Direct electric current treatment under physiologic saline conditions kills Staphylococcus epidermidis biofilms via electrolytic generation of hypochlorous acid.

The purpose of this study was to investigate the mechanism by which a direct electrical current reduced the viability of Staphylococcus epidermidis biofilms in conjunction with ciprofloxacin at physiologic saline conditions meant to approximate those in an infected artificial joint. Biofilms grown in CDC biofilm reactors were exposed to current for 24 hours in 1/10(th) strength tryptic soy broth containing 9 g/L total NaCl. Dose-dependent log reductions up to 6.7 log(10) CFU/cm(2) were observed with the application of direct current at all four levels (0.7 to 1.8 mA/cm(2)) both in the presence and absence of ciprofloxacin. There were no significant differences in log reductions for wells with ciprofloxacin compared to those without at the same current levels. When current exposures were repeated without biofilm or organics in the medium, significant generation of free chlorine was measured. Free chlorine doses equivalent to the 24 hour endpoint concentration for each current level were shown to mimic killing achieved by current application. Current exposure (1.8 mA/cm(2)) in medium lacking chloride and amended with sulfate, nitrate, or phosphate as alternative electrolytes produced diminished kills of 3, 2, and 0 log reduction, respectively. Direct current also killed Pseudomonas aeruginosa biofilms when NaCl was present. Together these results indicate that electrolysis reactions generating hypochlorous acid from chloride are likely a main contributor to the efficacy of direct current application. A physiologically relevant NaCl concentration is thus a critical parameter in experimental design if direct current is to be investigated for in vivo medical applications.

Plasma and plasma derivatives in therapeutic plasmapheresis.

In therapeutic plasmapheresis, patient plasma is withdrawn and a colloid replacement solution is infused in its place. A 4% to 5% human serum albumin solution in saline is the preferred replacement solution in most instances, even though this practice causes transient mild deficiencies of most plasma proteins. Albumin solutions are pasteurized for viral inactivation, are very unlikely to cause a febrile or allergic reaction, and are convenient to store and administer. Single-donor plasma must be type specific, which requires advance knowledge of patient blood type, and must be ordered and usually thawed before use. It also carries a higher risk of reactions. On the plus side, it replaces all plasma constituents and is appropriate for patients with thrombotic thrombocytopenic purpura or an existing coagulopathy. Neither cryosupernatant plasma, which is relatively deficient in the proteins in cryoprecipitate, nor plasma derived from pools that have been virally inactivated with detergents and organic solvents has been shown to produce better outcomes than fresh frozen plasma for any indication.

Matching capacity to demand: a regional dashboard reduces ambulance avoidance and improves accessibility of receiving hospitals.

OBJECTIVES: ambulance diversion is a dangerous repercussion of emergency department (ED) crowding and can reflect fragmentation and a lack of coordination in designating optimal patient offload sites for prehospital providers. The objective of this study was to evaluate whether proactive destination selection through the Regional Emergency Patient Access and Coordination (REPAC) program would enhance capacity and ED flow management. METHODS: the REPAC system provides a dashboard that synthesizes real-time capacity and acuity data for all three adult EDs in the city of Calgary, assigning a color code to reflect receiving status. It assigns destination for the next patient transported by emergency medical services (EMS) by categorizing ED sites as having either a favorable (green/yellow) status or unfavorable (orange/red) status. Three time windows were analyzed: a 6-month window prior to REPAC implementation (pre), the first 6-month window immediately following (post1), and the second 6-month period following (post2). Primary outcomes of interest were the proportion of time spent in favorable versus unfavorable status and EMS avoidances for all adult ED sites in the region (percentage of total time with any center on EMS bypass). Information on total number of ED visits, percentage of patients arriving by EMS transports, admission rates, patient acuity (Canadian Triage and Acuity Score), age, and length of stay (LOS) for admitted and discharged patients was collected. The Kruskal-Wallis test was employed for primary outcome analysis. RESULTS: implementation of the REPAC system resulted in an increase in the proportion of total time region hospitals reported favorable status (57.5% vs. 64.1%) pre versus post1, an effect that was accentuated at 1 year (post2, 78.7%; p < 0.001 for both comparisons). There was a concomitant decrease in EMS avoidances as a result of the REPAC system, 4.4% to 1.8% (pre vs. post1), also further improved at 1 year to 0.6% (p < 0.001 for both comparisons). CONCLUSIONS: proactive EMS destination selection through a real-time integrated electronic surveillance system enhances regional capacity and flow management while significantly reducing ambulance diversions.

A biofilm growth protocol and the design of a magnetic field exposure setup to be used in the study of magnetic fields as a means of controlling bacterial biofilms.

