Histological inflammatory activity can predict endoscopic relapse in patients with ulcerative colitis who have achieved mucosal healing.

BACKGROUND AIMS: Current therapeutic goals in ulcerative colitis (UC) include clinical and endoscopic remission, named mucosal healing (MH). Despite MH, a proportion of patients suffer a clinical relapse, which has been related to histological inflammation. We aimed to identify which histopathological features or histopathological index cut-off was associated with endoscopic relapse (ER) in UC patients with MH. METHODS: Retrospective analysis of UC patients who underwent surveillance colonoscopy showing complete MH (endoscopic Mayo subscore=0) with random biopsies, and at least one more endoscopy along the follow-up. After a consensus meeting, expert pathologist performed histological assessment according to Simplified Geboes Score (SGS), Nancy Index (NI) and Robarts Histopathological Index (RHI). Other histopathological features were also evaluated. Patients were followed until ER or last endoscopy performed showing persistence of MH. RESULTS: A total of 95 patients (150 colonoscopies) were included. After mean follow-up of 31.2 months (SD 21.7), 33 patients (34.7%) suffered ER. Neutrophils in lamina propria (OR 2.6; P = 0.037), within the epithelium (OR 2.6; P = 0.03), SGS ≥3.1 (OR 2.6; P = 0.037), NI ≥2 (OR 2.6; P = 0.03) and RHI ≥5 (OR 2.6; P = 0.037) were associated with ER in univariate analysis. In multivariate analysis, eosinophils in the lamina propria (HR 2.5; P = 0.01) and clinical remission<12 months (HR 3.2; P = 0.002) were associated with ER. CONCLUSIONS: Histopathological findings in UC patients who have achieved endoscopic MH may predict ER. Standardized histopathology reports according to the presence of neutrophils, eosinophils or to defined cut-off of validated histopathologic indexes may represent a useful tool to predict ER and should be considered at therapeutic and surveillance decision process.

Comparison of original and biosimilar infliximab (CTP-13) in biologic-naïve patients with Crohn's disease and ulcerative colitis: a retrospective, multicenter real-life study in Spain.

PURPOSE: biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naïve, IBD patients in the real life clinical practice. METHODS: a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naïve patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naïve patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. RESULTS: two hundred and thirty-nine IBD biologic-naïve patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn's disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. CONCLUSIONS: this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.

Adalimumab for Induction of Histological Remission in Moderately to Severely Active Ulcerative Colitis.

BACKGROUND: Histological remission represents a target distinct from endoscopic healing in ulcerative colitis (UC) and seems a better predictor of clinical outcomes. AIMS: The aim of this study was to assess the ability of adalimumab to achieve histological remission in UC patients. METHODS: Single-center, retrospective, open-label study of patients treated with adalimumab. Eligible patients were anti-TNF naïve adults with moderately to severely active UC. The Mayo score including endoscopy was performed at baseline and weeks 8 and 52. Histological activity was scored using the Geboes Index. The primary endpoint was histological remission, defined as a Geboes grade ≤ 3.0, at week 52. RESULTS: We included 34 patients. At week 8, 6 of 34 patients (17.6%) achieved histological remission. At week 52, 9 patients (26.5%, intention to treat; 31%, per protocol) had histological remission. Patients had a significant and progressive reduction in the most severe subgrades of Geboes Index from baseline at weeks 8 and 52. At weeks 8 and 52, 50 and 61.8% of patients achieved mucosal healing (Mayo endoscopic subscore 0-1). All patients who achieved histological remission also had mucosal healing. At week 8, 85.3 and 20.6% of patients achieved clinical response (decrease in Mayo score ≤ 3 points) or remission (Mayo score ≤ 2), respectively. At week 52, the corresponding values were 67.6 and 52.9%, respectively. At week 52, agreement between histological remission and mucosal healing was fair (kappa 0.293). Agreement between histological remission and Mayo endoscopic subscore 0 was good (kappa 0.71). CONCLUSIONS: Adalimumab was able to achieve histological remission in anti-TNF naïve patients with moderately to severely active UC.

