Real-world use of mycophenolate mofetil in inflammatory bowel disease: Results from the ENEIDA registry.

BACKGROUND: Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. AIMS: Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. METHODS: IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. RESULTS: A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). CONCLUSION: Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Effectiveness and Safety of the Switch from Remicade® to CT-P13 in Patients with Inflammatory Bowel Disease.

BACKGROUND AND AIMS: To evaluate the clinical outcomes in patients with IBD after switching from Remicade® to CT-P13 in comparison with patients who maintain Remicade®. METHODS: Patients under Remicade® who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade® to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade®. RESULTS: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. CONCLUSIONS: Switching from Remicade® to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade® to CT-P13 was safe.

Post-operative morbidity and mortality of a cohort of steroid refractory acute severe ulcerative colitis: Nationwide multicenter study of the GETECCU ENEIDA Registry.

BACKGROUND: Despite the increased use of rescue medical therapies for steroid refractory acute severe ulcerative colitis, mortality related to this entity still remains high. We aimed to assess the mortality and morbidity related to colectomy and their predictive factors in steroid refractory acute severe ulcerative colitis, and to evaluate the changes in mortality rates, complications, indications of colectomy, and the use of rescue therapy over time. METHODS: We performed a multicenter observational study of patients with steroid refractory acute severe ulcerative colitis requiring colectomy, admitted to 23 Spanish hospitals included in the ENEIDA registry (GETECCU) from 1989 to 2014. Independent predictive factors of mortality were assessed by binary logistic regression analysis. Mortality along the study was calculated using the age-standardized rate. RESULTS: During the study period, 429 patients underwent colectomy, presenting an overall mortality rate of 6.3% (range, 0-30%). The main causes of death were infections and post-operative complications. Independent predictive factors of mortality were: age ≥50 years (OR 23.34; 95% CI: 6.46-84.311; p < 0.0001), undergoing surgery in a secondary care hospital (OR 3.07; 95% CI: 1.01-9.35; p = 0.047), and in an emergency setting (OR 10.47; 95% CI: 1.26-86.55; p = 0.029). Neither the use of rescue medical treatment nor the type of surgical technique used (laparoscopy vs. open laparotomy) influenced mortality. The proportion of patients undergoing surgery in an emergency setting decreased over time (p < 0.0001), whereas the use of rescue medical therapy prior to colectomy progressively increased (p > 0.001). CONCLUSIONS: The mortality rate related to colectomy in steroid refractory acute severe ulcerative colitis varies greatly among hospitals, reinforcing the need for a continuous audit to achieve quality standards. The increasing use of rescue therapy is not associated with a worse outcome and may contribute to reducing emergency surgical interventions and improve outcomes.

Long-Term Efficacy and Safety of Cyclosporine in a Cohort of Steroid-Refractory Acute Severe Ulcerative Colitis Patients from the ENEIDA Registry (1989-2013): A Nationwide Multicenter Study.

OBJECTIVES: To determine the efficacy and safety of cyclosporine (CyA) in a large national registry-based population of patients with steroid-refractory (SR) acute severe ulcerative colitis (ASUC) and to establish predictors of efficacy and adverse events. METHODS: Multicenter study of SR-ASUC treated with CyA, based on data from the ENEIDA registry. SR-ASUC patients treated with infliximab (IFX) or sequential rescue therapy (CyA-IFX or IFX-CyA) were used as comparators. RESULTS: Of 740 SR-ASUC patients, 377 received CyA, 131 IFX and 63 sequential rescue therapy. The cumulative colectomy rate was higher in the CyA (24.1%) and sequential therapy (32.7%) than in the IFX group (14.5%; P=0.01) at 3 months and 5 years. There were no differences in early and late colectomy between CyA and IFX in patients treated after 2005. 62% of patients receiving CyA remained colectomy-free in the long term (median 71 months). There were no differences in mortality between CyA (2.4%), IFX (1.5%) and sequential therapy (0%; P=0.771). The proportion of patients with serious adverse events (SAEs) was lower in CyA (15.4%) than in IFX treated patients (26.5%) or sequential therapy (33.4%; P<0.001). This difference in favor of CyA was maintained when only patients treated after 2005 were analyzed. CONCLUSIONS: Treatment with CyA showed a lower rate of SAE and a similar efficacy to that of IFX thereby supporting the use of either CyA or IFX in SR-ASUC. In addition, the risk-benefit of sequential CyA-IFX for CyA non-responders is acceptable.

[Adherence and fidelity in patients treated with intragastric balloon]. / Adherencia y fidelidad en el paciente tratado con balon intragastrico.

A correct treatment of obesity needs a program of habits modification regardless of the selected technique, especially if it is minimally invasive as the intragastric balloon (BIG). The adherence of the obese patients with regard to recommended drugs measures to medium- and long-term is less than 50%. Given that the results obtained using the technique of gastric balloon must be seen influenced by adherence to the modification of habits program and its fulfillment, we reviewed series published in attention to the program proposed with the BIG. The series published to date provide few details about the used Therapeutic Programs as well as the adherence of patients to them, and even less concerning the Monitoring Plan and the loyalty of the patient can be seen. We conclude the convenience to agree on a follow-up strategy, at least the 6 months during which the BIG remain in the stomach.

A comparative study of two histological techniques for the identification of cytomegalovirus infection in colorectal biopsies from patients with chronic inflammatory bowel disease.

