HLA-DQ de enfermedad celíaca en pacientes con enfermedad inflamatoria intestinal crónica

Introducción: La enfermedad celíaca (EC) y la Enfermedad Inflamatoria Intestinal Crónica (EIIC, que incluye CU –colitis ulcerosa- y ECr –Enfermedad de Crohn-) son enfermedades cuya incidencia y prevalencia va en aumento, y en las que se consideraba que tener una de ellas aumentaba la predisposición a la otra. El HLA-DQ 2 y DQ8, de riesgo de EC (HLA-EC), tiene un alto valor predictivo negativo, estando presente en el 95-99% de los celíacos. Nuestra hipótesis era que el HLA-EC no es más frecuente en la EIIC. Material y método: Se incluyeron prospectivamente pacientes adultos con EIIC, de origen caucásico, de nuestra Unidad de EIIC. Se les realizaba entrevista, estudio de su historia clínica y extracción sanguínea. El HLA se analizaba en el Centro de Transfusiones de la Comunidad Valenciana (CTCV). Los controles eran adultos de la Comunidad Valenciana que habían sido donantes de órganos. El análisis (SPSS y Statsgraphics) incluyó: Chi2, regresión logística, ANOVA, fracción etiológica (FE) y preventiva (FP) y la corrección de Holm-Bonferroni para el análisis de alelos. Resultados: Se analizó 1034 sujetos (457 casos y 577 controles; 38% de mujeres en el grupo control, frente a 39% en CU y 49% en ECr). Los resultados más relevantes fueron: La frecuencia del HLA-EC es más elevada en el grupo control (39.34%) que en los pacientes con EIIC (34.14%), sin ser una diferencia significativa (p=0.0852). No hay diferencias significativas en la frecuencia de HLA-EC por grupos (controles, CU y ECr), aunque se observa una tendencia a que sea menor en la CU (p=0.0571), con una FP del 11%. El HLA-EC tiende a ser menos frecuente en mujeres con EIIC que en controles (34% vs 43%, p=0.0565, FP=14%). La frecuencia de DQ2.5 en la CU (16.43%) es significativamente menor respecto al grupo control (23.74%), p = 0.0287, FP=8%. Ser mujer, con HLA-DQ2.5, reduce casi en un 50% las posibilidades de tener colitis ulcerosa (p= 0.0466). FP=13% HLA-DQ8: EII (13.13%) < controles (17.50%), p= 0.054. FP=5% El HLA-DQ8 es significativamente menos frecuente en ECr que en controles (p=0.0217; FP=7%). La frecuencia de HLA-DQ2.2 en la Enfermedad de Crohn (34.0%) es significativamente mayor respecto al grupo control (22.7%), p = 0.001 y FE=15%, sin observar diferencias entre sexos. La agrupación de los alelos DQA1 y DQB1 es diferente según se trate del grupo control, ECr y CU, apareciendo como significativos, en nuestra muestra y tras la corrección de Holm-Bonferroni, el DQA1*01:04: más frecuente en la CU (p=0.036) y el DQA1*02:01: más frecuente en la ECr (p=0.0392). El HLA-DQB1*03:01 se relaciona con el fenotipo de CU extensa (p=0.0392). Conclusión: El HLA-EC no es más frecuente en la EII que en la población general, de hecho, el HLA-DQ2.5 es menos frecuente en la CU y el HLA-DQ8 en la ECr, suponiendo un factor protector. Por otro lado, el HLA-DQ2.2 confiere mayor riesgo de desarrollo de una ECr. La distribución de los alelos DQ es diferente en pacientes con ECr, CU y población general

Diagnosis delay and follow-up strategies in colorectal cancer. Prognosis implications: a study protocol

<p>Abstract</p> <p>Background</p> <p>Controversy exists with regard to the impact that the different components of diagnosis delay may have on the degree of invasion and prognosis in patients with colorectal cancer. The follow-up strategies after treatment also vary considerably. The aims of this study are: a) to determine if the symptoms-to-diagnosis interval and the treatment delay modify the survival of patients with colorectal cancer, and b) to determine if different follow-up strategies are associated with a higher survival rate.</p> <p>Methods/Design</p> <p>Multi-centre study with prospective follow-up in five regions in Spain (Galicia, Balearic Islands, Catalonia, Aragón and Valencia) during the period 2010-2012. Incident cases are included with anatomopathological confirmation of colorectal cancer (International Classification of Diseases 9th revision codes 153-154) that formed a part of a previous study (n = 953).</p> <p>At the time of diagnosis, each patient was given a structured interview. Their clinical records will be reviewed during the follow-up period in order to obtain information on the explorations and tests carried out after treatment, and the progress of these patients.</p> <p>Symptoms-to-diagnosis interval is defined as the time calculated from the diagnosis of cancer and the first symptoms attributed to cancer. Treatment delay is defined as the time elapsed between diagnosis and treatment. In non-metastatic patients treated with curative intention, information will be obtained during the follow-up period on consultations performed in the digestive, surgery and oncology departments, as well as the endoscopies, tumour markers and imaging procedures carried out.</p> <p>Local recurrence, development of metastases in the follow-up, appearance of a new tumour and mortality will be included as outcome variables.</p> <p>Actuarial survival analysis with Kaplan-Meier curves, Cox regression and competitive risk survival analysis will be performed.</p> <p>Discussion</p> <p>This study will make it possible to verify if the different components of delay have an impact on survival rate in colon cancer and rectal cancer. In consequence, this multi-centre study will be able to detect the variability present in the follow-up of patients with colorectal cancer, and if this variability modifies the prognosis. Ideally, this study could determine which follow-up strategies are associated with a better prognosis in colorectal cancer.</p

Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn's disease (ENDOCIR study): an open-label, multicentre, randomized trial.

