inflammatory bowel disease (IBD) units. The aim of this study was to evaluate the consequences of COVID-19 on the IBD Unit's activity and provide information on restructuring with available resources. METHODS: an observational study was performed in a referral hospital in Madrid (Spain). Type of appointment, loss of follow-up, hospital admission, treatment changes, endoscopic activity, surgeries and blood tests were evaluated between March 15th and May 15th, 2020. This data was compared with the usual activity a year before. RESULTS: among the 510 patients included, 476 (93.33 %) received had a remote consultation, representing an increase of 92.38 % compared with the previous year (0.95 %). There was a loss of follow-up in 26 patients (5.1 %) vs 15 (3.58 %) the previous year. A total of 60 (35.09 %) blood tests, 64 (76.19 %) endoscopies and all scheduled surgeries were suspended. Besides, 484 (94.9 %) patients remained adherent vs 417/419 (99.5 %) in the pre-pandemic period and 48 (9.41 %) reported symptoms of an IBD flare. Thirty-nine (7.6 %) patients developed symptoms suggestive of COVID-19. CONCLUSION: a large number of tests and on-site outpatient visit consultations were suspended. However, a rapid adaptation to telemedicine allowed these patients to be closely followed up. Although it was possible to maintain therapeutic compliance, with a loss to follow-up slightly higher than the previous year, suspensions and delays of tests could have significant negative consequences in the long term.

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients With Inflammatory Bowel Disease: Results From the Eneida Registry.

BACKGROUND: The effectiveness of the switch to another anti-tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. METHODS: We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. RESULTS: A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8-3; P < 0.0001) and ulcerative colitis vs Crohn's disease (HR, 1.6; 95% CI, 1.1-2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. CONCLUSIONS: Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

Real-life chromoendoscopy for neoplasia detection and characterisation in long-standing IBD.

OBJECTIVE: Outside clinical trials, the effectiveness of chromoendoscopy (CE) for long-standing IBD surveillance is controversial. We aimed to assess the effectiveness of CE for neoplasia detection and characterisation, in real-life. DESIGN: From June 2012 to 2014, patients with IBD were prospectively included in a multicentre cohort study. Each colonic segment was evaluated with white light followed by 0.4% indigo carmine CE. Specific lesions' features were recorded. Optical diagnosis was assessed. Dysplasia detection rate between expert and non-expert endoscopists and learning curve were ascertained. RESULTS: Ninety-four (15.7%) dysplastic (1 cancer, 5 high-grade dysplasia, 88 low-grade dysplasia) and 503 (84.3%) non-dysplastic lesions were detected in 350 patients (47% female; mean disease duration: 17 years). Colonoscopies were performed with standard definition (41.5%) or high definition (58.5%). Dysplasia miss rate with white light was 40/94 (57.4% incremental yield for CE). CE-incremental detection yield for dysplasia was comparable between standard definition and high definition (51.5% vs 52.3%, p=0.30). Dysplasia detection rate was comparable between expert and non-expert (18.5% vs 13.1%, p=0.20). No significant learning curve was observed (8.2% vs 14.2%, p=0.46). Sensitivity, specificity, and positive and negative predictive values for dysplasia optical diagnosis were 70%, 90%, 58% and 94%, respectively. Endoscopic characteristics predictive of dysplasia were: proximal location, loss of innominate lines, polypoid morphology and Kudo pit pattern III-V. CONCLUSIONS: CE presents a high diagnostic yield for neoplasia detection, irrespectively of the technology and experience available in any centre. In vivo, CE optical diagnosis is highly accurate for ruling out dysplasia, especially in expert hands. Lesion characteristics can aid the endoscopist for in situ therapeutic decisions. TRIAL REGISTRATION NUMBER: NCT02543762.

Timing of Thiopurine or Anti-TNF Initiation Is Associated with the Risk of Major Abdominal Surgery in Crohn's Disease: A Retrospective Cohort Study.