BACKGROUND: the role that cytomegalovirus (CMV) plays in inflammatory bowel disease (IBD) is controversial. The diagnosis of CMV infection in IBD depends on viral identification with hematoxylin-eosin (HE) or immunohistochemistry (IHC). Our aim was to compare the sensitivity of HE and IHC for this diagnosis in IBD patients. PATIENTS AND METHODS: a case-control study. Our database was searched for IBD patients with HE- or IHC-based CMV-positivity from 1997 to 2007. Controls were selected among IBD inpatients matched for age and year of diagnosis with CMV. Their clinical characteristics were analyzed. HE and IHC were performed on biopsies from cases and controls at 6 months before and after inclusion in the study. In the statistical analysis, p values below 0.05 were considered significant. RESULTS: ten IBD patients with CMV infection were identified. IBD-CMV patients were more steroid-resistant or steroid-dependent (p = 0.03), and underwent a higher number of colonic biopsies (p = 0.03). From 97 biopsies analyzed, 12 were HE-negative and IHC-positive, and 3 showed reversed results. The sensitivity of HE was 58.6%, 95% CI (38.9-78.3), and that of IHC was 89.7%, 95% CI (76.8-100). We did not find a good level of agreement between both techniques: kappa value 0.55, 95% CI (0.36-0.75). CMV positivity with IHC was associated with the use of more than one immunosuppressant drug, OR 13.5, 95%CI (1.2-152.2). Antiviral treatment was useful for CMV patients with steroid-dependent and steroid-refractory IBD. CONCLUSIONS: IHC shows a 30% higher sensitivity than HE for the diagnosis of CMV infection in IBD patients. There is no good level of agreement between both histological techniques.

[Acute cholestatic hepatitis after atorvastatin reintroduction]. / Hepatitis colestásica aguda tras la reintroducción de atorvastatina.

Consumption of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA) inhibitors, known as statins, has been associated with elevated transaminase levels but rarely with acute hepatitis. Recently, several cases of acute hepatitis secondary to atorvastatin therapy have been published. We report the case of a 72-year-old man who developed acute cholestatic hepatitis after reinitiating treatment with atorvastatin at a higher dose than that previously prescribed. After treatment discontinuation, the patient made a full recovery, with normalization of clinical and laboratory findings.

Stability in a metapopulation model with density-dependent dispersal.

A spatially explicit metapopulation model with positive density-dependent migration is analysed. We obtained conditions under which a previously stable system can be driven to instability caused by a density-dependent migration mechanism. The stability boundary depends on the rate of increase of the number of migrants on each site at local equilibrium, on the intrinsic rate of increase at local level, on the number of patches, and on topological aspects regarding the connectivity between patches. A concrete example is presented illustrating the dynamics on the dispersal-induced unstable regime.

Synchronism in a metapopulation model.

We consider a spatially explicit meta-population model with interaction among the two nearest neighbors to relate, with a simple mathematical expression, chaos in the local, uncoupled, populations, the degree of interaction among patches, size of the meta-population, and the stability of the synchronized attractor. Since synchronism is strongly correlated with extinction, our results can provide useful information on factors leading to population extinction.

A prospective trial of self-expanding metal coated stents in the palliation of malignant dysphagia.

OBJECTIVE: To analyze the use of self-expanding metal coated esophageal stents a palliative therapy of malignant dysphagia. METHOD: We performed a one year prospective study placing 12 stents in 10 patients with malignant dysphagia. RESULTS: The insertion mean time was lower than 25 min, and most of our patients (70%) reported a good tolerance. Dysphagia score improved immediately and it lasted until death with no occlusions. Complications appeared early, 17% at the time of placement, with one patient having a life-threatening complication. The probability for these patients not to develop any complications after the three first weeks will be about 60%. CONCLUSIONS: Self-expanding metal coated esophageal stents provide a fast and lasting relief in malignant dysphagia, with a good tolerance.

Characterization of anti-erythrocyte autoantibodies in non-Hodgkin's lymphoma patients in Brazil.

The existence of an association between autoimmune phenomena and lymphoproliferative neoplasms is well known. In Campinas at the University Hospital, seventy-seven adult patients with non-Hodgkin's lymphoma (NHL) were studied at diagnosis. The histological subgroup of NHL was performed using Kiel criteria and all patients were characterized by clinical and laboratory examinations according to the Ann Arbor staging. The results of the immunohaematological evaluation of our patients with NHL showed that: 28% presented erythrocyte autoantibodies (auto anti-I or auto-IgG without specificity) but only one developed haemolytic anaemia. There was a weak correlation between low-grade lymphoma and erythrocyte autoantibodies.

Molecular cloning, sequencing, and analysis of the cDNA for rabbit muscle glycogen debranching enzyme.

Six peptides were isolated from glycogen debranching enzyme purified from rabbit muscle, and their sequences were determined. A cDNA library made from rabbit muscle using random hexamer primers was screened with oligonucleotide probes constructed in accordance with these peptide sequences. Seven cDNA clones comprising the open reading frame were found, whereas oligo(dT) cDNA libraries yielded no positive clones because of the long 3'-nontranslated region of 2.3 kb. The open reading frame of 4665 bases codes for a 1555-amino-acid protein of M(r) 177,542. Compared to the sequence from human muscle, there are an additional 40 amino acid residues upstream from the N-terminus, and the next 10 residues show no homology. For the remaining 1505 residues, the two sequences exhibit an identity of 93%. The four consensus sequences commonly found at the carboxy termini of beta-strands in the alpha/beta barrel domains of amylases and glucanotransferases are also found in the N-terminal half of the debranching enzyme, suggesting that this structural domain may be present. This and other evidence suggests that the N-terminal half may encompass the transferase activity, leaving the glucosidase activity for the C-terminal half. The latter shows no significant homology to known proteins. An unusual feature of the sequence is the presence of three pairs of adjacent cysteines, which may explain inhibition of the enzyme by organic arsenites.