scholarly journals Therapeutic Rationale for Endotoxin Removal with Polymyxin B Immobilized Fiber Column (PMX) for Septic Shock

2021 ◽  
Vol 22 (4) ◽  
pp. 2228
Author(s):  
Hisataka Shoji ◽  
Steven M. Opal
Keyword(s):  
Septic Shock ◽  
Organ Dysfunction ◽  
Survival Benefit ◽  
Controlled Trial ◽  
Antigen Expression ◽  
Polymyxin B ◽  
Term Survival ◽  
Surface Antigen Expression ◽  
Sepsis And Septic Shock

Endotoxin removal therapy with polymyxin B immobilized fiber column (PMX) has been clinically applied for sepsis and septic shock patients since 1994. The effectiveness and usefulness of this therapy have been demonstrated for more than a quarter of a century. However, a documented survival benefit has not yet been demonstrable in a large, multicenter, randomized and controlled trial. Following the findings derived from a large sepsis clinical trial with PMX in North America, a new trial is ongoing to determine if PMX has a long-term survival benefit when administered to septic patients. Another approach to support a survival benefit from intervention with PMX is to utilize a detailed analysis available from a large clinical data base. The endotoxin adsorption capacity of PMX columns in vitro and the effectiveness of PMX columns can be further demonstrable in animal models. The capability of PMX and details of its mechanism of action to intervene in the sepsis cascade and impede organ dysfunction in septic patients is not fully understood. The surface antigen expression in monocytes and neutrophils are improved after PMX therapy. Immunomodulatory effects as a result of endotoxin removal and/or other mechanisms of action have been suggested. These effects and other potential immune effects may explain some of the improved effects upon organ dysfunction of sepsis and septic shock patients. Endotoxemia may be involved in the pathophysiology of other diseases than sepsis. A rapid diagnostic method to detect and target endotoxemia could allow us to practice precision medicine and expand the clinical indications of endotoxin removal therapy.

scholarly journals Effects of endotoxin adsorber hemoperfusion on sublingual microcirculation in patients with septic shock: a randomized controlled trial

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shih-Hong Chen ◽  
Wing-Sum Chan ◽  
Chih-Min Liu ◽  
Ching-Tang Chiu ◽  
Anne Chao ◽  
...  
Keyword(s):  
Septic Shock ◽  
Controlled Trial ◽  
Polymyxin B ◽  
Vessel Density ◽  
Control Group ◽  
Sublingual Microcirculation ◽  
Norepinephrine Infusion ◽  
Risk Of Mortality ◽  
Protocol Registration ◽  
Sepsis And Septic Shock

Abstract Background Endotoxins can induce an excessive inflammatory response and result in microcirculatory dysfunction. Polymyxin-B hemoperfusion (PMX-HP) has been recognized to effectively remove endotoxins in patients with sepsis and septic shock, and a rat sepsis model revealed that PMX-HP treatment can maintain a better microcirculation. The primary aim of this study was to investigate the effect of PMX-HP on microcirculation in patients with septic shock. Methods Patients with septic shock were enrolled and randomized to control and PMX-HP groups. In the PMX-HP group, patients received the first session of PMX-HP in addition to conventional septic shock management within 24 h after the onset of septic shock; the second session of PMX-HP was provided after another 24 h as needed. Results Overall, 28 patients finished the trial and were analyzed. The mean arterial pressure and norepinephrine infusion dose did not differ significantly between the control and PMX-HP groups after PMX-HP treatment. At 48 h after enrollment, total vessel density (TVD) and perfused vessel density (PVD) were higher in the PMX-HP group than in the control group [TVD 24.2 (22.1–24.9) vs. 21.1 (19.9–22.9) mm/mm2; p = 0.007; PVD 22.9 (20.9–24.9) vs. 20.0 (18.9–21.6) mm/mm2, p = 0.008]. Conclusions This preliminary study observed that PMX-HP treatment improved microcirculation but not clinical outcomes in patients with septic shock at a low risk of mortality. Nevertheless, larger multicenter trials are needed to confirm the effect of PMX-HP treatment on microcirculation in patients with septic shock at intermediate- and high-risk of mortality. Trial registration ClinicalTrials.gov protocol registration ID: NCT01756755. Date of registration: December 27, 2012. First enrollment: October 6, 2013. https://clinicaltrials.gov/ct2/show/NCT01756755

scholarly journals Fluids in Sepsis and Septic Shock (FISSH): protocol for a pilot randomised controlled trial

BMJ Open ◽  
2017 ◽  
Vol 7 (7) ◽  
pp. e017602 ◽  
Author(s):  
Bram Rochwerg ◽  
Tina Millen ◽  
Peggy Austin ◽  
Michelle Zeller ◽  
Frédérick D’Aragon ◽  
...  
Keyword(s):  
Septic Shock ◽  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Pilot Randomised Controlled Trial ◽  
Randomised Controlled ◽  
Sepsis And Septic Shock

scholarly journals Increasing the Interaction of Borrelia burgdorferi with Decorin Significantly Reduces the 50 Percent Infectious Dose and Severely Impairs Dissemination