INTRODUCTION: Early stages of Crohn's disease [CD] are predominantly inflammatory and early treatment could be useful to change the natural history of CD. We aimed to evaluate the impact of early treatment in our cohort of CD patients. METHODS: We retrospectively reviewed clinical records of all CD patients at our centre who have received immunomodulators. Time from diagnosis to first CD-related major abdominal surgery or end of follow-up was considered. Dates of diagnosis, of starting immunomodulators (thiopurines / anti-tumour necrosis factor [TNF]), and of the first CD-related surgery when appropriate were collected. RESULTS: Of 422 patients who received thiopurines, 189 operated patients started thiopurines after a median of 117 months (interquartile range [IQR] 44-196) since diagnosis; non-operated patients, after a median of 30 months [IQR 6-128], p < 0,005. Odds ratio [OR] for surgery was 1.006 (95% confidence interval [CI]1.004-1008) for each month of delay in starting thiopurines. Among 272 patients who received anti-TNFs, 137 operated patients started anti-TNFs after a median of 166 months [IQR 90-233] since diagnosis; non-operated patients after a median of 59 months [IQR 14-162]; p < 0,005. OR for surgery was 1.008 [95% CI 1.005-1.010] for each month of delay in starting anti-TNFs. Among 467 patients who received thiopurines and/or anti-TNF, 210 operated patients started any immunomodulator after a median of 120 months [IQR 48-197] since diagnosis and non-operated patients after a median of 30 months [IQR 6-126], p < 0,005. OR for surgery was 1.008 [95% CI 1.005-1.010] for each month of delay in starting immunomodulators. CONCLUSIONS: In our experience, time between diagnosis and thiopurine or anti-TNF initiation was associated with the risk of major abdominal surgery in Crohn's disease.

Visceral leishmaniasis as an unusual infectious complication in a patient with Crohn's disease treated with infliximab / Leishmaniasis visceral como una complicación infecciosa inusual en un paciente con enfermedad de Crohn tratados con infliximab

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Development of quality standards in inflammatory bowel disease management and design of an evaluation tool of nursing care.

BACKGROUND AND AIMS: nursing management of inflammatory bowel disease (IBD) is highly relevant for patient care and outcomes. However, there is evidence of substantial variability in clinical practices. The objectives of this study were to develop standards of healthcare quality for nursing management of IBD and elaborate the evaluation tool "Nursing Care Quality in IBD Assessment" (NCQ-IBD) based on these standards. METHODS: a 178-item healthcare quality questionnaire was developed based on a systematic review of IBD nursing management literature. The questionnaire was used to perform two 2-round Delphi studies: Delphi A included 27 IBD healthcare professionals and Delphi B involved 12 patients. The NCQ-IBD was developed from the list of items resulting from both Delphi studies combined with the Scientific Committee´s expert opinion. RESULTS: the final NCQ-IBD consists of 90 items, organized in13 sections measuring the following aspects of nursing management of IBD: infrastructure, services, human resources, type of organization, nursing responsibilities, nurse-provided information to the patient, nurses training, annual audits of nursing activities, and nursing research in IBD. Using the NCQ-IBD to evaluate these components allows the rating of healthcare quality for nursing management of IBD into 4 categories: A (highest quality) through D (lowest quality). CONCLUSION: the use of the NCQ-IBD tool to evaluate nursing management quality of IBD identifies areas in need of improvement and thus contribute to an enhancement of care quality and reduction in clinical practice variations.

Desarrollo de estándares de calidad para la enfermedad inflamatoria intestinal y diseño de un instrumento de evaluación de los cuidados de enfermería / Development of quality standards in inflammatory bowel disease management and design of an evaluation tool of nursing care

Introducción y objetivos: el manejo de la enfermedad inflamatoria intestinal (EII) por enfermería es muy relevante, sin embargo, existe una gran variabilidad en su práctica clínica. El objetivo de esta investigación es desarrollar estándares de calidad asistencial del manejo de la EII por enfermería, para elaborar un “Instrumento de Evalua - ción de la Calidad Asistencial de la EII por Enfermería” (IEC-EII). Métodos: tras una búsqueda bibliográfica del manejo de la EII por enfermería se elaboró un cuestionario de 178 ítems de calidad asistencial. Con este cuestionario, se realizaron dos estudios Delphi a dos rondas: Delphi A dirigido a 27 profesionales sanitarios en EII y Delphi B a 12 pacientes. Con los ítems de ambos estudios Delphi, se elaboró una lista que, junto con la opinión experta del Comité Científico, contribuyó a desarrollar el IEC-EII. Resultados: el IEC-EII se compone de 90 ítems, subdivididos en 13 dimensiones que miden aspectos del manejo de la EII por enfermería como: infraestructura, servicios, recursos humanos, tipo de organización, competencias asumidas por enfermería, información de enfermería al paciente, formación de enfermería, revisiones anuales de la actividad de enfermería e investigación de enfermería de EII. La evaluación de estos aspectos mediante el IEC-EII permite clasificar la calidad asistencial en EII por enfermería en 4 categorías de la A a la D. Siendo A el nivel de calidad superior y D el inferior. Conclusiones: el IEC-EII puede contribuir a aumentar la calidad asistencial de enfermería en EII y reducir su variabilidad, puesto que la evaluación ayudará a detectar sus deficiencias mejorables (AU)

