Week 2: How to Treat Sepsis - PDF

Week 2: How to treat a complex bacterial infection as sepsis Wednesday, 20 March 2024 12:18 Erin Flatley By Carl Flatley, Erin’s Dad. It’s been over a decade now since my daughter died. Erin was about to complete her master’s in elementary school education and was looking forward to life as a teache...

Week 2: How to treat a complex bacterial infection as sepsis Wednesday, 20 March 2024 12:18 Erin Flatley By Carl Flatley, Erin’s Dad. It’s been over a decade now since my daughter died. Erin was about to complete her master’s in elementary school education and was looking forward to life as a teacher. We mourn her loss as if it happened yesterday, but I also often wonder about all the young lives she would have touched and changed for the better. Erin died of sepsis, resulting from a minor outpatient surgical procedure. The surgery went as planned and Erin was discharged but she continued to feel an abnormal amount of pain, despite the administration of strong pain killers. We returned to the hospital where a blood test showed Erin’s white blood cell count to be higher than it should be – in fact it was double. We didn’t learn about the results of this blood test until after Erin died. She was prescribed a cream rather than an antibiotic and sent home. The pain grew worse. Erin had problems urinating and had to be catheterized. At one point, her urine began to look cloudy. Her abdomen became puffy. Back at the hospital, Erin wasn’t considered to be an urgent case. Blood tests showed very high white blood cell counts and the doctor thought Erin may have a kidney infection and she was finally prescribed an antibiotic. However, this medicine was not given to Erin for hours. And then Erin waited for a CAT scan. And waited. She began shaking and thrashing about. A different doctor prescribed Erin three more antibiotics but five hours later, they had not yet been given to Erin. I could see there was something wrong when he came to visit. Erin’s heart rate was high, her blood pressure was low. It was at that point that I heard the doctor say he thought Erin may be “septic.” We were told she could die. At three a.m. the next morning, we called the hospital from our home, where we had gone for a quick nap. We were told that we had better come. Erin’s sister came a bit later and when she left the room for a few minutes, she heard a Code Blue in the ICU. It was for Erin. At her bedside on that dreadful day in 2002, she asked me to help her, but I couldn’t. Erin died from sepsis on April 30, 2002, she was only 23 years old. The case study above describes a case of sepsis, several striking features can be distilled from this description of events that happened to Erin. A paper by Xu and coworkers was the first to provide insights into the pathogenesis of sepsis and the culmination of catastrophic events that septicemia or septic shock may lead to, in particular the involvement of the immune process of NETosis (see paper below). How can these new developments result in better sepsis patient care? What in vitro and in vivo models are being used to provide improved care in the future? Many questions remain to be answered… In this weeks’ assignment you are expected to first discuss the case and added information following the classical 7-step procedure. After the learning goals have been established, general learning goals will be defined as well as specific goals. Different expert groups are expected to tackle this complicated and very broad subject of interrelated topics. Each expert group will answer both the general learning goals as well as a set of related specific learning goals. Include in your answering the sources that are given below (check that each of these sources will be used) but you are strongly advised to search for more scientific resources. At the end of the second tutorial group meeting, each student is expected to have a comprehensive understanding and will be able to give a scientifically sound view on this complex disease and its treatment options. Your tutor will divide the tutorial group members into expert groups. Each expert group will prepare a document of max. 4 pages that, when finished, is to be distributed to all other tutorial group members, on the working day before the day of the second tutorial group meeting. The expert group will also prepare a 15 min. presentation of the learning goals that have been prepared and will end their presentation with 2 multiple choice questions on the topic of the specific learning goals. These questions will form the basis for the group discussion on the specific topic. Relevant literature (for direct links to the literature check out the KeyLinks Resources): Cases Page 1 Relevant literature (for direct links to the literature check out the KeyLinks Resources): https://www.sepsis.org/faces/erin-flatley/Links to an external site. Extracellular histones are major mediators of death in sepsis. Xu J, Zhang X, Pelayo R, Monestier M, Ammollo CT, Semeraro F, Taylor FB, Esmon NL, Lupu F, Esmon CT. Nat Med. 2009 Nov;15(11):1318-21. PMID: 19855397 Neutrophil extracellular traps kill bacteria. Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Science. 2004 Mar 5;303(5663):1532-5. PMID: 15001782 Severe sepsis and septic shock. Angus DC, van der Poll T. N Engl J Med. 2013 Nov 21;369(21):2063. doi: 10.1056/NEJMc1312359. PMID: 24256390 Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Hotchkiss RS1, Monneret G, Payen D. Nat Rev Immunol. 2013 Dec;13(12):862-74. doi: 10.1038/nri3552. Epub 2013 Nov 15. Getting sepsis therapy right. Hotchkiss RS, Sherwood ER. Science. 2015 Mar 13;347(6227):1201-2. Immunosuppression in sepsis: a novel understanding of the disorder and a new therapeutic approach. Hotchkiss RS1, Monneret G, Payen D. Lancet Infect Dis. 2013 Mar;13(3):260-8. doi: 10.1016/S1473-3099(13)70001-X. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Rudd KE, et al. Lancet. 2020 Jan 18;395(10219):200-211. doi: 10.1016/S0140-6736(19)32989-7. PMID: 31954465 The role of extracellular histones in COVID-19. De Vries et al., J Intern Med. 2023 Mar;293(3):275-292. Chapter 3 - Janeways Immunobiology – The Induced Responses of Innate Immunity (For those interested: https://www.youtube.com/watch?v=RpOVCc_G8tULinks to an external site. Expert lecture of this week Practical on histone-mediated cytotoxicity These sources represent an advised set of sources that you may use. It is advised to search for additional reliable sources to answer specific questions and issues that are of relevance to this weeks’ topic and that are not fully covered by the sources given here. NETs are fragile tissues composed of nuclear components and granules that in many cases trap and kill pathogens extracellularly. The NETs formation can be triggered by a multitude of stimuli both in-vitro and in-vivo under different pathophysiological conditions. Different stimuli lead to different types of NETs formation, and the same stimulus can also induce different types of NETs formation. Up to now, the formation of NETs is mainly divided into two types: (i) suicidal NETs: NETs are released when the nuclear membrane ruptures (Figuer 1); (ii) vital NETs: neutrophils are able to continue their immune function after NETs release Learning Goal 1 Cases Page 2 Cases Page 3 Cases Page 4 Cases Page 5 Learning Goal 2 Cases Page 6 Cases Page 7 Cases Page 8 Cases Page 9 Cases Page 10 Learning Goal 3 How is NETosis involved in sepsis_Nichanti Duijckers (i6... Cases Page 11 How is NETosis involved in sepsis_Nichanti Duijckers (i6... Cases Page 12 Cases Page 13 Cases Page 14 Learning Goal 4 MBS1202_week2_group2_expertgroup4_240321 Cases Page 15 MBS1202_week2_group2_expertgroup4_240321 Cases Page 16 Cases Page 17 Cases Page 18 Cases Page 19