Risk of bleeding following double balloon enteroscopy in patients on continued antiplatelet and/or anticoagulation therapy.

Background and study aims Anticoagulation (AC) and antiplatelet (AP) therapy may increase the risk of gastrointestinal bleeding after double balloon enteroscopy (DBE); however, limited data are currently available regarding the incidence. The aim of this study was to assess the incidence and clinical characteristics of post-DBE bleeding in patients on AC and AP therapy. Patients and methods The medical records of patients who underwent DBE between 2009 and 2013 at Mayo Clinic, Florida, were retrospectively reviewed. Patients were divided into three groups: 1) continued AP therapy; 2) AC therapy; and 3) neither AP nor AC at the time of DBE. Follow-up data were collected at 60 days and 1 year. Results A total of 683 patients were identified; 43 on AC, 183 on AP and 457 not on AP or AC therapy. The most common indication for DBE was obscure gastrointestinal bleeding in the groups on and not on AP (85.3 % vs 70.9 %, P  < 0.0001). There was no statistical difference in post-DBE bleeding rates in patients on AP vs not on AP at 60 days (11.5 % vs 7.5 %, P  = 0.12) or 1 year (19.9 % vs 15.7 %, P  = 0.23). Rates of bleeding in patients on AC were 11.6 % within 60 days and 22.5 % within 1 year. Multivariate analysis reflected American Society of Anesthesiologist > 3 and indication for DBE of GI bleeding were independent risk factors for post-DBE bleeding within 1 year. Conclusions Continued antiplatelet use at the time of DBE was not an independent risk factor for bleeding post-DBE at 60 days or 1 year of follow up.

Outcomes in Patients with Left Ventricular Assist Devices, Pacemakers, and Implantable Cardioverter Defibrillators Undergoing Single Balloon Enteroscopy.

OBJECTIVES: Obscure overt gastrointestinal bleeding can be challenging to evaluate in patients with electronic cardiac devices such as continuous flow left ventricular assist devices (LVADs), pacemakers (PPMs), and implantable cardioverter defibrillators (ICDs). Limited data exist on the utility and safety of single balloon enteroscopy (SBE) in patients with cardiac devices. We aimed to evaluate the safety, efficacy, diagnostic, and therapeutic outcomes of the aforementioned devices in patients undergoing SBE. METHODS: A retrospective study was performed using the medical records of 57 patients undergoing SBE at our institution from 2010 to 2014. Patients were divided into two groups: those with cardiac devices and those without. Data on comorbidities, complications, findings, diagnostic, and therapeutic yield were compared. t Test and logistic regression assessed the association between dependent and independent variables. For continuous data, the results were summarized as mean difference and standard deviation. For dichotomous data, the results were summarized as odds ratio and 95% confidence intervals. RESULTS: The overall age in patients with cardiac devices was 67.89 ± 6.96 versus 66.03 ± 11.95 years in the control. The cardiac device group was composed of 42.1% women; the control comprised 21.1% women. There were 19 patients with cardiac devices; 8 (LVAD + ICD), 1 (LVAD + PPM + ICD), 2 (PPM + ICD), 6 (PPM), 2 (ICD); 38 patients were in the control group. Patients with cardiac devices were hospitalized more often than patients without devices; this finding was not statistically significant (odds ratio 1.826, 95% confidence interval 0.544-6.128, P = 0.389). Procedure times were longer in the cardiac device group, 65.16 ± 49.92 minutes, when compared with the control, 57.40 ± 20.42, but it also did not reach statistical significance (mean difference 7.758, 95% confidence interval -11.360 to 26.876, P = 0.049). There was no statistically significant difference in major or minor events between patients with cardiac devices and the control group. Diagnostic and therapeutic yield and rebleeding rates were similar across both groups. CONCLUSIONS: Patients in the cardiac device group did not appear to be at any more significant risk than those without cardiac devices. Furthermore, diagnostic and therapeutic yield and rebleeding rates appear to be similar across both groups. Clinicians may perform SBE in these patients safely and effectively, with good overall outcomes.

Carbon dioxide versus room air insufflation during balloon-assisted enteroscopy: A systematic review with meta-analysis.