Impacto de la incorporación de la enfermera a una unidad de enfermedad inflamatoria intestinal / Impact of the incorporation of a nurse in an inflammatory bowel disease unit

INTRODUCCIÓN: La complejidad y el volumen crecientes de los pacientes con enfermedad inflamatoria intestinal (EII) obligan a desarrollar equipos multidisciplinares. La enfermería especializada debería ser parte de estas unidades tal y como se recoge en diferentes documentos de consenso. OBJETIVOS: Evaluar el impacto que la incorporación de la enfermería a la Unidad de EII del Hospital Universitario Puerta de Hierro Majadahonda (HUPHM) ha tenido desde el punto de vista asistencial, económico e investigador. MÉTODOS: Recogida prospectiva de la actividad desempeñada por la enfermera de la Unidad de EII del HUPHM desde marzo del 2010 hasta diciembre del 2014. RESULTADOS: En este periodo se ha producido un aumento progresivo de la demanda asistencial, que ha alcanzado los 1.558 pacientes atendidos por nuestra Unidad. La asistencia proporcionada por la enfermera alcanzó un total de 5.293 correos electrónicos y de 678 llamadas telefónicas. Con ello, se estima que esta actividad ha supuesto un ahorro de 3.504 consultas médicas presenciales así como de 852 visitas al Servicio de Urgencias. Otras actividades realizadas han sido la monitorización de tratamientos con medicamentos biológicos y no biológicos (8.371 controles analíticos), la extracción de 342 analíticas, el seguimiento de 1.047 pruebas diagnósticas e interconsultas a otras especialidades médicas, la educación sanitaria en la autoadministración de medicamentos a 114 pacientes, la realización de 158 granulocitoaféresis y la participación en 25 proyectos de investigación. CONCLUSIONES: La incorporación de la enfermera especializada a la Unidad de EII tiene un gran impacto beneficioso tanto desde el punto de vista asistencial y económico como investigador

INTRODUCTION: Multidisciplinary units are needed because of the growing complexity and volume of patients with inflammatory bowel disease (IBD). OBJECTIVES: To evaluate the healthcare, economic and research impact of incorporating a nurse into the IBD unit of the Puerta de Hierro Majadahonda University Hospital. METHODS: We prospectively recorded the activity carried out by the nurse of the IBD unit from March 2010 to December 2014. RESULTS: During this period, healthcare demand progressively increased, with 1,558 patients being attended by our unit. The healthcare provided by the nurse included 5,293 electronic mails and 678 telephone calls. We estimated that this activity represented a saving of 3,504 in-person medical consultations and 852 accident and emergency department visits. Other activities consisted of monitoring treatments with biological and non-biological agents (8,371 laboratory tests), extraction of 342 blood samples, follow-up of 1047 diagnostic tests and consultations with other medical specialties, health education in self-administration of drugs in 114 patients, the performance of 158 granulocyte apheresis procedures, and participation in 25 research projects. CONCLUSION: The incorporation of a specialised nurse in an IBD unit had major economic, healthcare and research benefits

[Impact of the incorporation of a nurse in an inflammatory bowel disease unit]. / Impacto de la incorporación de la enfermera a una unidad de enfermedad inflamatoria intestinal.

INTRODUCTION: Multidisciplinary units are needed because of the growing complexity and volume of patients with inflammatory bowel disease (IBD). OBJECTIVES: To evaluate the healthcare, economic and research impact of incorporating a nurse into the IBD unit of the Puerta de Hierro Majadahonda University Hospital. METHODS: We prospectively recorded the activity carried out by the nurse of the IBD unit from March 2010 to December 2014. RESULTS: During this period, healthcare demand progressively increased, with 1,558 patients being attended by our unit. The healthcare provided by the nurse included 5,293 electronic mails and 678 telephone calls. We estimated that this activity represented a saving of 3,504 in-person medical consultations and 852 accident and emergency department visits. Other activities consisted of monitoring treatments with biological and non-biological agents (8,371 laboratory tests), extraction of 342 blood samples, follow-up of 1047 diagnostic tests and consultations with other medical specialties, health education in self-administration of drugs in 114 patients, the performance of 158 granulocyte apheresis procedures, and participation in 25 research projects. CONCLUSION: The incorporation of a specialised nurse in an IBD unit had major economic, healthcare and research benefits.

