Sweeney TE, Schultz B, Khatri P, et al. “Pilot study of a novel serum mRNA gene panel for diagnosis of acute septic arthritis” World Journal of Orthopedics. Dec 2019.
Septic arthritis is an orthopedic emergency requiring immediate surgical intervention. Current diagnostic standard of care is an invasive joint aspiration. Aspirations provide information about the inflammatory cells in the sample within a few hours, but there is often ambiguity about whether the source is infectious (e.g. bacterial) or non-infectious (e.g. gout). Cultures can take days to result, so decisions about surgery are often made with incomplete data. Novel diagnostics are thus needed. The “Sepsis MetaScore” (SMS) is an 11-mRNA host immune blood signature that can distinguish between infectious and non-infectious acute inflammation. It has been validated in multiple cohorts across heterogeneous clinical settings.
Sweeney TE, Liesenfeld O, May L. “Diagnosis of bacterial sepsis: why are tests for bacteremia not sufficient?” Expert Review of Molecular Diagnostics. Aug 2019.
Rapid diagnosis of sepsis, and its underlying causes, is of great interest. With pathogen detection techniques showing a multitude of limitations for clinical utility in early sepsis workflow, probing the host immune response to infection has gained increased interest. This editorial explores the belief that the initial treatment of patients with sepsis will be best supported by ultra-rapid tools that can inform on the ‘two axes’ of sepsis (diagnosis of infection and estimate of severity) at the time of initial presentation.
Gunsolus I, Sweeney TE, et al. “Diagnosing and managing sepsis by probing the host response to infection: Advances, opportunities, and challenges.” Journal of Clinical Microbiology. Jul 2019.
Sepsis is a major source of mortality and morbidity globally. Accurately diagnosing sepsis remains challenging due to the heterogeneous nature of the disease, and delays in diagnosis and intervention contribute to high mortality rates. Measuring the host response to infection enables more rapid diagnosis of sepsis than is possible through direct detection of the causative pathogen, and recent advances in host response diagnostics and prognostics hold promise for improving outcomes.
Sweeney, TE, et al. “Unsupervised analysis of transcriptomics in bacterial sepsis across multiple datasets reveals three robust clusters.” Critical Care Medicine. Mar 2018.
A 33 gene expression test has identified three sepsis subtypes (Inflammopathic, Adaptive, and Coagulopathic), developed and validated via advanced informatics methods. The Adaptive subtype is associated with a lower clinical severity and lower mortality rate, and the Coagulopathic subtype is associated with higher mortality and clinical coagulopathy. These findings may enable a precision medicine approach of matching novel immunomodulatory therapies with septic patients most likely to benefit.
Sweeney TE, et al. “A community approach to mortality prediction in sepsis via gene expression analysis.” Nature Communications. Feb 2018.
The HostDx Sepsis severity gene set, exclusively licensed from Stanford by Inflammatix, when combined with clinical severity scores (the current standard of care), demonstrated a substantial increase in prognostic power for 30-day mortality (i.e., an AUC increase of 10 percent, from 77 percent to 87 percent). This would translate to an ability to rule out approximately 20 percent more sepsis cases, compared to clinical severity scores alone. Such findings suggest this approach could help save substantial resources by avoiding unnecessary care.