Glucocorticoid-induced glaucoma is a secondary open-angle glaucoma. About 40% of the general population may develop elevated intraocular pressure on prolonged glucocorticoid treatment secondary to damages in the trabecular meshwork (TM), a tissue that regulates intraocular pressure. Therefore, identifying the key molecules responsible for glucocorticoid-induced ocular hypertension is crucial. In this study, Dickkopf-related protein 1 (Dkk1), a canonical Wnt signaling inhibitor, was found to be elevated in the aqueous humor and TM of glaucoma patients. At the signaling level, Dkk1 enhanced glucocorticoid receptor (GR) signaling, whereas Dkk1 knockdown or Wnt signaling activators decreased GR signaling in human TM cells as indicated by luciferase assays. Similarly, activation of the GR signaling inhibited Wnt signaling. At the protein level, glucocorticoid-induced extracellular matrix was inhibited by Wnt activation using Wnt activators or Dkk1 knockdown in primary human TM cells. In contrast, inhibition of canonical Wnt signaling by b-catenin knockdown increased glucocorticoidinduced extracellular matrix proteins. At the physiological level, adenovirus-mediated Wnt3a expression decreased glucocorticoid-induced ocular hypertension in mouse eyes. In summary, Wnt and GR signaling inhibit each other in the TM, and canonical Wnt signaling activators may prevent the adverse effect of glucocorticoids in the eye.
In this study population, lower baseline ophthalmic artery blood flow velocities were associated with simultaneous structural and functional glaucoma progression after 4 years.
Purpose: Preventing CLABSI events in the dialysis inpatient population represents significant challenges. Bacteremia associated with lines or grafts are common health-associated infections that lead to adverse patient outcomes. Dialysis patients represent a much higher infection risk due to health frequency needs, more frequent hospitalizations, multiple comorbidity issues, fistula functionality, and multiple attempts for line access leading to additional complications, costs, morbidity, and mortality. Methods: An observational study was conducted including central line device days, CLABSI events, and possible confounding variables in admitted dialysis patients. All CLABSI data were identified according to the Centers for Disease Control and Prevention's National Healthcare Safety Network's definitions for CLABSIs. The intervention involved the removal of 70% alcohol swabs and alcohol hub disinfecting caps, then replacing with swabs containing 3.15% chlorhexidine gluconate/70% alcohol for central line hub disinfection and vascular graft access skin disinfection. Results: The 5-year preintervention period (2008–2012) involved 7568 central line days, 11 CLABSI events, and a 1.45 per 1000 device day rate. The 6-month trial period involved 1559 central line days and no CLABSI events. The 5-year postimplementation period (2013–2017) involved 9787 central line days, 5 CLABSI events, and a 0.51 per 1000 device day rate. The postimplementation period represented a statistically significant (P value=0.0493) reduction with 65% fewer CLABSI events compared with the preimplementation period. Limitations: A limitation was variations in scrub time and dry time during central venous catheter hub access. While we were comparing 2 products, behavioral practices using these 2 products were possible influencers and represent a possible confounding variable. Conclusions: This study found that using alcohol with chlorhexidine gluconate prior to accessing central line hubs and vascular grafts allows for reduction in CLABSI events and sustains statistically significant lower CLABSI rates in the inpatient dialysis population. HIGHLIGHTS Using alcohol with chlorhexidine gluconate (CHG) before accessing central line hubs helps reduce central line-associated bloodstream infection (CLABSI) events Using alcohol with CHG before accessing vascular grafts helps reduce CLABSI events A statistically significant reduction (65%) in CLABSI events occurred after use. Statistically significant lower CLABSI rates are sustainable with use of alcohol with CHG
Highlights
Using alcohol with CHG before accessing central line hubs helps reduce CLABSI events. Using alcohol with CHG before accessing vascular grafts helps reduce CLABSI events. A statistically significant reduction (65%) in CLABSI events occurred after use. Statistically significant lower CLABSI rates are sustainable with use of alcohol with CHG.
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