Factors Associated With Adherence to Helicobacter pylori Testing During Hospitalization for Bleeding Peptic Ulcer Disease.

BACKGROUND & AIMS: Guidelines recommend testing patients with peptic ulcer disease for Helicobacter pylori infection. We sought to identify factors associated with adherence to testing for H pylori in patients hospitalized for bleeding ulcers and to evaluate whether performing these tests affect risk for rebleeding. METHODS: We performed a retrospective study of 830 inpatients who underwent endoscopy from 2011 through 2016 for gastrointestinal bleeding from gastric or duodenal ulcers. We searched electronic medical records for evidence of tests to detect H pylori by biopsy, serologic, or stool antigen analyses. We used multivariable models to identify clinical, demographic, and endoscopic factors associated with testing for H pylori. Kaplan-Meier analysis was performed to determine whether H pylori testing altered risk for the composite outcome of rebleeding or death within 1 year of admission. RESULTS: Among the patients hospitalized for bleeding peptic ulcer disease during the 6-year period, 19% were not tested for H pylori within 60 days of index endoscopy. Hospitalization in the intensive care unit (ICU) was the factor most frequently associated with nonadherence to H pylori testing guidelines (only 66% of patients in the ICU were tested vs 90% of patients not in the ICU; P < .01), even after we adjusted for ulcer severity, coagulation status, extent of blood loss, and additional factors (adjusted odds ratio, 0.42; 95% CI, 0.27-0.66). Testing for H pylori was associated with a 51% decreased risk of rebleeding or death during the year after admission (adjusted hazard ratio 0.49; 95% CI, 0.36-0.67). CONCLUSIONS: In an analysis of hospitalized patients who underwent endoscopy for gastrointestinal bleeding from gastric or duodenal ulcers, we found admission to the ICU to be associated with failure to test for H pylori infection. Failure to test for H pylori was independently associated with increased risk of rebleeding or death within 1 year of hospital admission. We need strategies to increase testing for H pylori among inpatients with bleeding ulcers.

Minor Hematochezia Decreases Use of Venous Thromboembolism Prophylaxis in Patients with Inflammatory Bowel Disease.

BACKGROUND: Despite increased risk of venous thromboembolism (VTE) among hospitalized patients with inflammatory bowel disease (IBD), pharmacologic prophylaxis rates remain low. We sought to understand the reasons for this by assessing factors associated with VTE prophylaxis in patients with IBD and the safety of its use. METHODS: This was a retrospective cohort study conducted among patients hospitalized between January 2013 and August 2018. The primary outcome was VTE prophylaxis, and exposures of interest included acute and chronic bleeding. Medical records were parsed electronically for covariables, and logistic regression was used to assess factors associated with VTE prophylaxis. RESULTS: There were 22,499 patients studied, including 474 (2%) with IBD. Patients with IBD were less likely to be placed on VTE prophylaxis (79% with IBD, 87% without IBD), particularly if hematochezia was present (57% with hematochezia, 86% without hematochezia). Among patients with IBD, admission to a medical service and hematochezia (adjusted odds ratio 0.27; 95% CI, 0.16-0.46) were among the strongest independent predictors of decreased VTE prophylaxis use. Neither hematochezia nor VTE prophylaxis was associated with increased blood transfusion rates or with a clinically significant decline in hemoglobin level during hospitalization. CONCLUSION: Hospitalized patients are less likely to be placed on VTE prophylaxis if they have IBD, and hematochezia may drive this. Hematochezia appeared to be minor and was unaffected by VTE prophylaxis. Education related to the safety of VTE prophylaxis in the setting of minor hematochezia may be a high-yield way to increase VTE prophylaxis rates in patients with IBD.

Intestinal Crypts Assume the Fetal Position in Response to Injury.

Distinct stem/progenitor cells generate intestinal epithelium during fetal and postnatal life. In a recent issue of Nature, Nusse and Savage et al. use helminth infection to show that Lgr5+ intestinal stem cells are replaced by fetal-like progenitors following injury, suggesting that some fetal developmental pathways are repurposed during injury-induced tissue regeneration.

mRNA decay factor AUF1 maintains normal aging, telomere maintenance, and suppression of senescence by activation of telomerase transcription.

Inflammation is associated with DNA damage, cellular senescence, and aging. Cessation of the inflammatory cytokine response is mediated in part through cytokine mRNA degradation facilitated by RNA-binding proteins, including AUF1. We report a major function of AUF1-it activates telomerase expression, suppresses cellular senescence, and maintains normal aging. AUF1-deficient mice undergo striking telomere erosion, markedly increased DNA damage responses at telomere ends, pronounced cellular senescence, and rapid premature aging that increases with successive generations, which can be rescued in AUF1 knockout mice and their cultured cells by resupplying AUF1 expression. AUF1 binds and strongly activates the transcription promoter for telomerase catalytic subunit Tert. In addition to directing inflammatory cytokine mRNA decay, AUF1 destabilizes cell-cycle checkpoint mRNAs, preventing cellular senescence. Thus, a single gene, AUF1, links maintenance of telomere length and normal aging to attenuation of inflammatory cytokine expression and inhibition of cellular senescence.