Background and study aims Carbon dioxide (CO2) insufflation has been suggested to be an ideal alternative to room air insufflation to reduce trapped air within the bowel lumen after balloon assisted enteroscopy (BAE). We performed a systematic review and meta-analysis to assess the safety and efficacy of utilizing CO2 insufflation as compared to room air during BAE. Patients and methods The primary outcome is mean change in visual analog scale (VAS; 10 cm) at 1, 3, and 6 hours to assess pain. Secondary outcomes include insertion depth (anterograde or retrograde), adverse events, total enteroscopy rate, diagnostic yield, mean anesthetic dosage, and PaCO2 at procedure completion. We searched MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until May 2015. Multiple independent extractions were performed, the process was executed as per the standards of the Cochrane collaboration. Results Four randomized controlled trials (RCTs) were included in the meta-analysis. VAS at 6 hours favored CO2 over room air (MD 0.13; 95 % CI 0.01, 0.25; p = 0.03). Anterograde insertion depth (cm) was improved in the CO2 group (MD, 58.2; 95 % CI 17.17, 99.23; p = 0.005), with an improvement in total enteroscopy rate in the CO2 group (RR 1.91; 95 % CI 1.20, 3.06; p = 0.007). Mean dose of propofol (mg) favored CO2 compared to air (MD, - 70.53; 95 % CI - 115.07, - 25.98; P = 0.002). There were no differences in adverse events in either group. Conclusions Despite the ability of CO2 to improve insertion depth and decrease amount of anesthesia required, further randomized control trials are needed to determine the agent of choice for insufflation in balloon assisted enteroscopy.

Timing of single balloon enteroscopy: significant or not?

BACKGROUND: The development of balloon assisted enteroscopy (BAE) has revolutionized diagnostic and therapeutic modalities for small-bowel disorders. Although the role of emergent esophagogastroduodenoscopy and colonoscopy for upper and lower gastrointestinal bleeding is well defined, there is scarce data with regard to emergent BAE for gastrointestinal bleeding. STUDY: We performed a retrospective cohort study including 110 hospitalized patients with obscure gastrointestinal bleeding who underwent single balloon enteroscopy (SBE) between January 2010 and August 2013. Patients were divided into two groups based on procedures performed emergently (within 24 hours) versus non-emergently (greater than 24 hours). Data on patient demographics, hemodynamic characteristics, type of obscure bleed, lesions identified, location of lesions, endoscopic intervention performed, need for further surgical or radiological intervention, diagnostic and therapeutic yield, and adverse events were compared between groups. Independent samples t test and Fisher's exact test were used to assess the association between dependent and independent variables. For continuous data, the results were summarized as mean difference and 95 % confidence intervals (CI), and for binary as odds ratio and 95 %CI. RESULTS: Although patients in the group where enteroscopy was performed within 24 hours had a significantly higher incidence of radiological intervention (10.0 % vs. 0.0 %, P = 0.019), the diagnostic and therapeutic yields between the two groups were not significantly different. Additionally, there were no statistically significant differences between the groups for overt and occult bleeding, transfusion requirements, type and location of lesions, endoscopic intervention performed, or adverse events. Hospital stay was shorter in the patients who had SBE within 24 hours of admission (6.2 vs. 11.3 days, P < 0.001). CONCLUSIONS: Although the diagnostic and therapeutic yields of SBE were not significantly different between patients having the procedure within 24 hours and those having it later, the early SBE group required more interventional radiology procedures. While endoscopists may not necessarily have to perform emergent assessment within 24 hours in patients with obscure gastrointestinal bleeding (OGIB) for greater diagnostic or therapeutic yield, early intervention may allow for earlier stabilization and thus shorter hospital stays. Prospective studies further evaluating these findings are indicated.

The safety and efficacy of single balloon enteroscopy in the elderly.

BACKGROUND: Single balloon enteroscopy (SBE) is an important tool in the management of small bowel disease with limited data available on its performance in the elderly. We aimed to evaluate the safety, efficacy, diagnostic and therapeutic outcomes of SBE in the elderly. METHODS: A retrospective review was performed on 366 patients undergoing 428 SBEs from 2010 to 2014. Patients were divided into different age groups: control <55, 55-64, 65-74 and ⩾75 years. Data on comorbidities, complications, findings, diagnostic and therapeutic yield were compared between groups. RESULTS: Anterograde and retrograde SBE were performed in 340 and 49 patients, respectively, with 63 patients requiring more than 1 procedure. Diagnostic yield was significantly higher for age ⩾75 years compared with <55, 66.3% versus 50%, odds ratio (OR) 1.97 [95% confidence interval (CI) 1.14-3.41]. Therapeutic yield was significantly higher in all three older age groups compared with <55 years, 20.3%: 55-64 years, 44.4%, OR 3.13(95% CI 1.7-5.78); 65-74 years, 42%, OR 2.84 (95% CI 1.59-5.06); and >75 years, 47.5%, OR 3.55 (95% CI 1.96-6.43). No significant difference was seen between age groups in complications or failures. Our overall complication rate was 2.3% with 5 minor and 5 major complications. There was a higher yield of angioectasias in the elderly. Argon plasma coagulation (APC) and multipolar electrocoagulation were used more often in older age groups. CONCLUSION: SBE is safe in elderly patients and delivers higher diagnostic and therapeutic yields compared to younger patients. The elderly are more likely to have angioectasias and undergo APC and electrocoagulation.

