The Renin-Angiotensin System in Liver Disease.

The renin-angiotensin system (RAS) is a complex homeostatic entity with multiorgan systemic and local effects. Traditionally, RAS works in conjunction with the kidney to control effective arterial circulation, systemic vascular resistance, and electrolyte balance. However, chronic hepatic injury and resulting splanchnic dilation may disrupt this delicate balance. The role of RAS in liver disease, however, is even more extensive, modulating hepatic fibrosis and portal hypertension. Recognition of an alternative RAS pathway in the past few decades has changed our understanding of RAS in liver disease, and the concept of opposing vs. "rebalanced" forces is an ongoing focus of research. Whether RAS inhibition is beneficial in patients with chronic liver disease appears to be context-dependent, but further study is needed to optimize clinical management and reduce organ-specific morbidity and mortality. This review presents the current understanding of RAS in liver disease, acknowledges areas of uncertainty, and describes potential areas of future investigation.

High Number of Door Openings Increases the Bacterial Load of the Operating Room.

Background: Operating room (OR) traffic and door openings have emerged as potential modifiable risk factors for the development of surgical site infections. Methods: This study compared the microbial load of a Control OR without traffic versus a Simulated OR with the traffic in a typical orthopedic surgery case. Air particle counts and colony forming units (CFUs) were measured. A novel iOS app was developed to provide real-time door counts. Results: There were 1,862 particles >5.0 mcm in the Simulated OR compared with 56 in the Control OR. The CFUs from plates in the Simulated OR ranged from 4-22 (on brain heart infusion [BHI] agar), 2-266 (on mannitol salt agar [MSA]), and 1-19 (on Pseudomonas isolation agar [PIA]), while all plates in the Control OR grew 0-1 CFUs. Conclusions: High number of door openings leads to more airborne bacteria in the OR and viable bacterial on OR surfaces. The increased bacterial load throughout the OR was independent of distance from the door.

Mapping bacterial biofilms on recovered orthopaedic implants by a novel agar candle dip method.

While the detrimental effects of periprosthetic joint infections (PJIs) are well known, the process of biofilm formation on orthopaedic hardware is unclear. Previous work has shown that encasement of explant hardware in agar can aid in identifying biofilms. This study tested the utility of agar 'candle dip' method in detecting and mapping the location of biofilm on infected orthopedic components. Explant components from 15 patients were rinsed, briefly submerged in agar to create a surface coating, and incubated. Larger components were coated by pipetting agar over them. After incubation, colony outgrowth on the component surface was documented (candle dip status). Data were compared with clinical laboratory results (clinical culture status) and the PJI diagnosis using Musculoskeletal Infection Society criteria (MSIS status). All six patients classified as MSIS and clinical culture positive were also positive with the candle dip technique. Of the nine candle dip negative cases, four were positive and five were negative for both MSIS and clinical culture status. Candle dip may be negative in few cases due to the residual antibiotic eluting from the spacers, limiting the growth of bacterial biofilms on the components. The candle dip method shows promise for biofilm mapping but requires additional testing to evaluate the clinical diagnostic potential.

Reduction in Pseudomonas aeruginosa and Staphylococcus aureus biofilms from implant materials in a diffusion dominated environment.

Antibiotic-loaded calcium sulfate beads (CS-B) are used to treat biofilm-related periprosthetic joint infections (PJI). A previous study has shown that such beads are effective in reducing lawns biofilms grown on agar plates; however, the ability of CS-B to eradicate biofilms grown on solid orthopedic material surfaces has not been investigated. We grew biofilms of bioluminescent strains of Pseudomonas aeruginosa Xen41 and a USA300 MRSA Staphylococcus aureus SAP231 on ultra-high molecular weight polyethylene (PE), hydroxyapatite (HA), and 316L stainless steel (SS) coupons for three days under static growth conditions, with daily nutrient exchange. The coupons were rinsed with sterile phosphate buffered saline (PBS) to remove planktonic bacteria and placed in a petri dish, surrounded by four either antibiotic vancomycin and tobramycin loaded (CS-BV+T ) or unloaded beads (CS-BU ). A thin layer of agar was overlaid to simulate a periprosthetic infection where an implant abuts soft tissue and then incubated for 72 h. The amount of biofilm was measured by bioluminescence imaging (BLI) for activity and viable cell count (CFUs). Coupons exposed to CS-BV+T showed a significant reduction in the amount of biofilm within 24 h, regardless of the bacterial strain or material type. The coupons exposed to control CS-BU had no effect on bacteria over 72 h. Statement of Clinical Significance: Antibiotic-loaded calcium sulfate beads (CS-B) were effective in significantly reducing mature biofilms of P. aeruginosa and S. aureus from orthopedic relevant surfaces in our in vitro agar model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3081-3085, 2018.

Antibiotic loaded calcium sulfate bead and pulse lavage eradicates biofilms on metal implant materials in vitro.

Pulse lavage (PL) debridement and antibiotic loaded calcium sulfate beads (CS-B) are both used for the treatment of biofilm related periprosthetic joint infection (PJI). However, the efficacy of these alone and in combination for eradicating biofilm from orthopaedic metal implant surfaces is unclear. The purpose of the study was to understand the efficacy of PL and antibiotic loaded CS-B in eradicating bacterial biofilms on 316L stainless steel (SS) alone and in combination in vitro. Biofilms of bioluminescent strains of Pseudomonas aeruginosa Xen41 and a USA300 MRSA Staphylococcus aureus SAP231 were grown on SS coupons for 3 days. The coupons were either, (i) debrided for 3 s with PL, (ii) exposed to tobramycin (TOB) and vancomycin (VAN) loaded CS-B for 24 h, or (iii) exposed to both. An untreated biofilm served as a control. The amount of biofilm was measured by bioluminescence, viable plate count and confocal microscopy using live/dead staining. PL alone reduced the CFU count of both strains of biofilms by approximately 2 orders of magnitude, from an initial cell count on metal surface of approximately 109 CFU/cm2 . The antibiotic loaded CS-B caused an approximate six log reduction and the combination completely eradicated viable biofilm bacteria. Bioluminescence and confocal imaging corroborated the CFU data. While PL and antibiotic loaded CS-B both significantly reduced biofilm, the combination of two was more effective than alone in removing biofilms from SS implant surfaces. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2349-2354, 2018.