Similar regulation of human inducible nitric-oxide synthase expression by different isoforms of the RNA-binding protein AUF1.

The ARE/poly-(U) binding factor 1 (AUF1), a protein family consisting of four isoforms, is believed to mediate mRNA degradation by binding to AU-rich elements (ARE). However, evidence exists that individual AUF1 isoforms may stabilize ARE-containing mRNAs. The 3'-untranslated region of the human inducible nitric-oxide synthase (iNOS) contains five AREs, which promote RNA degradation. We have recently shown that the RNA-binding protein KSRP is critically involved in the decay of the iNOS mRNA. In this study we examined the effects of the individual AUF1 isoforms on iNOS expression. Overexpression of each AUF1 isoform reduces iNOS expression on mRNA and protein levels to the same extent by modulation of mRNA stability. Accordingly, knockdown of all or individual AUF1 isoforms by an RNA interference approach enhances iNOS expression. The AUF1 effect on iNOS expression is dependent on the iNOS 3'-untranslated region sequence, as demonstrated in transfection experiments with a reporter mRNA. Binding studies showed that all AUF1 isoforms interact with the same AU-rich region in the iNOS-3'-untranslated region. Cytokine stimulation altered intracellular AUF1 binding activities. These data demonstrate that AUF1 is an important factor that promotes iNOS mRNA degradation. Furthermore, all individual AUF1 isoforms act in a similar manner.

Active ingredients in sunscreens act as topical penetration enhancers for the herbicide 2,4-dichlorophenoxyacetic acid.

Agricultural workers are encouraged to use sunscreen to decrease the risk of UV-related skin cancer. Our previous studies have shown certain commercial sunscreens to be penetration enhancers. The focus of this project is to determine whether active ingredients in sunscreen formulations (i.e., the UV absorbing components and insect repellants for the sunscreen/bug repellant combinations) also act as dermal penetration enhancers for herbicides in vitro. The total percentages of 2,4-dichlorophenoxyacetic acid (2,4-D) penetrating through hairless mouse skin in 24 h ranged from 54.9 +/- 4.7 for the no sunscreen control to 86.9 +/- 2.5 for padimate-o. Of the active ingredients tested (7.5% octyl methoxycinnamate, 7% octocrylene, 0.6% oxybenzone, 5% homosalate, 5% octyl salicylate, 8% padimate-o, 10% sulisobenzone, and 9.5% and 19% N,N-diethyl-m-toluamide [DEET]), all but octocrylene led to a significant increase in total 2,4-D penetration as compared to the control (P < 0.05), and only octocrylene and oxybenzone did not significantly decrease the corresponding lag time. Octyl salicylate (P < 0.01) and octyl methoxycinnimate (P < 0.05) significantly increased the 3H2O penetration across mouse skin, indicating physical damage to the stratum corneum. Additional studies demonstrated that the penetration enhancement seen across hairless mouse skin also occurred with human skin. Thus, the active ingredients of sunscreen formulations enhance dermal penetration of the moderately lipophilic herbicide 2,4-D.

Effects of active sunscreen ingredient combinations on the topical penetration of the herbicide 2,4-dichlorophenoxyacetic acid.

Sunscreen use can reduce the incidence of certain skin cancers. However, a number of commercially available formulations have been shown to enhance the transdermal penetration of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). Most of the active ingredients used in these compounds can individually act as penetration enhancers. Commercial sunscreens frequently contain multiple active ingredients in order to provide broad sunscreen protection. The purpose of this study was therefore to examine the effect of these active ingredient combinations on the transdermal absorption of 2,4-D in vitro. All six of the combinations tested resulted in increased cumulative penetration (P <0.01) and faster lag times (P <0.05). The 2,4-D cumulative penetration in the presence of the OFF! Deepwoods combination was significantly greater than the absorption with either the individual ingredients or their average (P <0.05). A systematic study designed to isolate the chemicals responsible for this enhancement demonstrated that with UV absorbers DEET synergistically increased the 2,4-D penetration and that DEET's cumulative enhancement properties correlate with its concentration. By contrast, octocrylene significantly slowed the lag time when used in combinations and was the only active ingredient that showed any antagonistic effects on 2,4-D penetration. Because none of the active ingredient combinations were able to inhibit dermal uptake of 2,4-D, it seems that proper selection of inert ingredients may be the most feasible solution for reducing penetration enhancement.