Association between caffeine consumption and nonalcoholic fatty liver disease: a systemic review and meta-analysis.

OBJECTIVES: Caffeine consumption is reported to be associated with reduced hepatic fibrosis in patients with chronic liver diseases. We performed a systematic review and meta-analysis to assess the association between caffeine consumption and prevalence or hepatic fibrosis of nonalcoholic fatty liver disease (NAFLD) in observational studies. METHODS: We searched the literature of all languages from PubMed, EMBASE, and the Cochrane library from 1 January 1980 through 10 January 2015. Total caffeine consumption was defined as the daily intake of caffeine (mg/day) from all caffeine-containing products. Combined and subgroup analyses stratified by study designs, study locations, and type of caffeine intake were performed. RESULTS: Four cross-sectional and two case control studies with a total of 20,064 subjects were included in the meta-analysis. Among these, three studies with 18,990 subjects were included in the analysis for prevalence of NAFLD while the other three studies with 1074 subjects were for hepatic fibrosis. Total caffeine consumption (mg/day) was not significantly associated with either the prevalence [pooled mean difference (MD) 2.36; 95% confidence interval (CI) -35.92 to 40.64] or hepatic fibrosis (higher versus lower stages; pooled MD -39.95; 95% CI -132.72 to 52.82) of NAFLD. Subgroup analyses stratified by study designs and locations were also not significant. However, after stratifying by type of caffeine intake, regular coffee caffeine intake (mg/day) was significantly associated with reduced hepatic fibrosis of NAFLD (pooled MD -91.35; 95% CI -139.42 to -43.27; n = 2 studies). CONCLUSION: Although total caffeine intake is not associated with the prevalence or hepatic fibrosis of NAFLD, regular coffee caffeine consumption may significantly reduce hepatic fibrosis in patients with NAFLD.

Fucosylation and protein glycosylation create functional receptors for cholera toxin.

Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors using its B subunit (CTB). The ganglioside (glycolipid) GM1 is thought to be the sole CT receptor; however, the mechanism by which CTB binding to GM1 mediates internalization of CT remains enigmatic. Here we report that CTB binds cell surface glycoproteins. Relative contributions of gangliosides and glycoproteins to CTB binding depend on cell type, and CTB binds primarily to glycoproteins in colonic epithelial cell lines. Using a metabolically incorporated photocrosslinking sugar, we identified one CTB-binding glycoprotein and demonstrated that the glycan portion of the molecule, not the protein, provides the CTB interaction motif. We further show that fucosylated structures promote CTB entry into a colonic epithelial cell line and subsequent host cell intoxication. CTB-binding fucosylated glycoproteins are present in normal human intestinal epithelia and could play a role in cholera.

Enhanced transfer of a photocross-linking N-acetylglucosamine (GlcNAc) analog by an O-GlcNAc transferase mutant with converted substrate specificity.

O-Linked ß-N-acetylglucosamine (O-GlcNAc) is a post-translational modification of proteins in multicellular organisms. O-GlcNAc modification is catalyzed by the O-GlcNAc transferase (OGT), which transfers N-acetylglucosamine (GlcNAc) from the nucleotide sugar donor UDP-GlcNAc to serine or threonine residues of protein substrates. Recently, we reported a novel metabolic labeling method to introduce the diazirine photocross-linking functional group onto O-GlcNAc residues in mammalian cells. In this method, cells are engineered to produce diazirine-modified UDP-GlcNAc (UDP-GlcNDAz), and the diazirine-modified GlcNAc analog (GlcNDAz) is transferred to substrate proteins by endogenous OGT, producing O-GlcNDAz. O-GlcNDAz-modified proteins can be covalently cross-linked to their binding partners, providing information about O-GlcNAc-dependent interactions. The utility of the method was demonstrated by cross-linking highly O-GlcNAc-modified nucleoporins to proteins involved in nuclear transport. For practical application of this method to a broader range of O-GlcNAc-modified proteins, efficient O-GlcNDAz production is critical. Here we examined the ability of OGT to transfer GlcNDAz and found that the wild-type enzyme (wtOGT) prefers the natural substrate, UDP-GlcNAc, over the unnatural UDP-GlcNDAz. This competition limits O-GlcNDAz production in cells and the extent of O-GlcNDAz-dependent cross-linking. Here we identified an OGT mutant, OGT(C917A), that efficiently transfers GlcNDAz and, surprisingly, has altered substrate specificity, preferring to transfer GlcNDAz rather than GlcNAc to protein substrates. We confirmed the reversed substrate preference by determining the Michaelis-Menten parameters describing the activity of wtOGT and OGT(C917A) with both UDP-GlcNAc and UDP-GlcNDAz. Use of OGT(C917A) enhances O-GlcNDAz production, yielding improved cross-linking of O-GlcNDAz-modified molecules both in vitro and in cells.

