Impact of cytomegalovirus on outcomes in acute severe ulcerative colitis: a retrospective observational study.

Background: Concomitant cytomegalovirus (CMV) is highly prevalent in acute severe ulcerative colitis (ASUC) but data for outcomes of CMV positivity in ASUC and the benefit of antiviral therapy remain unclear. Objectives: We aim to determine the impact of CMV positivity, and antiviral therapy, on outcomes such as colectomy-free survival, length of hospital stay and readmission rate, among hospitalized patients with ASUC. Design: This is a retrospective, multicentre study of patients admitted with ASUC. Methods: CMV positivity was diagnosed from blood CMV DNA and inpatient colonic biopsies. Background demographics and disease characteristics, clinical characteristics and outcomes during admission and long-term outcomes were obtained from electronic medical records and compared according to the presence of CMV and the use of antiviral therapy. Results: CMV was detected in 40 (24%) of 167 ASUC admissions. Previous steroid exposure was the only clinical predictor of CMV positivity on multivariate analysis. Outcomes of greater requirement for rescue therapy (60% versus 33%), longer hospital stay (14.3 versus 9.9 days) and higher readmission rates at 3 and 12 months were associated with CMV positivity. No difference was found in the rate of colectomy or colectomy-free survival. Antiviral therapy was not associated with a lower risk of colectomy but did extend the time to colectomy (126 versus 36 days). Conclusion: CMV positivity was associated with worse outcomes of need for rescue therapy, hospital stay and readmissions. Antiviral therapy was not found to reduce the risk of colectomy but did extend the time to colectomy. Further prospective studies will be required to more clearly determine its benefit in patients with concomitant CMV and ASUC.

Cytomegalovirus reactivation in acute severe ulcerative colitis Cytomegalovirus (CMV) is a highly prevalent virus that may result in concominant reactivation in patients with acute severe ulcerative colitis and potentially worsen their outcomes. Our study aims to determine the impact of presence of CMV in patients with acute severe ulcerate colitis requiring hospitalisation and its association with outcomes including risk of surgical resection of colon, length of hospital stay, readmission rate, as well as effect of outcomes amongst those treated with antivirals for CMV. Our results did not find a significant association between detection of CMV on surgical risk, though outcomes including longer hospital stays, higher readmission rate were found. Antiviral use was not associated with lower risk of surgery but was found to prolong time to surgery. Given that our study was based on retrospective data, further prospective studies will be required to examine the benefit of antiviral use in outcomes for those with concominant CMV and acute severe ulcerative colitis. We conclude from our study that while having concomitant CMV with acute severe uclerative colitis may not necessarily increase risk for surgery, patients may still have worse outcomes in other areas therefore the detection of CMV should be considered a significant and clinically relevant result.

Tallman lettering as a strategy for differentiation in look-alike, sound-alike drug names: the role of familiarity in differentiating drug doppelgangers.

Tallman lettering, capitalizing the dissimilar portions of easily confused drug names, is one strategy for reducing medication errors. We assessed the efficacy of Tallman lettering in a visually complex environment using a change detection method with healthcare providers and laypeople. In addition, the effect of familiarity with the drug name was assessed using a subset of responses collected from healthcare providers. Both healthcare providers and laypeople detected changes in confusable pairs of drug names more often (P < 0.0001) and more quickly (P < 0.05) when changes were presented in Tallman lettering, though the benefits were more pronounced for healthcare providers (p < 0.05). Familiarity with both drug names in a confusable pair mitigated the benefit of Tallman lettering. Results are discussed in terms of bottom-up and top-down attentional systems for processing of information in the context of the varied healthcare environments.

Functional group selective derivatization and gas-phase fragmentation reactions of plasmalogen glycerophospholipids.

A reaction strategy involving functional group selective modification of the O-alkenyl-ether double bond within plasmenyl ether containing lipids using iodine and methanol, in conjunction with functional group selective derivatization of amine-containing lipids using a novel (13)C1-S,S'-dimethylthiobutanoylhydroxysuccinimide ester ((13)C1-DMBNHS) reagent, is shown to improve the capabilities of 'shotgun' high resolution/accurate mass spectrometry for comprehensive lipidome analysis. Importantly, the characteristic mass shifts introduced as a result of these derivatization reactions enables the resolution and unambiguous identification of isobaric mass plasmenyl- and plasmanyl-ether containing lipid species from within crude complex lipid extracts, without need for chromatographic fractionation or additional lipid extraction steps prior to analysis. Additionally, the positive ionization mode tandem mass spectrometry fragmentation behavior of the derivatized plasmenyl ether containing glycerophosphocholine and glycerophosphoethanolamine lipids are shown to yield abundant characteristic product ions that directly enable the assignment of their molecular lipid identities.

Comprehensive lipidome profiling of isogenic primary and metastatic colon adenocarcinoma cell lines.

A "shotgun" lipidomics strategy consisting of sequential functional group selective chemical modification reactions coupled with high-resolution/accurate mass spectrometry and "targeted" tandem mass spectrometry (MS/MS) analysis has been developed and applied toward the comprehensive identification, characterization and quantitative analysis of changes in relative abundances of >600 individual glycerophospholipid, glycerolipid, sphingolipid and sterol lipids between a primary colorectal cancer (CRC) cell line, SW480, and its isogenic lymph node metastasized derivative, SW620. Selective chemical derivatization of glycerophosphoethanolamine and glycerophosphoserine lipids using a "fixed charge" sulfonium ion containing, d(6)-S,S'-dimethylthiobutanoylhydroxysuccinimide ester (d(6)-DMBNHS) reagent was used to eliminate the possibility of isobaric mass overlap of these species with the precursor ions of all other lipids in the crude extracts, thereby enabling their unambiguous assignment, while subsequent selective mild acid hydrolysis of plasmenyl (vinyl-ether) containing lipids using formic acid enabled these species to be readily differentiated from isobaric mass plasmanyl (alkyl-ether) containing lipids. Using this approach, statistically significant differences in the abundances of numerous lipid species previously identified as being associated with cancer progression or that play known roles as mediators in a range of physiological and pathological processes were observed between the SW480 and SW620 cells. Most notably, these included increased plasmanylcholine and triglyceride lipid levels, decreased plasmenylethanolamine lipids, decreased C-16 containing sphingomyelin and ceramide lipid levels, and a dramatic increase in the abundances of total cholesterol ester and triglyceride lipids in the SW620 cells compared to those in the SW480 cells.

Combination of large volume sample stacking and reversed pH junction in capillary electrophoresis for online preconcentration of glycoforms of recombinant human erythropoietin.

Resolution of glycoforms of a glycoprotein is usually a challenge for an analytical chemist, which is often associated with the difficulty of detecting a large number of glycoforms with sufficient sensitivity. CE is the main workhorse for the analysis of glycoproteins; however, the current methods are only applicable to high concentration samples. Therefore, the development of online preconcentration approaches is important for the CE analysis of glycoproteins. In this study, we present a combined strategy for online preconcentrating glycoforms of glycoproteins, which couples two individual online preconcentration techniques, i.e., large volume sample stacking (LVSS) and reversed pH junction (RPHJ). LVSS allows for compressing a large injected sample volume into a narrow sample zone, contributing to the main sensitivity improvement, while RPHJ coordinates the preconcentration process to improve the resolution. This strategy was verified with recombinant human erythropoietin (rhEPO), a typical glycoprotein, as the test analyte, and the effects of experimental conditions were investigated. It was found that there is a compromise between sensitivity enhancement and resolution for online preconcentration of glycoprotein glycoforms. By using this strategy, the detection sensitivity can be improved by 50-100 times for rhEPO.