Five centuries of The Angus Method
The dystopian future of sepsis research
This report is presented in memorian of Willian "Buck” Rogers. He spent 500 years frozen and floating adrift in outer space. He was returned to Earth in 2487 and died of sepsis in 2489.
The year is 2055. Almost one million members of the World Sepsis Federation tune their accessory brains simultaneously to an important announcement from the Sepsis Consensus Task Force. The Task Force has been discussing the 7th Sepsis definitions (Sepsis-7) in a brain call for three weeks and they have voted on the definitive version of the updated sepsis diagnostic tool.
Sepsis in the 2050s has a different approach. Artificial intelligence has helped big pharma develop many new antibiotic classes, so rational antimicrobial prescription is no longer an issue. We live in a more is more world. The 2043 6th Sepsis Consensus has abandoned the concept of triaging for early antibiotics in favor of giving early antibiotics for every patient with presumed infection. A crisis succeeded, task force members were accused of playing big pharma's game, and many argued that sepsis definitions are useless if we prescribe antibiotics to all presumably infected patients. Those dissidents were suppressed, the most susceptible through scorn and indifference, and the stubborn succumbed to outright research defunding.
In 2055, it is all about triaging patients to receive a mix of monoclonal antibodies to regulate the immune response. The pharmaceutical industry has developed one monoclonal antibody against each known inflammatory mediator or receptor. Now, the Critical Care community has to decide how to use these antibodies and the Task Force will define how to identify the patients for research and prescription.
There is a revival of older diagnostic tools. Older task force members are nostalgic about the days of Sepsis-3. The crude simplicity of qSOFA criteria still allures them to a state of “those were the greatest times”. In their bright years, they could triage a patient for early antibiotics without a computer. All they needed was to stand by the patient and follow simple instructions. The senior Task Force members supported the revival, in association with digital versions of physically deceased members.
It is important to explain the role of Mind Apps in 2055 medicine. Modern physicians consult deceased critical care pundits about glycemic control, pneumatic leg compression, nitric oxide, etc. The Task Force uses the Panelist version of the app, and many deceased members of the previous Consensus Task Forces are active in the 2055 Consensus Conference.
The return to 2016 definitions (Sepsis-3) was proposed by the older physical members of the panel in association with the deceased members. The younger members, who had started practicing after 2037 Sepsis-5, were afraid to oppose them.
The 2037 definition was a major accomplishment. Scientists have trained artificial intelligence to identify sepsis using trillions of data points from millions of patients worldwide. As you know, those were the early times of the Global Monitoring Initiative, the megaproject that connected all ICU beds worldwide in a single electronic register.
Sepsis-5 leveraged the Angus Method, named after the prominent early-21st-century intensivist. The method explores the correlation between
electronic data records and patient outcomes and defines a disease as a set of physiologic variables linked to worse outcomes. Sepsis-3 was the first Consensus Definition under the Angus Method, i.e. diagnostic by prognostic variables obtained from medical records, a feat widely recognized as a conceptual breakthrough.
Sepsis-3 was indeed very simple. It postulates that sepsis can be identified with no more than a presumed infection and a plain set of vital signs (qSOFA) to predict a higher probability of longer ICU LOS or mortality. qSOFA thresholds were fine-tuned to avoid excessive inclusions in sepsis protocols and the consequent therapeutic, billing, and quality control effects of labeling a patient as septic.
As I said, the older and deceased members wanted the simplicity back. They argued that the Sepsis-5 and Sepsis-6 definitions were trained using Sepsis-3 and Sepsis-4 definitions (Sepsis-4 uses SOFA-2 instead of SOFA), so they are no more than a complex way to predict the presence of Sepsis-3/4 criteria. There is no need for such a complication to diagnose sepsis.
The older and deceased members’ shift towards simplicity didn’t go unnoticed. Many have participated in all Consensus Task Forces since Sepsis-3, and one participated in Sepsis-2. Critics say they are trying to revert 40 years of a discussion dominated by themselves since 2016. Now, the most influential Task Force members want Sepsis-3 back, this time to select patients to regulate the inflammatory response using a mix of monoclonal antibodies.
Is nostalgia a feature of uploaded minds? Will they become ever more nostalgic? One thing is sure. All physically alive members want to be uploaded to the Mind App and participate in future Sepsis Consensus. No one would dare not to upload the mind of a deceased member of the Task Force Class. This is the #1 rule.
It's 2521. The World Sepsis Federation gathers in Rio to celebrate 500 years of the Angus Method. They took Rio because most members of the Consensus Panel are Brazilians. The unparalleled ability to socialize and perform circumstantial imitation led Brazilian intensivists to the highest positions many generations ago. The Federation headquarters is also located in Rio. There they preserve the large backups of the uploaded minds of hundreds of physically deceased members and their descendants who are also inborn members of The Task Force Class. The hereditary succession started right at the beginning of the 22nd century. Since then, the younger's duty has been to occupy key funding agencies worldwide.
The idea of triaging patients for -omics assessment and immune regulation with monoclonal antibodies, as discussed in Sepsis-7, was abandoned in 2185, in the Sepsis-23 Consensus Panel. The regulation therapy never worked, and no one was interested in keeping the production of those monoclonal antibodies.
Sepsis-23 was a particularly revolutionary Consensus. They concluded that pre-clinical results of immune regulation couldn't be replicated because in the pre-clinical setting you know when sepsis starts but it is impossible to know when sepsis starts in a patient, hence defining sepsis as a triage tool is ineffective. The right receipt of antibodies was never found, no matter how the successive Task Forces refined the thresholds for heart rate, leukocytes, and bilirubin from Sepsis-7 to Sepsis-22.
The Sepsis-23 rupture was consequential. The Task Force deliberated to accept only their descendants to prevent revolutions. Nevertheless, the gradual acknowledgment of impossible translation made sepsis pre-clinical research useless. All the pre-clinical field of sepsis research faded and died. In 2204, the Shock Journal was finally closed without publishing the pre-clinical description of a single effective therapy in two and a half centuries.
In 2521, we don't discuss sepsis physiopathology or any mechanistic approach to disease. Most members of the Task Force never thought of biological plausibility. Only a few early-21st-century members occasionally speak about it, but they are so old, they have accumulated so many bugs and so much information in their AI minds that they seldom say anything.
The Angus Method is now absolute. We have five centuries of medical records to update the 2490 Sepsis-47 definitions. Updates are now 30 to 40 years apart. There is no need to hurry because most of the members have already left their physical bodies, and the ones that are still physical know they will be in the Task Force forever. In 2521, the Sepsis Consensus Task Force evaluates the best oxygen saturation within the normal range, a pressing issue for the critical care community.
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Cool prediction!