Uso de la enterografía por resonancia magnética en el manejo de la enfermedad de Crohn de intestino delgado: primer año de experiencia / Using of magnetic resonance enterography in the management of Crohn's disease of the small intestine: first year of experience

Objetivo: describir la experiencia de dos centros terciarios durante el primer año de uso de la enterografía por resonancia magnética (enteroRM) para el manejo de la enfermedad de Crohn (EC): indicaciones e influencia en la toma de decisiones clínicas. Material y métodos: estudio descriptivo retrospectivo. Se incluyeron de forma consecutiva a pacientes a los que se realizaba una enteroRM. Se recogieron los datos epidemiológicos y clínicos de los pacientes, la indicación de la prueba y como influyó sobre la toma de decisiones clínicas en los 10 días posteriores a la realización de la prueba radiológica. Resultados: se realizaron 24 enteroRM por sospecha de EC y 126 por seguimiento clínico en pacientes con EC conocida: clínica suboclusiva en 53 (42%), monitorización de los tratamientos médicos en 34 (27%), completar el estudio por ileocolonoscopia incompleta en 16 (13%), estudio de extensión en intestino delgado en 15 (12%) y finalmente la sospecha de EC complicada en 8 pacientes (6%). La realización de la enteroRM influyó en el tratamiento en 83 (55,3%) pacientes. Dieciséis (10,7%) pacientes con inmunosupresores, 41 pacientes (27,3%) iniciaron o cambiaron de anti-TNFa, en 15 pacientes (10%) se indicó la cirugía y en 3 pacientes (2%) la enteroRM indujo a cambiar de terapia combinada a monoterapia. La enteroRM en la sospecha de EC influyó menos en las decisiones clínicas que cuando se indicaba por seguimiento (p < 0,05). Conclusiones: la enteroRM ayudó a decidir en más de la mitad de los pacientes, en especial en el seguimiento clínico para el manejo de las terapias biológicas y la indicación de la cirugía. Fue menos útil cuando la indicación fue la sospecha de EC(AU)

Objective: to describe the experience at two tertiary centres during the first year of use of magnetic resonance enterography (MRE) for the management of Crohn’s disease (CD): indications and influence of the technique in clinical decision making. Material and method: retrospective descriptive study in which patients who underwent MRE were included consecutively. Epidemiological and clinical data were collected from the patients, as well as the indication for the study and how it influenced clinical decision making in the 10 days following the radiological study. Results: 24 MREs were performed in suspected CD and 126 known CD; partial bowel obstruction in 53 patients (42%), monitoring of medical treatment in 34 (27%), due to incomplete ileocolonoscopy in 16 (13%), extension study of the small intestine in 15 (12%) and suspected complicated CD in 8 patients (6%). The MRE influenced in a change in treatment in 83 (55.3%) patients: 16 (10.7%) started with immunosuppressants, 41 (27.3%) with anti- TNFa were started on or switched, 15 (10%) were ordered surgery and in 3 (2%) changed from combined therapy to monotherapy. The MRE had less influence on clinical decision making in the group in which the indication was suspected CD (p < 0.05). Conclusions: the use of MRE helped on decision making in more than half of patients, especially with regards to decisions related to the use of biological therapies and the indication for surgery. MRE was less useful in suspected CD patients(AU)

Using of magnetic resonance enterography in the management of Crohn's disease of the small intestine: first year of experience.

