The Canonical Wnt Signaling Pathway Inhibits the Glucocorticoid Receptor Signaling Pathway in the Trabecular Meshwork.

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 ß-catenin knockdown increased glucocorticoid-induced 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.

The use of 3.15% chlorhexidine gluconate/70% alcohol hub disinfection to prevent central line-associated bloodstream infections in dialysis patients.

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.

Ophthalmology in Critical Care.

Ophthalmic disease encountered in the intensive care unit (ICU) has a wide spectrum of prevalence and severity. Prolonged exposure of the cornea is common and preventable. Trauma, glaucoma, infection, vascular disease, and burns are among the potential causes of vision loss. Patients are predisposed to ocular complications by the ICU environment and critical illness itself. Critically ill patients require prioritization of life-sustaining interventions, and less emphasis is placed on ophthalmic disease, leading to missed opportunities for vision-saving intervention. It is therefore imperative for intensivists, nurses, and other providers to have an increased awareness and understanding of the broad range of ocular conditions potentially seen in the ICU.

Baseline retrobulbar blood flow is associated with both functional and structural glaucomatous progression after 4†years.

BACKGROUND/AIMS: Previous studies suggest that vascular abnormalities are involved in the pathogenesis of open-angle glaucoma. This study aims to examine the relationship of baseline retrobulbar blood flow measurements with functional and structural glaucomatous progression in patients with open-angle glaucoma over 4 years. METHODS: In this study, 112 patients with open-angle glaucoma were examined at baseline and 78 with retrobulbar blood flow assessments were followed to 4 years. Colour Doppler imaging was used to evaluate retrobulbar blood flow. Structural disease progression was examined with optical coherence tomography and Heidelberg Retinal Tomography III. Functional disease progression was monitored with automated perimetry using Humphrey visual fields. Mixed-model analysis of covariance was used to test for significance of changes from baseline to 4-year follow-up. Two-sample t tests and χ2 tests were used to test for baseline blood flow differences between patients who progressed and those who did not progress. RESULTS: Patients who progressed structurally had a statistically significant lower baseline mean ophthalmic artery peak systolic velocity (PSV) (p=0.024) and ophthalmic artery end diastolic velocity (EDV) (p=0.012) compared with those who did not progress. Similarly, a lower baseline mean ophthalmic artery PSV (p=0.031) and ophthalmic artery EDV (p=0.005) were associated with patients who progressed functionally compared with those who did not progress after 4 years. CONCLUSIONS: In this study population, lower baseline ophthalmic artery blood flow velocities were associated with simultaneous structural and functional glaucoma progression after 4 years.

Guide of Hypertensive Crisis Pharmacotherapy.

BACKGROUND: Cardiovascular diseases (CVD) are the number one cause of death globally compared to any other cause. CVD accounts for approximately 17.3 million deaths per year and are rising. Hypertension is the leading risk factor for cardiovascular diseases. Approximately, 80 million people suffer from hypertension in the U.S. While, majority of these individuals are on antihypertensive medications only 54% of individuals with hypertension are optimally controlled. Heart failure and stroke are some of the devastating complications of uncontrolled hypertension. Hypertensive crisis can be classified as either an urgency or emergency; difference between the two is the presence of end organ damage, which is noted in hypertensive emergency. Hypertensive crisis is usually treated by parenteral antihypertensive medications. The main drug classes of drugs for treatment are nitrates, calcium channel blockers, dopamine-1 agonists, adrenergic-blocking agents etc. CONCLUSION: In this review, we discuss approach to management of hypertensive crisis and each drug class with its physiology and complications.