Background and aims: nursing management of inflammatory bowel disease (IBD) is highly relevant for patient care and outcomes. However, there is evidence of substantial variability in clinical practices. The objectives of this study were to develop standards of healthcare quality for nursing management of IBD and elaborate the evaluation tool “Nursing Care Quality in IBD Assessment” (NCQ-IBD) based on these standards. Methods: a 178-item healthcare quality questionnaire was developed based on a systematic review of IBD nursing management literature. The questionnaire was used to perform two 2-round Delphi studies: Delphi A included 27 IBD healthcare professionals and Delphi B involved 12 patients. The NCQ-IBD was developed from the list of items resulting from both Delphi studies combined with the Scientific Committee’s expert opinion. Results: the final NCQ-IBD consists of 90 items, organized in 13 sections measuring the following aspects of nursing management of IBD: infrastructure, services, human resources, type of organization, nursing responsibilities, nurse-provided information to the patient, nurses training, annual audits of nursing activities, and nursing research in IBD. Using the NCQ-IBD to evaluate these components allows the rating of healthcare quality for nursing management of IBD into 4 categories: A (highest quality) through D (lowest quality). Conclusions: the use of the NCQ-IBD tool to evaluate nursing management quality of IBD identifies areas in need of improvement and thus contribute to an enhancement of care quality and reduction in clinical practice variations (AU)

Adalimumab is effective in long-term real life clinical practice in both luminal and perianal Crohn's disease. The Madrid experience

Objetivo Evaluar la eficacia y seguridad de adalimumab en pacientes con enfermedad de Crohn (EC) de la comunidad de Madrid e identificar los factores predictivos de respuesta.MétodosEstudio multicéntrico retrospectivo de todos los pacientes con EC tratados con adalimumab en 9 hospitales de la Comunidad de Madrid (España). Se llevó a cabo análisis univariado y multivariado de predictores de respuesta.Resultados174 pacientes incluidos (50% varones) con una mediana de seguimiento de 40 semanas. El 30% tenía enfermedad fistulosa perianal activa al inicio de la terapia con adalimumab. El 59% habían sido tratados previamente con infliximab, siendo la pérdida de respuesta (42,2%) la causa más frecuente de la retirada del fármaco. Un 33% de los pacientes necesitaron aumentar la dosis de todos los demás cada semana. La mediana del tiempo para este aumento de la dosis fue de 33 semanas (rango 2-120). Los porcentajes de respuesta completa a las 4 semanas, 6 meses y al final del seguimiento fueron de 63, 70 y 63% en la enfermedad luminal y 49, 50 y 41% en la enfermedad perianal, respectivamente. La prevalencia de eventos adversos fue de 18% (más frecuente: 5 abscesos) provocando la retirada del fármaco en el 21% de ellos.ConclusionesEl adalimumab es eficaz y seguro en el tratamiento de la EC, incluso en los casos refractarios a infliximab(AU)

Objective To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response.MethodsMulticenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed.Results174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to everyweek. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them.ConclusionsAdalimumab is effective and safe for the management of CD, even in refractory cases to infliximab(AU)

Adalimumab is effective in long-term real life clinical practice in both luminal and perianal Crohn's disease. The Madrid experience.

OBJECTIVE: To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response. METHODS: Multicenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed. RESULTS: 174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to every week. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them. CONCLUSIONS: Adalimumab is effective and safe for the management of CD, even in refractory cases to infliximab.

Nursing resources and responsibilities according to hospital organizational model for management of inflammatory bowel disease in Spain.

