Charged 2026

Author: Jamesie Lussos

  • The Sepsis Umbrella

    When most people hear the diagnosis of sepsis, they think of one of two things: oh my god or…what the heck is that? However, when I see the diagnosis of sepsis, my mind turns to one thing which I call the sepsis umbrella. For the sepsis umbrella to make sense, let’s first define what sepsis is and why this particular disease is so baffling. 

     

    Sepsis is often defined as an uncontrolled systemic immunological response to an infection through which progression can result in organ dysfunction and death. This is not the only definition of sepsis as, in 2016, sepsis was redefined as a “life threatening organ dysfunction caused by a dysregulated host response to infection”, aka Sepsis-3 (Singer, et al.). If this wasn’t already convoluted enough, it gets worse as there is an additional subsection of sepsis known as septic shock. Septic shock is a highly severe form of sepsis where “underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone” (Shankar-Hari, et al.). This is a lot to unravel and there’s no better place to start then with the actual symptoms and progression of sepsis.

     

    At this point you probably won’t be surprised when I tell you that, like its definition, the symptoms of sepsis are very non-specific. A patient with a mild case can appear almost asymptomatic while other sepsis patients can be at death’s door. So how is sepsis even diagnosed? Generally, a patient diagnosed with sepsis will have a pre-existing infection such as skin or wound infections, infections to a surgical site, or even viral infections. The initial infection must also present with symptoms that fall under the systemic inflammatory response syndrome (SIRS) or the multiorgan dysfunction syndrome (MODS) criteria to be qualified as sepsis. 

     

    The SIRS criteria consist of four key symptoms: fever, tachycardia (elevated heart rate), tachypnea (breathing fast), and leukocytosis (elevated white blood cell count). To have sepsis a patient must have an initial infection coupled with 2 of the SIRS symptoms. As the infection and uncontrolled immune response progresses past the SIRS criteria, the patient begins to experience a decline in peripheral vascular perfusion (decreased blood flow to peripheral tissues) and tissue hypoperfusion (decreased blood flow to the organs). At this point the patient is entering septic shock as their body continues its inflammatory response with decreased blood movement and increased organ dysfunction. If the patient is being treated at this time but continues to decline, then they have reached MODS criteria and are in critical state. Unfortunately, there is a 75% mortality rate after MODS is reached.

    So why bring all of this up? While sepsis is a diagnosis on its own, it is not a disease that begins without an initiating infection. This is important because it can have massive effects on the way we study sepsis. Consider this: sepsis can stem from any form of infection including viral infections, fungal infections, and bacterial infections. Each of these infections have a different infectious process and they can result in sepsis at different rates, frequencies, and severities.

     

     Furthermore, when do we classify an infection as being septic rather than a natural progression of the disease? For example, there are many symptom similarities between severe COVID-19 (progressed infection leading to decreased oxygen levels, tachycardic, fever, etc.) as sepsis, which could classify many COVID-19 patients as having sepsis. And yet, these patients are not classified as having sepsis. Additionally, a patient with cancer may produce laboratory results that correlate with sepsis but not actually be septic. How do you narrow this down to form one conclusive definition and treatment? Simply put, you can’t. Sepsis is, by its epidemiology and definition, an umbrella term. 

     

    This sepsis umbrella is detrimental for scientists studying sepsis. To counter this, I’d like to propose a new use of the sepsis umbrella. Instead of diagnosing sepsis at any progressed infection with uncontrolled immune response, we should shift to describing an infection as becoming septic rather than being sepsis. While this may seem like a simple change, it opens the door for researchers to specify what they are studying and to consider how individual pathogens are able to produce such drastic responses. Shifting our use of sepsis would also prevent infections, such as COVID -19, from being ruled out of this definition due to their prevalence or acute manifestations. Ultimately, getting rid of the sepsis umbrella isn’t the answer but we do need to learn how to close it. After all, opening an umbrella indoors is bad luck. 

     

     

    References:

    Center of disease control: What is sepsis – https://www.cdc.gov/sepsis/what-is-sepsis.html

    Gyawali, B., Ramakrishna, K., & Dhamoon, A. S. (2019). Sepsis: The evolution in definition, pathophysiology, and management. SAGE open medicine, 7, 2050312119835043. https://doi.org/10.1177/2050312119835043

     

    Huang, M., Cai, S., & Su, J. (2019). The Pathogenesis of Sepsis and Potential Therapeutic Targets. International journal of molecular sciences, 20(21), 5376. https://doi.org/10.3390/ijms20215376

     

    Koçak Tufan, Z., Kayaaslan, B., & Mer, M. (2021). COVID-19 and Sepsis. Turkish journal of medical sciences, 51(SI-1), 3301–3311. https://doi.org/10.3906/sag-2108-239

     

    Mahapatra S, Heffner AC. Septic Shock. [Updated 2022 Jun 21]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430939/

     

    Markwart, R., Saito, H., Harder, T., Tomczyk, S., Cassini, A., Fleischmann-Struzek, C., Reichert, F., Eckmanns, T., & Allegranzi, B. (2020). Epidemiology and burden of sepsis acquired in hospitals and intensive care units: a systematic review and meta-analysis. Intensive care medicine, 46(8), 1536–1551. https://doi.org/10.1007/s00134-020-06106-2

     