Capsule Studies Performed in a Tertiary Care Center Versus Community Referrals Prior to Single-Balloon Enteroscopy: Does It Matter?

BACKGROUND AND AIMS: Within the community, patients with positive capsule endoscopy (CE) are often referred to centers performing balloon-assisted enteroscopy. There is limited data evaluating the concordance and diagnostic/therapeutic yield of CE performed in the community versus CE conducted at institutions experienced with enteroscopy. The primary aim of this retrospective study was to evaluate the concordance between CE and SBE after CE was performed either in the community or at our tertiary care center. METHODS: A total of 141 patients were analyzed after selecting patients undergoing evaluation of obscure GI bleeding from January 2010 to May 2014. Forty-seven CE were performed inside and the remaining 94 CE were performed at outside institutions prior to single-balloon enteroscopy at our institution. Agreement beyond chance was evaluated using kappa coefficient. A p value <5% was considered significant. RESULTS: The most frequent findings on CE were vascular lesions in 39 patients (41.5%) within the referral group and 23 within inside patients (48.9%), followed by active bleeding/clots in 23 patients (24.5%) and in 14 patients (29.8%) respectively. There was a fair degree of concordance in the referral group for vascular lesions 0.23 (0.03-0.42) compared to a good degree in the inside group 0.65 (0.44-0.87). Fair agreement was found looking at ulcers within the referral group 0.29 (0.06-0.65) compared to a moderate agreement in the inside group 0.55 (0.17-0.94). CONCLUSIONS: Degree of concordance for vascular lesions and ulcers was significantly higher for patients undergoing CE at our institution compared to those referred from the community. Patients referred to tertiary care centers for balloon-assisted enteroscopy may benefit from advanced endoscopists re-reading the capsule findings or even potentially repeating CE in hemodynamically stable patients if the study is not available.

Cellular metabolism of unnatural sialic acid precursors.

Carbohydrates, in addition to their metabolic functions, serve important roles as receptors, ligands, and structural molecules for diverse biological processes. Insight into carbohydrate biology and mechanisms has been aided by metabolic oligosaccharide engineering (MOE). In MOE, unnatural carbohydrate analogs with novel functional groups are incorporated into cellular glycoconjugates and used to probe biological systems. While MOE has expanded knowledge of carbohydrate biology, limited metabolism of unnatural carbohydrate analogs restricts its use. Here we assess metabolism of SiaDAz, a diazirine-modified analog of sialic acid, and its cell-permeable precursor, Ac4ManNDAz. We show that the efficiency of Ac4ManNDAz and SiaDAz metabolism depends on cell type. Our results indicate that different cell lines can have different metabolic roadblocks in the synthesis of cell surface SiaDAz. These findings point to roles for promiscuous intracellular esterases, kinases, and phosphatases during unnatural sugar metabolism and provide guidance for ways to improve MOE.

Recognition of diazirine-modified O-GlcNAc by human O-GlcNAcase.

The mammalian O-GlcNAc hydrolase (OGA) removes O-GlcNAc from serine and threonine residues on intracellular glycoproteins. OGA activity is sensitive to N-acyl substitutions to O-GlcNAc, with alkyl diazirine-modified O-GlcNAc (O-GlcNDAz) being completely resistant to removal by OGA. Using homology modeling, we identified OGA residues proximal to the N-acyl position of O-GlcNAc substrate. Mutation of one of these residues, C215, results in mutant enzymes that are able to hydrolytically remove O-GlcNDAz from a model compound. Further, the C215A mutant is capable of removing O-GlcNDAz from a peptide substrate. These results can be used to improve metabolism of O-GlcNAc analogs in cells. In addition, the enzyme specificity studies reported here provide new insight into the active site of OGA, an important drug target.