BACKGROUND: Nurses play an important role in the multidisciplinary management of inflammatory bowel disease (IBD), but little is known about this role and the associated resources. OBJECTIVE: To improve knowledge of resource availability for health care activities and the different organizational models in managing IBD in Spain. METHODS: Cross-sectional study with data obtained by questionnaire directed at Spanish Gastroenterology Services (GS). Five GS models were identified according to whether they have: no specific service for IBD management (Model A); IBD outpatient office for physician consultations (Model B); general outpatient office for nurse consultations (Model C); both, Model B and Model C (Model D); and IBD Unit (Model E) when the hospital has a Comprehensive Care Unit for IBD with telephone helpline, computer, including a Model B. Available resources and activities performed were compared according to GS model (chi-square test and test for linear trend). RESULTS: Responses were received from 107 GS: 33 Model A (31%), 38 Model B (36%), 4 Model C (4%), 16 Model D (15%) and 16 Model E (15%). The model in which nurses have the most resources and responsibilities is the Model E. The more complete the organizational model, the more frequent the availability of nursing resources (educational material, databases, office, and specialized software) and responsibilities (management of walk-in appointments, provision of emotional support, health education, follow-up of drug treatment and treatment adherence) (p<0.05). CONCLUSIONS: Nurses have more resources and responsibilities the more complete is the organizational model for IBD management. Development of these areas may improve patient outcomes.

Qualitative study on WIC Program strategies to promote breastfeeding practices in Puerto Rico: what do nutritionist/dietician's think?

The purpose of this study is to better understand Nutritionist-Dietician opinions concerning WIC Program strategies to promote breastfeeding in Puerto Rico. Four groups of nutritionists-dietitians were recruited to take part in focus group discussions. Each focus group lasted for approximately 1 h and the researchers completed a debriefing sheet after each meeting. The group discussions were taped and transcribed. The participants identified hospital barriers, lack of family support and problems related to the mother as the three principal reasons that Puerto Rican mothers do not breastfeed their babies or stop breastfeeding early. An individual meeting was the most frequently mentioned WIC strategy that was meant to convince mothers to breastfeed their infants. Nevertheless, the focus group participants recognized that the effort and time available for such meetings is limited. From these groups, one theme that emerged is that the WIC Program in Puerto Rico should collaborate with hospitals to arrange for WIC-sponsored nutritionist-dietitians to visit the WIC participants during their maternity hospital stay, and in their homes.

Contribution of nurses to the quality of care in management of inflammatory bowel disease: a synthesis of the evidence.

BACKGROUND: The purpose of quality of care programs is to improve patient outcomes. In programs targeting patients with inflammatory bowel disease (IBD), nurses play a key role. AIM: To know the available scientific evidence on the quality of care in IBD management, at the levels of structure, process and outcome, in relation to nurses. METHODS: Systematic search in MEDLINE, EMBASE, Índice Médico Español, Cochrane Library, and grey literature. Inclusion criteria were: 1) documents referring IBD; 2) documents providing relevant information on nurses' involvement in the management of IBD; and 3) an original article. RESULTS: A total of 284 documents were identified, 15 of which were included: 8 related with structure, 12 with process, and 6 with outcomes. Some documents treated more than one level. At the level of structure, services should incorporate specialist nurses as part of the multidisciplinary team, as well as resources to facilitate patient access to nursing care. Notable at the process level, organizational aspects and nurses' competencies and skills in the management of IBD have been described. Among the outcomes mentioned are clinical outcomes, quality of life, and patient satisfaction attributable to nursing staff. No evidence was found about the association between structure or process issues with patient outcomes. Most of the studies reviewed have methodological limitations. CONCLUSIONS: The available evidence provide useful information for the design of standards of structure and process relating to nurses' management of IBD. The IBD nurses' challenge is to provide evidence that these standards help improve health outcomes in patients.

