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.

Vitamin E nanoemulsion activity on stored red blood cells.

BACKGROUND: Stored red blood cells (RBCs) undergo numerous changes that have been termed RBC storage lesion, which can be related to oxidative damage. Vitamin E is an important antioxidant, acting on cell lipids. Thus, this study aimed to investigate vitamin E activity on stored RBCs. METHODS: We prepared a vitamin E nanoemulsion that was added to RBC units and stored at 4 °C. Controls, without vitamin E, were kept under the same conditions. Reactive oxygen species (ROS) production was monitored for up to 35 days of storage. RBC elasticity was also evaluated using an optical tweezer system. RESULTS: Vitamin E-treated samples presented a significant decrease in ROS production. Additionally, the elastic constant for vitamin E-treated RBCs did not differ from the control. CONCLUSION: Vitamin E decreased the amount of ROS in stored RBCs. Because vitamin E acts on lipid oxidation, results suggest that protein oxidation should also be considered a key factor for erythrocyte elastic properties. Thus, further studies combining vitamin E with protein antioxidants deserve attention, aiming to better preserve overall stored RBC properties.

The use of a potential novel tool in virtual crossmatching for platelet transfusion in platelet refractoriness.

BACKGROUND AND OBJECTIVES: Transfusion support for immune-mediated platelet refractoriness (PR) is clinically challenging, technically laborious and costly. The development of 'EpHLA/EpVix software' has been used successfully to select kidney donors. Here, we sought to evaluate this new software as a tool for platelet virtual crossmatch (VxM). MATERIALS AND METHODS: This is a prospective study from 2007 to 2014 of PR patients in a tertiary hospital. Platelet components selected by HLAMatchmaker program were crossmatched by EpHLA/EpVix, anti-human globulin complement-dependent lymphocytotoxicity test (AHG-CDC), flow cytometry platelet crossmatch (FCxM) and then compared. Effectiveness of platelet components transfused was evaluated by CCI. RESULTS: Ninety-seven crossmatched platelet transfusions for 27 patients were enrolled. Partial matches were analysed for 75 transfusions by the 3 methods, and 22% showed discrepant results among the assays. After further analysis, data showed that all divergent cases could be explained by HPA alloimmunization, prozone effect (FCxM), low sensitivity of AHG-CDC and possible interference in FCxM/AHG-CDC assays. Notably, sensitivity and specificity of VxM analysis was excellent (100%). Satisfactory CCI counts were obtained for the majority (22/30) of the transfusions. CONCLUSION: The new EpHLA/EpVix method showed to be effective, feasible and fast for VxM at no cost and able to minimize labour on donor identification. However, platelet crossmatching may be a necessary step because EpHLA/EpVix does not formally exclude HPA alloimmunization.

The Effect of inotropes and vasopressors on mortality: a meta-analysis of randomized clinical trials.

BACKGROUND: Inotropes and vasopressors are frequently administered to critically ill patients in order to improve haemodynamic function and restore adequate organ perfusion. However, some studies have suggested a possible association between inotrope administration and increased mortality. We therefore performed a meta-analysis of randomized trials published in the last 20 yr to investigate the effect of these drugs on mortality. METHODS: BioMedCentral, PubMed, Embase and the Cochrane Central Register were searched (all updated April 8th, 2015). Inclusion criteria were: random allocation to treatment, at least one group receiving an inotropic or vasopressor drug compared with at least one group receiving a non-inotropic/vasopressor treatment, study published after 1st January 1994, and systemic drug administration. Exclusion criteria were overlapping populations, studies published as abstract only, crossover studies, paediatric studies and lack of data on mortality. RESULTS: A total of 28 280 patients from 177 trials were included. Overall, pooled estimates showed no difference in mortality between the group receiving inotropes/vasopressors and the control group [4255/14 036 (31.7%) vs. 4277/14 244 (31.8%), risk ratio=0.98 (0.96-1.01), P for effect=0.23, P for heterogeneity=0.30, I2=6%]. A reduction in mortality was associated with inotrope/vasopressor therapy use in settings of vasoplegic syndromes, sepsis and cardiac surgery. Levosimendan was the only drug associated with improvement in survival. Subgroup analysis did not identify any groups with increased mortality associated with inotrope/vasopressor therapy. CONCLUSIONS: Our systematic review found that inotrope/vasopressor therapy is not associated with differences in mortality in the overall population and in the majority of subsettings.

The effect of different dietary levels of canola meal on growth performance, nutrient digestibility, and gut morphology of broiler chickens.

This study evaluated the effects of different levels of canola meal in broiler diets on growth performance, nutrient digestibility, and duodenal morphometry. A total of 320 one-day-old Cobb broilers were used in a 35-d experiment. A completely randomized design with 5 levels of canola meal (0, 10, 20, 30, and 40%) as a substitute for soybean meal was used with 8 replicates of 8 birds each. The basal diets were formulated based on corn and soybean meal to meet nutrient requirements of broiler chickens. The levels of canola meal were evaluated with a polynomial regression at 5% of significance. Weight gain and average BW showed a quadratic response (P = 0.03 and P = 0.04, respectively), decreasing with the addition of 40% canola meal. The apparent nutrient digestibility of DM (P < 0.0001), CP (P < 0.0001), and nitrogen-free extract (P < 0.0001) decreased linearly with increased levels of canola meal. A quadratic effect was observed for villus height (P = 0.003), decreasing up to a 20% inclusion of canola meal in the diet and increasing beyond that level. In conclusion, canola meal can be added up to 16.7% in diets for broilers without affecting the key variables of growth performance. It can be added up to 20% with no negative effect on the CP digestibility, but there was a linear decrease in the digestibility of DM and nitrogen-free extract with increased inclusion of canola meal. Additionally, a quadratic response to canola was observed for villus height with a maximum at 23.6% canola meal.

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.

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.