Search

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 in short stenoses next to the anastomosis of previous surgeries. Self-expandable metal stents (SEMS) could 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", multicenter, 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 and 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’s quality of life at one year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aims will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at one 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 novostenosis in CD. Trial registration: ClinicalTrials.gov, NCT 04330846. Registered on April 1, 2020. https://clinicaltrials.gov/ct2/home

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 (

BACKGROUND: Optimal thresholds for golimumab concentrations during maintenance for important outcomes are lacking. AIM: The aim of the study was to investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. METHODS: This multicentre, cross-sectional study included UC patients on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. RESULTS: Fifty-two patients were included. Median golimumab trough concentrations (µg/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS =2 + faecal calprotectin

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce.; METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered.; RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection.; CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies. Copyright © 2022. Published by Elsevier Ltd.

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.

Resumen Vedolizumab (VDZ), un anticuerpo monoclonal humanizado que se une especificamente a -α4β7-integrina, aprobado para el tratamiento de la enfermedad de Crohn (EC) y la colitis ulcerosa (CU), ha demostrado su eficacia en ensayos clinicos controlados. Objetivo Describir una poblacion tratada con VDZ y evaluar su efectividad y seguridad a largo plazo en practica clinica. Metodos Estudio observacional y multicentrico en pacientes con enfermedad inflamatoria intestinal tratados con VDZ durante al menos un ano. Se evaluaron los indices de actividad, niveles de calprotectina fecal y proteina C reactiva, hospitalizaciones, cirugias y eventos adversos. Resultados Se analizaron un total de 73 pacientes (43 CU y 30 EC). El 74 y 23% de CU y el 90 y 37% de EC habian llevado previamente mas de un anti-TNF y mas de un inmunosupresor respectivamente. VDZ se suspendio en 17 pacientes (23%), 10 CU y 7 EC, debido a la falta o perdida de respuesta antes del primer ano o a eventos adversos. Veintisiete (63%) CU y 16 (53%) pacientes con EC requirieron intensificacion de la dosis. A los 6 meses, el 70 y 42% de CU y el 80 y 43% de EC lograron respuesta clinica y remision respectivamente. Al ano, el 58 y 35% de CU y el 47 y 43% de EC mantuvieron la respuesta clinica y la remision, respectivamente. La proteina C reactiva disminuyo significativamente tanto en la EC como en la CU. Sin embargo, la disminucion de la calprotectina fecal se logro durante el seguimiento solo en CU pero no en EC. Ocho pacientes con EC que habian sido tratados previamente con ustekinumab evitaron la cirugia al ano. En 8 CU (18,6%) se realizo colectomia y 4 EC (13,3%) necesitaron cirugia. Seis pacientes (8%) (5 UC y una enfermedad de Crohn) tuvieron eventos adversos. El uso concomitante de corticoides o inmunomoduladores no aumento la efectividad. A mayor numero de anti-TNF previos, menos remision en la CU y respuesta en la EC. Conclusiones Tras un ano de VDZ se induce respuesta y remision clinica en una no desdenable proporcion de pacientes refractarios a diferentes biologicos o inmunosupresores. VDZ puede considerarse una alternativa en intolerantes a inmunosupresores con pocos eventos adversos.

Aim To evaluate the effectiveness and safety of tofacitinib in ulcerative colitis [UC] in real life. Methods Patients from the prospectively maintained ENEIDA registry and treated with tofacitinib due to active UC were included. Clinical activity and effectiveness were defined based on Partial Mayo Score [PMS]. Short-term response/remission was assessed at Weeks 4, 8, and 16. Results A total of 113 patients were included. They were exposed to tofacitinib for a median time of 44 weeks. Response and remission at Week 8 were 60% and 31%, respectively. In multivariate analysis, higher PMS at Week 4 (odds ratio [OR] = 0].2; 95% confidence interval [CI] = 0].1–0.4) was the only variable associated with lower likelihood of achieving remission at Week 8. Higher PMS at Week 4 [OR = 0.5; 95% CI = 0.3–0.7] and higher PMS at Week 8 [OR = 0.2; 95% CI = 0.1–0.5] were associated with lower probability of achieving remission at Week 16. A total of 45 patients [40%] discontinued tofacitinib over time. Higher PMS at Week 8 was the only factor associated with higher tofacitinib discontinuation [hazard ratio = 1.5; 95% CI = 1.3–1.6]. A total of 34 patients had remission at Week 8; of these, 65% had relapsed 52 weeks after achieving remission; the dose was increased to 10 mg/12 h in nine patients, and five of them reached remission again. Seventeen patients had adverse events. Conclusions Tofacitinib is effective and safe in UC patients in real practice, even in a highly refractory cohort. A relevant proportion of patients discontinue the drug over time, mainly due to primary failure.

Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

Este artículo se encuentra disponible en la siguiente URL: https://www.nature.com/articles/s41598-021-88823-2.pdf En este artículo también participan: Jose Maria Paredes-Arquiola, Maia Boscá-Watts, Jose Maria Huguet, Rafael Gil-Borrás y Josefa Rodríguez-Morales. Intestinal dysbiosis is key in the onset and development of Crohn’s disease (CD). We evaluated the microbiota changes in CD patients before and after a six-month anti-TNF treatment, comparing these changes with the microbiota of healthy subjects. This prospective multicenter observational study involved 27 CD patients initiating anti-TNF treatment and 16 healthy individuals. Inflammatory activity was determined at baseline, 3 and 6 months, classifying patients into responders and nonresponders. Fecal microbiota was analyzed by massive genomic sequencing thought 16S rRNA amplicon sequencing before and after six months of anti-TNF treatment. The CD cohort showed a decrease in genera of the class Clostridia, short-chain fatty acid producers, and an increase in the phylum Proteobacteria (p < 0.01) versus the healthy cohort. After anti-TNF treatment, the phylum Proteobacteria also increased in non-responders versus responders (13/27) (p < 0.005), with the class Clostridia increasing. In addition, alpha diversity increased in responders versus non-responders (p < 0.01), tending towards eubiosis. An association was found (p < 0.001) in the F.prausnitzii/E.coli ratio between responders and non-responders. The F/E ratio was the most accurate biomarker of anti-TNF response (area under the curve 0.87). Thus, anti-TNF treatment allows partial restoration of intestinal microbiota in responders and the F.prausnitzii/E.coli ratio can provide a reliable indicator of response to anti-TNF in CD.

Primary Thyroid Lymphoma (PTL) is an uncommon disease, although its incidence is of 5%. Ultrasound and Fine Needle Aspiration Cytology (FNAC) usually do not provide the diagnosis. Surgery is one of the treatment options because it enables histological diagnosis and can also relieve compression symptoms in patients with rapid growth cervical mass. We present 7 cases of PTL diagnosed in the last 10 years in our unit. Five were female (71.4%) and 2 were male (28.6%). The mean age was 64.2 (range: 40 - 81); 4 patients (57.1%) had associated Hashimoto’s Thyroiditis (HT). One patient (14.2%) had concomitant Graves disease. 5 cases presented with compressive symptoms and cervical mass. Ultrasound was not diagnostic in any case. FNAC was diagnostic only in one patient (14.3%). Five patients underwent total thyroidectomy (71.4%). All the cases were diagnosed with lymphoma postoperatively. Two interventions consisted of left hemithyroidectomies (28.6%). No complications appeared. 5 patients (71.4%) were classified as Mucosa-Associated Lymphoid Tissue (MALT) lymphoma. We also observed 1 Follicular grade I lymphoma and 1 Burkitt case. When the extension study was done, 1 patient was at stage IIIE (14%), 2 at IIE (28.5%) and 4 at IE (57.14%). Rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) and Iphosphamide, ethoposide and high dose Cytarabine (IVAC) were the treatment scheme when chemotherapy was used (in three cases). Two cases were treated only with total thyroidectomy, and 2 with total thyroidectomy and rituximab, and the latter was MALT. Complete Remission (CR) was achieved in all patients in the first year. All are still alive and in CR. In our experience, PTL diagnose can be challenging before surgery. Although surgery is not the gold standard for treatment, when it is done, it should be curative in MALT lymphomas confined to the thyroid.

We present the case of a pair of 45-year-old monozygotic twins (A and B) diagnosed with Crohn's disease (CD) at age 20 (A) and 22 (B) with similar presenting symptoms: diarrhea, fever and weight loss. Both of them had duodenal and ileocolonic disease (A2, L3+L4 according to Montreal classification); twin B also presented jejunal involvement and perianal disease (B1p). They received treatment with antibiotics, corticosteroids, 5-ASA, azathioprine and anti-TNF with a poor control of activity. They both developed a coloduodenal fistula that required surgery. Twin A developed the fistula 12 years after the first presentation; fistula closure with duodenorraphy and ileocolonic resection with gastrojejunostomy was performed. Twin B developed the fistula 22 years after the first presentation, and right colectomy, partial duodenectomy and duodenorraphy was carried out. Both developed an enterocutaneous fistula during the postoperative period. With intensive medical treatment, both twins remain asymptomatic.

Background: 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. Methods/Design: Multi-centre study with prospective follow-up in five regions in Spain (Galicia, Balearic Islands, Catalonia, Aragon 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). 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. 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. Local recurrence, development of metastases in the follow-up, appearance of a new tumour and mortality will be included as outcome variables. Actuarial survival analysis with Kaplan-Meier curves, Cox regression and competitive risk survival analysis will be performed., This study has received a grant for each participating group from the Ministry of Science and Innovation, Carlos III Institute, Healthcare Research Fund; PS09/00663, PI09/01800, PS09/00954, PS09/01614 and PS09/01375. In addition, the study has received the support of the Health Promotion and Preventive Activities - Primary Healthcare Network, which is supported by other grants from the Ministry of Health ISCIII-RETCI G03/170 and RD06/0018.; The study is also partially supported by a XUGA grant (08CSA073916PR) and the Galician Network for Colorectal Cancer Research.