Marcadores de evolución de la enfermedad inflamatoria intestinal tratada con inmunomoduladores o agentes biológicos / Markers of the course of inflammatory bowel disease treated with immunomodulators or biological agents

ResumenEl inicio de un tratamiento inmunosupresor o biológico en un paciente con enfermedad inflamatoria intestinal puede ver modificada la historia natural de su enfermedad; por el contrario, la eficacia no es universal y se pueden acarrear efectos adversos graves.ResumenSe trata de encontrar factores capaces de predecir la respuesta a las diferentes opciones terapéuticas con el fin de poder elegir con mejor criterio la alternativa terapéutica más adecuada a cada paciente. Esto cobraría más importancia aún si el clínico pudiera modificar alguno de estos marcadores de evolución para tener así la posibilidad de cambiar la evolución de la enfermedad del paciente.ResumenSe han estudiado marcadores epidemiológicos, biológicos, clínicos, endoscópicos, radiológicos, genéticos e incluso proteómicos, además de otros relativos a la propia enfermedad o al tratamiento en cuestión. La utilidad real de cada uno de ellos y la evidencia que los sostiene se discuten brevemente en este trabajo(AU)

AbstractImmunosuppressive or biological treatment in patients with inflammatory bowel disease can modify the natural history of their disease, although these treatments are not universally effective and can have severe adverse effects. Attempts have been made to identify predictive factors of response to the various therapeutic options in order to aid the choice of the most appropriate therapeutic alternative in each patient. The possibility of modifying any one of these predictive factors would be of great interest since it would provide the opportunity to alter the course of the disease. Epidemiological, biological, clinical, endoscopic, radiological, genetic and even proteomic markers have been studied, in addition to others related to the disease itself or to specific treatments. The present article briefly discusses the real use of each of these markers and the evidence supporting their utility(AU)

[Markers of the course of inflammatory bowel disease treated with immunomodulators or biological agents]. / Marcadores de evolución de la enfermedad inflamatoria intestinal tratada con inmunomoduladores o agentes biológicos.

Immunosuppressive or biological treatment in patients with inflammatory bowel disease can modify the natural history of their disease, although these treatments are not universally effective and can have severe adverse effects. Attempts have been made to identify predictive factors of response to the various therapeutic options in order to aid the choice of the most appropriate therapeutic alternative in each patient. The possibility of modifying any one of these predictive factors would be of great interest since it would provide the opportunity to alter the course of the disease. Epidemiological, biological, clinical, endoscopic, radiological, genetic and even proteomic markers have been studied, in addition to others related to the disease itself or to specific treatments. The present article briefly discusses the real use of each of these markers and the evidence supporting their utility.

Long-term oral tacrolimus therapy in refractory to infliximab fistulizing Crohn's disease: a pilot study.

AIMS: To evaluate efficacy and safety of oral tacrolimus in cases of fistulizing Crohn's disease (FCD), which is refractory to conventional therapy including infliximab. METHODS: Patients with fistulas, previously and unsuccessfully treated with all conventional therapy (i.e., antibiotics, azathioprine, or 6-mercaptopurine and infliximab), were enrolled in a prospective, uncontrolled, open-label study of long-term treatment with oral tacrolimus (0.05 mg/kg every 12 h). The evaluation of the clinical response was complemented by use of the perianal Crohn's disease activity index (PCDAI) and magnetic resonance imaging-based score (MRS) with determined periodicity. RESULTS: Ten patients were included in the study (enterocutaneous fistula, 3 patients; perianal fistula, 4 patients; rectovaginal fistula, 3 patients) with 6 to 24 months of follow-up. Five patients were steroid-dependent, and 4 patients needed maintenance treatment with immunosuppressant agents. Four patients (40%) achieved complete clinical responses, which were verified by PCDAI and MRS. Five patients (50%) achieved partial responses (i.e., important decreases in fistula drainage, size, discomfort, and PCDAI/MRS values). Decreases in both the PCDAI and MRS were statistically significant (P < 0.05). All steroid-dependent patients stopped therapy with prednisone, and concomitant immunosuppressive therapy was tapered. The response was maintained, and no new flare-up of the disease was observed. Only mild adverse events were detected (1 patient withdrew from treatment due to headache), and no case of nephrotoxicity or diabetes was detected. One patient had received no benefit from therapy after 6 months. CONCLUSIONS: Oral tacrolimus could be an effective and safe treatment for patients with FCD, even if there has been no response to infliximab treatment. Randomized studies are needed to compare oral tacrolimus with infliximab in terms of efficacy, safety, and costs.

Ethical issues in nutritional sciences for the next century: nutrition research and counseling of nutraceutical supplementation and disease

Ethical issues pertaining research and counseling in nutritional sciences will be arising in this new century. This issue will be of great importance especially in the area of nutraceutical supplementation and disease (pharmacological nutrition). Steps to insure bioethical correctness are discussed in this paper.