Background: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. Methods/design: Exploratory study as "proof-of-concept", multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. Discussion: The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD

Using Interpretable Machine Learning to Identify Baseline Predictive Factors of Remission and Drug Durability in Crohn’s Disease Patients on Ustekinumab

Ustekinumab has shown efficacy in Crohn's Disease (CD) patients. To identify patient profiles of those who benefit the most from this treatment would help to position this drug in the therapeutic paradigm of CD and generate hypotheses for future trials. The objective of this analysis was to determine whether baseline patient characteristics are predictive of remission and the drug durability of ustekinumab, and whether its positioning with respect to prior use of biologics has a significant effect after correcting for disease severity and phenotype at baseline using interpretable machine learning. Patients' data from SUSTAIN, a retrospective multicenter single-arm cohort study, were used. Disease phenotype, baseline laboratory data, and prior treatment characteristics were documented. Clinical remission was defined as the Harvey Bradshaw Index <= 4 and was tracked longitudinally. Drug durability was defined as the time until a patient discontinued treatment. A total of 439 participants from 60 centers were included and a total of 20 baseline covariates considered. Less exposure to previous biologics had a positive effect on remission, even after controlling for baseline disease severity using a non-linear, additive, multivariable model. Additionally, age, body mass index, and fecal calprotectin at baseline were found to be statistically significant as independent negative risk factors for both remission and drug survival, with further risk factors identified for remission

Ferric Carboxymaltose Improves the Quality of Life of Patients with Inflammatory Bowel Disease and Iron Deficiency without Anaemia

Background: Iron deficiency (ID) without anaemia is a common comorbidity associated with inflammatory bowel disease (IBD) that has a negative impact on health-related quality of life (HRQoL). Methods: This multicentre, prospective, observational study examined the response to, safety of and impact on HRQoL of a single 500 mg dose of intravenous ferric carboxymaltose (FCM) in patients with IBD and ID without anaemia. The diagnostic criteria for ID were low serum ferritin (&lt;30 &micro;g/L in the absence of inflammatory activity or &lt;100 &micro;g/L with inflammation) and transferrin saturation index (TSAT) &lt; 16%. The effect on iron levels and HRQoL, according to the health status questionnaires SF-12v2 and EQ-5D, was evaluated 1 month after FCM infusion in an outpatient setting. Results: Of the 105 patients who received FCM, 98 patients completed the study. After 1 month, a single dose of FCM significantly increased serum ferritin, serum iron and TSAT. Importantly, patients reported fewer ID symptoms and problems on all EQ-5D dimensions. They also had higher EQ-5D visual analogue scale and SF-12v2 scores after treatment. FCM had similar clinical effects on men and women and on patients with Crohn&rsquo;s disease (n = 66) and ulcerative colitis (n = 32). Conclusion: A single dose of FCM rapidly restored iron parameters and significantly improved patients&rsquo; symptoms and HRQoL at 1 month after treatment

IBD or strongyloidiasis?

Introduction: Strongyloides has been shown to infrequently mimic inflammatory bowel disease (IBD) or to disseminate when a patient with IBD and unrecognized strongyloides is treated with immunosupression. Case report: A man from Ecuador, living in Spain for years, with a history of type 2 diabetes mellitus and psoriasis treated with topical corticosteroids, was admitted to the hospital with an 8-month history of diarrhoea. Blood tests showed hyperglycemia, hyponatremia, elevated CRP and faecal calprotectin. Colonoscopy suggested IBD. The patient improved with steroids, pending biopsy results, and he was discharged. Biopies were compatible with IBD, but careful examination revealed strongyloides. He was given a prescription of albendazole. He had to be readmitted due to SIADH, which resolved with fluid restriction. Upon discharge albendazole was prescribed again. The patient skipped most of the out-patient-clinic visits. He returned a year later on 10 mg/week methotrexate, asymptomatic, with 20% eosinophilia, and admitting he had never taken the strongyloides treatment for economical reasons. He then received a week of oral albendazol at the hospital. Biopsies and blood cell count were afterwards normal (eosinophils 3.1%) and serology for strongyloides antibodies was negative. Discussion: This case is of interest for four rarely concurring reasons. It's a worm infection that mimics IBD; the infection was diagnosed by colon biopsy; the infection caused a SIADH; and, most interestingly, even though the patient is on immunosupression, he remains asymptomatic

Subcutaneous Infliximab [CT-P13], a True Biologic 2.0. Real Clinical Practice Multicentre Study

Background: Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is characterized by chronic relapsing intestinal inflammation. There are few data on the efficacy and safety in clinical practice of infliximab (CT-P13) in subcutaneous formulation (SC) for the treatment of patients with IBD. Methods: Multicenter, prospective study of patients with IBD in clinical remission, who had their treatment changed from intravenous (IV) infliximab to SC. Two groups of patients were evaluated according to whether they were on IV infliximab treatment at standard or intensified doses before the switch. Results: A total of 30 patients were on standard dosing and another 30 in intensified therapy. Treatment persistence in both groups at 6 months was greater than 95%. In both groups after the change, neither the biomarkers of inflammation nor the activity indices underwent significant changes at 3 and 6 months compared to the baseline value. Similarly, in both groups, infliximab trough levels showed a significant increase 3 and 6 months after the change to SC. No serious adverse events were registered. Conclusions: The CT-P13 SC brings a new anti-TNF era. Achieving much higher drug levels that are constant over time opens new paths to explore the management of patients with IBD: less immunogenicity, better perianal disease control and higher achievement of mucosal healing