2007 ◽  
Vol 75 (9) ◽  
pp. 4272-4281 ◽  
Author(s):  
Qilong Xu ◽  
Sunita V. Seemanaplli ◽  
Kristy McShan ◽  
Fang Ting Liang
Keyword(s):  
Borrelia Burgdorferi ◽  
Severe Combined Immunodeficiency ◽  
Protein A ◽  
Antigen Expression ◽  
In Vitro Assays ◽  
Infectious Dose ◽  
Surface Antigen Expression ◽  
Immunocompetent Mice ◽  
Surface Adhesins

ABSTRACT Tight regulation of surface antigenic expression is crucial for the pathogenic strategy of the Lyme disease spirochete, Borrelia burgdorferi. Here, we report the influence of increasing expression of decorin-binding protein A (DbpA), one of the most investigated spirochetal surface adhesins, on the 50% infectious dose (ID50), dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi in the murine host. Our in vitro assays showed that increasing DbpA expression dramatically increased the interaction of B. burgdorferi with decorin and sensitivity to growth inhibition/killing by anti-DbpA antibodies; however, this increased interaction did not affect spirochetal growth and replication in the presence of decorin. Increasing DbpA expression significantly reduced ID50 values and severely impaired dissemination in severe combined immunodeficiency (SCID) and immunocompetent mice. During infection of SCID mice, B. burgdorferi with increased DbpA expression was able to effectively colonize heart and skin tissues, but not joint tissues, completely abrogating arthritis virulence. Although increasing DbpA expression did not affect spirochetal persistence in the skin, it diminished the ability of B. burgdorferi to persist in the heart and joint tissues during chronic infection of immunocompetent mice. Taken together, the study highlights the importance of controlling surface antigen expression in the infectivity, dissemination, tissue colonization, pathogenicity, and persistence of B. burgdorferi during mammalian infection.

scholarly journals Rho-Proteins and Downstream Pathways as Potential Targets in Sepsis and Septic Shock: What Have We Learned from Basic Research

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1844
Author(s):  
Maria Luísa da Silveira Hahmeyer ◽  
José Eduardo da Silva-Santos
Keyword(s):  
Septic Shock ◽  
Actin Polymerization ◽  
Current Knowledge ◽  
Cecal Ligation ◽  
Experimental Models ◽  
Rho Proteins ◽  
Growing Cell ◽  
Sepsis And Septic Shock

Sepsis and septic shock are associated with acute and sustained impairment in the function of the cardiovascular system, kidneys, lungs, liver, and brain, among others. Despite the significant advances in prevention and treatment, sepsis and septic shock sepsis remain global health problems with elevated mortality rates. Rho proteins can interact with a considerable number of targets, directly affecting cellular contractility, actin filament assembly and growing, cell motility and migration, cytoskeleton rearrangement, and actin polymerization, physiological functions that are intensively impaired during inflammatory conditions, such as the one that occurs in sepsis. In the last few decades, Rho proteins and their downstream pathways have been investigated in sepsis-associated experimental models. The most frequently used experimental design included the exposure to bacterial lipopolysaccharide (LPS), in both in vitro and in vivo approaches, but experiments using the cecal ligation and puncture (CLP) model of sepsis have also been performed. The findings described in this review indicate that Rho proteins, mainly RhoA and Rac1, are associated with the development of crucial sepsis-associated dysfunction in different systems and cells, including the endothelium, vessels, and heart. Notably, the data found in the literature suggest that either the inhibition or activation of Rho proteins and associated pathways might be desirable in sepsis and septic shock, accordingly with the cellular system evaluated. This review included the main findings, relevance, and limitations of the current knowledge connecting Rho proteins and sepsis-associated experimental models.

scholarly journals The impact of duration of organ dysfunction on the outcome of patients with severe sepsis and septic shock

Clinics ◽  
2008 ◽  
Vol 63 (4) ◽  
Author(s):  
Flávio G. R. Freitas ◽  
Reinaldo Salomão ◽  
Nathalia Tereran ◽  
Bruno Franco Mazza ◽  
Murillo Assunção ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Organ Dysfunction ◽  
Sepsis And Septic Shock ◽  
The Impact

Sepsis

2020 ◽  
Author(s):  
Steven P LaRosa ◽  
Steven M. Opal
Keyword(s):  
Intensive Care Unit ◽  
Septic Shock ◽  
Severe Sepsis ◽  
Intensive Care ◽  
Organ Dysfunction ◽  
Fluid Resuscitation ◽  
Multiorgan Failure ◽  
Sepsis Management ◽  
The Past ◽  
Sepsis And Septic Shock

Sepsis, along with the multiorgan failure that often accompanies this condition, is a leading cause of mortality in the intensive care unit. Although modest improvements in the prognosis have been made over the past two decades and promising new therapies continue to be investigated, innovations in the management of septic shock are still required. This chapter discusses the definitions, epidemiology, and pathogenesis (including microbial factors, host-derived mediators, and organ dysfunction) relating to sepsis. Management of severe sepsis and septic shock is also described.  This review contains 5 figures, 11 tables, and 99 references. Keywords:Organ dysfunction, sepsis, septic shock, infection, bacteremia, fluid resuscitation, vasopressor

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