OBJECTIVE: to describe the experience at two tertiary centres during the first year of use of magnetic resonance enterography (MRE) for the management of Crohn's disease (CD): indications and influence of the technique in clinical decision making. MATERIALS AND METHODS: retrospective descriptive study in which patients who underwent MRE were included consecutively. Epidemiological and clinical data were collected from the patients, as well as the indication for the study and how it influenced clinical decision making in the 10 days following the radiological study. RESULTS: 24 MREs were performed in suspected CD and 126 known CD; partial bowel obstruction in 53 patients (42%), monitoring of medical treatment in 34 (27%), due to incomplete ileocolonoscopy in 16 (13%), extension study of the small intestine in 15 (12%) and suspected complicated CD in 8 patients (6%). The MRE influenced in a change in treatment in 83 (55.3%) patients: 16 (10.7%) started with immunosuppressants, 41 (27.3%) with anti-TNFα were started on or switched, 15 (10%) were ordered surgery and in 3 (2%) changed from combined therapy to monotherapy. The MRE had less influence on clinical decision making in the group in which the indication was suspected CD (p < 0.05). CONCLUSIONS: the use of MRE helped on decision making in more than half of patients, especially with regards to decisions related to the use of biological therapies and the indication for surgery. MRE was less useful in suspected CD patients.

Expression of a novel non-coding mitochondrial RNA in human proliferating cells.

Previously, we reported the presence in mouse cells of a mitochondrial RNA which contains an inverted repeat (IR) of 121 nucleotides (nt) covalently linked to the 5' end of the mitochondrial 16S RNA (16S mtrRNA). Here, we report the structure of an equivalent transcript of 2374 nt which is over-expressed in human proliferating cells but not in resting cells. The transcript contains a hairpin structure comprising an IR of 815 nt linked to the 5' end of the 16S mtrRNA and forming a long double-stranded structure or stem and a loop of 40 nt. The stem is resistant to RNase A and can be detected and isolated after digestion with the enzyme. This novel transcript is a non-coding RNA (ncRNA) and several evidences suggest that the transcript is synthesized in mitochondria. The expression of this transcript can be induced in resting lymphocytes stimulated with phytohaemagglutinin (PHA). Moreover, aphidicolin treatment of DU145 cells reversibly blocks proliferation and expression of the transcript. If the drug is removed, the cells re-assume proliferation and over-express the ncmtRNA. These results suggest that the expression of the ncmtRNA correlates with the replicative state of the cell and it may play a role in cell proliferation.

Seasonal environmental changes modulate the prolactin receptor expression in an eurythermal fish.

Eurythermal fish have evolved compensatory responses to the cyclical seasonal changes of the environment. The complex adaptive mechanisms include the transduction of the physical parameters variations into molecular signals. Studies in carp have indicated that prolactin and growth hormone expression is associated with acclimatization, suggesting that the pituitary gland is a relevant physiological node in the generation of the homeostatic rearrangement that occurs in this adaptive process. Here, we report the cloning and characterization of a full-length carp prolactin receptor cDNA, which codes for the long form of the protein resembling that found in mammalian prolactin receptors. We identified up to three receptor transcript isoforms in different tissues of the teleost and assessed cell- and temporal-specific transcription and protein expression in carp undergoing seasonal acclimatization. The distinctive pattern of expression that carp prolactin receptor (cPRLr) depicts upon seasonal acclimatization supports the hypothesis that prolactin and its receptor are clearly involved in the new homeostatic stage that the eurythermal fish needs to survive during the cyclical changes of its habitat.

Integrative medicine: a paradigm shift in medical education and practice

The use of alternative/complementary medicine has been increasing considerably. Conventional medicine must begin to address issues related to the use, safety, regulation, research and education of alternative/complementary medicine. Integrative medicine combines conventional medicine and alternative complementary practices. Integrative medicine is an innovative approach to medicine and medical education. It involves the understanding of the interaction of the mind, body and spirit and how to interpret this relationship in the dynamics of health and disease. Integrative medicine shifts the orientation of the medical practice from disease based approach to a healing based approach. It does not reject conventional medicine nor uncritically accepts unconventional practices. Integrative medicine is an effective, more fulfilling human approach to medicine based on the benefit of the patient by following good medicine practices in a scientific manner.