The use of prosthetic implants is increasing both in the United States and around the world and there is a concomitant rise in cases of biofilm-based, persistent infections that are quite serious and virtually impervious to antibiotic treatment. The development of alternate therapies that do not involve long term use of high levels of antibiotics or surgical intervention is needed. Based on the success of using electric or magnetic fields to alter certain physiological processes, it is hypothesized that relatively low level magnetic fields, in conjunction with the appropriate antibiotic, may be able to help control and eventually clear bacterial biofilms on a prosthetic. In order to test this hypothesis, it is necessary to first develop a means of growing laboratory grade biofilms on specific materials in a way that is repeatable between experiments and that can be reproduced by other laboratories. Secondly, a means of applying controlled magnetic fields to the surfaces supporting the biofilms at a defined temperature must be developed. This article addresses both of these points.

Evidence based therapeutic apheresis in autoimmune and other hemolytic anemias.

PURPOSE OF REVIEW: This article reviews recent publications that bear on the evidential basis for therapeutic apheresis in diseases in which hemolytic anemia is a prominent feature. RECENT FINDINGS: Therapeutic plasma exchange continues to be reported sporadically in severe autoimmune hemolytic anemia, with inconsistent results. Autoimmune deficiency of ADAMTS13 has provided a compelling rationale for therapeutic plasma exchange in some patients with thrombotic thrombocytopenic purpura; conversely such deficiency is consistently absent in certain clinically similar syndromes for which therapeutic plasma exchange is not or may not be beneficial. Refinements in assays for ADAMTS13 should further clarify its role in idiopathic thrombotic thrombocytopenic purpura. Oral iron chelators have shown promise in recent trials in chronically transfused patients with sickle cell disease and may provide an alternative to red cell exchange to prevent iron overload. SUMMARY: The proper role of therapeutic plasma exchange in the treatment of autoimmune hemolytic anemia remains uncertain. Therapeutic plasma exchange continues to be indicated for idiopathic thrombotic thrombocytopenic purpura regardless of ADAMTS13 levels, but more accessible and physiological ADAMTS13 assays may raise questions about the rationale for and value of plasma exchange in ADAMTS13 nondeficient patients. Oral iron chelation may obviate the need for red cell exchange as a means to prevent iron overload in chronically transfused patients with sickle cell disease.

Therapeutic apheresis: use of human serum albumin, fresh frozen plasma and cryosupernatant plasma in therapeutic plasma exchange.

In therapeutic plasma exchange, patient plasma is removed and a colloid replacement solution is infused in its stead. A solution of 4-5% human serum albumin in saline is the recommended replacement solution in most instances, even though it leads to transient mild deficiencies of most plasma proteins. Albumin solutions are pasteurized to inactivate viruses, carry a very low risk of febrile and allergic reactions, and are convenient to store and administer. Fresh frozen plasma, which must be type specific and needs to be ordered in advance and thawed before use, carries a higher risk of reactions; however, it replaces all plasma constituents and is appropriate for patients with thrombotic thrombocytopenic purpura or a pre-existing coagulopathy. Neither cryosupernatant plasma, which is relatively depleted of the proteins in cryoprecipitate, nor pooled plasma that has been virally inactivated with organic solvents and detergents has been shown to be superior to fresh frozen plasma for any indication.

Engineering approaches for the detection and control of orthopaedic biofilm infections.

Artificial joints are subject to chronic infections associated with bacterial biofilms, which only can be eradicated by the traumatic removal of the implant followed by sustained intravenous antibiotic therapy. We have adopted an engineering approach to develop electrical-current-based approaches to bacterial eradication and microelectromechanical systems that could be embedded within the implanted joint to detect the presence of bacteria and to provide in situ treatment of the infection before a biofilm can form. In the former case we will examine the combined bactericidal effects of direct and indirect electrical fields in combination with antibiotic therapy. In the latter case, bacterial detection will occur by developing a microelectromechanical-systems-based biosensor that can "eavesdrop" on bacterial quorum-sensing-based communication systems. Treatment will be effected by the release of a cocktail of pharmaceutical reagents contained within integral reservoirs associated with the implant, including a molecular jamming signal that competitively binds to the bacteria's quorum sensing receptors (which will "blind" the bacteria, preventing the production of toxins) and multiple high dose antibiotics to eradicate the planktonic bacteria. This approach is designed to take advantage of the relatively high susceptibility to antibiotics that planktonic bacteria display compared with biofilm envirovars. Here we report the development of a generic microelectromechanical systems biosensor that measures changes in internal viscosity in a base fluid triggered by a change in the external environment.

An approach to evidence-based therapeutic apheresis.

This review is derived from a memorial lecture honoring Dr. Francis Morrison, a former President of the American Society For Apheresis (ASFA). The author had numerous professional contacts with Dr. Morrison through ASFA in the early 1990s, having served with him on the Board of Directors and followed him as President, and also came to know him well on a personal level. Professionally, Dr. Morrison stood out as a courtly gentleman with a marvelous baritone voice whose ability to facilitate organization contributed to a growing sense of dignity and purpose in the affairs of the society. On the personal side, however, there wasn't an ounce of pretension in him. He was accessible and down-to-earth; a genuine character with an active and appealing sense of humor. Not surprisingly, he seemed to have a wealth of insight and "common sense," and since the topic of this study is a kind of common sense approach to assessing the effectiveness of therapeutic apheresis, it seems a fitting way to honor his memory.