     Shankar-Hari, M., Phillips, G. S., Levy, M. L., Seymour, C. W., Liu, V. X., Deutschman, C. S., Angus, D. C., Rubenfeld, G. D., Singer, M., & Sepsis Definitions Task Force (2016). Developing a New Definition and Assessing New Clinical Criteria for Septic Shock: For the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315(8), 775–787. https://doi.org/10.1001/jama.2016.0289

     

    Singer, M., Deutschman, C. S., Seymour, C. W., Shankar-Hari, M., Annane, D., Bauer, M., Bellomo, R., Bernard, G. R., Chiche, J. D., Coopersmith, C. M., Hotchkiss, R. S., Levy, M. M., Marshall, J. C., Martin, G. S., Opal, S. M., Rubenfeld, G. D., van der Poll, T., Vincent, J. L., & Angus, D. C. (2016). The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 315(8), 801–810. https://doi.org/10.1001/jama.2016.0287

     

    World health organization: Sepsis – https://www.who.int/news-room/fact-sheets/detail/sepsis

  • How Scientists Tackle Chronic Osteomyelitis using Bioactive Glass

    If you asked doctors how to treat chronic osteomyelitis, they would likely all say the same thing: antibiotics, amputation, or bone grafts. However, if you asked the scientists at Galeazzi Orthopedic Institute, you might get told that the best way to treat chronic osteomyelitis is with bioactive glass S53P4, one of the most recent and promising medical advancements for bone treatment. But what makes bioactive glass S53P4 so special? 

    First off, we need to understand what osteomyelitis is, and subsequently what chronic osteomyelitis is. Osteomyelitis is an infection of the bone tissue which can occur due to bone damage, surrounding soft tissue damage, or nearby surgery which allows pathogens to penetrate the protective outer layer of the bone. Once within the bone, pathogens can cause varying degrees of bone loss as the infection progresses. Ultimately, this bone loss can result in limb amputation, sepsis, or even death as a progressed infection can result in organ failure. 

    As mentioned above, the traditional treatments for osteomyelitis consist of antibiotics to kill the responsible pathogen and stop the spread of the infection; however, antibiotics are not always the best option as they can affect other microorganisms in the body. Furthermore, overuse of antibiotics in a clinical setting has allowed for the development of antibiotic resistant pathogens, such as methicillin resistant staphylococcus aureus (MRSA), which will eventually render antibiotics useless. Furthermore, higher degrees of bone loss can result in a very weak bone which cannot be treated with antibiotics alone. So, what are our other options? 

    Figure 1: Xray of a knee with osteomyelitis, as highlighted in red.

    Clinically, if you want to avoid losing a limb, the next best options would be antibiotic loaded polymethylmethacrylate beads (PMMA) or bone grafting. Both of these methods work through the surgical removal of the necrotic bone tissue and the replacement of that bone tissue with PMMA or fresh bone from a graft.

    Visual depiction of PMMA in bone
    Figure 2: Xray of PMMA that is packed into the tibia of a patient after the removal of necrotic bone from osteomyelitis.

     

    However, there are some drawbacks as these methods are only designed to fill the bone cavity left behind from the infection, provide limited local antibiotics, and take a long time to produce results. Sadly, bone doesn’t grow overnight! So, what if there was something that could fill the bone cavity, stimulate bone growth, and was naturally antibiotic resistant?

    Enter bioactive glass S53P4 (BAG S53P4). Bioactive glass itself is a silica based biodegradable glass which has been shown to have antibiotic, osteoconductive, and angiogenic properties. Which is essentially a way of saying it stimulates bone growth and blood vessel growth all while repelling those pesky pathogens! BAG S53P4 takes it a step further and is composed of SiO2, Na2O, CaO, and P2O5 which further stimulates bone growth by chemically binding to surrounding bone. This almost sounds too good to be true, so researchers at Galeazzi Orthopedic Institute set out to understand how BAG S53P4 is so effective and determine its safety in a clinical setting. 

    To determine the source of BAG S53P4s antibiotic properties and to evaluate its safety, the research team took 27 patients with chronic long bone osteomyelitis from antibiotic resistant pathogens and treated them using the bioactive glass.  From their study, they were able to determine that the antibiotic resistant properties of BAG S53P4 stems from its contact with an aqueous solution. By contacting an aqueous solution, BAG S53P4 activates the release of ions which increase the surrounding pH. This increased pH creates a hostile environment for bacterial growth stopping infection in its tracks. As a result, 90% of the treated patients showed no signs of infection after 18 months. X Rays of the patient treated with BAG S53P4 were also taken over the course of 18 months. From these X Rays, the team was able to determine that the vascularization and bone growth seen in these patients far surpassed that of previous methods and was equally safe in its application. 

    Figure 3: Before and after Xray’s of a patient treated with BAG S53P4 over the course of 2 years for chronic osteomyelitis.

    Ultimately, this research determined that BAG S53P4 was a safe and effective treatment for patients suffering from chronic osteomyelitis. So next time you’re asked how to treat chronic osteomyelitis, consider the less traditional route and give BAG S53P4 a try!  

    Source:

    Drago, L., Romanò, D., De Vecchi, E., Vassena, C., Logoluso, N., Mattina, R., & Romanò, C. L. (2013). Bioactive glass BAG-S53P4 for the adjunctive treatment of chronic osteomyelitis of the long bones: An in vitro and prospective clinical study. BMC Infectious Diseases, 13(1), 1-8.

    https://pubmed.ncbi.nlm.nih.gov/24325278/